Europium(III) Functionalized Covalent Organic Framework as Sensitive and Selective Fluorescent Switch for Detection of Uranium.

Uranium poses severe health risks due to its radioactivity and chemical toxicity if released into the environment. Therefore, there is an urgent demand to develop sensing materials in situ monitoring of uranium with high sensitivity and stability. In this work, a fluorescent Eu3+-TFPB-Bpy is synthesized by grafting Eu3+ cation onto TFPB-Bpy covalent organic framework (COF) synthesized through Schiff base condensation of monomers 1,3,5-tris(4-formylphenyl)benzene (TFPB) and 5,5'-diamino-2,2'-bipyridine (Bpy). The fluorescence of Eu3+-TFPB-Bpy is enhanced compared with that of TFPB-Bpy, which is originated from the intramolecular rotations of building blocks limited by the bipyridine units of TFPB-Bpy coordinated with Eu3+. More significantly, Eu3+-TFPB-Bpy is a highly efficient probe for sensing UO22+ in aqueous solution with the luminescence intensity efficiently amplified by complexation of UO22+ with Eu3+. The turn-on sensing capability was derived from the resonance energy transfer occurring from UO22+ to the Eu3+-TFPB-Bpy. The developed probe displayed desirable linear range from 5 nM to 5 µM with good selectivity and rapid response time (2 s) for UO22+ in mining wastewater. This strategy provides a vivid illustration for designing luminescence lanthanide COF hybrid materials with applications in environmental monitoring.

Hydrogen-Bonded Cocrystals Encapsulating CsPbBr3 Perovskite Nanocrystals with Enhancement of Charge Transport for Photocatalytic Reduction of Uranium.

At present, poor stability and carrier transfer efficiency are the main problems that limit the development of perovskite-based photoelectric technologies. In this work, hydrogen-bonded cocrystal-coated perovskite composite (PeNCs@NHS-M) is easily obtained by inducing rapid crystallization of melamine (M) and N-hydroxysuccinimide (NHS) with PeNCs as the nuclei. The outer NHS-M cocrystal passivates the undercoordinated lead atoms by forming covalent bonds, thereby greatly reducing the trap density while maintaining good structure stability for perovskite nanocrystals. Moreover, benefiting from the interfacial covalent band linkage and long-range ordered structures of cocrystals, the charge transfer efficiency is effectively enhanced and PeNCs@NHS-M displays superior photoelectric performance. Based on the excellent photoelectric performance and abundant active sites of PeNCs@NHS-M, photocatalytic reduction of uranium is realized. PeNCs@NHS-M exhibits U(VI) reduction removal capability of up to 810.1 mg g-1 in the presence of light. The strategy of cocrystals trapping perovskite nanocrystals provides a simple synthesis method for composites and opens up a new idea for simultaneously improving the stability and photovoltaic performance of perovskite.

MicroRNA-377-3p exacerbates chronic obstructive pulmonary disease through suppressing ZFP36L1 expression and inducing lung fibroblast senescence.

Chronic obstructive pulmonary disease (COPD) is a leading aging related cause of global mortality. Small airway narrowing is recognized as an early and significant factor for COPD development. Senescent fibroblasts were observed to accumulate in lung of COPD patients and promote COPD progression through aberrant extracellular matrix (ECM) deposition and senescence-associated secretory phenotype (SASP). On the basis of our previous study, we further investigated the the causes for the increased levels of miR-377-3p in the blood of COPD patients, as well as its regulatory function in the pathological progression of COPD. We found that the majority of up-regulated miR-377-3p was localized in lung fibroblasts. Inhibition of miR-377-3p improved chronic smoking-induced COPD in mice. Mechanistically, miR-377-3p promoted senescence of lung fibroblasts, while knockdown of miR-377-3p attenuated bleomycin-induced senescence in lung fibroblasts. We also identified ZFP36L1 as a direct target for miR-377-3p that likely mediated its pro senescence activity in lung fibroblasts. Our data reveal that miR-377-3p is crucial for COPD pathogenesis, and may serve as a potential target for COPD therapy.

CDK12 inhibition upregulates ATG7 triggering autophagy via AKT/FOXO3 pathway and enhances anti-PD-1 efficacy in colorectal cancer.

