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Nanozymes and cyclic GMP-AMP synthase (cGAS) the stimulator of interferon genes (STING) signaling pathway, as powerful organons, can remodel the tumor microenvironment (TME) to increase efficacy and overcome drug resistance in cancer immunotherapy. Nanozymes have the potential to manipulate the TME by producing reactive oxygen species (ROS), which lead to positive oxidative stress in tumor cells. Cyclic dinucleotide (2′,3′-cGAMP), as a second messenger, exists in the TME and can regulate it to achieve antitumor activity. In this work, Co,N-doped carbon dots (CoNCDs) were used as a model nanozyme to evaluate the properties of the anti-tumor mechanism, and effective inhibition of S180 tumor was achieved. Based on CoNCDs' good biocompatibility and therapeutic effect on the tumor, we then introduced the cGAS–STING agonist, and the combination of the CoNCDs and STING agonist significantly inhibited tumor growth, and no significant systemic toxicity was observed. The combined system achieved the enhanced tumor synergistic immunotherapy through TME reprogramming via the peroxidase-like activity of the CoNCDs and cGAS–STING signaling pathway agonist synergistically. Our work provides not only a new effective way to reprogram TME in vivo, but also a promising synergic antitumor therapy strategy. [ABSTRACT FROM AUTHOR]

2′, 3′-cGAMP (CDN) as cGAS-STING pathway agonist is extensively used in tumor treatment. However, due to its negatively charged nature (containing two phosphate groups) and high hydrophilicity, CDN faces challenges in crossing cell membranes, resulting in reduced efficiency of its use. Additionally, CDN is susceptible to inactivation through phosphodiesterase hydrolysis. Therefore, the development of a new drug delivery system for CDN is necessary to prevent hydrolysis and enhance targeted accumulation in tumors, as well as improve cellular uptake for STING activation. In this study, we have developed peptide-polymer nanofibers (PEG-Q11) that incorporate thymine (T) and arginine (R) residues to facilitate complexation with CDN through the principles of Watson-Crick base pairing with thymine and favorable electrostatic interactions and bidentate hydrogen bonding with arginine side chains. The entrapment efficiency (EE) of PEG-Q11T3R4@CDN was found to be 51% higher than that of PEG-Q11@CDN. Due to its favorable biocompatibility, PEG-Q11T3R4@CDN was employed for immunotherapy in mouse CT26 tumors. In local tumor treatment, the administration of PEG-Q11T3R4@CDN at a low dose and through a single injection exhibited inhibitory effects. Furthermore, the local injection of PEG-Q11T3R4@CDN resulted in systemic therapeutic responses, effectively suppressing tumor metastasis by activating CD8 + T cells to target distant tumors. This research not only underscores the potential of PEG-Q11T3R4@CDN as an efficient therapeutic agent but also highlights its ability to achieve long-lasting systemic therapeutic outcomes following local treatment. Consequently, PEG-Q11T3R4@CDN represents a promising strategy for immunization. • A nucleobase was used to modify self-assembled peptide loading CDN for the first time. • The new platform interacted with CDN via H-bonding and favorable electrostatic interactions to improve the dose of CDN loaded. • The new platform boosted the effect of CDN release, and realized a single administration of CDN. • The new platform strongly influenced tumor immunotherapy in proximal and distal tumors. [ABSTRACT FROM AUTHOR]

