Conductive Covalent Organic Frameworks with Conductivity- and Pre-Reduction-Enhanced Electrochemiluminescence for Ultrasensitive Biosensor Construction.

Covalent organic frameworks (COFs) have attracted widespread attention in the electrochemiluminescence (ECL) field owing to their high load capacity of ECL luminophores and porous structures, but their ECL performance is still limited by the intrinsic poor conductivity (generally <10-8 S m-1). To address this shortcoming, we used 2,3,6,7,10,11-hexaaminotriphenylene (HATP) and 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP) to synthesize a conductive COF (HHTP-HATP-COF, conductivity = 3.11 × 10-4 S m-1). Compared with HATP, HHTP, and low-conductive HHTP-DABZ-COF, HHTP-HATP-COF exhibited superior ECL performance, not only because HHTP-HATP-COF possessed massive ECL luminophores but also because its conductive porous framework accelerated charge transport in the whole framework and improved the utilization ratio of ECL luminophores. More interestingly, the ECL intensity of the HHTP-HATP-COF/S2O82- system was further improved after pre-reduction electrolysis due to the accumulation of HHTP-HATP-COF cation radicals. The experimental results showed that the ECL intensity of the HHTP-HATP-COF/S2O82- system after pre-reduction was about 1.64-, 3.96-, 6.88-, and 8.09-fold higher than those of HHTP-HATP-COF/S2O82-, HHTP-DABZ-COF/S2O82-, HHTP/S2O82-, and HATP/S2O82- systems, respectively. Considering the superior ECL property of the HHTP-HATP-COF/S2O82- system after pre-reduction, it was used as a high-efficient ECL beacon together with an aptamer/protein proximity binding-induced three-dimensional bipedal DNA walker to construct an ultrasensitive biosensor for thrombin detection, which displayed broad linearity (100 aM to 1 nM) with a detection limit of 62.1 aM. Overall, the work offered effective ways to increase ECL performance by the enhancement of conductivity and by the pre-reduction, proposing new ideas to design high-efficiency COF-based ECL materials and endowing conductive COFs with ECL biosensor application for the first time.

Highly Stable Covalent Organic Framework Nanosheets as a New Generation of Electrochemiluminescence Emitters for Ultrasensitive MicroRNA Detection.

A pyrene-based sp2 carbon-conjugated covalent organic framework (COF) nanosheet (Py-sp2c-CON) with strong and stable electrochemiluminescence (ECL) emission was constructed by C═C polycondensation of tetrakis(4-formylphenyl)pyrene (TFPPy) and 2,2'-(1,4-phenylene)diacetonitrile, which was employed as a highly efficient ECL emitter to fabricate an ECL biosensor for the first time. The Py-sp2c-CON exhibited higher ECL intensity and efficiency than those of TFPPy, bulk Py-sp2c-COF, and imine-linked pyrene COF, not only because the pyrene luminophores and aggregation-induced emissive luminogens (cyano-substituted phenylenevinylene) were topologically linked into Py-sp2c-CON, which greatly increased the immobilization amount of luminophores and decreased the aggregation-caused quenching effect and nonradiative transition but also because the porous ultrathin structure of Py-sp2c-CON effectively shortened transport distances of an electron, ion, and co-reactant (S2O82-), which made more ECL luminophores be activated and thus efficiently increased the utilization ratio of luminophores. More interestingly, when Bu4NPF6 was introduced into the Py-sp2c-CON/S2O82- system as a co-reaction accelerator, the ECL signal of Py-sp2c-CON was further amplified. As expected, the average ECL intensity of the Py-sp2c-CON/S2O82-/Bu4NPF6 system was about 2.03, 5.76, 24.31, and 190.33-fold higher than those of Py-sp2c-CON/S2O82-, Py-sp2c-COF/S2O82-, TFPPy/S2O82,- and imine-linked pyrene COF/S2O82- systems. Considering these advantages, the Py-sp2c-CON/S2O82-/Bu4NPF6 system was employed to prepare an ECL biosensor for microRNA-21 detection, which exhibited a broad linear response (100 aM to 1 nM) and a low detection limit (46 aM). Overall, this work demonstrated that sp2 carbon CONs can be directly used as a high-performance ECL emitter, thus expanding the application scope of COFs and opening a new horizon to develop new types of ECL emitters.

