Recovery strategies and mechanisms of anammox reaction following inhibition by environmental factors: A review.

Anaerobic ammonium oxidation (anammox) is a promising biological method for treating nitrogen-rich, low-carbon wastewater. However, the application of anammox technology in actual engineering is easily limited by environmental factors. Considerable progress has been investigated in recent years in anammox restoration strategies, significantly addressing the challenge of poor reaction performance following inhibition. This review systematically outlines the strategies employed to recover anammox performance following inhibition by conventional environmental factors and emerging pollutants. Additionally, comprehensive summaries of strategies aimed at promoting anammox activity and enhancing nitrogen removal performance provide valuable insights into the current research landscape in this field. The review contributes to a comprehensive understanding of restoration strategies of anammox-based technologies.

Nano-selenium alleviates cadmium-induced neurotoxicity in cerebrum via inhibiting gap junction protein connexin 43 phosphorylation.

Cadmium (Cd) as a ubiquitous toxic heavy metal is reported to affect the nervous system. Selenium (Se) has been shown to have antagonistic effects against heavy metal toxicity. In addition, it shows potential antioxidant and anti-inflammatory properties. Thus, the purpose of this study was to determine the possible mechanism of brain injury after high Cd exposure and the mitigation of Nano-selenium (Nano-Se) against Cd-induced brain injury. In this study, the Cd-treated group showed a decrease in the number of neurons in brain tissue, swelling of the endoplasmic reticulum and mitochondria, and the formation of autophagosomes. Nano-Se intervention restored Cd-caused alterations in neuronal morphology, endoplasmic reticulum, and mitochondrial structure, thereby reducing neuronal damage. Furthermore, we found that some differentially expressed genes were involved in cell junction and molecular functions. Subsequently, we selected eleven (11) related differentially expressed genes for verification. The qRT-PCR results revealed the same trend of results as determined by RNA-Seq. Our findings also showed that Nano-Se supplementation alleviated Cx43 phosphorylation induced by Cd exposure. Based on immunofluorescence colocalization it was demonstrated that higher expression of GFAP and lower expressions of Cx43 were restored by Nano-Se supplementation. In conclusion, the data presented in this study establish a direct association between the phosphorylation of Cx43 and the occurrence of autophagy and neuroinflammation. However, it is noteworthy that the introduction of Nano-Se supplementation has been observed to mitigate these alterations. These results elucidate the relieving effect of Nano-Se on Cd exposure-induced brain injury.

Lysine 63-linked ubiquitination of tau oligomers contributes to the pathogenesis of Alzheimer's disease.

Ubiquitin-modified tau aggregates are abundantly found in human brains diagnosed with Alzheimer's disease (AD) and other tauopathies. Soluble tau oligomers (TauO) are the most neurotoxic tau species that propagate pathology and elicit cognitive deficits, but whether ubiquitination contributes to tau formation and spreading is not fully understood. Here, we observed that K63-linked, but not K48-linked, ubiquitinated TauO accumulated at higher levels in AD brains compared with age-matched controls. Using mass spectrometry analyses, we identified 11 ubiquitinated sites on AD brain-derived TauO (AD TauO). We found that K63-linked TauO are associated with enhanced seeding activity and propagation in human tau-expressing primary neuronal and tau biosensor cells. Additionally, exposure of tau-inducible HEK cells to AD TauO with different ubiquitin linkages (wild type, K48, and K63) resulted in enhanced formation and secretion of K63-linked TauO, which was associated with impaired proteasome and lysosome functions. Multipathway analysis also revealed the involvement of K63-linked TauO in cell survival pathways, which are impaired in AD. Collectively, our study highlights the significance of selective TauO ubiquitination, which could influence tau aggregation, accumulation, and subsequent pathological propagation. The insights gained from this study hold great promise for targeted therapeutic intervention in AD and related tauopathies.

Optimization of Electron Transport Pathway: A Novel Strategy to Solve the Photocorrosion of Ag-Based Photocatalysts.