As the world's fourth most deadly cancer, colorectal cancer (CRC) still needed the novel therapeutic drugs and target urgently. Although cyclin-dependent kinase 12 (CDK12) has been shown to be implicated in the malignancy of several types of cancer, its functional role and mechanism in CRC remain largely unknown. Here, we found that suppression of CDK12 inhibited tumor growth in CRC by inducing apoptosis. And CDK12 inhibition triggered autophagy by upregulating autophagy related gene 7 (ATG7) expression. Inhibition of autophagy by ATG7 knockdown and chloroquine (CQ) further decreased cell viability induced by CDK12 inhibition. Further mechanism exploration showed that CDK12 interacted with protein kinase B (AKT) regulated autophagy via AKT/forkhead box O3 (AKT/FOXO3) pathway. FOXO3 transcriptionally upregulated ATG7 expression and autophagy when CDK12 inhibition in CRC. Level of CDK12 and p-FOXO3/FOXO3 ratio were correlated with survival in CRC patients. Moreover, CDK12 inhibition improved the efficacy of anti-programmed cell death 1(PD-1) therapy in CRC murine models by enhancing CD8 + T cells infiltration. Thus, our study founded that CDK12 inhibition upregulates ATG7 triggering autophagy via AKT/FOXO3 pathway and enhances anti-PD-1 efficacy in CRC. We revealed the roles of CDK12/FOXO3/ATG7 in regulating CRC progression, suggesting potential biomarkers and therapeutic target for CRC.

The role and mechanism of tight junctions in the regulation of salivary gland secretion.

Tight junctions (TJs) are cell-cell interactions that localize at the most apical portion of epithelial/endothelial cells. One of the predominant functions of TJs is to regulate material transport through paracellular pathway, which serves as a selective barrier. In recent years, the expression and function of TJs in salivary glands has attracted great interest. The characteristics of multiple salivary gland TJ proteins have been identified. During salivation, the activation of muscarinic acetylcholine receptor and transient receptor potential vanilloid subtype 1, as well as other stimuli, promote the opening of acinar TJs by inducing internalization of TJs, thereby contributing to increased paracellular permeability. Besides, endothelial TJs are also redistributed with leakage of blood vessels in cholinergic-stimulated submandibular glands. Furthermore, under pathological conditions, such as Sjögren's syndrome, diabetes mellitus, immunoglobulin G4-related sialadenitis, and autotransplantation, the integrity and barrier function of TJ complex are impaired and may contribute to hyposalivation. Moreover, in submandibular glands of Sjögren's syndrome mouse model and patients, the endothelial barrier is disrupted and involved in hyposecretion and lymphocytic infiltration. These findings enrich our understanding of the secretory mechanisms that link the importance of epithelial and endothelial TJ functions to salivation under both physiological and pathophysiological conditions.

Research progress on the association between trimethylamine/trimethylamine-N-oxide and neurological disorders.

Trimethylamine-N-oxide (TMAO) is a common intestinal metabolite. The Choline in the nutrient forms TMA under the action of the gut microbiota, which passes through the liver and eventually forms TMAO. Initial studies of TMAO focused on cardiovascular disease, but as research progressed, TAMO's effects were found to be multisystem and closely related to the development of neurological diseases. Intestinal tract is the organ with the largest concentration of bacteria in human body, and the composition and metabolism of gut microbiota affect human health. As a two-way communication axis connecting the central nervous system and the gastrointestinal tract, the brain-gut axis provides the structural basis for TMAO to play its role. This article will review the correlation between TMA/TMAO and neurological diseases in order to find new directions and new targets for the treatment of neurological diseases.

Alterations of nasal microbiome in eosinophilic chronic rhinosinusitis.