Two Birds with One Stone: Surface Functionalization and Delamination of Multilayered Ti3C2Tx MXene by Grafting a Ruthenium(II) Complex to Achieve Conductivity-Enhanced Electrochemiluminescence.

Two-dimensional (2D) nanosheets have captured significant attention in constructing highly efficient electrochemiluminescent (ECL) materials because their high surface area and fully exposed postmodification sites could greatly increase the loading amount of luminophores. However, traditional 2D nanosheets as carriers exhibited natively poor electrical conductivity that restricted the electrochemical activation and the utilization ratio of ECL luminophores. Herein, to overcome this drawback, we utilized conductive 2D Ti3C2Tx MXene nanosheets as carriers to graft Ru(bpy)2(mcpbpy)2+ (bpy = 2,2'-bipyridine, mcpbpy = 4-(4'-methyl-[2,2'-bipyridin]-4-yl) butanoic acid) via a dehydrative condensation reaction and electrostatic interaction. Interestingly, Ru(bpy)2(mcpbpy)2+ played the role of "two birds with one stone", where Ru(bpy)2(mcpbpy)2+ acted as both an ECL luminophore and an intercalation molecule to achieve surface functionalization and delamination of multilayered Ti3C2Tx successfully, obtaining 2D ultrathin Ru-complex-grafted MXene nanosheets (Ru@MXene). Owing to the high load capacity and superior electrical conductivity of an ultrathin 2D MXene nanosheet, the obtained Ru@MXene exhibited a superb ECL emission. As expected, compared with the nonconductive 2D ultrathin metal-organic layers (MOLs) as carriers to graft Ru(bpy)2(mcpbpy)2+, the ECL intensity and ECL efficiency of Ru@MXene presented about 5-fold and 1.7-fold enhancement, respectively. Considering these advantages, Ru@MXene was applied to construct an ECL sensor for ultrasensitive determination of mucin 1 (MUC1), which displayed superb sensitivity (100 ag/mL to 10 ng/mL) with a low detection limit of 26.9 ag/mL. Overall, the conductivity-enhanced ECL based on Ru@MXene opened a fire-new chapter to develop splendent performance ECL emitters and shed new light on the application potential of conductive materials in the bioanalysis field.

Matrix Coordination-Induced Electrochemiluminescence Enhancement of Tetraphenylethylene-Based Hafnium Metal-Organic Framework: An Electrochemiluminescence Chromophore for Ultrasensitive Electrochemiluminescence Sensor Construction.

Here, we discovered that rigidifying the tetraphenylethylene (TPE)-based ligand H4TCBPE (H4TCBPE = 1,1,2,2-tetra(4-carboxylbiphenyl)ethylene) into Hf-based metal-organic framework (Hf-TCBPE) could lead to a stronger electrochemiluminescence (ECL) emission in comparison to H4TCBPE aggregates and H4TCBPE monomers. Due to the lack of close-packed TCBPE chromophores in Hf-TCBPE, which was required for aggregation-induced ECL (AI-ECL) enhancement, we defined this unprecedented phenomenon as matrix coordination-induced ECL (MCI-ECL) enhancement. The strong ECL intensity of Hf-TCBPE not only originated from the fixation of the TCBPE ligand between Hf6 clusters that restricted the intramolecular free motions of TCBPE and suppressed the nonradiative relaxation but also stemmed from the high porosity of Hf-TCBPE that rendered both internal and external TCBPE chromophores able to be excited. Considering the unique ECL characteristic of Hf-TCBPE, we combined the new ECL indicator of Hf-TCBPE as well as the phosphate-terminal ferrocene (Fc)-labeled hairpin DNA (Fc-HP3) aptamer together as a signal probe (Hf-TCBPE/Fc-HP3), which was employed to construct a novel "off-on" ECL sensor for ultrasensitive mucin 1 (MUC1) detection with the assistance of the exonuclease III (Exo III)-assisted recycling amplification strategy. As expected, the ECL sensor displayed a desirable linear response range from 1 fg/mL to 1 ng/mL and the detection limit down to 0.49 fg/mL. The MCI-ECL enhancement demonstrated by the Hf-TCBPE developed a new and promising strategy to design and synthesize high-performance metal-organic framework (MOF)-based ECL materials for constructing ultrasensitive ECL sensors.