Although Ag-containing photocatalysts exhibit excellent photocatalytic ability, they present great challenges owing to their photocorrosion and ease of reduction. Herein, an electron acceptor platform of Ag2O/La(OH)3/polyacrylonitrile (PAN) fiber was constructed using a heterojunction strategy and electrospinning technology to develop a novel photocatalytic membrane with a redesigned electron transport pathway. Computational and experimental results demonstrate that the optimized electron transport pathway included intercrystal electron transfer induced by the La-O bond between Ag2O and La(OH)3 as well as electron transfer between the catalyst crystal and electrophilic PAN membrane interface. In addition, the photocatalytic performance of the Ag2O/La(OH)3 membrane for tetracycline (TC) removal was still above 97% after five photocatalytic reaction cycles. Furthermore, the carrier life was greatly extended. Mechanistic study revealed that photogenerated holes on the Ag2O/La(OH)3 membrane were the main reactive species in TC degradation. Overall, this study proposes a novel electron transport pathway strategy that effectively solves the problems of photocatalyst photocorrosion and structural instability.

Nitrate Bioreduction under Cr(VI) Stress: Crossroads of Denitrification and Dissimilatory Nitrate Reduction to Ammonium.

This study explored the response of NO3--N bioreduction to Cr(VI) stress, including reduction efficiency and the pathways involved (denitrification and dissimilatory nitrate reduction to ammonium (DNRA)). Different response patterns of NO3--N conversion were proposed under Cr(VI) suppress (0, 0.5, 5, 15, 30, 50, and 80 mg/L) by evaluating Cr(VI) dose dependence, toxicity accumulation, bioelectron behavior, and microbial community structure. Cr(VI) concentrations of >30 mg/L rapidly inhibited NO3--N removal and immediately induced DNRA. However, denitrification completely dominated the NO3--N reduction pathway at Cr(VI) concentrations of <15 mg/L. Therefore, 30 and 80 mg/L Cr(VI) (R4 and R6) were selected to explore the selection of the different NO3--N removal pathways. The pathway of NO3--N reduction at 30 mg/L Cr(VI) exhibited continuous adaptation, wherein the coexistence of denitrification (51.7%) and DNRA (13.6%) was achieved by regulating the distribution of denitrifiers (37.6%) and DNRA bacteria (32.8%). Comparatively, DNRA gradually replaced denitrification at 80 mg/L Cr(VI). The intracellular Cr(III) accumulation in R6 was 6.60-fold greater than in R4, causing more severe oxidant injury and cell death. The activated NO3--N reduction pathway depended on the value of nitrite reductase activity/nitrate reductase activity, with 0.84-1.08 associated with DNRA activation and 1.48-1.57 with DNRA predominance. Although Cr(VI) increased microbial community richness and improved community structure stability, the inhibition or death of nitrogen-reducing microorganisms caused by Cr(VI) decreased NO3--N reduction efficiency.

Abietane diterpenoids from Orthosiphon wulfenioides with NLRP3 inflammasome inhibitory activity.

Wulfenioidones A - K (1-11) were abietane diterpenoids with highly oxidized 6/6/6 aromatic tricyclic skeleton isolated from the whole plant of Orthosiphon wulfenioides, and their planar structures and absolute configurations were elucidated by spectroscopic data interpretation, electronic circular dichroism calculation as well as X-ray crystallography analysis. Bioactivity screening indicated that compounds 1-4, 6 and 8 exhibited lactate dehydrogenase (LDH) inhibition effect with IC50 values ranging from 0.23 to 3.43 µM by preventing the mononuclear macrophage cell pyroptosis induced by double signal stimulation of LPS and nigericin. Western Blot analyses of Caspase-1 and IL-1ß down-regulation exhibited that compound 1 could selectively inhibit NLRP3 inflammasome, and the cell morphological observation further supported that compound 1 prevented macrophage cell pyroptosis.

Excessive salt intake accelerates the progression of cerebral small vessel disease in older adults.