BACKGROUND: Exposure to microbes may be important in the development of chronic rhinosinusitis (CRS). Dysbiosis of the nasal microbiome is considered to be related to CRS with nasal polyps (CRSwNP). The link between the nasal microbiota and eosinophilic CRSwNP (eCRSwNP) has rarely been studied. OBJECTIVE: The aim of this study was to rigorously characterize nasal dysbiosis in a cohort of patients with eCRSwNP and compare the nasal microbiomes of these patients with those of healthy controls (HCs). METHODS: We performed a cross-sectional study of 34 patients with eCRSwNP, 10 patients without CRSwNP, and 44 HCs by using 16S rRNA gene sequencing. An independent cohort of 14 patients with eCRSwNP, 9 patients without CRSwNP, and 11 HCs was used to validate the results. RESULTS: Compared with the nasal microbiome of healthy controls, the nasal microbiome of patients with eCRSwNP was characterized by higher α-diversity (Shannon and Chao1 index) and a distinct composition of microbes. Notably, the distinct differences in microbial composition between patients with eCRSwNP and HCs were significantly correlated with eCRSwNP disease status. Furthermore, in a diagnostic model generated by using these differences, a combination of 15 genera could be used to distinguish patients with eCRSwNP from HCs, with an area under the curve of approximately 0.8 in both the exploration and validation cohorts. CONCLUSION: Our study establishes the compositional alterations in the nasal microbiome in eCRSwNP and suggests the potential for using the nasal microbiota as a noninvasive predictive classifier for the diagnosis of eCRSwNP.

Structural Isomerism of Covalent Organic Frameworks Causing Different Electrochemiluminescence Effects and Its Application for the Detection of Arsenic.

The structural isomerism of the covalent organic framework (COF) has a significant effect on the electrochemiluminescence (ECL) performance. Herein, we report a pair of isomeric COFs, (TFPB-BD(OMe)2-H and TAPB-BD(OMe)2-H), based on the different directions of imine linkages and further conversion of the imine to the quinoline structure. The obtained two isomeric COFs with the same composition and similar structures exhibit dramatic differences in the photoelectrochemical and ECL fields. Indeed, TFPB-BD(OMe)2-H demonstrates robust ECL emission superior to that of TAPB-BD(OMe)2-H. The difference in ECL performance is due to the stronger polar interaction of TFPB-BD(OMe)2-H than that of TAPB-BD(OMe)2-H. The polarity is derived from the uneven charge distribution within the framework and enhances the electron interactions. In addition, the ordered conjugate skeleton provides high-speed charge transport channels for carrier transport. Therefore, the TFPB-BD(OMe)2-H presents a smaller band gap energy and stronger polarization interaction, which are more favorable to charge migration to achieve stronger ECL signals. Furthermore, we describe a convenient ECL sensor for detecting toxic As(V) with an outstanding detection property and ultralow detection limit. This work provides a guiding principle for the design and development of ECL organic luminophores.

Guest Molecular Assembly Strategy in Covalent Organic Frameworks for Electrochemiluminescence Sensing of Uranyl.

The application of covalent organic frameworks (COFs) in electrochemiluminescence (ECL) is promising in environmental monitoring. Developing an emerging design strategy to expand the class of COF-based ECL luminophores is highly desirable. Here, a COF-based host-guest system was constructed through guest molecular assembly to deal with nuclear contamination analysis. The efficient charge transport network was formed by inserting an electron-withdrawing guest tetracyanoquinodimethane (TCNQ) into the open space of the COF host (TP-TBDA; TP = 2,4,6-trihydroxy-1,3,5-benzenetricarbaldehyde and TBDA = 2,5-di(thiophen-2-yl)benzene-1,4-diamine) with an electron-donating property; the construction of the COF-based host-guest system (TP-TBDA@TCNQ) triggered the ECL emission of non-emitting TP-TBDA. Furthermore, the dense active sites in TP-TBDA were utilized to capture the target substance UO22+. The presence of UO22+ broke the charge-transfer effect in TP-TBDA@TCNQ, resulting in the weakening of the ECL signal, thus the established ECL system integrating the low detection limit with high selectivity monitors UO22+. This COF-based host-guest system provides a novel material platform for constructing late-model ECL luminophores and creates an opportunity for the vigorous ECL technology.

Reversed Regulation Effects of ssDNA on the Mimetic Oxidase and Peroxidase Activities of Covalent Organic Frameworks.

