Liver-on-a-Chip Integrated with Label-Free Optical Biosensors for Rapid and Continuous Monitoring of Drug-Induced Toxicity.

Drug toxicity assays using conventional 2D static cultures and animal studies have limitations preventing the translation of potential drugs to the clinic. The recent development of organs-on-a-chip platforms provides promising alternatives for drug toxicity/screening assays. However, most studies conducted with these platforms only utilize single endpoint results, which do not provide real-time/ near real-time information. Here, a versatile technology is presented that integrates a 3D liver-on-a-chip with a label-free photonic crystal-total internal reflection (PC-TIR) biosensor for rapid and continuous monitoring of the status of cells. This technology can detect drug-induced liver toxicity by continuously monitoring the secretion rates and levels of albumin and glutathione S-transferase α (GST-α) of a 3D liver on-a-chip model treated with Doxorubicin. The PC-TIR biosensor is based on a one-step antibody functionalization with high specificity and a detection range of 21.7 ng mL-1 to 7.83 x 103 ng mL-1 for albumin and 2.20 ng mL-1 to 7.94 x 102 ng mL-1 for GST-α. This approach provides critical advantages for the early detection of drug toxicity and improved temporal resolution to capture transient drug effects. The proposed proof-of-concept study introduces a scalable and efficient plug-in solution for organ-on-a-chip technologies, advancing drug development and in vitro testing methods by enabling timely and accurate toxicity assessments.

Genomic and Metagenomic Insights into the Distribution of Nicotine-degrading Enzymes in Human Microbiota.

Introduction: Nicotine degradation is a new strategy to block nicotine-induced pathology. The potential of human microbiota to degrade nicotine has not been explored. Aims: This study aimed to uncover the genomic potentials of human microbiota to degrade nicotine. Methods: To address this issue, we performed a systematic annotation of Nicotine-Degrading Enzymes (NDEs) from genomes and metagenomes of human microbiota. A total of 26,295 genomes and 1,596 metagenomes for human microbiota were downloaded from public databases and five types of NDEs were annotated with a custom pipeline. We found 959 NdhB, 785 NdhL, 987 NicX, three NicA1, and three NicA2 homologs. Results: Genomic classification revealed that six phylum-level taxa, including Proteobacteria, Firmicutes, Firmicutes_A, Bacteroidota, Actinobacteriota, and Chloroflexota, can produce NDEs, with Proteobacteria encoding all five types of NDEs studied. Analysis of NicX prevalence revealed differences among body sites. NicX homologs were found in gut and oral samples with a high prevalence but not found in lung samples. NicX was found in samples from both smokers and non-smokers, though the prevalence might be different. Conclusion: This study represents the first systematic investigation of NDEs from the human microbiota, providing new insights into the physiology and ecological functions of human microbiota and shedding new light on the development of nicotine-degrading probiotics for the treatment of smoking-related diseases.

Altered fecal microbiome and metabolome in adult patients with non-cystic fibrosis bronchiectasis.

BACKGROUND: Emerging experimental and epidemiological evidence highlights a crucial cross-talk between the intestinal flora and the lungs, termed the "gut-lung axis". However, the function of the gut microbiota in bronchiectasis remains undefined. In this study, we aimed to perform a multi-omics-based approach to identify the gut microbiome and metabolic profiles in patients with bronchiectasis. METHODS: Fecal samples collected from non-CF bronchiectasis patients (BE group, n = 61) and healthy volunteers (HC group, n = 37) were analyzed by 16 S ribosomal RNA (rRNA) sequencing. The BE group was divided into two groups based on their clinical status: acute exacerbation (AE group, n = 31) and stable phase (SP group, n = 30). Further, metabolome (lipid chromatography-mass spectrometry, LC-MS) analyses were conducted in randomly selected patients (n = 29) and healthy volunteers (n = 31). RESULTS: Decreased fecal microbial diversity and differential microbial and metabolic compositions were observed in bronchiectasis patients. Correlation analyses indicated associations between the differential genera and clinical parameters such as bronchiectasis severity index (BSI). Disease-associated gut microbiota was screened out, with eight genera exhibited high accuracy in distinguishing SP patients from HCs in the discovery cohort and validation cohort using a random forest model. Further correlation networks were applied to illustrate the relations connecting disease-associated genera and metabolites. CONCLUSION: The study uncovered the relationships among the decreased fecal microbial diversity, differential microbial and metabolic compositions in bronchiectasis patients by performing a multi-omics-based approach. It is the first study to characterize the gut microbiome and metabolome in bronchiectasis, and to uncover the gut microbiota's potentiality as biomarkers for bronchiectasis. TRIAL REGISTRATION:  This study is registered with ClinicalTrials.gov, number NCT04490447.

