Fluorometric and colorimetric quantitative analysis platform for acid phosphatase by cerium ions-directed AIE and oxidase-like activity.

A facile and sensitive fluorescent and colorimetric dual-readout assay for detection of acid phosphatase (ACP) was developed via Ce(III) ions-directed aggregation-induced emission (AIE) of glutathione-protected gold nanoclusters (GSH-AuNCs) and oxidase-mimicking activity of Ce(IV) ions. Free Ce(IV) ions exhibited a strong oxidase-mimetic activity, catalytically oxidizing colorless 3,3',5,5'-tetramethylbenzidine (TMB) into its blue product oxTMB in the presence of dissolved O2, thus triggering a remarkable color reaction detected visually. ACP can hydrolyze L-ascorbic acid-2-phosphate (AAP) with the production of ascorbic acid (AA). The AA is able to reduce Ce(IV) ions to Ce(III) ions, thus quenching the oxidase-mimetic activity of Ce(IV) ions. Meanwhile, Ce(III) ions induce AIE of GSH-AuNCs, resulting in the enhancement of the fluorescence signal of GSH-AuNCs. Both the fluorescent and colorimetric dual-mode analysis platforms exhibit a sensitive response to ACP, providing detection limits as low as 0.101 U/L and 0.200 U/L, respectively. Besides, this fabricated dual-mode detection platform holds the potential for analysis of ACP in human serum samples and screening inhibitors for ACP. With good performance and practicability, this study shows promising application in the convenient and reliable determination of ACP activity.

Porous Poly(ionic Liquid) Membrane with Metal Nanoparticle Gradient: A Smart Actuator for Visualizing Chemical Reactions.

Poly(ionic liquid) (PIL)-based porous membranes are extensively investigated as soft polymer actuators. While PILs have shown significant advancements in membrane fabrication and stabilization of metal nanoparticles (MNPs), research on integrating MNPs into porous membranes to achieve actuation behavior under multiple stimuli is limited. Herein, this work presents a new paradigm for designing a porous PIL-polyacrylic acid (PAA) membrane with a distinct MNP gradient via a top-bottom diffusion approach involving a metal salt precursor solution and NaBH4 as a reducing agent. The strong binding sites provided by PILs, combined with the gradient distribution of -COO- groups across the membrane cross-section, play a significant role in controlling the MNPs' gradient distribution. Interestingly, the MNPs within the membrane display excellent catalytic activity in exothermic reactions such as H2O2 decomposition, dissipating uneven heat that quickly permeates the membrane network. This induces asymmetrical swelling of polymer chains, resulting in rapid membrane bending. Furthermore, such MNP-loaded membrane could serve as a portable test paper for visually monitoring H2O2. This advancement paves the way for the development of intricate smart actuation materials and expands their practical applications in various real-life scenarios.

Smart Hydrogen Atoms in Heterocyclic Cations of 1,2,4-Triazolium-Type Poly(ionic liquid)s.

