Molecular insights into effects of chemical conditioning on dissolved organic phosphorus transformation and bioavailability during sludge composting.

Phosphorus is enriched in waste activated sludge (WAS) during wastewater treatment, and organic phosphorus (OP) is a potential slow-release P fertilizer. The chemical coagulants used in sludge dewatering leave numerous residues in WAS that affect sludge composting. In this study, the effects of polyaluminum chloride (PAC) and polyferric sulfate (PFS) on the bioconversion of dissolved OP (DOP) during sludge composting were investigated. The results revealed that PFS conditioning promoted the transformation and bioavailability of DOP, whereas PAC conditioning inhibited. Results indicated that PFS conditioning enhanced the transformation of OP molecules in the thermophilic phase. Through oxidation and dehydrogenation reactions, 1-hydroxy-pentane-3,4-diol-5-phosphate and D-ribofuranose 5-phosphate with high bioactivity were generated in the PFS-conditioned compost. Enzymatic hydrolysis experiments further verified that PFS conditioning enhanced the DOP bioavailability in the compost, whereas PAC conditioning inhibited it. The study has provided molecular insights into the effects of chemical conditioning on DOP conversion during sludge composting.

The ecology of the sewer systems: Microbial composition, function, assembly, and network in different spatial locations.

Microbial induced concrete corrosion (MICC) is the primary deterioration affecting global sewers. Disentangling ecological mechanisms in the sewer system is meaningful for implementing policies to protect sewer pipes using trenchless technology. It is necessary to understand microbial compositions, interaction networks, functions, alongside assembly processes in sewer microbial communities. In this study, sewer wastewater samples and microbial samples from the upper part (UP), middle part (MP) and bottom part (BP) of different pipes were collected for 16S rRNA gene amplicon analysis. It was found that BP harbored distinct microbial communities and the largest proportion of unique species (1141) compared to UP and MP. The community in BP tended to be more clustered. Furthermore, significant differences in microbial functions existed in different spatial locations, including the carbon cycle, nitrogen cycle and sulfur cycle. Active microbial sulfur cycling indicated the corrosion risk of MICC. Among the environmental factors, the oxidation‒reduction potential drove changes in BP, while sulfate managed changes in UP and BP. Stochasticity dominated community assembly in the sewer system. Additionally, the sewer microbial community exhibited numerous positive links. BP possessed a more complex, modular network with higher modularity. These deep insights into microbial ecology in the sewer system may guide engineering safety and disaster prevention in sewer infrastructure.

Mechanistic insights into chemical conditioning on transformation of dissolved organic matter and plant biostimulants production during sludge aerobic composting.

Inorganic coagulants (aluminum and iron salt) are widely used to improve sludge dewaterability, resulting in numerous residues in dewatered sludge. Composting refers to the controlled microbial process that converts organic wastes into fertilizer, and coagulant residues in dewatered sludge can affect subsequent compost efficiency and resource recycling, which remains unclear. This work investigated the effects of two typical metal salt coagulants (poly aluminum chloride [PAC] and poly ferric sulfate [PFS]) conditioning on sludge compost. Our results revealed that PAC conditioning inhibited composting with decreased peak temperature, microbial richness, enzymatic reaction intensities, and compost quality, associated with decreased pH and microbial toxicity of aluminum. Nevertheless, PFS conditioning selectively enriched Pseudoxanthomonas sp. and resulted in more fertile compost with increased peak temperature, enzymatic reaction intensities, and humification degree. Spectroscopy and mass difference analyses indicated that PFS conditioning enhanced reaction intensities of labile biopolymers at the thermophilic stage, mainly comprising hydrolyzation (H2O), dehydrogenation (-H2, -H4), oxidation (+O1H2), and other reactions (i.e., +CH2, C2H4O1, C2H6O1). Unlike the common composting process primarily conducts humification at the cooling stage, PFS conditioning changed the main occurrence stage to the thermophilic stage. Non-targeted metabolomics revealed that indole (a humification intermediate) is responsible for the increased humification degree and indoleacetic acid content in the PFS-conditioned compost, which then promoted compost quality. Plant growth experiments further confirmed that the dissolved organic matter (DOM) in PFS-conditioned compost produced the maximum plant biomass. This study provided molecular-level evidence that PFS conditioning can promote humification and compost fertility during sludge composting, enabling chemical conditioning optimization for sustainable management of sludge.

