Echinococcus multilocularis serpin regulates macrophage polarization and reduces gut dysbiosis in colitis.

Helminths serve as principal regulators in modulating host immune responses, and their excretory-secretory proteins are recognized as potential therapeutic agents for inflammatory bowel disease. Nevertheless, our comprehension of the mechanisms underlying immunoregulation remains restricted. This investigation delves into the immunomodulatory role of a secretory protein serpin (Emu-serpin), within the larval stage of Echinococcus multilocularis. Our observations indicate that Emu-serpin effectively alleviates dextran sulfate sodium-induced colitis, yielding a substantial reduction in immunopathology and an augmentation of anti-inflammatory cytokines. Furthermore, this suppressive regulatory effect is concomitant with the reduction of gut microbiota dysbiosis linked to colitis, as evidenced by a marked impediment to the expansion of the pathobiont taxa Enterobacteriaceae. In vivo experiments demonstrate that Emu-serpin facilitates the expansion of M2 phenotype macrophages while concurrently diminishing M1 phenotype macrophages, alongside an elevation in anti-inflammatory cytokine levels. Subsequent in vitro investigations involving RAW264.7 and bone marrow macrophages reveal that Emu-serpin induces a conversion of M2 macrophage populations from a pro-inflammatory to an anti-inflammatory phenotype through direct inhibition. Adoptive transfer experiments reveal the peritoneal macrophages induced by Emu-serpin alleviate colitis and gut microbiota dysbiosis. In summary, these findings propose that Emu-serpin holds the potential to regulate macrophage polarization and maintain gut microbiota homeostasis in colitis, establishing it as a promising candidate for developing helminth therapy for preventing inflammatory diseases.

Association between home and community-based services utilization and self-rated health among Chinese older adults with chronic diseases: evidence from the 2018 China Health and Retirement Longitudinal Study.

BACKGROUND: As global aging intensifies, older adults with chronic diseases are of increasing concern. Home and community-based services (HCBSs) have been proven to promote self-rated health (SRH) in older adults, but no research explored the associations between the use of overall HCBSs, three different types of HCBSs (health care, daily care, and social support services) and SRH among older adults with chronic diseases. Consequently, this study applies a national publicly available database to examine these associations among older adults with chronic diseases. METHODS: 8,623 older adults with chronic diseases (≥ 60 years old) were included in this study. SRH was evaluated applying a concise question with a 1 - 5 scale. HCBSs utilization was assessed through the question, "What kind of HCBSs were used in the community?". Univariate general linear regression models aimed to compare the mean values of SRH in terms of HCBSs utilization in each group. This study is a cross-sectional study design and the relationship between HCBSs utilization and SRH was assessed by multilevel linear regression. RESULTS: The mean score for SRH among the respondents was 3.19, of whom 20.55% used one or more HCBSs, 19.47% utilized health care services, 2.44% utilized social support services, and only 0.55% utilized daily care services. The use of HCBSs was found to be linked to SRH among older adults with chronic diseases (ß = 0.085, SE = 0.025, p < 0.001). SRH among older adults with chronic diseases was strongly linked to the use of health care and social support services (ß = 0.068, SE = 0.025, p < 0.001; ß = 0.239, SE = 0.063, p < 0.001, respectively). However, there was no significant association between the use of daily care services and SRH among older adults with chronic diseases. CONCLUSION: This study revealed that HCBSs utilization was positively and significantly linked to SRH in Chinese older adults with chronic diseases. Furthermore, this study supposes the low utilization of social support and daily care services may be due to a mismatch between supply and demand. The government should offer the targeted HCBSs for older adults with chronic diseases according to their unique features to enhance their health status.

The relationship between home and community-based healthcare services utilization and depressive symptoms in older adults in rural China: a moderated mediation model.