ConspectusDiscovering and constructing molecular functionality platforms for materials chemistry innovation has been a persistent target in the fields of chemistry, materials, and engineering. Around this task, basic scientific questions can be asked, novel functional materials can be synthesized, and efficient system functionality can be established. Poly(ionic liquid)s (PILs) have attracted growing interest far beyond polymer science and are now considered an interdisciplinary crossing point between multiple research areas due to their designable chemical structure, intriguing physicochemical properties, and broad and diverse applications. Recently, we discovered that 1,2,4-triazolium-type PILs show enhanced performance profiles, which are due to stronger and more abundant supramolecular interactions ranging from hydrogen bonding to metal coordination, when compared with structurally similar imidazolium counterparts. This phenomenon in our view can be related to the smart hydrogen atoms (SHAs), that is, any proton that binds to the carbon in the N-heterocyclic cations of 1,2,4-triazolium-type PILs. The replacement of one carbon by an electron-withdrawing nitrogen atom in the broadly studied heterocyclic imidazolium ring will further polarize the C-H bond (especially for C5-H) of the resultant 1,2,4-triazolium cation and establish new chemical tools for materials design. For instance, the H-bond-donating strength of the SHA, as well as its BroÌ·nsted acidity, is increased. Furthermore, polycarbene complexes can be readily formed even in the presence of weak or medium bases, which is by contrast rather challenging for imidazolium-type PILs. The combination of SHAs with the intrinsic features of heterocyclic cation-functionalized PILs (e.g., N-coordination capability and polymeric multibinding effects) enables new phenomena and therefore innovative materials applications.In this Account, recent progress on SHAs is presented. SHA-related applications in several research branches are highlighted together with the corresponding materials design at size scales ranging from nano- to micro- and macroscopic levels. At a nanoscopic level, it is possible to manipulate the interior and outer shapes and surface properties of PIL nanocolloids by adjusting the hydrogen bonds (H-bonds) between SHAs and water. Owing to the interplay of polycarbene structure, N-coordination, and the polymer multidentate binding of 1,2,4-triazolium-type PILs, metal clusters with controllable size at sub-nanometer scale were successfully synthesized and stabilized, which exhibited record-high catalytic performance in H2 generation via methanolysis of ammonia borane. At the microscopic level, SHAs are found to efficiently catalyze single crystal formation of structurally complex organics. Free protons in situ released from the SHAs serve as organocatalysts to activate formation of C-N bonds at room temperature in a series of imine-linked crystalline porous organics, such as organic cages, macrocycles and covalent organic frameworks; meanwhile the concurrent "salting-out" effect of PILs as polymers in solution accelerated the crystallization rate of product molecules by at least 1 order of magnitude. At the macroscopic scale, by finely regulating the supramolecular interactions of SHAs, a series of functional supramolecular porous polyelectrolyte membranes (SPPMs) with switchable pores and gradient cross-sectional structures were manufactured. These membranes demonstrate impressive figures of merit, ranging from chiral separation and proton recognition to switchable optical properties and real-time chemical reaction monitoring. Although the concept of SHAs is in the incipient stage of development, our successful examples of applications portend bright prospects for materials chemistry innovation.

Hierarchically Porous Poly(ionic liquid) - Organic Cage Composite Membrane for Efficient Iodine Capture.

The effective capture of iodine with high volatility and poisonousness is significant for reprocessing the spent nuclear fuel. In this article, we report a hierarchically porous poly(ionic liquid)-organic cage composite membrane (PIL@CC3) possessing a gradient content distribution of CC3 cage crystals throughout the membrane to capture iodine vapor. The introduction of microporous CC3 can significantly enhance the uptake capacity of iodine up to 980 mg g-1 , which is superior to that of a pristine PIL membrane carrying large meso- and macropores (99 mg g-1 ), and CC3 crystalline powder (662 mg g-1 ). Such enhanced performance benefits from the micro-meso-macroporous structure of the PIL@CC3 membrane in which the large meso- and macropores facilitate the mass transfer of iodine molecules from the external environment into the surface of the CC3 crystal, followed by diffusion of iodine molecules from the CC3 surface into the interior and exterior pores of the CC3 crystal. In addition, the asymmetric distribution of CC3 crystals across the PIL@CC3 membrane also displays its advantage in intercepting trace iodine, revealing its great potential for practical application. This study provides an idea for constructing hierarchically porous membrane composites for the removal of toxic vapors.

Sub-8 nm networked cage nanofilm with tunable nanofluidic channels for adaptive sieving.