Remote ischemic preconditioning (RIPC) is a minimally invasive method that provides protection by reducing injury to the heart, kidneys, brain and other tissues or organs. RIPC may improve the outcome in patients undergoing surgery. Although the role of RIPC has been studied, the results remain controversial. It is difficult to confirm whether RIPC has a kidney protective effect and the understanding of the preconditioning signal pathway involved remains unclear. In the present study, the effect of RIPC in urology was evaluated. The protection against renal damage was assessed by investigating the potential mediator, hypoxia‑inducible factor‑1α (HIF‑1α), and the functional adrenomedullin (ADM) pathway. Male Sprague‑Dawley (SD) rats were used in the present study. The animal model of kidney damage induced by ischemia reperfusion (IR) was used to investigate the protective effect of the acute and delayed phase RIPC. Furthermore, the protective effects of RIPC mediated by a HIF‑1α‑ADM pathway were assessed. The indexes of renal function and oxidative damage indicators were measured by Cr, BUN, mALB, β2‑MG, MPO, MDA and SOD assays, and the expression of HIF‑1α and ADM were detected by western blot analysis, immunohistochemistry and ELISA assays. Tubular score, determined using hematoxylin and eosin staining, was used to evaluate renal tissue damage. Applying RIPC prevented IR‑induced renal dysfunction and oxidative damage by decreasing Cr, BUN, mALB, β2‑MG, MPO, MDA levels and increasing SOD activity. Findings showed that delayed RIPC had an improved effect compared with acute treatment. Delayed RIPC also upregulated the expression of HIF‑1α and ADM, indicating that the protective effect of the delayed RIPC may be associated with a HIF‑1α‑ADM‑mediated mechanism. The effect of the delayed RIPC to reduce IR‑induced renal damage and increase ADM expression was enhanced by HIF‑1α agonists DMOG and BAY 85‑3934, whereas the effect was whittled by HIF‑1α antagonists YC‑1 and 2‑MeOE2. Furthermore, receiving ADM also offered protection to the kidney in comparison with the IR+Vehicle group. These findings suggest that RIPC prevents IR‑mediated renal damage by HIF‑1α via an ADM humoral pathway. In the present study, RIPC provided an effective renal protection. ADM could also offer protection regulated by HIF‑1α in renal tissue. However, the mechanism of ADM as a protective factor in RIPC requires further research. [ABSTRACT FROM AUTHOR]

Aim: To compare the efficacy and safety of synthetic and biological meshes in ventral hernia repair (VHR) and abdominal wall reconstruction (AWR). Methods: We screened all clinical trials that reported the application of synthetic and biological meshes in VHR and AWR using Medline, Web of Science, and Embase (Ovid). Only comparative studies with similar baselines such as age, sex, body mass index, degree of wound contamination, and hernia defects between the intervention and control groups were included. Effect sizes with 95% confidence were pooled using a random- or fixed-effects model based on the size of heterogeneity. A sensitivity analysis was performed to test the stability of the results. Results: Ten studies with 1305 participants were included. Biological meshes were associated with significantly higher recurrence rate (OR, 2.09; 95% CI 1.42–3.08; I2 = 50%), surgical site infection (OR, 1.47; 95% CI 1.10–1.97; I2 = 30%), higher re-admission rate (OR, 1.51; 95% CI 1.05–2.17; I2 = 50%), and longer length of hospital stay (SMD, 0.37; 95% CI 0.10–0.65; I2 = 72%). Similar surgical site occurrence, re-operation rate, and mesh explantation rate were observed among biological and synthetic meshes. Biological meshes have no difference in recurrence rate as compared to synthetic meshes, between the clean-contaminated, and contamination-infected fields (OR, 1.41; 95% CI 0.41–4.87 vs 3.00; 95% CI 1.07–8.46; P = 0.36). Conclusion: Synthetic meshes are a safe alternative to biological meshes for VHR and AWR. Considering the high cost of biological meshes, synthetic meshes are more appropriate for the VHR and AWR. [ABSTRACT FROM AUTHOR]

The synthesized NiCo 2 O 4 mesoporous spheres (MS) displayed intrinsic peroxidase and oxidase-like activity were firstly reported. The catalytic mechanism of the oxidase-like activity of NiCo 2 O 4 MS was analyzed in detail using the electron spin resonance (ESR) method. It is found that NiCo 2 O 4 MS could directly oxidize 3,3′,5,5′-tetramethylbenzidine (TMB) but did not produce 1 O 2 and ·OH. And the mechanism of the peroxidase-like activity of NiCo 2 O 4 MS was also verified that the oxidation of TMB stemmed from not only ·OH but also 1 O 2 . Based on the NiCo 2 O 4 MS showed excellent peroxidase-like activity over a broad temperature range, especially at normal body temperature, a detection tool was designed for glucose determination in diabetics' serum samples. And this detection method based on NiCo 2 O 4 MS gave a lower limit of detection than the method using Co 3 O 4 NPs and NiO NPs, as the single-component oxides of NiCo 2 O 4 . Our study may open up the possibility to make a great influence on the next generation of enzyme mimetics system. [ABSTRACT FROM AUTHOR]