BACKGROUND: Studies have shown a close association between home and community-based healthcare services (HCBHS) utilization and depressive symptoms in older adults. However, no studies have explored the underlying mechanism of this relationship in rural China. This study was designed to evaluate the roles of instrumental activities of daily living (IADL) and marital status in the association between HCBHS utilization and depressive symptoms in Chinese rural older adults. METHODS: Data were obtained from the 2018 China Health and Retirement Longitudinal Study, and 5,981 rural respondents (≥ 60 years old) were included. Depression scores were calculated using the ten-item Center for Epidemiological Studies Depression Scale. Moderated mediation analysis was carried out applying Hayes' PROCESS macro (Model 7). RESULTS: HCBHS utilization had a direct and negative effect on depressive symptoms. Furthermore, marital status moderated the association between HCBHS utilization and IADL, which belonged to the indirect influence of the first half on the association between HCBHS utilization and depressive symptoms. HCBHS utilization was associated with IADL in single but not in married respondents. CONCLUSION: The results demonstrated that marital status moderated the indirect relationship between HCBHS utilization and depressive symptoms, with HCBHS utilization being negatively associated with IADL among single but not married respondents. The government should focus on rural older adults, especially those who are single and have poor IADL function, and improve the provision of HCBHS to alleviate depressive symptoms.

Effects of different custom-made mouthguard palatal extensions on the stress-state of dentoalveolar structures: a 3D-FEA.

OBJECTIVES: The present study aimed to simulate the influence of palatal extensions for custom-made mouthguards (MGs) on protecting dentoalveolar structures and to provide a theoretical basis for designing a comfortable MG. MATERIALS AND METHODS: Based on finite element analysis (3D-FEA), five groups of maxillary dentoalveolar models of wearing MGs were established: no MG on palatal side (NP), on palatal gingival margin (G0), 2 mm from the palatal gingival margin (G2), 4 mm from the palatal gingival margin (G4), 6 mm from the palatal gingival margin (G6), and 8 mm from the palatal gingival margin (G8). A cuboid was created to simulate the solid ground impacted in falls, a gradually increasing force was applied from 0 to 500 N on the vertical ground, and the distribution and peak values of the Critical modified von-Mises stress, maximum principal stress, and displacement of dentoalveolar models were calculated. RESULTS: Stress distribution range, stress, and deformation peak value of dentoalveolar models increased as the impact strength increased, at 500 N. Maximum critical modified von-Mises stress, peak maximum principal stress and maximum displacement of dentoalveolar models G4, G3, G2, G1, G0, and NP were 154.5 MPa, 154.5 MPa, 154.4 MPa, 154.7 MPa, 154.4 MPa, and 154.7 MPa; 191.65 MPa, 192.11 MPa, 191.62 MPa, 191.81 MPa, 191.56 MPa, and 191.62 MPa; and 88.78 µm, 88.57 µm, 88.19 µm, 88.67 µm, 88.43 µm, and 89.04 µ, respectively. However, the position of the MG palatal edge had little effect on stress distribution, stress, and deformation peak values of the dentoalveolar models. CONCLUSIONS: Different extension ranges of the MG palatal edge have little effect on the protective effects of MGs on maxillary teeth and maxilla. An MG with palatal extension on the gingival margin is more appropriate than other models and may help dentists to design a suitable MG and increase its usage. CLINICAL RELEVANCE: MGs with palatal extensions on the gingival margin may provide a more comfortable wearing experience for individuals involved in sports and encourage increased MG usage.

Use of Postpartum Magnetic Resonance Imaging for Diagnosis and Classification of Retained Placenta Tissue.

OBJECTIVE: To study the potential application of magnetic resonance imaging (MRI) for classification of retained placental tissue (RPT) in the uterus postnatally. METHODS: Twenty-two patients with clinically or pathologically proven RPT were studied. RESULTS: The thickness ratio (D1/D2) of invaded (D1) to normal (D2) myometrium could be categorized into 3 groups (>0.6, 0.1-0.6, and <0.1) correlating with the 3 types of RPT: accreta vera (RPA), increta (RPI), and percreta (RPP) (r = -0.861, P < 0.01). After uterine arterial embolization, the RPT showed lower signal intensity than the myometrium without flow voids on T2-weighted images. Two cases of RPP showed gradual enhancement, except 1 case of infection and 2 cases that did not involve enhancement examinations, whereas 17 cases of RPA and RPI showed early enhancement. CONCLUSIONS: Magnetic resonance imaging can facilitate diagnosis of RPT severity. Dynamic contrast enhancement can indicate RPT activity and blood supply, thereby ensuring appropriate clinical decision making.

Ligand "switching on" fluorescence of HIV-1 RNA-templated copper nanoclusters for ligand-RNA interaction assays.