Biological cell membrane featuring smart mass-transport channels and sub-10 nm thickness was viewed as the benchmark inspiring the design of separation membranes; however, constructing highly connective and adaptive pore channels over large-area membranes less than 10 nm in thickness is still a huge challenge. Here, we report the design and fabrication of sub-8 nm networked cage nanofilms that comprise of tunable, responsive organic cage-based water channels via a free-interface-confined self-assembly and crosslinking strategy. These cage-bearing composite membranes display outstanding water permeability at the 10-5 cm2 s-1 scale, which is 1-2 orders of magnitude higher than that of traditional polymeric membranes. Furthermore, the channel microenvironments including hydrophilicity and steric hindrance can be manipulated by a simple anion exchange strategy. In particular, through ionically associating light-responsive anions to cage windows, such 'smart' membrane can even perform graded molecular sieving. The emergence of these networked cage-nanofilms provides an avenue for developing bio-inspired ultrathin membranes toward smart separation.

A Versatile Strategy for the Generation of Air-stable Radical-functionalized Materials.

The exploration of a facile approach to create structurally versatile substances carrying air-stable radicals is highly desired, but still a huge challenge in chemistry and materials science. Herein, a non-contact method to generate air-stable radicals by exposing pyridine/imidazole ring-bearing substances to volatile cyanuric chloride vapor, harnessed as a chemical fuel is reported. This remarkable feat is accomplished through a nucleophilic substitution reaction, wherein an intrinsic electron transfer event transpires spontaneously, originating from the chloride anion (Cl- ) to the cationic nitrogen (N+ ) atom, ultimately giving rise to pyridinium/imidazolium radicals. Impressively, the generated radicals exhibit noteworthy stability in the air over one month owing to the delocalization of the unpaired electron through the extended and highly fused π-conjugated pyridinium/imidazolium-triazine unit. Such an approach is universal to diverse substances, including organic molecules, metal-organic complexes, hydrogels, polymers, and organic cage materials. Capitalizing on this versatile technique, surface radical functionalization can be readily achieved across diverse substrates. Moreover, the generated radical species showcase a myriad of high-performance applications, including mimicking natural peroxidase to accelerate oxidation reactions and achieving high-efficiency near-infrared photothermal conversion and photothermal bacterial inhibition.

[Effects of Chinese herbal medicine Dusuqing Granule on toll-like receptor 4 signaling in multiple organ injury induced by bacterial pneumonia in aged rats].

OBJECTIVE: To study the protective mechanism of Dusuqing Granule, a compound Chinese herbal medicine, on the senile multiple organ injury caused by bacterial pneumonia by observing the expression changes of molecules related to toll-like receptor 4 (TLR4) signaling. METHODS: A total of 55 male Sprague-Dawley aged rats were divided into control group, untreated group, Dusuqing group and lomefloxacin group. There were 25 rats in the untreated group and 10 rats in each of the other three groups. Multiple organ injury in a rat model of pneumonia was induced by injection of Klebsiella pneumoniae through tracheal intubation. By means of immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR), examinations were made on mRNA expressions of lipopolysaccharide-binding protein (LBP), CD14, TLR4 and interleukin-1 receptor-associated kinase-1 (IRAK-1) in the tissues of the lung, heart and small intestine, and also on the protein expressions of TLR4, tumor necrosis factor receptor-associated factor 6 (TRAF6) and nuclear factor-κB (NF-κB). RESULTS: Expressions of LBP, CD14, TLR4 and IRAK-1 mRNAs in the tissues of the lung, heart and small intestine in the untreated group were stronger than those in the control group (P<0.01 or Plt;0.05). The protein expressions of TLR4, TRAF6 and NF-κB were increased dramatically in the untreated group as compared with the control group (Plt;0.01 or Plt;0.05). Compared with the untreated group, the expressions of LBP, CD14, TLR4 and IRAK-1 mRNAs in the tissues of the lung, heart and small intestine in the Dusuqing group were weakened significantly (Plt;0.01 or Plt;0.05). Meanwhile, the protein expressions of TLR4, TRAF6 and NF-κB were decreased markedly in the Dusuqing group (Plt;0.01 or Plt;0.05). CONCLUSION: Dusuqing Granule is effective in suppressing toll-like receptor signal transduction activation and reducing the secretion of cytokines and inflammatory mediators, which can further reduce the organ tissue injury. Dusuqing Granule can decrease the levels of TLR signal transduction activation including the targets LBP, CD-14, TLR4, IRAK-1, TRAF6 and NF-κB, which is different from the special inhibitor that acts only on some segments.