BACKGROUND: It is unclear whether excessive salt intake accelerates the progression of cerebral small vessel disease (CSVD). The major objective of this study was to investigate the harmful effect of excessive salt intake on the progression of CSVD in older individuals. METHODS: Between May 2007 and November 2010, 423 community-dwelling individuals aged 60 years and older were recruited from the Shandong area, China. Salt intake was estimated using 24-hour urine collection for 7 consecutive days at baseline. Participants were classified into low, mild, moderate and high groups according to the salt intake estimation. CSVD including white matter hyperintensities (WMHs), lacunes, microbleeds and an enlarged perivascular space (EPVS) were determined using brain magnetic resonance imaging. RESULTS: During an average of five years of follow-up, the WMH volume and WMH-to-intracranial ratio were increased in the four groups. However, the increasing trends in the WMH volume and WMH-to-intracranial ratio were significantly faster in the higher salt intake groups compared with the lower salt intake groups (Padjusted < 0.001). The cumulative hazard ratios of new-incident WMHs (defined as those with Fazekas scale scores ≥ 2), new-incident lacunes, microbleeds or an EPVS, as well as composites of CSVD, were respectively 2.47, 2.50, 3.33, 2.70 and 2.89 for the mild group; 3.72, 3.74, 4.66, 4.01 and 4.49 for the moderate group; and 7.39, 5.82, 7.00, 6.40 and 6.61 for the high group, compared with the low group after adjustment for confounders (Padjusted < 0.001). The risk of new-incident WMHs, lacunes, microbleeds or an EPVS, and composites of CSVD was significantly increased with each 1-standard-deviation increment in salt intake (Padjusted < 0.001). CONCLUSION: Our data indicates that excessive salt intake is an important and independent contributor to the progression of CVSD in older adults.

A polygenic risk score improves risk stratification of coronary artery disease: a large-scale prospective Chinese cohort study.

AIMS: To construct a polygenic risk score (PRS) for coronary artery disease (CAD) and comprehensively evaluate its potential in clinical utility for primary prevention in Chinese populations. METHODS AND RESULTS: Using meta-analytic approach and large genome-wide association results for CAD and CAD-related traits in East Asians, a PRS comprising 540 genetic variants was developed in a training set of 2800 patients with CAD and 2055 controls, and was further assessed for risk stratification for CAD integrating with the guideline-recommended clinical risk score in large prospective cohorts comprising 41 271 individuals. During a mean follow-up of 13.0 years, 1303 incident CAD cases were identified. Individuals with high PRS (the highest 20%) had about three-fold higher risk of CAD than the lowest 20% (hazard ratio 2.91, 95% confidence interval 2.43-3.49), with the lifetime risk of 15.9 and 5.8%, respectively. The addition of PRS to the clinical risk score yielded a modest yet significant improvement in C-statistic (1%) and net reclassification improvement (3.5%). We observed significant gradients in both 10-year and lifetime risk of CAD according to the PRS within each clinical risk strata. Particularly, when integrating high PRS, intermediate clinical risk individuals with uncertain clinical decision for intervention would reach the risk levels (10-year of 4.6 vs. 4.8%, lifetime of 17.9 vs. 16.6%) of high clinical risk individuals with intermediate (20-80%) PRS. CONCLUSION: The PRS could stratify individuals into different trajectories of CAD risk, and further refine risk stratification for CAD within each clinical risk strata, demonstrating a great potential to identify high-risk individuals for targeted intervention in clinical utility.

Callicarpanes A-L, Twelve New Clerodane Diterpenoids with NLRP3 Inflammasome Inhibitory Activity from Callicarpa integerrima.

Twelve new clerodane diterpenoids named callicarpanes A-L (1-12), together with eight known compounds (13-20), were isolated from Callicarpa integerrima. Their structures were determined by comprehensive spectroscopic data. The calculated chemical shifts were used to identify relative configurations using DP4+ analysis. The absolute configurations (AC) were assigned based on quantum chemical calculations and X-ray single-crystal diffraction methods. Compounds 1, 3, 5, 9, 10, 12, 15, 16, and 19 showed significant inhibitory activity for NLRP3 inflammasome activation, with the IC50 against lactate dehydrogenase (LDH) release ranging from 0.08 to 4.78 µM. Further study revealed that compound 10 repressed IL-1ß secretion and caspase-1 maturation in J774A.1 cell as well as blocked macrophage pyroptosis.