Ligand-RNA interaction assay provides the basis for developing new RNA-binding small molecules. In this study, fluorescent copper nanoclusters (CuNCs) were first prepared using two kinds of HIV-1 RNA targets, rev-responsive element (RRE) and transactivator response element (TAR) RNA, as new templates, and it was found that the fluorescence of the single RNA-templated CuNCs was negligible. Using neomycin as a model drug, the fluorescence could be augmented (approximately 6 times) for the neomycin/RNA-templated CuNCs. Thus, a novel method was developed for ligand-RNA interactions by observing the fluorescence changes in CuNCs prepared using RNA before and after the addition of ligands. The preparation parameters of neomycin/RNA-CuNCs were optimized. The as-prepared CuNCs were characterized using UV-vis spectroscopy, fluorescence spectroscopy, and high-resolution transmission electron microscope. Circular dichroism spectral analysis showed that RRE and TAR were inclined to form a double-stranded structure after interaction with neomycin, which was more conducive to the formation of CuNCs. The interactions of neomycin and three test drugs (amikacin, gentamicin, and tobramycin) with RNA were investigated using the proposed method, and the binding constants and number of binding sites were obtained through theoretical calculations. This study provides a novel approach for ligand-RNA interaction assays.

Reduced coupling between global signal and cerebrospinal fluid inflow in patients with depressive disorder: A resting state functional MRI study.

BACKGROUND: Depressed patients often suffer from sleep disturbance, which has been recognized to be responsible for glymphatic dysfunction. The purpose of this study was to investigate the coupling strength of global blood­oxygen-level-dependent (gBOLD) signals and cerebrospinal fluid (CSF) inflow dynamics, which is a biomarker for glymphatic function, in depressed patients and to explore its potential relationship with sleep disturbance by using resting-state functional MRI. METHODS: A total of 138 depressed patients (112 females, age: 34.70 ± 13.11 years) and 84 healthy controls (29 females, age: 36.6 ± 11.75 years) participated in this study. The gBOLD-CSF coupling strength was calculated to evaluate glymphatic function. Sleep disturbance was evaluated using the insomnia items (item 4 for insomnia-early, item 5 for insomnia-middle, and item 6 for insomnia-late) of The 17-item Hamilton Depression Rating Scale for depressed patients, which was correlated with the gBOLD-CSF coupling strength. RESULTS: The depressed patients exhibited weaker gBOLD-CSF coupling relative to healthy controls (p = 0.022), possibly due to impairment of the glymphatic system. Moreover, the gBOLD-CSF coupling strength correlated with insomnia-middle (r = 0.097, p = 0.008) in depressed patients. Limitations This study is a cross-sectional study. CONCLUSION: Our findings shed light on the pathophysiology of depression, indicating that cerebral waste clearance system deficits are correlated with poor sleep quality in depressed patients.

Development of robust and standardized cantilever sensors based on biotin/NeutrAvidin coupling for antibody detection.

A cantilever-based protein biosensor has been developed providing a customizable multilayer platform for the detection of antibodies. It consists of a biotin-terminated PEG layer pre-functionalized on the gold-coated cantilever surface, onto which NeutrAvidin is adsorbed through biotin/NeutrAvidin specific binding. NeutrAvidin is used as a bridge layer between the biotin-coated surface and the biotinylated biomolecules, such as biotinylated bovine serum albumin (biotinylated BSA), forming a multilayer sensor for direct antibody capture. The cantilever biosensor has been successfully applied to the detection of mouse anti-BSA (m-IgG) and sheep anti-BSA(s-IgG) antibodies. As expected, the average differential surface stress signals of about 5.7 ± 0.8 × 10(-3) N/m are very similar for BSA/m-IgG and BSA/s-IgG binding, i.e., they are independent of the origin of the antibody. A statistic evaluation of 112 response curves confirms that the multilayer protein cantilever biosensor shows high reproducibility. As a control test, a biotinylated maltose binding protein was used for detecting specificity of IgG, the result shows a signal of bBSA layer in response to antibody is 5.8 × 10(-3) N/m compared to bMBP. The pre-functionalized biotin/PEG cantilever surface is found to show a long shelf-life of at least 40 days and retains its responsivity of above 70% of the signal when stored in PBS buffer at 4 °C. The protein cantilever biosensor represents a rapid, label-free, sensitive and reliable detection technique for a real-time protein assay.