Corticosteroids alleviate lipopolysaccharide-induced inflammation and lung injury via inhibiting NLRP3-inflammasome activation.

The role of corticosteroids in acute lung injury (ALI) remains uncertain. This study aims to determine the underlying mechanisms of corticosteroid treatment for lipopolysaccharide (LPS)-induced inflammation and ALI. We used corticosteroid treatment for LPS-induced murine ALI model to investigate the effect of corticosteroid on ALI in vivo. Moreover, LPS-stimulated macrophages were used to explore the specific anti-inflammatory effects of corticosteroids on NLRP3-inflammasome in vitro. We found corticosteroids attenuated LPS-induced ALI, which manifested in reduction of the alveolar structure destruction, the infiltration of neutrophils and the inflammatory cytokines release of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) in Lung. In vitro, when NLRP3-inflammasome was knocked out, inflammatory response of caspase-1 activation and IL-1ß secretion was obviously declined. Further exploration, our results showed that when corticosteroid preprocessed macrophages before LPS primed, it obviously inhibited the activation of caspase-1 and the maturation of IL-1ß, which depended on inhibiting the nuclear factor-κB (NF-κB) signal pathway activation. However, when corticosteroids intervened the LPS-primed macrophages, it also negatively regulated NLRP3-inflammasome activation through suppressing mitochondrial reactive oxygen species (mtROS) production. Our results revealed that corticosteroids played a protection role in LPS-induced inflammation and ALI by suppressing both NF-κB signal pathway and mtROS-dependent NLRP3 inflammasome activation.

Graphene Oxide-Based Nanomaterials: An Insight into Retinal Prosthesis.

Retinal prosthesis has recently emerged as a treatment strategy for retinopathies, providing excellent assistance in the treatment of age-related macular degeneration (AMD) and retinitis pigmentosa. The potential application of graphene oxide (GO), a highly biocompatible nanomaterial with superior physicochemical properties, in the fabrication of electrodes for retinal prosthesis, is reviewed in this article. This review integrates insights from biological medicine and nanotechnology, with electronic and electrical engineering technological breakthroughs, and aims to highlight innovative objectives in developing biomedical applications of retinal prosthesis.

Noninvasive Glucose Monitoring with a Contact Lens and Smartphone.

Diabetes has become a chronic metabolic disorder, and the growing diabetes population makes medical care more important. We investigated using a portable and noninvasive contact lens as an ideal sensor for diabetes patients whose tear fluid contains glucose. The key feature is the reversible covalent interaction between boronic acid and glucose, which can provide a noninvasive glucose sensor for diabetes patients. We present a phenylboronic acid (PBA)-based HEMA contact lens that exhibits a reversible swelling/shrinking effect to change its thickness. The difference in thickness can be detected in a picture taken with a smartphone and analyzed using software. Our novel technique offers the following capabilities: (i) non-enzymatic and continuous glucose detection with the contact lens; (ii) no need for an embedded circuit and power source for the glucose sensor; and (iii) the use of a smartphone to detect the change in thickness of the contact lens with no need for additional photo-sensors. This technique is promising for a noninvasive measurement of the glucose level and simple implementation of glucose sensing with a smartphone.

Macrolides protect against Pseudomonas aeruginosa infection via inhibition of inflammasomes.