Nonlinear Relationship Between Macrocytic Anemia and Decompensated Hepatitis B Virus Associated Cirrhosis: A Population-Based Cross-Sectional Study.

Background: Mean corpuscular volume (MCV) is major used as an indicator for the differential diagnosis of anemia. Macrocytic anemia in decompensated cirrhosis is common. However, the relationship between macrocytic anemia and decompensated hepatitis B virus (HBV) associated cirrhosis has not been fully addressed. Methods: In this cross-sectional study, a total of 457 patients diagnosed decompensated HBV associated cirrhosis who met all inclusion criteria from 2011 to 2018 were analyzed. Association between macrocytic anemia and the liver damaged (Model for End Stage Liver Disease (MELD) score) were examined using multiple logistic regression analyses and identified using smooth curve fitting. Results: Compared with normocytic anemia, MCV and MELD are significantly positively correlated in macrocytic anemia (p < 0.001). A non-linear relationship of MCV and MELD association was found though the piecewise linear spline models in patients with decompensated HBV associated cirrhosis. MCV positive correlated with MELD when the MCV was greater than 98.2 fl (regression coefficient = 0.008, 95% CI 0.1, 0.4). Conclusion: Macrocytic anemia may be a reliable predictor for mortality because it is closely related to the degree of liver damage in patients with decompensated HBV associated cirrhosis.

Overcoming Aggregation-Induced Quenching by Metal-Organic Framework for Electrochemiluminescence (ECL) Enhancement: Zn-PTC as a New ECL Emitter for Ultrasensitive MicroRNAs Detection.

Polycyclic aromatic hydrocarbons (PAHs) as traditional electrochemiluminescence (ECL) luminophores have been widely applied in the analysis field. However, their ECL intensity and efficiency are still limited due to the aggregation-induced quenching (ACQ) effect of PAHs. Hence, to overcome this limitation, we put forward a new strategy to increase the ECL intensity and efficiency by eliminating the ACQ effect of PAHs through the coordinative immobilization of PAHs within metal-organic frameworks (MOFs). As anticipated, the proof-of-concept experiment indicated that the coordinative immobilization of perylene-3,4,9,10-tetracarboxylate (PTC) into a Zn-PTC MOF could distinctly increase the ECL intensity and efficiency compared with H4PTC aggregates and H4PTC monomers. The reason for the ECL enhancement of Zn-PTC was that the immobilization of PTC within the MOF effectively amplified the distance between perylene rings of PTC ligands and thus eliminated the ACQ effect. Furthermore, the PTC into Zn-PTC was stacked in an edge-to-edge mode to form J-aggregation, which was also conducive to ECL enhancement. On the basis of the excellent ECL performance, we utilized Zn-PTC as a new ECL emitter combined with exonuclease III-stimulated target cycling and DNAzyme-assisted cycling dual amplification strategies to construct an ECL sensor for microRNA-21 detection, which had a wide signal response (100 aM to 100 pM) with a detection limit of 29.5 aM. Overall, this work represents a new and convenient method to overcome the ACQ effect of PAHs and boost the ECL performance, which opens a new horizon for developing high-performance ECL materials, thus offering more opportunities for building highly sensitive ECL biosensors.

Highly efficient electrochemiluminescence resonance energy transfer material constructed from an AIEgen-based 2D ultrathin metal-organic layer for thrombin detection.

A facile strategy to design a highly efficient electrochemiluminescence resonance energy transfer (ECL-RET) system was proposed by using an AIEgen-based 2D ultrathin metal-organic layer (MOL) to coordinatively immobilize energy donors and acceptors simultaneously, in which the distance between adjacent donor-acceptor pairs was precise and short for obtaining high ECL-RET efficiency.