Optimization of DNA hybridization efficiency by pH-driven nanomechanical bending.

The accessibility and binding affinity of DNA are two key parameters affecting the hybridization efficiency in surface-based biosensor technologies. Better accessibility will result in a higher hybridization efficiency. Often, mixed ssDNA and mercaptohexanol monolayers are used to increase the hybridization efficiency and accessibility of surface-bound oligonucleotides to complementary target DNA. Here, no mercaptohexanol monolayer was used. We demonstrate by differential microcantilever deflection measurements at different pH that the hybridization efficiency peaks between pH 7.5 and 8.5. At low pH 4.5, hydration and electrostatic forces led to tensile surface stress, implying the reduced accessibility of the bound ssDNA probe for hybridization. In contrast, at high pH 8.5, the steric interaction between neighboring ssDNA strands was decreased by higher electrostatic repulsive forces, bending the microcantilever away from the gold surface to provide more space for the target DNA. Cantilever deflection scales with pH-dependent surface hybridization efficiency because of high target DNA accessibility. Hence, by changing the pH, the hybridization efficiency is adjusted.

Business Model Innovation Paths of Manufacturing Oriented towards Green Development in Digital Economy.

China's manufacturing industry has been confronted with the issue of extensive development with high input, high consumption, and high emissions for a long time, and its green development is the key to reaching carbon neutrality in China. Under the digital economy, business model innovation is the fundamental means of the green development of manufacturing enterprises. Four representative listed companies in China's manufacturing were selected as typical cases for the case study. Through open, axial, and selective coding that is based on proceduralized grounded theory, this study profoundly explores business model innovation paths of the manufacturing industry oriented towards green development in the digital economy following the research logic of "green development orientation-business model innovation process-business model innovation result". Moreover, this study further compares the differences among paths and discusses each path's effectiveness and applicable conditions. Results show that: (1) Four green business model innovation paths are revealed based on the four green development orientations: efficiency-oriented path, value-oriented path, user-oriented path, and ecology-oriented path. (2) Different enterprises pursue distinct business model innovation paths. The scientific premise for enterprises to opt for the optimal innovation path is the matching of upgrading demands, existing conditions, and path characteristics. Ultimately, the following policy implications are offered: First, promote the green innovation of business models in the manufacturing industry. Second, consider enterprises' heterogeneity and implement differentiated support policies. This study can serve as theoretical support and decision-making reference for business model innovation and green development in manufacturing enterprises.

Peptide-RNA complexation-induced fluorescence "turn on" displacement assay for the recognition of small ligands targeting HIV-1 RNA.

The regulator of expression of virion (Rev) protein binds specifically to the Rev-responsive element (RRE) RNA in order to regulate the expression of the human immunodeficiency virus (HIV)-1 genes. Fluorescence indicator displacement assays have been used to identify ligands that can inhibit the Rev-RRE interaction; however, the small fluorescence indicators cannot fully replace the Rev peptide or protein. As a result, a single rhodamine B labeled Rev (RB-Rev) model peptide was utilized in this study to develop a direct and efficient Rev-RRE inhibitor screening model. Due to photon-induced electron transfer quenching of the tryptophan residue on the RB fluorophore, the fluorescence of RB in Rev was weakened and could be dramatically reactivated by interaction with RRE RNA in ammonium acetate buffer (approximately six times). The interaction could reduce the electron transfer between tryptophan and RB, and RRE could also increase RB fluorescence. The inhibitor screening model was evaluated using three known positive Rev-RRE inhibitors, namely, proflavin, 6-chloro-9-[3-(2-chloroethylamino)propylamino]-2-methoxyacridine (ICR 191), and neomycin, as well as a negative drug, arginine. With the addition of the positive drugs, the fluorescence of the Rev-RRE decreased, indicating the displacement of RB-Rev. This was confirmed using atomic force microscopy (AFM) and the fluorescence was essentially unaffected by the addition of arginine. The results demonstrated that RB-Rev can be used as a fluorescent probe for recognizing small ligands that target RRE RNA. The Rev-RRE inhibitor screening model offers a novel approach to evaluating and identifying long-acting Rev inhibitors.

Acquired mucoid phenotype of Acinetobacter baumannii: Impact for the molecular characteristics and virulence.