Different types of natural K+ channels share similar core modules and cation permeability characteristics. In this study, we have developed novel artificial K+ channels by rebuilding the core modules of natural K+ channels in artificial systems. All the channels displayed high selectivity for K+ over Na+ and exhibited a selectivity sequence of K+≈Rb+ during the transport process, which is highly consistent with the cation permeability characteristics of natural K+ channels. More importantly, these artificial channels could be efficiently inserted into cell membranes and mediate the transmembrane transport of K+, disrupting the cellular K+ homeostasis and eventually triggering the apoptosis of cells. These findings demonstrate that, by rebuilding the core modules of natural K+ channels in artificial systems, the structures, transport behaviors, and physiological functions of natural K+ channels can be mimicked in synthetic channels. [ABSTRACT FROM AUTHOR]

Different types of natural K+ channels share similar core modules and cation permeability characteristics. In this study, we have developed novel artificial K+ channels by rebuilding the core modules of natural K+ channels in artificial systems. All the channels displayed high selectivity for K+ over Na+ and exhibited a selectivity sequence of K+≈Rb+ during the transport process, which is highly consistent with the cation permeability characteristics of natural K+ channels. More importantly, these artificial channels could be efficiently inserted into cell membranes and mediate the transmembrane transport of K+, disrupting the cellular K+ homeostasis and eventually triggering the apoptosis of cells. These findings demonstrate that, by rebuilding the core modules of natural K+ channels in artificial systems, the structures, transport behaviors, and physiological functions of natural K+ channels can be mimicked in synthetic channels. [ABSTRACT FROM AUTHOR]

Background: Due to limited technical demand, single-port sleeve gastrectomy (SPSG) is a feasible laparoscopic technique for sleeve gastrectomy (SG). Nonetheless, difficulties exist when performing the single-port technique, and in this study, we aim to describe a slight maneuver that can improve the SPSG procedure. Methods: Patients who underwent laparoscopic SG between January 2022 and May 2023 at our hospital were included. The patients were classified into two groups: (1) SPSG and (2) multiple-port SG (MPSG). The parameters for this analysis were the patients' age, gender, weight, body mass index (BMI), conversion rate, drainage placement, 30-day readmission rate, and postoperative complications. Postoperative one-month and three-month percentages of total weight loss (%TWL) were calculated and compared. Results: 171 patients were included in this study: (1) the SPSG group (n = 96) and (2) the MPSG group (n = 75). No statistically significant difference was observed within the preoperative (age, gender, height, weight, and BMI) and the perioperative parameters between SPSG and MPSG (operation time, drainage placement, 30-day readmission) (p > 0.05). Per Clavien–Dindo's grading, two patients in the SPSG group suffered grade 1 complications; for the MPSG group, one patient sustained grade 2 and another suffered grade 3b complication. No statistical significance was observed on the %TWL between the two groups (p > 0.05). Conclusion: Our study found that performing SPSG in specific patient is feasible and non-inferior when compared to the MPSG. Further studies will be needed to elucidate better the efficacy and safety of performing SPSG. [ABSTRACT FROM AUTHOR]

In engineering practice, deep learning is commonly used for small-sample fault diagnosis of mechanical equipment under heavy noise interference. In recent years, many researchers have used attentional neural operators based on CNNs to extract feature representations from complex data. However, the current attentional neural operator-based fault diagnosis method still has the following limitations: (1) CNN performs poorly in global feature extraction and is unable to capture the global dependencies of long sequential signals. (2) Neural operators have a serious information loss problem in multi-level feature computation, which is unfavorable for processing sensor signals that are long and contain complex noise. To address these problems, we innovatively design an efficient attentional neural operator, and also propose a new lightweight model called CSDANet. Firstly, the spatial interaction between local and global in vibration signals is facilitated by introducing a multi-level convolution and layer scaling strategies; secondly, We designed a feature channel with long-term memory capacity to cope with the adverse effects of information loss on the model; Finally, a vibration signal feature extractor is proposed to obtain richer feature mapping from the original one-dimensional sensor signals, which significantly improves the ability of the attention module to perceive multi-frequency domain noise features while consuming less computational resources. The results of two experiments demonstrate that the proposed approach accommodates advantages of lightweight and robustness in small-sample fault diagnosis tasks, compared to the existing mainstream Transformer and CNN fault diagnosis frameworks. [ABSTRACT FROM AUTHOR]