Nanomaterials with enzyme mimetic activity have attracted extensive attention, especially in the regulation of their catalytic activities by biomolecules or other polymers. Here, a covalent organic framework (Tph-BT COF) with excellent photocatalytic activity is constructed by Schiff base reaction, and its mimetic oxidase activity and peroxidase activity is inversely regulated via single-stranded DNA (ssDNA). Under light-emitting diode (LED) light irradiation, Tph-BT exhibited outstanding oxidase activity, which efficiently catalyzed oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) to produce blue oxTMB, and ssDNA, especially those with poly-thymidine (T) sequences, can significantly inhibit its oxidase activity. On the contrary, Tph-BT showed weak peroxidase activity, and the presence of ssDNA, particularly poly-cytosine (C) sequences, can remarkably enhance the peroxidase activity. The influence of base type, base length, and other factors on the activities of two enzymes is also studied, and the results reveal that the adsorption of ssDNA on the surface of Tph-BT prevented intersystem crossing (ISC) and energy transfer processes to reduce 1 O2 generation, while the electrostatic interaction between ssDNA and TMB enhanced Tph-BT's affinity for TMB to facilitate the electron transfer from TMB to • OH. This study investigates multitype mimetic enzyme activities of nonmetallic D-A conjugated COFs and demonstrates their feasibility of regulation by ssDNA.

Phosphatidylglucose alleviates atherosclerosis by increasing cholesterol alienation to bile acids and cholesterol efflux in ApoE-/- mice.

BACKGROUND: Phosphatidylcholine (PC) is considered to be the major dietary source for choline, which is associated with atherosclerosis progress. Thus, phosphatidylglucose (PG) was prepared by enzymatic modification of PC to investigate the effects on atherosclerosis in apolipoprotein E deficient (ApoE-/- ) mice, as well as to investigate its dose-response relationship. RESULTS: The results showed that dietary PG significantly decreased the atherosclerotic lesion area in a dose-dependent manner. Further studies found that intervention with a 0.8 g kg-1 and 2 g kg-1 PG diet for 4 months significantly decreased free cholesterol level and thus reduced total cholesterol levels in serum. The results of cholesterol distribution among lipoproteins showed that dietary PG significantly decreased low-density lipoprotein levels in ApoE-/- mice. In addition, only administration of high-dose PG significantly reduced total cholesterol levels in liver tissues by 31.2%. Furthermore, mice treated with high-dose PG had an expanded bile acid pool and increased the ratio of conjugated bile acids to unconjugated bile acids in the liver, serum and gallbladder by increasing hepatic gene expression of primary and conjugated bile acid synthesis. Additionally, low-dose and high-dose PG significantly increased total fecal sterols by 20.8% and 11.9%, respectively, by increasing sitosterol and ethylcoprostanol levels. CONCLUSION: These results indicate that PG alleviated atherosclerosis in a dose-dependent manner by increasing cholesterol alienation to bile acids and cholesterol efflux. © 2023 Society of Chemical Industry.

Rapid Charge Transfer Enabled by Noncovalent Interaction through Guest Insertion in Supercapacitors based on Covalent Organic Frameworks.

Covalent organic frameworks (COFs) have been proposed for electrochemical energy storage, although the poor conductivity resulted from covalent bonds limits their practical performance. Here, we propose to introduce noncovalent bonds in COFs through a molecular insertion strategy for improving the conductivity of the COFs as supercapacitor. The synthesized COFs (MI-COFs) establish equilibriums between covalent bonds and noncovalent bonds, which construct a continuous charge transfer channel to enhance the conductivity. The rapid charge transfer rate enables the COFs to activate the redox sites, bringing about excellent electrochemical energy storage behavior. The results show that the MI-COFs exhibit much better performance in specific capacitance and capacity retention rate than those of most COFs-based supercapacitors. Moreover, through simply altering inserted guests, the mode and strength of noncovalent bond can be adjusted to obtain different energy storage characteristics. The introduction of noncovalent bonds is an effective and flexible way to enhance and regulate the properties of COFs, providing a valuable direction for the development of novel COFs-based energy storage materials.

Assembling Alkaline-Responsive Chitosan@Giant Liposomes through an Ultrasound-Integrated Microfluidic Approach.