Restriction of intramolecular motions (RIM) by metal-organic frameworks for electrochemiluminescence enhancement:2D Zr12-adb nanoplate as a novel ECL tag for the construction of biosensing platform.

Herein, a new phenomenon of enhanced electrochemiluminescence (ECL) emission by restricting intramolecular motion in the 2D ultra-thin Zr12-adb (adb = 9,10-anthracene dibenzoate) metal-organic framework (MOF) nanoplate was discovered for the first time. The coordination immobilization of adb in porous ultra-thin Zr12-adb nanoplate endowed the Zr12-adb excellent ECL performance, including stronger ECL signal and higher ECL efficiency relative to those of H2adb monomers and H2adb aggregates. In the 2D Zr12-adb nanoplate, the bridging ligand adb was stretched and fixed between two Zr12 clusters, which restricted intramolecular rotations and suppressed unnecessary energy loss caused by self-rotation, thereby remarkably improved the ECL intensity and efficiency. More importantly, the porous ultra-thin structure of Zr12-adb MOF nanoplate not only allowed the coreactants to diffuse into the MOF interior, making both internal and external adb be excited, but also shortened the migration distance of electrons, ions, coreactants and coreactant intermediates, which further improved the ECL efficiency of Zr12-adb and overcame the shortcoming of H2adb aggregates in which the internal luminophores were not easily excited. Regarding the excellent ECL properties above, Zr12-adb nanoplate was selected as a new ECL emitter incorporated with the bipedal walking molecular machine together to fabricate a biosensor for sensitive detection of mucin 1. The enhanced ECL by restriction of intramolecular motions in MOFs provided a new pathway to improve ECL intensity and efficiency, which lighted up a lamp for the design and manufacture of high-performance ECL materials based on MOFs, thus offering new opportunities to develop ultrasensitive ECL biosensors.

An AIEgen-based 2D ultrathin metal-organic layer as an electrochemiluminescence platform for ultrasensitive biosensing of carcinoembryonic antigen.

In this work, a novel two-dimensional (2D) ultrathin metal-organic layer (MOL) based on the aggregation-induced emission (AIE) ligand H4ETTC (H4ETTC = 4',4''',4''''',4'''''''-(ethene-1,1,2,2-tetrayl)tetrakis(([1,1'-biphenyl]-4-carboxylic acid))) was developed and used to construct a novel electrochemiluminescence (ECL) aptasensor for ultrasensitive detection of carcinoembryonic antigen (CEA). The newly synthesized AIE luminogen (AIEgen)-based MOL (Hf-ETTC-MOL) yielded a higher ECL intensity and efficiency than did H4ETTC monomers, H4ETTC aggregates and 3D bulk Hf-ETTC-MOF. This improvement occurred not only because the ETTC ligands were coordinatively immobilized in a rigid MOL matrix, which restricted the intramolecular free rotation and vibration of these ligands and then reduced the non-radiative transition, but also because the porous ultrathin 2D MOL greatly shortened the transport distances of ions, electrons, coreactant (triethylamine, TEA) and coreactant intermediates (TEA˙ and TEA˙+), which made more ETTC luminophores able to be excited and yielded a high ECL efficiency. On the basis of using the Hf-ETTC-MOL as a novel ECL emitter and rolling circle amplification (RCA) as a signal amplification strategy, the constructed ECL aptasensor exhibited a linear range from 1 fg mL-1 to 1 ng mL-1 with a detection limit of 0.63 fg mL-1. This work has opened up new prospects for developing novel ECL materials and is expected to lead to increased interest in using AIEgen-based MOLs for ECL sensing.

A highly sensitive self-enhanced aptasensor based on a stable ultrathin 2D metal-organic layer with outstanding electrochemiluminescence property.