Intelligent magnetic materials are capable of responding to environmental stimuli in an on/off manner. The photo- and thermal-responsive nanogel layer was surface-grafted onto several magnetic nanoparticles to prepare the magnetic imprinted nanoparticles (Fe3O4 MIPs). The Fe3O4 MIPs show dramatic temperature and light, dual-dependent rebinding and release characteristics for lysozyme. Above the volume phase transition temperature of the PNIPAAm, the imprinted protein (lysozyme) can be selectively separated from egg whites and the activity remained unchanged. By combining low temperature and UV irradiation, a more finely tuned release of the binding protein can be achieved. Time-dependent antibacterial activity was observed, and it was found that Fe3O4 MIPs-loaded lysozyme almost completely suppressed the growth of E. coli with the continuous lysozyme release. More importantly, the Fe3O4 MIPs could easily be separated by an external magnetic field and can be recycled. The photo- and thermal-responsive Fe3O4 MIPs pave a new way for the development of an advanced, sustainable material for use in bioseparation, drug delivery, and antibacterial materials. [ABSTRACT FROM AUTHOR]

The multifunctional hemin@carbon dot hybrid nanozymes (hemin@CD) with simultaneous peroxidase-like activity and fluorescence signalling property was prepared for the first time. Based on these properties, hemin@CD was applied to develop a dual-channel fluorescent probe for H2O2 and H2O2-based biocatalytic systems. By virtue of the peroxidase-like activity, hemin@CD can catalyze the oxidative coupling of 4-aminoantipyrine with phenol in the presence of H2O2 to form a pink-red quinoneimine dye with a maximum absorbance at 505 nm. Under the excitation wavelength of 480 nm, the green fluorescence of hemin@CD peaks at 540 nm and is quenched by the generated quinoneimine dye due to an inner filter effect, and also by H2O2 because of dynamic quenching. Thus, a colorimetric and fluorimetric dual-channel optical probe for H2O2 is obtained. Due to the glucose/xanthine transformations under formation of H2O2 by the relevant oxidase catalysis, the probe can be applied for detection of glucose and xanthine. The colorimetric detection limits for H2O2, glucose and xanthine are 0.11, 0.15, 0.11 μM, and the and fluorimetric detection limits are 0.15, 0.15, 0.12 μM, respectively. [ABSTRACT FROM AUTHOR]

Camptothecin (CPT) is a potent and broad-spectrum anti-tumor drug, but its clinical application is limited due to its poor water solubility, toxicity, and low drug-loading potential. Different delivery protocols have been developed to optimize the therapeutic effects of CPT. In this study, CPT was modified into a dimer (CPT-Mal-CPT), in which two CPT molecules are connected by a reduction-responsive maleimide thioether bond. Moreover, biocompatible methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG–PCL)-loaded CPT-Mal-CPT nanoparticles were prepared to overcome the limits of CPT application. The power X-ray diffractometer (PXRD) results indicate low crystallinity and amorphous nature of CPT-Mal-CPT. The CPT-Mal-CPT-loaded micelles showed a drug-loading content of 9.6% and a drug-loading efficiency of 56%. In addition, dimeric CPT micelles showed reduction-responsive release under 10-mM dithiothreitol (DTT), while negligible CPT release was detected in the absence of DTT. MTT assay indicated that cytotoxicity of dimeric CPT micelle was similar to free CPT. [ABSTRACT FROM AUTHOR]

Abstract Nanozymes' activities could be regulated by a simple and effective pH change in an in situ manner. In this work, for the first time, the peroxidase-like activity of Ni/Co layered double hydroxides (LDHs) was regulated via the alkaline-promoted reaction of fluorogenic substrate homovanillic acid and H 2 O 2 , and a promising tool for pH sensing was developed over the pH range of 8.3–9.6. As peroxidase nanozyme model, Ni/Co LDHs showed ease of preparation, low-cost, and water-solubility, which played an important role in this luminescence system. Based on the pH-dependent regulation of the Ni/Co LDHs activity, we constructed the bioassay platform for the determination urea, urease, penicillin G, and penicillinase with a wide linear range of 17–1000 µM, 3.3–270 mU mL−1, 3.3–1300 µM and 3.3–100 mU mL−1, respectively. This study not only demonstrated the alkaline-promoted modulation the nanozymes' activities, but also established a facile approach to develop novel bioassays. Graphical abstract fx1 Highlights • The alkaline-promoted regulating Ni/Co LDHs' peroxidase-like activity has been explored. • A pH sensor was developed based on the system of Ni/Co LDHs-HVA-H 2 O 2. • A platform for the detection urea, urease, penicillin G, and penicillinase was established. [ABSTRACT FROM AUTHOR]