Inhibitory effect of microplastics derived organic matters on humification reaction of organics in sewage sludge under alkali-hydrothermal treatment.

Alkali-hydrothermal treatment (AHT) of sewage sludge is often used to recover value-added dissolved organic matters (DOM) enriched with artificial humic acids (HA). Microplastics (MPs), as emerging contaminants in sewage sludge, can leach organic compounds (MP-DOM) during AHT, which potentially impact the characteristics of thermally treated sludge's DOM. This study employed spectroscopy and Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR-MS) to explore the impacts of MPs on DOM composition and transformation during AHT. The biological effects of DOM were also investigated by hydroponic experiments. The results showed that the leaching of MP-DOM led to a substantial increase in DOC content of DOM of thermally treated sludge. Conversely, the HA content significantly decreased in the presence of MPs, resulting in a decline of plant growth facilitation degree. FT-ICR-MS analysis revealed that the reduction in HA content was characterized by a notable decline in the abundance of O6-7 and N1-3O6-7 molecules. Reactomics results indicated that the leaching of MP-DOM inhibited the Maillard reaction but bolstered oxidation reactions. The inhibition of Maillard reaction, resulting in a decrease in crucial precursors (dicarbonyl compounds, ketoses, and deoxyglucosone), was responsible for the decrease of HA content. The primary mechanism responsible for inhibiting the Maillard reaction was the consumption of reactive amino reactants through two pathways. Firstly, the leaching of organic acids in MP-DOM caused decrease of sludge pH, leading to the protonation of amino groups. Secondly, the lipid-like compounds in MP-DOM underwent oxidation (-2H+O), producing fatty aldehydes that consumed the reactive amino reactants. These discoveries offer enhanced insights into the specific contribution of MPs to the composition, transformation, bioactivity of DOM during AHT process.

Diversity, composition, metabolic characteristics, and assembly process of the microbial community in sewer system at the early stage.

Sewer systems play vital roles in wastewater treatment facilities, and the microbial communities contribute significantly to the transformation of domestic wastewater. Therefore, this study conducted a 180-day experiment on a sewer system and utilized the high-throughput sequencing technology to characterize the microbial communities. Additionally, community assembly analysis was performed to understand the early-stage dynamics within the sewer system. The results demonstrated that the overall diversity of microbial communities exhibited fluctuations as the system progressed. The dominant phyla observed were Chloroflexi, Bacteroidetes, Firmicutes, and Proteobacteria, accounting for over 85.4% of the total relative abundances. At the genus level, bacteria associated with fermentation displayed a high relative abundance, particularly during days 75 to 180. A random-forest machine-learning model identified a group of microbes that confirmed the substantial contribution of fermentation. During the process of fermentation, microorganisms predominantly utilized propionate formation as the main pathway for acidogenesis, followed by acetate and butyrate formation. In terms of nitrogen and sulfur cycles, dissimilatory nitrate reduction and assimilatory sulfate reduction played significant roles. Furthermore, stochastic ecological processes had a dominant effect during the experiment. Dispersal limitation primarily governed the assembly process almost the entire experimental period, indicating the strong adaptability and metabolic plasticity of microorganisms in response to environmental variations. This experiment provides valuable insights into the metabolic mechanisms and microbial assembly associated with sewer systems.

Item selection methods in multidimensional computerized adaptive testing for forced-choice items using Thurstonian IRT model.