Mucoid phenotype is an important adaptive defense response for Acinetobacter baumannii (A. baumannii). The aim of this study was to analyze the impact of mucoid phenotype for the molecular characteristics and virulence of A. baumannii. We observed that the colonies of mucoid A. baumannii were moist, with an elevated surface, and the wire drawing result was positive. Transmission electron microscopy data showed that the outer wall of the mucoid colonies was not smooth, had protruding pseudopodia, and was surrounded by a layer of unknown material. Antibiotic susceptibility testing showed that the mucoid strains were multidrug resistant. Notably, the mucoid phenotype and antibiotic resistance were not correlated with the amount of biofilm produced by A. baumannii. MLST data demonstrated that the mucoid A. baumannii strains belonged to type ST2. Most (82.6 %, 38/46) of the multidrug-resistant nonmucoid strains also belonged to the molecular type ST2 and to other types, including ST129, ST158, ST195, ST80 and ST3. Moreover, mucoid A. baumannii strains were more virulent than nonmucoid isolates in a mouse model. The comparative transcriptomic data indicated that 15 genes, especially IX87_RS16955 (acnA), IX87_RS10800 (XanP), IX87_RS12875 (GlmM), IX87_RS00885 and IX87_RS12395 (bfr), were possibly associated with the phenotype and virulence of mucoid A. baumannii. In conclusions, the study comprehensively describes the molecular characteristics and virulence regulatory mechanism of mucoid A. baumannii, and provides novel insights for the prevention and treatment of infections associated with these strains.

RNA-dependent RNA polymerase (RdRp) inhibitors: The current landscape and repurposing for the COVID-19 pandemic.

The widespread nature of several viruses is greatly credited to their rapidly altering RNA genomes that enable the infection to persist despite challenges presented by host cells. Within the RNA genome of infections is RNA-dependent RNA polymerase (RdRp), which is an essential enzyme that helps in RNA synthesis by catalysing the RNA template-dependent development of phosphodiester bonds. Therefore, RdRp is an important therapeutic target in RNA virus-caused diseases, including SARS-CoV-2. In this review, we describe the promising RdRp inhibitors that have been launched or are currently in clinical studies for the treatment of RNA virus infections. Structurally, nucleoside inhibitors (NIs) bind to the RdRp protein at the enzyme active site, and nonnucleoside inhibitors (NNIs) bind to the RdRp protein at allosteric sites. By reviewing these inhibitors, more precise guidelines for the development of more promising anti-RNA virus drugs should be set, and due to the current health emergency, they will eventually be used for COVID-19 treatment.

MiR­30e and miR­92a are related to atherosclerosis by targeting ABCA1.

Atherosclerosis is a chronic disease characterized by the accumulation of lipids and fibrous elements in the large arteries, which is the principal cause of coronary artery disease. Dysregulated exosomal microRNA (miRNA) levels in serum have been identified in patients with various diseases, including CAD. In the present study, nine candidate miRNAs were detected in the plasma exosome from 42 patients with coronary atherosclerosis, and a higher expression of miR­30e and miR­92a was identified in patients. Following bioinformatics analysis and confirmation through immunoblotting, it was demonstrated that ATP binding cassette (ABC)A1 is a direct target of miR­30e, and miR­92a. Furthermore, a negative correlation was identified between plasma miR­30e and ABCA1, or miR­30e and cholesterol. Thus, the results of the present study suggest that the miR­30e level in exosomes from serum may have the potential to be a novel diagnostic biomarker for coronary atherosclerosis.

Deregulation of miR-520d-3p promotes hepatocellular carcinoma development via lncRNA MIAT regulation and EPHA2 signaling activation.

MicroRNA-520d-3p (miR-520d-3p) is a novel cancer-related miRNA and functions as a tumor suppressor in human cancers. However, the expression patterns and mechanisms of miR-520d-3p involved in hepatocellular carcinoma (HCC) remain rarely known. Here, we found that the expression levels of miR-520d-3p in HCC tissues and cells were significantly lower than in tumor-adjacent tissues and L02 cells. Decreased level of miR-520d-3p was relevant to poor overall survival, whereas miR-520d-3p up-regulation resulted in a marked inhibition of cell growth, migration and invasion. In addition, the long non-coding RNA, myocardial infarction associated transcript (MIAT) was up-regulated in both HCC tissues and cell lines. MIAT suppressed the expression and function of miR-520d-3p. Moreover, erythropoietin-producing hepatocellular A2 (EPHA2) was speculated and confirmed as a direct target of miR-520d-3p. We also demonstrated that MIAT may function as a sponge competitive endogenous RNA for miR-520d-3p, and thus regulate the molecular expression of EPHA2. In summary, our study has identified a novel signaling pathway through which miR-520d-3p exerts its anticarcinogenic roles and suggested that the MIAT/miR-520d-3p/EPHA2 may be a new target for HCC therapy.