Electrospinning micro-nanofibers immobilized aerobic denitrifying bacteria for efficient nitrogen removal in wastewater.

Electrospinning micro-nanofibers with exceptional physicochemical properties and biocompatibility are becoming popular in the medical field. These features indicate its potential application as microbial immobilized carriers in wastewater treatment. Here, aerobic denitrifying bacteria were immobilized on micro-nanofibers, which were prepared using different concentrations of polyacrylonitrile (PAN) solution (8%, 12% and 15%). The results of diameter distribution, specific surface area and average pore diameter indicated that 15% PAN micro-nanofibers with tighter surface structure were not suitable as microbial carriers. The bacterial load results showed that the cell density (OD600) and total protein of 12% PAN micro-nanofibers were 107.14% and 106.28% higher than those of 8% PAN micro-nanofibers. Subsequently, the 12% PAN micro-nanofibers were selected for aerobic denitrification under the different C/N ratios (1.5-10), and stable performance was obtained. Bacterial community analysis further manifested that the micro-nanofibers effectively immobilized bacteria and enriched bacterial structure under the high C/N ratios. Therefore, the feasibility of micro-nanofibers as microbial carriers was confirmed. This work was of great significance for promoting the application of electrospinning for microbial immobilization in wastewater treatment.

Differential effects of nitrate and ammonium on the growth of algae and microcystin production by nitrogen-fixing Nostoc sp. and non-nitrogen-fixing Microcystis aeruginosa.

Cyanotoxins produced by cyanobacteria are a significant threat to human health. However, their responses to nitrogen (N) supplies could differ between N-fixing and non-N-fixing species, which has been poorly understood. This study aimed to compare the responses of the non-N-fixing Microcystis aeruginosa and N-fixing Nostoc sp. to varying concentrations of nitrate and ammonium. This comparison had been conducted by analyzing chlorophyll-a contents, maximum quantum efficiencies of photosystem II, microcystin production, and related gene expressions. Our findings revealed that nitrate substantially stimulated the growth of both M. aeruginosa and Nostoc sp. with biomass increase by 366.2 ± 56.5 and 93.0 ± 14.0%, respectively, at 16 mg-N/L. In contrast, high ammonium concentrations suppressed their growth. Furthermore, the intracellular concentration of microcystins produced by M. aeruginosa was higher under high nitrate. Extracellular microcystins showed an opposite trend to increases in nitrate and ammonium. Ammonium increases the production and releases microcystin from Nostoc sp. N metabolism genes showed a similar trend with toxin formation genes, which were up-regulated under the high N treatments. This study provides valuable insights into the impacts of N supplies on growths of N- and non-N-fixing cyanobacteria, as well as microcystin production, which helps to develop effective strategies for managing cyanobacterial blooms.

Delay Minimization in RIS-Assisted URLLC Systems under Reliability Constraints.

The ultra-reliable and low-latency communication (URLLC) systems are expected to support the stringent quality of service (QoS) demands in the Internet of Things (IoT) networks. In order to support the strict latency and reliability constraints, it is preferable to deploy a reconfigurable intelligent surface (RIS) in the URLLC systems to improve the link quality. In this paper, we focus on the uplink of an RIS-assisted URLLC system, and we propose to minimize the transmission latency under the reliability constraints. To solve the non-convex problem, a low-complexity algorithm is proposed by using the Alternating Direction Method of Multipliers (ADMM) technique. The RIS phase shifts optimization, which is typically non-convex, is efficiently solved by formulating as a Quadratically Constrained Quadratic Programming (QCQP) problem. Simulation results verify that our proposed ADMM-based method is able to achieve better performance than the conventional semi-definite relaxation (SDR)-based method with lower computational complexity. Our proposed RIS-assisted URLLC system is able to significantly reduce the transmission latency, which highlights the great potential in deploying RIS in the IoT networks with strict reliability requirements.