Multidimensional computerized adaptive testing for forced-choice items (MFC-CAT) combines the benefits of multidimensional forced-choice (MFC) items and computerized adaptive testing (CAT) in that it eliminates response biases and reduces administration time. Previous studies that explored designs of MFC-CAT only discussed item selection methods based on the Fisher information (FI), which is known to perform unstably at early stages of CAT. This study proposes a set of new item selection methods based on the KL information for MFC-CAT (namely MFC-KI, MFC-KB, and MFC-KLP) based on the Thurstonian IRT (TIRT) model. Three simulation studies, including one based on real data, were conducted to compare the performance of the proposed KL-based item selection methods against the existing FI-based methods in three- and five-dimensional MFC-CAT scenarios with various test lengths and inter-trait correlations. Results demonstrate that the proposed KL-based item selection methods are feasible for MFC-CAT and generate acceptable trait estimation accuracy and uniformity of item pool usage. Among the three proposed methods, MFC-KB and MFC-KLP outperformed the existing FI-based item selection methods and resulted in the most accurate trait estimation and relatively even utilization of the item pool.

Intracavity filtering effect in a dual-output linear-cavity all-PM fiber laser mode-locked by NPE.

We have demonstrated a stable and low-noise all-polarization-maintaining (PM) ultrafast erbium-doped fiber laser mode-locked via nonlinear polarization evolution (NPE) in a linear cavity with dual outputs. A detailed design strategy is presented. The all-PM configuration enhances the capability of resistance to environmental fluctuations. Self-starting mode-locking is realized by using a non-reciprocal phase shifter. The dual-output structure offers the intracavity filtering effect, where the reflective port serves as a bandpass spectral filter, significantly improving the transmissive-port optical properties. The laser directly generates ultrashort pulses with a pulse duration of 129 fs operating at a fundamental repetition rate of 105.8 MHz. The integrated root-mean-square (RMS) relative intensity noise from 10 Hz to 10 MHz is ∼0.008%, and the integrated RMS timing jitter from 5 kHz to 10 MHz is ∼36f s. Long-term stability is confirmed in 25 h with a RMS power fluctuation of  ∼0.10%. Our high-performance fiber laser is a prospective candidate for low-noise applications.

Manufacturing-Enabled Tunability of Linear and Nonlinear Epsilon-Near-Zero Properties in Indium Tin Oxide Nanofilms.

Epsilon-near-zero (ENZ) materials have attracted great interest due to their exotic linear and nonlinear responses, which makes it significant to tune ENZ wavelengths for wavelength-dependent applications. However, studies to achieve tunability in a wide spectral range and link the fabrication parameters with linear and nonlinear ENZ properties have been uncovered. ENZ indium tin oxide (ITO) nanofilms are fabricated by magnetron sputtering, through which the control of ENZ properties is demonstrated. Factors in the sputtering process, such as the gas ratio and annealing, have a great impact on the ITO samples. Tunable ENZ parameters are listed to provide a beneficial database for ENZ ITO, mainly attributed to the change of carrier concentration. The influence of ENZ parameters on optical characteristics via annealing treatment is further explored. The ENZ wavelength is blue-shifted by 609 nm, and the intrinsic loss is reduced by 63.2%, while the ITO samples exhibit better linear scattering properties and stronger field intensity enhancement. Additionally, the laser testing system illustrates the change from reverse saturable absorption to saturable absorption with an absolute modulation depth of 21.9%, improved by 222.1%, and the nonlinear refractive index n2 and nonlinear absorption coefficient ß are 2.07 × 10-16 m2 W-1 and -3.16 × 10-10 m W-1 for post-annealed ITO samples, respectively. The proposed sputtering protocol offers a feasible technique to control the linear and nonlinear ENZ performance, which has great potential in laser technology and nanophotonics.

A Generalized Diagnostic Classification Modeling Framework Integrating Differential Speediness: Advantages and Illustrations in Psychological and Educational Testing.