This paper presents the fabrication of an alkaline-responsive drug carrier, chitosan@giant liposome (CS-GL), by using an ultrasound-integrated microfluidic approach. On the microfluidic chip, water/oil/water droplets are first prepared and then move through an area of ultrasonic radiation to improve the regional saturation of organic solvent and accelerate its removal. At the same time, phospholipid molecules in the oil phase of the droplets are efficiently self-assembled into giant liposomes (GLs). Subsequently, microfluidic channels combined with an up-down separated structure can help in the fabrication and purification of the GLs. Due to the electrostatic interaction between the amino group of chitosan and the phosphate group of phospholipids, the GLs and chitosan are assembled into CS-GLs. The change of ζ potential after this operation indicates that chitosan is coated on the surface of GLs. The formed CS-GLs are monodispersed with a 54.1 ± 0.7 µm diameter and high drug encapsulation efficiency (∼96%), and the structural integrity can be kept without leakage of contents for more than a week in an acid medium (pH = 1.2). When this structure is placed in an aqueous solution of pH = 7.8, chitosan precipitates gradually and detaches from the GL, causing its rupture. The drug encapsulated in a single CS-GL can be rapidly released within 4 s, and 99.6% of the CS-GL carriers can complete the release within 10 min.

A Review of the Role of the Antiplatelet Drug Ticagrelor in the Management of Acute Coronary Syndrome, Acute Thrombotic Disease, and Other Diseases.

P2Y12 inhibitors, including aspirin, are key components of dual-antiplatelet therapy (DAPT), which is the optimal therapeutic strategy for preventing arterial thrombosis in patients with acute coronary syndromes (ACS) who underwent stent implantation. Ticagrelor is a cyclopentyl-triazole pyrimidine antiplatelet drug that was the first reversible oral P2Y12 receptor antagonist. Compared with clopidogrel, ticagrelor exerts a faster onset and offset of function by reversible and selective inhibition of platelet aggregation in ACS patients, including those with coronary artery blood revascularization. Despite improvement in stent materials, stent thrombosis (ST) due to high on-treatment platelet reactivity (HPR) to clopidogrel continues to occur. In addition to antiplatelet aggregation, ticagrelor displays pleiotropic cardioprotective effects, including improving coronary blood flow, reducing myocardial necrosis after an ischemic event, and anti-inflammatory effects. The benefits of ticagrelor over clopidogrel were consistent in the PLATO results, with lower incidence of the primary endpoint. Also, in 2020, the findings from the phase 3 THALES trial (NCT03354429) showed that aspirin combined with 90 mg of ticagrelor significantly reduced the rates of stroke and death compared with aspirin alone in patients with AIS or TIA. Here, we review recent research on the superiority of ticagrelor over clopidogrel, discuss the pharmacological mechanism, and present future perspectives. This review aims to present the roles of ticagrelor in the management of acute coronary syndrome, acute thrombotic disease, and other diseases.

Local Skull Thinning is One of Risks for the Ruptured Arachnoid Cysts With Chronic Subdural Hematoma in Adults: Thirty-two Clinical Reports.

OBJECTIVE: Chronic subdural hematomas (CSDHs) in young people are uncommon, rupture of arachnoid cysts (ACs) is one of the reasons for young patients. The detailed features of CSDHs associated with ACs remain poorly understood. The objective of this study is to analyze the characteristics of risks for the rupture of ACs with CSDH in Adults. METHODS: The CT scans of 1231 patients who were diagnosed as CSDH were reviewed between Jan 2009 and Jan 2019 in the Department of Neurotrauma in Beijing Tian Tan Hospital, Capital Medical University/China National Clinical Research Center for Neurological Diseases. The clinical features, treatments, and prognosis of 32 patients with ACs were analyzed. RESULTS: Ruptured ACs with CSDH were diagnosed in 32 patients in 1231 CSDH cases, which account for 2.60%. Headache was the commonest presenting symptom. According to the Takizawa' classification, there were 22 cases for Type A, 9 for Type B and 1 for Type C. Thinning or external convex of the calvarium was demonstrated in 17/32 cases (53.1%). Thirty-one patients were treated with burr hole irrigation. Favorable outcomes were achieved in all patients. CONCLUSIONS: The presence of ACs should be taken into consideration in young and middle-aged patients with CSDH. For those patients were found ACs in conventional medical examination, especially those whose imaging examinations demonstrated thinning or external convex of the calvarium, it was crucial to remind them to avoid the occurrence of traumatic brain injury (TBI). Burr hole irrigation is still the preferred treatment for ruptured ACs with CSDH.

Metal Cluster Triggered-Assembling Heterogeneous Au-Ag Nanoclusters with Highly Loading Performance and Biocompatible Capability.