Comparing different venous thromboembolism risk assessment machine learning models in Chinese patients.

OBJECTIVE: Venous thromboembolism (VTE) is a fatal complication and the most common preventable cause of death in hospitals. The risk-to-benefit ratio of thromboprophylaxis depends on the performance of the risk assessment model. A linear model, the Padua model, is recommended for medical inpatients in the United States but is not suitable for Chinese inpatients due to differences in race and disease spectrum. Currently, machine learning (ML) methods show advantages in modeling complex data patterns and have been applied to clinical data analysis. This study aimed to build VTE risk assessment ML models among Chinese inpatients and compare the predictive validity of the ML models with that of the Padua model. METHODS: We used 376 patients, including 188 patients with VTE, to build a model and then evaluate the predictive validity of the model in a consecutive clinical dataset from Peking Union Medical College Hospital. Nine widely used ML methods were trained on the model derivation set and then compared with the Padua model. RESULTS: Among the nine ML methods, random forest (RF), boosting-based methods, and logistic regression achieved a higher specificity, Youden index, positive predictive value, and area under the receiver operating characteristic curve than the Padua model on both the test and clinical validation sets. However, their sensitivities were inferior to that of the Padua model. Combined with the receiver operating characteristic curve, RF, as the best performing model, maintained high specificity with relatively better sensitivity and captured VTE patients' patterns more precisely. CONCLUSIONS: Advances in ML technology provide powerful tools for medical data analysis, and choosing models conforming to the disease pattern would achieve good performance. Popular ML models do not surpass the Padua model on all indicators of validity, and the drawback of low sensitivity should be improved upon in the future.

[An experimental study of bronchoscopic lung volume reduction medicine].

OBJECTIVE: To evaluate the effect and safety of experimental bronchoscopic lung volume reduction (BLVR) using an one-way valve designed independently. METHODS: The animal study was carried out from June to December 2008. Totally 36 valves were implanted in the target bronchi of 12 healthy male goats. CT scan, artery blood gas exchange and lung pathology were performed after 2, 4, 8 and 12 weeks. RESULTS: All the valves were implanted successfully, but 3 valves were expectorated at the end. The procedure was well tolerated. CT scan showed that for more than 45% (15/33) of the valves, the target lung tissue had collapsed. Lung pathology showed that the alveolar space was deflated and collapsed. Lymphocytes and monocytes infiltrated the interstitial tissue with some degree of fibrosis. CONCLUSIONS: This animal study showed that the independently manufactured one way valve was effective and safe. The one way valve may be useful in the treatment of severe emphysema in the future.

[A model of multiple organ injury induced by Klebsiella pneumoniae pneumonia in aged rats].