To advance the theoretical foundation of incorporating response times (RTs) into diagnostic classification models (DCMs), this study attempts to further derive, test and illustrate a generalized modeling framework (known as the JVRT-LCDM) that can simultaneously analyze response accuracy and differential speediness based on an existing method (Zhan et al., British Journal of Mathematical and Statistical Psychology, 71(2), 262-286, 2018). The JVRT-LCDM not only provides fine-grained diagnostic feedback without strict model constraints but also clarifies the specific speed trajectory of individuals. Moreover, some existing models from psychometric literatures are included in the JVRT-LCDM as special cases. The feasibility of the JVRT-LCDM is investigated via a Monte Carlo simulation study using a Bayesian estimation scheme, and two empirical datasets are then analyzed to illustrate the applicability of the JVRT-LCDM in practice. The results indicate that (1) as a generalized and flexible model, the JVRT-LCDM realizes high correct classification rates and accurate speed parameter recovery; (2) the JVRT-LCDM outperforms the existing models in terms of model-data fit, diagnostic consistency, and estimation of specific individuals in practical cognitive diagnosis assessments; and (3) the JVRT-LCDM provides reliable evidence for nonconstant speed modeling.

Entecavir Monotherapy Prevents Hepatitis B Virus Recurrence After Liver Transplant for Chronic Hepatitis B Patients: A Long-Term Retrospective Study.

BACKGROUND: Limited data are available on the use of oral antiviral therapy, particularly the long-term use of entecavir monotherapy in patients with hepatitis B virus (HBV)-related diseases after liver transplant (LT). METHODS: The clinical data on consecutive patients who underwent LT for HBV-related diseases from 2011 to 2019 were prospectively collected and retrospectively analyzed. All patients received entecavir monotherapy alone during the follow-up period; viral serology/load and liver biochemical tests were performed regularly. RESULTS: Among the total of 89 patients were patients with decompensated cirrhosis (n = 27 [30%]), acute-on-chronic HBV (n = 21 [24%]), and hepatocellular carcinoma (HCC) (n = 41 [46%]). The median age of the patients was 50 years (range, 42-58 years), and the median follow-up was 37 months (range, 1-96 months). Before LT, 45 (51%) patients did not receive, whereas 44 (49%) were currently receiving, oral antiviral therapy. At the time of LT, serum level of HBV DNA of 34 (38%) patients was >20 IU/mL, with the median level being 270,000 IU/mL (range, 4270-2,020,000), and 53 patients (59%) had undetectable levels of HBV DNA (≤20 IU/mL). The cumulative rate of hepatitis B surface antigen loss was 79.8%, 100%, and 100% after 1 month, 1 year, and 5 years, respectively. Hepatitis B surface antigen positivity returned after seroclearance in 1 patient, who died of HCC recurrence with an undetectable level of HBV DNA. The overall survival rates at 1, 3, and 5 years after LT were 94.51%, 86.84%, and 85.27%, respectively. During the follow-up period, no entecavir adverse reactions or dose reductions were observed. CONCLUSIONS: Long-term entecavir monotherapy was highly effective in preventing HBV reactivation and HBV-related diseases.

Numerical analysis of synchronously pumped solid-state Raman lasers.

Considering the spatial distribution of laser beams and phonon waves, the SRS coupling wave equations in the transient regime are derived and normalized for the first time. The synchronously pumped solid-state Raman laser is simulated numerically to investigate the influences of the cavity length detuning, output coupling rate, dispersion, Raman gain and dephasing time of Raman mode on laser performances. It is found that the intensive pulse compression of first Stokes laser in synchronously pumped solid-state Raman laser stems from pulse width gain narrowing and intensity oscillation effects. The cavity length detuning, dispersion, Raman gain and dephasing time considerably affect the pulse width gain narrowing and intensity oscillation processes. The theoretical results can help the design and optimization of synchronously pumped solid-state Raman laser to generate ultrafast Raman laser output efficiently.

A diagnostic classification version of Schizotypal Personality Questionnaire using diagnostic classification models.