In this work, we firstly report the preparation of heterogeneously assembled structures Au-Ag nanoclusters (NCs) as good drug carriers with high loading performance and biocompatible capability. As glutathione-protected Au and Ag clusters self-assembled into porous Au-Ag NCs, the size value is about 1.358 (±0.05) nm. The morphology characterization revealed that the diameter of Au-Ag NCs is approximately 120 nm, as well as the corresponding potential ability in loading performance of the metal cluster triggered-assembling process. Compared with individual components, the stability and loading performance of heterogeneous Au-Ag NCs were improved and exhibit that the relative biocompatibility was enhanced. The exact information about this is that cell viability was approximately to 98% when cells were incubated with 100 µg mL-1 particle solution for 3 days. The drug release of Adriamycin from Au-Ag NCs was carried out in PBS at pH = 7.4 and 5.8, respectively. By simulating in vivo and tumor microenvironment, the release efficiency could reach over 65% at pH = 5.8 but less than 30% at pH = 7.2. Using an ultrasound field as external environment can accelerate the assembling process while metal clusters triggered assembling Au-Ag NCs. The size and morphology of the assembled Au-Ag NCs can be controlled by using different power parameters (8 W, 13 W, 18 W) under ambient atmosphere. Overall, a novel approach is exhibited, which conveys assembling work for metal clusters triggers into heterogeneous structures with porous characteristic. Its existing properties such as water-solubility, stability, low toxicity and capsulation can be considered as dependable agents in various biomedical applications and drug carriers in immunotherapies.

Bioinspired Pd-Cu Alloy Nanoparticles as Accept Agent for Dye Degradation Performances.

Dye degradation is a key reaction in organic decomposition production through electron donor transferring. Palladium (Pd) is the best-known element for synthesis Pd-based catalyst, the surface status determines the scope of relative applications. Here we first prepare Pd-Cu alloy nanoparticles (NPs) by co-reduction of Cu(acac)2 (acac = acetylacetonate) and Pd(C5HF6O2)2 in the presence of sodium borohydride (NaBH4) and glutathione (GSH). The obtained Pd-Cu is about ~10 nm with super-hydrophilicity in aqueous mediums. The structural analysis clearly demonstrated the uniform distribution of Pd and Cu element. The colloidal solution keeps stability even during 30 days. Bimetallic Pd-Cu NPs shows biocompatibility in form of cell lines (IMEF, HACAT, and 239 T) exposed to colloidal solution (50 µg mL-1) for 2 days. It shows the catalytic multi-performance for dye degradation such as methyl orange (MO), rhodamine B (RhB), and methylene blue (MB), respectively. The as-synthesized nanoparticles showed one of the best multiple catalytic activities in the industrially important (electro)-catalytic reduction of 4-nitrophenol (4-NP) to corresponding amines with noticeable reduced reaction time and increased rate constant without the use of any large area support. In addition, it exhibits peroxidase-like activity in the 3, 3', 5, 5'-Tetramethylbenzidine (TMB) color test and exhibit obvious difference with previous individual metal materials. By treated with high intensity focused ultrasound filed (HIFU), Pd-Cu NPs might be recrystallized and decreased the diameters than before. The enhancement in catalytic performance is observed obviously. This work expedites rational design and synthesis of the high-hierarchy alloy catalyst for biological and environment-friendly agents.

New Insight into Assembled Fe3O4@PEI@Ag Structure as Acceptable Agent with Enzymatic and Photothermal Properties.

Metal-based enzyme mimics are considered to be acceptable agents in terms of their biomedical and biological properties; among them, iron oxides (Fe3O4) are treated as basement in fabricating heterogeneous composites through variable valency integrations. In this work, we have established a facile approach for constructing Fe3O4@Ag composite through assembling Fe3O4 and Ag together via polyethyleneimine ethylenediamine (PEI) linkages. The obtained Fe3O4@PEI@Ag structure conveys several hundred nanometers (~150 nm). The absorption peak at 652 nm is utilized for confirming the peroxidase-like activity of Fe3O4@PEI@Ag structure by catalyzing 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2. The Michaelis-Menten parameters (Km) of 1.192 mM and 0.302 mM show the higher catalytic activity and strong affinity toward H2O2 and TMB, respectively. The maximum velocity (Vmax) value of 1.299 × 10-7 M·s-1 and 1.163 × 10-7 M·s-1 confirm the efficiency of Fe3O4@PEI@Ag structure. The biocompatibility illustrates almost 100% cell viability. Being treated as one simple colorimetric sensor, it shows relative selectivity and sensitivity toward the detection of glucose based on glucose oxidase. By using indocyanine green (ICG) molecule as an additional factor, a remarkable temperature elevation is observed in Fe3O4@PEI@Ag@ICG with increments of 21.6 ∘C, and the absorption peak is nearby 870 nm. This implies that the multifunctional Fe3O4@PEI@Ag structure could be an alternative substrate for formatting acceptable agents in biomedicine and biotechnology with enzymatic and photothermal properties.