Highlights • Bioimaging in acidic lysosomes for analytes is of great significance. • A pH-independent probe for sensing HOCl at lysosomal pH 5.0 was developed. • The new probe was successfully applied to visualize HOCl in living systems. Abstract As acidic organelles (pH 4.0–5.5) in living cells, lysosomes play key roles in numerous cellular biological processes, and associate with diverse diseases. Small molecular probes based fluorescence imaging techniques capable of providing information on target analytes in lysosomes are highly appreciated. Herein, for the first time we propose a new strategy of constructing pH-independent rhodamine based spiro-ring platform for lysosomal imaging applications. As a proof of concept, by incorporating lysosome specific moiety morpholine, a thio-lactone rhodamine analogue HN4MS for HOCl with high sensitivity, high selectivity and fast response at lysosomal pH value was developed. Moreover, possessing ability of imaging in lysosome organelles, the new probe was successfully applied to visualize exogenous and endogenous HOCl in living cells and tissues, which verified the present avenue for expansion of organelle targetable imaging tools. [ABSTRACT FROM AUTHOR]

A class of artificial K+ channels formed by pillararene‐cyclodextrin hybrid molecules have been designed and synthesized. These channels efficiently inserted into lipid bilayers and displayed high selectivity for K+ over Na+ in fluorescence and electrophysiological experiments. The cation transport selectivity of the artificial channels is tunable by varying the length of the linkers between pillararene and cyclodexrin. The shortest channel showed specific transmembrane transport preference for K+ over all alkali metal ions (selective sequence: K+ > Cs+ > Rb+ > Na+ > Li+), and is rarely observed for artificial K+ channels. The high selectivity of this artificial channel for K+ over Na+ ensures specific transmembrane translocation of K+, and generated stable membrane potential across lipid bilayers. Old pals: A pillararene‐cyclodextrin hybrid molecule with artificial K+ channel function is presented. The cation transport selectivity of the artificial channel is tunable. The high selectivity of this artificial channel for K+ over Na+ ensures specific transmembrane translocation of K+, and generated a stable membrane potential across lipid bilayers. [ABSTRACT FROM AUTHOR]

A class of artificial K+ channels formed by pillararene‐cyclodextrin hybrid molecules have been designed and synthesized. These channels efficiently inserted into lipid bilayers and displayed high selectivity for K+ over Na+ in fluorescence and electrophysiological experiments. The cation transport selectivity of the artificial channels is tunable by varying the length of the linkers between pillararene and cyclodexrin. The shortest channel showed specific transmembrane transport preference for K+ over all alkali metal ions (selective sequence: K+ > Cs+ > Rb+ > Na+ > Li+), and is rarely observed for artificial K+ channels. The high selectivity of this artificial channel for K+ over Na+ ensures specific transmembrane translocation of K+, and generated stable membrane potential across lipid bilayers. [ABSTRACT FROM AUTHOR]

Five unimolecular channels with different lengths are presented. The varying length of these channels has significant impact on their transmembrane transport properties, which are directly correlated with their antimicrobial activity and inversely correlated with their haemolytic toxicity. By further structural optimization, these new channels could reach high antimicrobial activity and very low haemolytic toxicity, with the potential to serve as systemic antibiotics. [ABSTRACT FROM AUTHOR]

Nanomaterial-based peroxidase-mimetics are an emerging research field that promises to produce alternatives to horseradish peroxidase for a variety of applications. Generally, some peroxidase-mimetics substrates are used in acidic condition (pH ≤ 7). Then, it is necessary to screen some peroxidase-mimetics substrates suitable for basic condition because that some peroxidase-mimetics leached ions in acidic solution. In this paper, using Ni/Co layered double hydroxides (LDHs) as a nano-peroxidase mimic model, we evaluated three fluorogenic substrates suitable for basic condition though experimental conditions, reaction kinetic and glucose detection assay. And the detection of glucose method based on homovanillic acid (HVA) as fluorescent substrate gave wide linear range (0.02–20 μM) and low detection limit (0.01 μM). We also developed a novel platform that could study the inhibitory effects of ascorbic acid and glutathione based on the system of Ni/Co LDHs-HVA-H 2 O 2 . [ABSTRACT FROM AUTHOR]