3D bulk metal-organic frameworks (MOFs) have received growing interest in electrochemiluminescence (ECL) assays because they can provide a high specific surface for loading a large quantity of ECL luminophores, but the ECL efficiency of bulk MOFs is still low since some interior luminophores are difficult to be excited. Herein, an ultrathin 2D metal-organic layer (MOL) for grafting self-enhanced ruthenium complexes (Ru-l-Lys) was first synthesized to greatly increase the utilization ratio of luminophores. Compared with 3D bulk MOFs, ultrathin 2D MOL could provide more accessible postmodification sites for grafting the Ru-l-Lys complexes; the self-enhanced Ru-l-Lys complexes on MOL were easily excited by electrons due to the shortened ion/electron-transport distance and the removal of diffusion barriers. Furthermore, the electron transfer path between the Ru(ii) luminophore and coreactant (l-Lys) was shortened and the energy loss of the luminophores decreased, which significantly improved the ECL efficiency. As expected, our work manifested that the Zr-MOL's loading amount of Ru-l-Lys was about 1.23-fold higher than that of a 3D bulk Zr-MOF, and the ECL intensity and efficiency of Ru-l-Lys-Zr-MOL were around 93.45-fold and 1.64-fold higher than those of control Ru-l-Lys-Zr-MOF, respectively. Considering all of these merits, in this work, we utilized the prepared Ru-l-Lys-Zr-MOL as a highly efficient ECL indicator for the first time to fabricate a highly sensitive self-enhanced aptasensor for mucin 1 (MUC1) determination. The proposed aptasensor showed high sensitivity with a linear range from 1 fg mL-1 to 100 pg mL-1 with a detection limit of 0.72 fg mL-1; it also exhibited excellent specificity and stability. It is noteworthy that this work not only provides a new strategy to design and synthesize high-performance ECL materials, but also opens a new way to develop ultrasensitive ECL sensors for bioanalysis.

Highly stable Ru-complex-grafted 2D metal-organic layer with superior electrochemiluminescent efficiency as a sensing platform for simple and ultrasensitive detection of mucin 1.

This work utilized ultrathin metal-organic layer (MOL) to immobilize luminophores for effectively shortening the ion/electron-transport distance and relieving the diffusional constraints of ion/electron, which greatly enhanced the ECL efficiency and intensity. Moreover, the MOL's immobilization amount of luminophores should be higher than these of bulk MOFs because MOLs possess more accessible postmodification sites for the luminophores with minimal diffusion barriers. As expected, our proof-of-concept experiment indicated that the Hf-MOL's loading number of Ru(bpy)2(mcpbpy)2+ was about 1.74 times that of a 3D mesoporous MOF (PCN-777), and the ECL efficiency and intensity of PEI@Ru-Hf-MOL were around 1.27 times and 14.5 times those of PEI@Ru-PCN-777, respectively. In view of these merits, this work utilized the prepared PEI@Ru-Hf-MOL as a highly efficient sensing platform for simple, rapid and sensitive detection of mucin 1, which exhibited a broad linearity from 1 fg/mL to 10 ng/mL and a low detection limit of 0.48 fg/mL. This work provided a practicable strategy to develop high-performance ECL materials, and therefore opened up a new avenue to design ultrasensitive ECL biosensors, which expanded the application potential of MOLs in ECL assays.

Synthesis of 2-cyclohexenone derivatives via gold(I)-catalyzed hydrative cyclization of 1,6-diynes.

The gold(I) complex (MeAuPPh3) was found to be a highly effective catalyst for the hydrative cyclization of 1,6-diynes to form the corresponding 3-methyl hex-2-enone derivatives with good to excellent yield. The proposed mechanism is described.

Highly Stable Mesoporous Luminescence-Functionalized MOF with Excellent Electrochemiluminescence Property for Ultrasensitive Immunosensor Construction.