Bio-immobilization and recovery of chromium using a denitrifying biofilm system: Identification of reaction zone, binding forms and end products.

Chromium is an important resource in strategic metals. Different from most studies focusing on the bio-reduction of hexavalent chromium [Cr(VI)], this study aims to achieve the immobilization and recovery of chromium using a sequencing batch biofilm reactor. Results showed that Cr(VI) removal efficiency remained more than 99%, and 97% of reduced Cr(III) was immobilized in the biofilm. Immobilization zone, chromium forms and extracellular polymeric substances composition changes were combined to reveal the mechanism of Cr(VI) reduction and immobilization. The chromium distribution in biofilm demonstrated that intercellular layer was the main active zone with an immobilization amount of 891.70±126.32 mg/g-VSS. The reduced products analysis confirmed that trivalent chromium [Cr(III)] chelated with carboxyl, amino and other functional groups and immobilized in the form of organic Cr(III). The digestion method realized a chromium recovery efficiency of 74.59%. This study provides an alternative method for the bioremediation and resources recovery in chromium polluted wastewater.

Systematical analysis of sludge treatment and disposal technologies for carbon footprint reduction.

This study aims to comprehensively analyze the Greenhouse Gases (GHGs) emissions from current sewage sludge treatment and disposal technologies (building material, landfill, land spreading, anaerobic digestion, and thermochemical processes) based on the database of Science Citation Index (SCI) and Social Science Citation Index (SSCI) from 1998 to 2020. The general patterns, spatial distribution, and hotspots were provided by bibliometric analysis. A comparative quantitative analysis based on life cycle assessment (LCA) put forward the current emission situation and the key influencing factors of different technologies. The effective GHG emissions reduction methods were proposed to mitigate climate change. Results showed that incineration or building materials manufacturing of highly dewatered sludge, and land spreading after anaerobic digestion have the best GHG emissions reduction benefits. Biological treatment technologies and thermochemical processes have great potential for reducing GHGs. Enhancement of pretreatment effect, co-digestion, and new technologies (e.g., injection of carbon dioxide, directional acidification) are major approaches to facilitate substitution emissions in sludge anaerobic digestion. The relationship between the quality and efficiency of secondary energy in thermochemical process and GHGs emission still needs further study. Solid sludge products generated by bio-stabilization or thermochemical processes are considered to have a certain carbon sequestration value and can improve the soil environment to control GHG emissions. The findings are useful for future development and processes selection of sludge treatment and disposal facing carbon footprint reduction.

Effect of lipoprotein(a) levels on long-term outcome in octogenarians with coronary artery disease after drug-eluting stent implantation.

BACKGROUND: High levels of lipoprotein(a) [Lp(a)] are linked to adverse cardiovascular events. The significance of Lp(a) for the survival of octogenarians with coronary artery disease (CAD) after drug-eluting stent (DES) insertion is, however, not known. The purpose of the study is to investigated the connection between Lp(a) and outcome in octogenarians with CAD after DES implantation. METHODS: We retrospectively enrolled a total of 506 consecutive octogenarians with CAD and DES implantation in our institution between January 2015 to August 2018. Two patient groups were established: a low group with plasma Lp(a) lower than 50 mg/dL (n = 408) and a high group with values above 50 mg/dL (n = 98). RESULTS: After following up for a median of 31.53 ± 8.22 months, Kaplan-Meier curves indicated that poorer outcome censored for major cardiovascular events (MACE), myocardial infarction (MI), and target vessel revascularization (TVR) in the high group relative to the low group (log-rank test p = 0.001, p = 0.008, and p < 0.001, respectively). High Lp(a) independently predicted MACE (hazard ratio (HR) 1.90; 95% confidence interval (CI) 1.28-2.84; p = 0.002), MI (HR 2.74; 95% CI 1.23-6.11; p = 0.014), and TVR (HR 3.65; 95% CI 1.99-6.69; p < 0.001) after covariate adjustment. CONCLUSIONS: High Lp(a) was also significantly related to poor long-term outcome in octogenarians with CAD after DES implantation.