Mirabegron is a muscle relaxing drug for the treatment of overactive bladder. The existing synthetic methods for mirabegron produced intermediate product 4-(2-(phenethylamino)ethyl)aniline, which complicated the final product purification process. In this study, we designed a new synthetic route for mirabegron with low cost starting materials and a production of mirabegron at a 99.6% purity and a 61% overall yield. Particularly, this new synthetic route did not produce side product 4-(2-(phenethylamino)ethyl)aniline, which significantly simplified the product purification process. [ABSTRACT FROM AUTHOR]

A series of pH-sensitive, cation-selective hydrazide macrocyclic channels have been synthesized. The macrocyclic channels bear multiple carboxyls in the inner cavity, which have a significant impact on their membrane-incorporation ability and NH4+ transport activity. Moreover, the K+/Cl− selectivities of the macrocyclic channels can be tuned by the pH value of the electrolyte. [ABSTRACT FROM AUTHOR]

Nanozymes are more stable, economical, and easier to produce than natural enzymes; however, their low activity in non-acidic environments and lack of substrate selectivity severely limit the applications of nanozymes. In this study, we developed Co- and N-doped carbon dot nanozymes (CoNCDs) that specifically exhibited peroxidase-like activity toward o-phenylenediamine in a non-acidic environment. Based on the peroxidase-like activity and fluorescence property of CoNCDs in a neutral environment, a one-pot multi-mode sensing platform (colorimetric and ratiometric fluorescence imaging) was developed to detect cholesterol and xanthine in solution and human serum samples. This platform was simple to operate, and the CoNCDs demonstrated a reduced detection time and an improved analytical performance compared to most of the reported nanozymes. Moreover, the improved peroxidase activity at neutral pH, good biocompatibility, and photostability of CoNCDs facilitated their use for monitoring endogenous H 2 O 2 levels in vivo. This study not only provides a novel approach for developing an acid pH-independent and substrate selectivity nanozyme but also demonstrates the application of ratiometric fluorescence imaging using the developed CoNCDs both in vitro and in vivo. [Display omitted] • CoNCDs showed the peroxidase-like activity at neutral and alkaline pH. • CoNCDs showed the substrate selectivity toward OPD, but no activity toward TMB and ABTS. • The one-pot multi-mode sensing platform for cholesterol and xanthine were developed. • CoNCDs was firstly applied to monitor H 2 O 2 in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Nanozymes are more stable, economical, and easier to produce than natural enzymes; however, their low activity in non-acidic environments and lack of substrate selectivity severely limit the applications of nanozymes. In this study, we developed Co- and N-doped carbon dot nanozymes (CoNCDs) that specifically exhibited peroxidase-like activity toward o-phenylenediamine in a non-acidic environment. Based on the peroxidase-like activity and fluorescence property of CoNCDs in a neutral environment, a one-pot multi-mode sensing platform (colorimetric and ratiometric fluorescence imaging) was developed to detect cholesterol and xanthine in solution and human serum samples. This platform was simple to operate, and the CoNCDs demonstrated a reduced detection time and an improved analytical performance compared to most of the reported nanozymes. Moreover, the improved peroxidase activity at neutral pH, good biocompatibility, and photostability of CoNCDs facilitated their use for monitoring endogenous H 2 O 2 levels in vivo. This study not only provides a novel approach for developing an acid pH-independent and substrate selectivity nanozyme but also demonstrates the application of ratiometric fluorescence imaging using the developed CoNCDs both in vitro and in vivo. [Display omitted] • CoNCDs showed the peroxidase-like activity at neutral and alkaline pH. • CoNCDs showed the substrate selectivity toward OPD, but no activity toward TMB and ABTS. • The one-pot multi-mode sensing platform for cholesterol and xanthine were developed. • CoNCDs was firstly applied to monitor H 2 O 2 in vitro and in vivo. [ABSTRACT FROM AUTHOR]