Pt NPs immobilized on a N-doped graphene@Al2O3 hybrid support as robust catalysts for low temperature CO oxidation.

Platinum nanoparticles (Pt NPs) immobilized on a N-doped graphene@Al2O3 hybrid support (Al2O3@CNx) were synthesized and employed for low temperature CO oxidation. The superior catalytic activity was attributed to a strong metal-support interaction between Pt NPs and the N-doped graphene surface which was also confirmed in the direct dehydrogenation reaction.

An Efficient Metal-Free Catalyst for Oxidative Dehydrogenation Reaction: Activated Carbon Decorated with Few-Layer Graphene.

Activated carbon (AC) has been widely used in the catalysis field because of its low cost, scalable production, high specific surface area, and abundant exposed edge. Because of the amorphous structure, traditional AC is unstable in presence of O2 at high temperature, which hinders the application of AC catalysts in oxidative dehydrogenation (ODH) of alkanes. Here, partially graphitic AC decorated with few-layer graphene is facilely fabricated by simple high-temperature calcination. The graphitic transformation significantly enhances the antioxidation property, long-term stability of AC during the ODH reaction, and especially dramatically increases the graphitic edge areas in which the active ketonic carbonyl groups are selectively formed in ODH reactions. A high reactivity with 41.5 % selectivity and 13.2 % yield to C4 alkenes were obtained at 450 °C over the optimized catalyst, which is superior to all the previously reported carbon catalysts and shows a great potential for industrial application.

Fabrication of MgO-rGO hybrid catalysts with a sandwich structure for enhanced ethylbenzene dehydrogenation performance.

MgO-rGO hybrid catalysts with a sandwich structure have been successfully prepared through a simple "solid-solid" method. Obviously enhanced reactivity is observed on the hybrid catalysts in ethylbenzene dehydrogenation reactions, which is attributed to the sandwich structure and the synergistic effect between MgO and rGO.

A Facile and Efficient Method to Fabricate Highly Selective Nanocarbon Catalysts for Oxidative Dehydrogenation.

Carbon nanotubes (CNTs) were used in oxidative dehydrogenation (ODH) reactions. Quinone groups on the CNT surface were identified as active sites for the dehydrogenation pathway. Liquid-phase oxidation with HNO3 is one way to generate various oxygen functionalities on the CNT surface but it produces a large amount of acid waste, limiting its industrial application. Here, a facile and efficient oxidative method to prepare highly selective CNT catalysts for ODH of n-butane is reported. Magnesium nitrate salts as precursors were used to produce defect-rich CNTs through solid-phase oxidation. Skeleton defects induced on the CNT surface resulted in the selective formation of quinone groups active for the selective dehydrogenation. The as-prepared catalyst exhibited a considerable selectivity (58 %) to C4 olefins, which is superior to that of CNTs oxidized with liquid HNO3 . Through the introduction of MgO nanoparticles on the CNT surface, the desorption of alkenes can be accelerated dramatically, thus enhancing the selectivity. This study provides an attractive way to develop new nanocarbon catalysts.

Nanosensors for cancer detection.

Cancer is a major burden in today's society and one of the leading causes of death in industrialised countries. Various avenues for the detection of cancer exist, most of which rely on standard methods, such as histology, ELISA, and PCR. Here we put the focus on nanomechanical biosensors derived from atomic force microscopy cantilevers. The versatility of this novel technology has been demonstrated in different applications and in some ways surpasses current technologies, such as microarray, quartz crystal microbalance and surface plasmon resonance. The technology enables label free biomarker detection without the necessity of target amplification in a total cellular background, such as BRAF mutation analysis in malignant melanoma. A unique application of the cantilever array format is the analysis of conformational dynamics of membrane proteins associated to surface stress changes. Another development is characterisation of exhaled breath which allows assessment of a patient's condition in a non-invasive manner.