Comprehensive safety profile evaluation of bivalirudin in Chinese ST-segment elevation myocardial infarction patients receiving percutaneous coronary intervention: a prospective, multicenter, intensive monitoring study.

BACKGROUND: This prospective, multi-center, intensive monitoring study aimed to systematically assess the occurrence of adverse events (AEs) and adverse drug reactions (ADRs), especially thrombocytopenia and bleeding, as well as their risk factors in Chinese ST-segment elevation myocardial infraction (STEMI) patients receiving bivalirudin as anticoagulant for percutaneous coronary intervention (PCI). METHODS: In total, 1244 STEMI patients undergoing PCI and receiving bivalirudin as anticoagulant were enrolled in the present study. Safety data were collected from hospital admission to 72 h after bivalirudin administration; in addition, patients were further followed up at the 30th day with safety data collected at that time. RESULTS: AEs, severe AEs, ADRs and severe ADRs were reported in 224 (18.0%), 15 (1.2%), 49 (3.9%) and 5 (0.4%) patients, respectively. Importantly, 4 (0.3%) patients were submitted to hospitalization and 6 (0.5%) patients died due to AEs, while 1 (0.1%) patient was submitted to hospitalization but no (0.0%) patient died due to ADRs. Meanwhile, thrombocytopenia and bleeding occurred in 24 (1.9%) and 21 (1.7%) patients, respectively. Further multivariate logistic analysis identified several important independent factors related to AEs, ADRs, thrombocytopenia or bleeding, which included history of cardiac surgery and renal function impairment, high CRUSADE risk stratification, elective operation and combination with glycoprotein IIb/IIIa inhibitors. Moreover, 4 multivariate models were constructed based on the above-mentioned factors, which all showed acceptable predictive value for AEs, ADRs, thrombocytopenia and bleeding, respectively. CONCLUSION: Bivalirudin is a well-tolerant anticoagulant in Chinese STEMI patients undergoing PCI procedure.

Aspulvins A-H, Aspulvinone Analogues with SARS-CoV-2 Mpro Inhibitory and Anti-inflammatory Activities from an Endophytic Cladosporium sp.

Eight new aspulvinone analogues, aspulvins A-H (1-8) and aspulvinones D, M, O, and R (9-12), were isolated from cultures of the endophytic fungus Cladosporium sp. 7951. Detailed spectroscopic analyses were conducted to determine the structures of the new compounds. All isolates displayed different degrees of inhibitory activity against the severe acute respiratory syndrome coronavirus 2 main protease (SARS-CoV-2 Mpro) at 10 µM. Notably, compounds 9, 10, and 12 showed potential SARS-CoV-2 Mpro inhibition with IC50 values of 10.3 ± 0.6, 9.4 ± 0.6, and 7.7 ± 0.6 µM, respectively. For all compounds except 3 and 4, the anti-inflammatory activity occurred by inhibiting the release of lactate dehydrogenase (LDH) with IC50 values ranging from 0.7 to 7.4 µM. Compound 10 showed the most potent anti-inflammatory activity by inhibiting Casp-1 cleavage, IL-1ß maturation, NLRP3 inflammasome activation, and pyroptosis. The findings reveal that the aspulvinone analogues 9, 10, and 12 could be promising candidates for coronavirus disease 2019 (COVID-19) treatment as they inhibit SARS-CoV-2 infection and reduce inflammatory reactions caused by SARS-CoV-2.

Fabrication of Pd/Sludge-biochar electrode with high electrochemical activity on reductive degradation of 4-chlorophenol in wastewater.