OBJECTIVE: To obtain more precise and rich information from the measurements for schizotypal personality disorder (SPD), a cutting-edge psychometric theory called diagnostic classification models (DCMs) was first employed in the present study to develop a diagnostic classification version of the Schizotypal Personality Questionnaire (DC-SPQ) based on the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders. METHODS: Under the framework of DCMs, 980 college students were recruited to calibrate item parameters of the Schizotypal Personality Questionnaire. Items that fit the psychometric characteristic would be selected to compose the DC-SPQ, prior to an analysis of its indexes. RESULTS: Results showed that the DC-SPQ had high reliability and validity in both the classical test theory and DCMs, in addition to showing a sensitivity of 0.921 and a specificity of 0.841 with area under receiver operating characteristic curve = 0.936. Meanwhile, the four-factor model proposed adequately fits with the data. More importantly, the DC-SPQ provides not only the general-level information similar to traditional questionnaires but also the symptom-level information with the posterior probability, which provides an insight into delivering the individual-specific intervention that is tailor made to schizotypal personality disorder. CONCLUSIONS: This study demonstrates that the DC-SPQ is very valuable for psychometric detection in that it can clarify the symptom being measured and provide more reasonable estimates.

Spectroscopic study on transformations of dissolved organic matter in coal-to-liquids wastewater under integrated chemical oxidation and biological treatment process.

A large amount of wastewater containing various toxic organic contaminants is produced during coal-to-liquids process. In this study, several spectroscopic methods were used to monitor the transformation of organic pollutants during an integrated chemical oxidation and biological process. The results showed that the hydrophobic acid fraction increased after Fenton oxidation, which was likely due to the production of small-molecule organic acids. Soluble microbial products were generated during biological treatment processes, which were degraded after ozonation; meanwhile, the hydrophilic base and acid components increased. Ultraviolet-visible spectroscopic analysis indicated that peaks at the absorption wavelengths of 280 and 254nm, which are associated with aromatic substances, were detected in the raw water. The aromatic substances were gradually removed, becoming undetectable after biological aeration filter (BAF) treatment. Fourier transform infrared spectroscopy analysis revealed that the functional groups of phenols; benzene, toluene, ethylbenzene, and xylene (BTEX); aromatic hydrocarbons; aliphatic acids; aldehydes; and esters were present in raw wastewater. The organic substances were oxidized into small molecules after Fenton treatment. Aromatic hydrocarbons were effectively removed through bioadsorption and biodegradation after BAF process. Biodegradable organic matter was reduced and finally became undetectable after anoxic-oxic treatment in combination with a membrane bioreactor. Four fluorescent components were fractionated and obtained via excitation-emission matrix parallel factor analysis (EEM-PARAFAC). Dissolved organic matter fractionation in conjunction with EEM-PARAFAC was able to monitor more precisely the evolution of characteristic organic contaminants.

Illumination on "Reserving Phloem and Discarding Xylem" and Quality Evaluation of Radix polygalae by Determining Oligosaccharide Esters, Saponins, and Xanthones.

The root of Polygala tenuifolia Willd. or Polygala sibirica L. exhibits protective effects on the central nervous system and is frequently used to treat insomnia, amnesia, and other cognitive dysfunction. In our study, we studied nine bioactive compounds spanning oligosaccharide esters, saponins, and xanthones by using a sensitive, efficient, and validated method established on ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry. The quantified result of interesting compounds proved that accumulation of those compounds were found in phloem rather than in xylem. By taking the standardized result of nine compound contents into account, the "Spider-web" analytical result of xylem and phloem from Radix polygalae (RP) unveiled the rationality of RP's classical use in clinic including discarding the xylem and reserving the phloem. Moreover, the remarkable variation was also revealed from the quantitative result of 45 samples with different diameters from the different origins, which did not significantly correlate with the variation of RP's diameter. Our study could shed the light on the quality assessment of RP for further research and illustrate the scientific connotation of the processing method of "discarding the xylem and reserving the phloem".