LINC00511 promotes gastric cancer progression by regulating SOX4 and epigenetically repressing PTEN to activate PI3K/AKT pathway.

Gastric cancer (GC) serves as a common malignancy. Long non-coding RNAs (lncRNAs) have been proven to regulate many cancers, including GC. Long intergenic non-protein-coding RNA 511 (LINC00511) has been poorly studied in GC, but its detailed regulatory mechanism has not been identified. Here, LINC00511 was detected to be highly expressed in GC cells. Functional assays were conducted and uncovered that LINC00511 boosted cell proliferation, migration, stemness and EMT process while inhibiting the apoptosis of GC cells. From a series of mechanism experiments, it was found that at the transcriptional level, LINC00511 recruited EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) to the promoter of PTEN (phosphatase and tensin homolog) and facilitated methylation of PTEN promoter. LINC00511 epigenetically repressed PTEN to activate the PI3K/AKT pathway. Moreover, SRY-box transcription factor 4 (SOX4) activated the transcription of LINC00511. At the post-transcriptional level, LINC00511 sponged miR-195-5p to elevate SOX4 expression in GC cells. On the whole, the present study disclosed that SOX4-induced LINC00511 activated SOX4 via competing endogenous RNA (ceRNA) pattern and epigenetically repressed PTEN to activate PI3K/AKT pathway by recruiting EZH2, thus facilitating GC cell proliferation, migration and stemness while inhibiting GC cell apoptosis.

Association between rectal douching and HIV acquisition: the mediating role of condom use and rectal bleeding in a national online sample of Chinese men who have sex with men.

OBJECTIVES: Previous studies have demonstrated that rectal douching (RD) is associated with HIV acquisition among men who have sex with men (MSM). However, the precise mechanism underlying the association between RD and HIV remains unclear. METHODS: We recruited participants over WeChat from October 2017 to October 2018. Respondents received mailed HIV self-testing kits, uploaded images of HIV self-test results and completed an online electronic questionnaire simultaneously. The questionnaire assessed sociodemographic characteristics, RD practices and sexual risk behaviours. HIV status was measured as the result of the HIV self-testing. The Baron and Kenny statistical method was used to assess the association between RD and HIV, controlling for condomless anal intercourse (CAI) and rectal bleeding. RESULTS: Of 1365 participants, 39.93% (545/1365) reported RD in the past 6 months, 60.07% had multiple male sexual partners and 43.08% had CAI in the past 6 months. The prevalence of HIV, based on self-testing, was 3.37% (46/1365). Multivariable logistic analysis showed RD was significantly associated with bottom sexual role (adjusted OR (aOR) 14.0; 95% CI 9.8 to 20.2), having multiple male sexual partners (aOR 1.8; 95% CI 1.4 to 2.2), CAI (aOR 1.3; 95% CI 1.0 to 1.6), rectal bleeding (aOR 2.0; 95% CI 1.6 to 2.6) and HIV infection (aOR 1.9; 95% CI 1.0 to 3.4). Baron and Kenny analysis found both CAI (aOR 2.2; 95% CI 1.2 to 4.1) and rectal bleeding (aOR 1.9; 95% CI 1.0 to 3.4) play a mediating role in the association between RD and HIV. CONCLUSIONS: Our study results confirmed the relationship between RD and HIV, and found CAI and rectal bleeding mediated HIV infection in Chinese MSM who douched. Strategies should be encouraged to strengthen health education and reduce high-risk sexual behaviour in order to reduce the risk of HIV in MSM who use enemas. Rectal microbicides may represent an efficient means of providing HIV prophylaxis among MSM.