Effective treatment and utilization of sludge contribute to achieve conventional carbon emission reduction and resource recovery, which is of great significance to realize carbon neutralization of WWTPs. Sludge carbonization derived biochar has attracted more interest because of high potential as catalytic materials. Therein, sludge-derived electrode exhibits a promising potential in the case of sludge utilization for electrocatalysis, however, electrocatalytic performance of the already reported sludge-derived electrode is unsatisfactory due to insufficient active sites. In this study, an efficient Pd/sludge-biochar loaded foam nickel (Pd-SAC@Ni) was successfully fabricated using simple pyrolysis and solidification method, and exhibited remarkable electrocatalytic performance for 4-chlorophenol (4-CP) degradation. Furthermore, the morphology, element distribution and crystal composition were characterized by SEM, EDS, XPS and XRD. The Pd-SAC@Ni electrode exhibited superior electrocatalytic performance than Ni, SAC@Ni, Pd-Ni electrodes. The reduction rate of 98.9% was achieved at current density of 5 mA cm-2, 4-CP concentration of 0.8 mM and initial pH of 7.0. Also, Pd-SAC@Ni electrode showed desirable reusability and achieved 98% of 4-CP removal after multiple runs of experiments. Moreover, the active hydrogen species (H*) generation capacity of electrodes was determined using tert-butanol (TBA) as trapping agent. The mechanism analysis demonstrated that direct reduction process and indirect reduction process both involved in the 4-CP degradation process, and their contribution were 19.5% and 80.5%, respectively. Then, the intermediates formed in the electrochemical degradation of 4-CP were revealed by HPLC and the plausible degradation pathway was proposed. This study provides a cost-effective approach for preparing sludge biochar electrode, and explored a novel way to promote resourceful utilization of sludge for carbon neutrality.

Optical biosensing of markers of mucosal inflammation.

We report the design and adaptation of iron/iron oxide nanoparticle-based optical nanobiosensors for enzymes or cytokine/chemokines that are established biomarkers of lung diseases. These biomarkers comprise ADAM33, granzyme B, MMP-8, neutrophil elastase, arginase, chemokine (C-C motif) ligand 20 and interleukin-6. The synthesis of nanobiosensors for these seven biomarkers, their calibration with commercially available enzymes and cytokines/chemokines, as well as their validation using bronchoalveolar lavage (BAL) obtained from a mouse model of TLR3-mediated inflammation are discussed here. Exhaled Breath Condensate (EBC) is a minimally invasive approach for sampling airway fluid in the diagnosis and management of various lung diseases in humans (e.g., asthma, COPD and viral infections). We report the proof-of-concept of using human EBC in conjunction with nanobiosensors for diagnosis/monitoring airway inflammation. These findings suggest that, with nanosensor technology, human EBC can be utilized as a liquid biopsy to monitor inflammation/remodeling in lung disease.

The IRE1α-XBP1s Arm of the Unfolded Protein Response Activates N-Glycosylation to Remodel the Subepithelial Basement Membrane in Paramyxovirus Infection.

Respiratory syncytial virus (RSV) causes severe lower respiratory tract infections (LRTI) associated with decreased pulmonary function, asthma, and allergy. Recently, we demonstrated that RSV induces the hexosamine biosynthetic pathway via the unfolded protein response (UPR), which is a pathway controlling protein glycosylation and secretion of the extracellular matrix (ECM). Because the presence of matrix metalloproteinases and matricellular growth factors (TGF) is associated with severe LRTI, we studied the effect of RSV on ECM remodeling and found that RSV enhances the deposition of fibronectin-rich ECM by small airway epithelial cells in a manner highly dependent on the inositol requiring kinase (IRE1α)-XBP1 arm of the UPR. To understand this effect comprehensively, we applied pharmacoproteomics to understand the effect of the UPR on N-glycosylation and ECM secretion in RSV infection. We observe that RSV induces N-glycosylation and the secretion of proteins related to ECM organization, secretion, or proteins integral to plasma membranes, such as integrins, laminins, collagens, and ECM-modifying enzymes, in an IRE1α-XBP1 dependent manner. Using a murine paramyxovirus model that activates the UPR in vivo, we validate the IRE1α-XBP1-dependent secretion of ECM to alveolar space. This study extends understanding of the IRE1α-XBP1 pathway in regulating N-glycosylation coupled to structural remodeling of the epithelial basement membrane in RSV infection.