Enhancement of Fenton oxidation for removing organic matter from hypersaline solution by accelerating ferric system with hydroxylamine hydrochloride and benzoquinone.

Fenton oxidation is generally inhibited in the presence of a high concentration of chloride ions. This study investigated the feasibility of using benzoquinone (BQ) and hydroxylamine hydrochloride (HA) as Fenton enhancers for the removal of glycerin from saline water under ambient temperature by accelerating the ferric system. It was found that organics removal was not obviously affected by chloride ions of low concentration (less than 0.1mol/L), while the mineralization rate was strongly inhibited in the presence of a large amount of chloride ions. In addition, ferric hydrolysis-precipitation was significantly alleviated in the presence of HA and BQ, and HA was more effective in reducing ferric ions into ferrous ions than HA, while the H2O2 decomposition rate was higher in the BQ-Fenton system. Electron spin resonance analysis revealed that OH production was reduced in high salinity conditions, while it was enhanced after the addition of HA and BQ (especially HA). This study provided a possible solution to control and alleviate the inhibitory effect of chloride ions on the Fenton process for organics removal.

[Diagnosis and treatment of multiple intracranial aneurysms].

OBJECTIVE: To explore the diagnosis and treatment strategy of multiple intracranial aneurysms (MIA). METHODS: We retrospectively analyzed 96 patients with MIA (234 aneurysms). The rupture site was determined on the basis of computed tomographic and angiographic findings, and the supposed ruptured aneurysm was treated with coiling OR clipping. All the patients' records were reviewed including all computed tomographic scans and angiograms. RESULTS: Twelve patients received conservative treatment, 56 patients were treated by endovascular embolization, and 28 patients received clipping; 44 patients received one-stage treatment, and 4 patients needed a second therapy. In 36 patients, only the ruptured aneurysm was eliminated. The clinical outcomes of these 84 patients evaluated by Glasgow Outcome Scale grades were: absence of deficits in 62 patients, minor deficits in 12 patients, major deficit in 8 patients; death occurred in 2 cases. Thirty patients were available for a 6-month follow-up with DSA, which revealed stable occlusion of the aneurysms in 29 patients and the need of a retreatment due to recanalization in only one patient. CONCLUSION: Correct localization of the rupture aneurysm based on a comprehensive diagnosis is key to MIA treatment. All the aneurysms should be treated in one session whenever possible to protect the patient from rebleeding.

Water Extract of Fructus Hordei Germinatus Shows Antihyperprolactinemia Activity via Dopamine D2 Receptor.

Objective. Fructus Hordei Germinatus is widely used in treating hyperprolactinemia (hyperPRL) as a kind of Chinese traditional herb in China. In this study, we investigated the anti-hyperPRL activity of water extract of Fructus Hordei Germinatus (WEFHG) and mechanism of action. Methods. Effect of WEFHG on serum prolactin (PRL), estradiol (E2), progesterone (P), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and hypothalamus protein kinase A (PKA) and cyclic adenosine monophosphate (cAMP) levels of hyperPRL rats were investigated. And effect of WEFHG on PRL secretion, D2 receptors, and dopamine transporters (DAT) was studied in MMQ, GH3, and PC12 cells, respectively. Results. WEFHG reduced the secretion of PRL in hyperPRL rats effectively. In MMQ cell, treatment with WEFHG at 1-5 mg/mL significantly suppressed PRL secretion and synthesis. Consistent with a D2-action, WEFHG did not affect PRL in rat pituitary lactotropic tumor-derived GH3 cells that lack the D2 receptor expression but significantly increased the expression of D2 receptors and DAT in PC12 cells. In addition, WEFHG reduced the cAMP and PKA levels of hypothalamus in hyperPRL rats significantly. Conclusions. WEFHG showed anti-hyperPRL activity via dopamine D2 receptor, which was related to the second messenger cAMP and PKA.

The extracellular domain of Bri2 (ITM2B) binds the ABri peptide (1-23) and amyloid beta-peptide (Abeta1-40): Implications for Bri2 effects on processing of amyloid precursor protein and Abeta aggregation.