OBJECTIVE: To reproduce a model of bacterial multiple organ injury (MOI) in aged rats. METHODS: Male Sprague-Dawley (SD) rats were used. The young rats were divided into young control group (YCG, n=10) and young model group (YMG, n=15), and the elderly, aged control group (ACG, n=10) and aged model group (AMG, n=25). The model of rats with Klebsiella pneumoniae pneumonia was produced by tracheal instillation of the bacteria, and injury to various organs was observed and evaluated with changes in biochemical parameters, pathological pictures and mortality. RESULTS: Between YMG and AMG, the mortality rates were 33.33% (5/15) and 60.00% (15/25), respectively, at 24 hours after instillation of the bacteria. Compared with YCG and ACG, the neutrophil percentage and white blood cell (WBC) counts in peripheral blood increased significantly in YMG and AMG groups (all P<0.01), the rates of dysfunction of the lungs, the heart and the liver, were 60%-100%. The respiratory dysfunction was evidenced by an increase in the arterial partial pressure of carbon dioxide (PaCO(2), P<0.01), and a decrease in the arterial partial pressure of oxygen (PaO(2), P<0.05 or P<0.01). Myocardial dysfunction was shown by a the sharp increase in creatine kinase (CK), creatine kinase isoenzyme MB (CK-MB) and lactate dehydrogenase (LDH), and that of the liver by changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST, P<0.05 or P<0.01). The pathological changes under light and electronic microscopy were obvious, and the main feature was infiltration of the inflammatory cells. Compared with YMG, PaO(2) in AMG dropped significantly, PaCO(2) increased, CK, CK-MB, LDH, ALT and AST also increased significantly (P<0.05 or P<0.01). The scores of pathological injury in the lungs, the heart and the small intestine in the AMG were obviously higher than that in YMG group (all P<0.05), and the same was trend in the liver and the kidney. CONCLUSION: The model of bacterial MOI in aged rats is reproduced successfully, and it mimics the pathogenesis of multiple organ dysfunction syndrome (MODS) which initiates from infection in the lungs. The model is simple and convenient to replicate with a high success rate. The MOI in the aged rats is characterized by the severity of the organ injury and a high mortality rate.

The lethality of tentacle-only extract from jellyfish Cyanea capillata is primarily attributed to cardiotoxicity in anaesthetized SD rats.

Previous studies in our laboratory have shown that tentacle-only extract (TOE) has similar hypotensive effects with nematocyst venom from jellyfish Cyanea capillata, and the experimental studies on the in vivo cardiovascular effects of TOE were further performed to explore the leading cause of death and analyze the basic physiopathologic change in anaesthztized SD rats. Plots of TOE dose versus time to death showed dose-dependent curvilinear relationship. ECG changed in a dose- and time-dependent manner. Haemodynamic parameters, including the heart rate, mean femoral arterial pressure, left ventricular developed pressure and the first derivative of left ventricular pressures, decreased, but left ventricular end-diastolic pressure did not increase. Arterial partial pressure of oxygen and oxygen saturation did not change. Lactate dehydrogenase, creatine kinase and MB isoenzyme of creatine kinase increased significantly. Histopathological examination showed congestion, haemorrhage, edema and denaturation in the heart; congestion, haemorrhage in the lung and acute congestion in the liver. Transmission electron microscopy examination found that parts of sarcomeric filaments disrupted, dissolved and disappeared, and parts of mitochondria swelled in cardiocytes. Laser scanning confocal microscope examination found that ventricular myocytes from adult rat were deformed and ultimately died within 30 min after TOE treatment. Our results reveal that cardiodepressive effect of C. capillata TOE is the leading cause of death and acute total heart failure is the basic physiopathologic change in anaesthetized SD rats.

In vitro and in vivo haemolytic studies of tentacle-only extract from jellyfish Cyanea capillata.

To approach the real haemolytic process of jellyfish toxins, both in vitro and in vivo haemolysis of tentacle-only extract (TOE) from jellyfish Cyanea capillata has been studied. Dose-response curves of the haemolytic activity of TOE in vitro were sigmoid shaped in both erythrocyte suspension and diluted whole blood, with the former more sensitive to TOE. The in vivo haemolysis increased sharply in the first 10 min and was followed by a gradual increase in the following 3h, with increasing blood potassium and lactic acid accordingly. SC5b-9 complexes were significantly up-regulated in vitro, but not in vivo. These results showed that the haemolysis of TOE in diluted whole blood and in vivo is not totally consistent with that in the erythrocyte suspension, and blood plasma might play a protective role against haemolysis. Thus we suggested that erythrocyte suspension can be used to test the damage of toxin on erythrocyte membrane, while the diluted whole blood may be more suitable to test the haemolysis of toxins.