In this work, a novel mesoporous luminescence-functionalized metal-organic framework (Ru-PCN-777) with high stability and excellent electrochemiluminescence (ECL) performance was synthesized by immobilizing Ru(bpy)2(mcpbpy)2+ on the Zr6 cluster of PCN-777 via a strong coordination bond between Zr4+ and -COO-. Consequently, the Ru(bpy)2(mcpbpy)2+ could not only cover the surface of PCN-777 but also graft into the interior of PCN-777, which greatly increased the loading amount of Ru(bpy)2(mcpbpy)2+ and effectively prevented the leaching of the Ru(bpy)2(mcpbpy)2+ resulting in a stable and high ECL response. Considering the above merits, we utilized the mesoporous Ru-PCN-777 to construct an ECL immunosensor to detect mucin 1 (MUC1) based on proximity-induced intramolecular DNA strand displacement (PiDSD). The ECL signal was further enhanced by the enzyme-assisted DNA recycling amplification strategy. As expected, the immunosensor had excellent sensitivity, specificity, and responded wide linearly to the concentration of MUC1 from 100 fg/mL to 100 ng/mL with a low detection limit of 33.3 fg/mL (S/N = 3). It is the first time that mesoporous Zr-MOF was introduced into ECL system to assay biomolecules, which might expand the application of mesoporous metal-organic frameworks (MOFs) in bioanalysis. This work indicates that the use of highly stable mesoporous luminescence-functionalized MOFs to enhance the ECL intensity and stability is a feasible strategy for designing and constructing high-performance ECL materials, and therefore may shed light on new ways to develop highly sensitive and selective ECL sensors.

[Clinically randomized controlled trials of moxibustion with salt in bamboo circle for treatment of periarthritis of shoulder].

OBJECTIVE: To assess the clinical therapeutic effect of moxibustion with salt in bamboo circle on periarthritis of shoulder. METHODS Eighty-six cases were randomly divided into a salt-moxibustion group and an electroacupuncture group, 43 cases in each group. The salt-moxibustion group was treated by moxibustion with salt in bamboo circle on the part of obvious pain and hot compress moxibustion on its periphery. The electroacupuncture group was treated with electroacupuncture at Jianyu (LI 15), Jianliao (TE 14), Jianzhen (SI 9), etc. After treatment, the analgesic effect and improvement degrees of active function of the shoulder joint were observed and 3 months later they were followed-up. RESULTS: The two therapies had analgesic effect and could improve active function of shoulder joint, but the salt-moxibustion group in the transient analgesic effect and the improvement degree of active function of the shoulder joint was better than the electroacupuncture group (P< 0.01, P < 0.05). Follow-up survey showed good clinical therapeutic effects in the two groups. The effective rates of pain and active function of shoulder joint were 97.7% and 93.0% in the salt-moxibustion group and 93.0% and 88.4% in the electroacupuncture group, respectively, with no significant differences between the two groups. CONCLUSION: Moxibustion with salt in bamboo circle has an obvious therapeutic effect on periarthritis of shoulder, and it has transient analgesic effect and improves active function of shoulder joint, with a stable and long-term therapeutic effect.

[Hair removal with intense pulsed light (IPL) for hairy skin grafts].

OBJECTIVE: To evaluate the hair-removal effect of IPL for hairy skin grafts. METHODS: 10 patients with hairy skin grafts were treated with IPL (ELITEplus) for hair removal 3 to 5 times at intervals of 2 months. The patients received IPL(610 - 1 000 nm) with spot size of 10 mm x 50 mm, pulse width of 5 msec with a delay of 2 - 20 msec, fluence of 30 - 38.3 J/cm2 . RESULTS: The treatment was well tolerated with no need of anesthesia in all the patients. The hairs were removed completely after 3 to 5 treatments. The treated site could be washed as usual with no need of dressing. There was no blister, infection, hyperpigmentation and scarring. Only vellus were existed during the follow-up period of 6 - 12 months. CONCLUSIONS: IPL is a safe and reliable method to remove unwanted hair on skin grafts. It can be easily performed with a lower complication.

[Hair removal with intense pulsed light].

OBJECTIVE: To evaluate the hair-removal effect of intense pulsed light (IPL). METHODS: The unwanted hairs were removed with ELITE plus IPL. The treatment took 3 - 5 procedures, with an interval of over 2 months. 341 patients underwent the treatment. RESULTS: All the patients were well tolerant without anesthesia. The unwanted hairs were wholly removed after 3 - 5 procedures. After operation, routine cleaning and make-up were allowed and bandaging was not necessary. There were blister in 3 cases and infection in 1 case. No pigmentation and scarring happened. Following-up of 3 - 6 months showed steady results with less regeneration of very thin and soft hair. CONCLUSIONS: IPL is an ideal hair-removal method because of the credible effect, simple operation, rapid treatment and no serious complications.