In Alzheimer's disease the amyloid beta-peptide (Abeta) aggregates in brain tissue and arteries. Abeta is proteolytically cleaved out from amyloid precursor protein (APP) by different secretases. Recently, the transmembrane protein ITM2B/Bri2, which is expressed in neurons and associated with familial British and Danish dementia, was shown to inhibit APP processing in transfected cells as well as in transgenic mice. Several mechanisms by which Bri2 can interfere with Abeta production and aggregation have been proposed. Herein, we studied recombinant human Bri2 (residues 90-236) containing the extracellular Brichos domain without the ABri23 peptide. Bri2(90-236) binds to ABri23, which suggests that these two parts interact during Bri2 biosynthesis, in line with proposed functions of Brichos domains in other proteins. Moreover, Bri2(90-236) binds Abeta1-40 and inhibits its aggregation and fibril formation. These data suggest a model for how the processing of Bri2 and APP are interrelated.

Mutations linked to interstitial lung disease can abrogate anti-amyloid function of prosurfactant protein C.

The newly synthesized proSP-C (surfactant protein C precursor) is an integral ER (endoplasmic reticulum) membrane protein with a single metastable polyvaline alpha-helical transmembrane domain that comprises two-thirds of the mature peptide. More than 20 mutations in the ER-lumenal CTC (C-terminal domain of proSP-C), are associated with ILD (interstitial lung disease), and some of the mutations cause intracellular accumulation of cytotoxic protein aggregates and a corresponding decrease in mature SP-C. In the present study, we showed that: (i) human embryonic kidney cells expressing the ILD-associated mutants proSP-C(L188Q) and proSP-C(DeltaExon4) accumulate Congo Red-positive amyloid-like inclusions, whereas cells transfected with the mutant proSP-C(I73T) do not; (ii) transfection of CTC into cells expressing proSP-C(L188Q) results in a stable CTC-proSP-C(L188Q) complex, increased proSP-C(L188Q) half-life and reduced formation of Congo Red-positive deposits; (iii) replacement of the metastable polyvaline transmembrane segment with a stable polyleucine transmembrane segment likewise prevents formation of amyloid-like proSP-C(L188Q) aggregates; and (iv) binding of recombinant CTC to non-helical SP-C blocks SP-C amyloid fibril formation. These results suggest that CTC can prevent the polyvaline segment of proSP-C from promoting formation of amyloid-like deposits during biosynthesis, by binding to non-helical conformations. Mutations in the Brichos domain of proSP-C may lead to ILD via loss of CTC chaperone function.

Role of aggregated medin in the pathogenesis of thoracic aortic aneurysm and dissection.

The pathogenesis of sporadic thoracic aortic aneurysm and dissection, which may lead to rupture of the aorta, remains largely unknown. Amyloid deposits, formed from the medin peptide, are very prevalent in the media of the thoracic aorta. We have studied the occurrence of medin-derived amyloid in specimens from patients with thoracic aortic aneurysm, aortic dissection type A and normal dimensioned aorta. Surprisingly, the amount of amyloid was significantly lower in the aneurysm and dissection groups (0.63+/-0.13 and 0.36+/-0.24 amyloid particles per mm2, respectively) compared to the control material (2.37+/-0.58). However, focal medin immunoreactivity not associated with amyloid was found more conspicuously in the media of the two diseased groups. Recent amyloid research indicates that prefibrillar oligomeric aggregates, rather than mature amyloid fibrils, are toxic to the surrounding cells. The non-amyloid medin immunoreactivity observed may represent such toxic oligomers. This is supported by the fact that aggregated medin induced death of aortic smooth muscle cells in vitro. In addition, cells incubated together with medin increased the production of matrix metalloproteinase-2, a protease that degrades elastin and collagen and subsequently weakens the vessel wall. We therefore propose that medin oligomers are involved in the degeneration process of sporadic thoracic aortic aneurysm and dissection.