Macrolides antibiotics have been effectively used in many chronic diseases, especially with Pseudomonas aeruginosa (P. aeruginosa) infection. The mechanisms underlying the therapeutic effects of macrolides in these diseases remain poorly understood. We established a mouse model of chronic lung infection using P. aeruginosa agar-beads, with azithromycin treatment or placebo. Lung injury, bacterial clearance, and inflammasome-related proteins were measured. In vitro, the inflammasomes activation induced by flagellin or ATP were assessed in LPS-primed macrophages with or without macrolides treatment. Plasma IL-18 levels were determined from patients who were diagnosed with bronchiectasis isolated with or without P. aeruginosa and treated with azithromycin for 3-5 days. Azithromycin treatment enhanced bacterial clearance and attenuated lung injury in mice chronically infected with P. aeruginosa, which resulted from the inhibition of caspase-1-dependent IL-1ß and IL-18 secretion. In vitro, azithromycin and erythromycin inhibited NLRC4 and NLRP3 inflammasomes activation. Plasma IL-18 levels were higher in bronchiectasis patients with P. aeruginosa isolation compared with healthy controls. Azithromycin administration markedly decreased IL-18 secretion in bronchiectasis patients. The results of this study reveal that azithromycin and erythromycin exert a novel anti-inflammatory effect by attenuating inflammasomes activation, which suggests potential treatment options for inflammasome-related diseases.

Asthma and bronchiectasis exacerbation.

Bronchiectasis and asthma are common respiratory diseases worldwide. However, the influence of asthma on bronchiectasis remains unclear. The objective of this study is to analyse the effects of asthma on bronchiectasis exacerbation.Data from inpatients diagnosed with bronchiectasis with or without asthma at Shanghai Pulmonary Hospital (Shanghai, China) between January 2013 and December 2014 were retrospectively collected and analysed. 249 patients with only bronchiectasis and 214 patients with both bronchiectasis and asthma were included in the study. Follow-up records were used to evaluate the effect of asthma on bronchiectasis exacerbation.The variables found to be independently associated with bronchiectasis exacerbations were age (OR 1.07, 95% CI 1.03-1.11; p<0.001), duration of symptoms (OR 1.06, 95% CI 1.03-1.09; p<0.001), the presence of asthma (OR 2.6, 95% CI 1.15-5.88; p=0.021), forced expiratory volume in 1 s <50% predicted (OR 4.03, 95% CI 1.75-9.26; p=0.001), isolation of Pseudomonas aeruginosa in sputum (OR 2.41, 95% CI 1.00-5.79; p=0.05) and lung lesion extension to more than two lobes (OR 2.73, 95% CI 1.16-6.45; p=0.022).The existence of asthma was associated with an independent increase in risk of bronchiectasis exacerbation.

[Effects of exogenous MeJA, SA and two kinds of endophytic fungi on physiology and total phenols content of seedlings of Bletilla striata].

Tissue culture seedlings of Bletilla striata were treated with MeJA, SA and two kinds of endophytic fungi in order to study the effects of those treatments on the physiology and total phenols content. The method of tissue culture was used to culture seeds into seedlings, and then different treatments were applied on them to observe and measure the changes of physiology and total phenols content. We find that the growth of seedlings treated with SA was poor, which treated with 40 µmol•L⁻¹ MeJA, 50 mL•L⁻¹ Hypocrea koningii and 10 mL•L⁻¹ Trichoderma koningiopsis showed better. The activity of SOD, POD and CAT was at a high level under SA treatment of each concentration. The activity of SOD and POD increased as the rise of MeJA concentration, while CAT was highest at 80 µmol•L⁻¹. The activity of SOD and POD increased with the increasing of the concentration of H. koningii treatment, while CAT reached the highest at 1 mL•L⁻¹. The activity of SOD, POD and CAT increased first and then declined with the concentration of T. koningiopsis increasing, and the highest activity was at 10 mL•L⁻¹. The contents of MDA, soluble protein and proline were increased more or less under the four treatments. The content of polysaccharide was at a high level under 60 µmol•L⁻¹ of MeJA. The total phenols content was at a high level under 40 µmol•L⁻¹ of MeJA, 60 µmol•L⁻¹ of SA, 1 mL•L⁻¹ of H. koningii and 10 mL•L⁻¹ of T. koningiopsis. The results indicated that the addition of exogenous MeJA, SA and endophytic fungi under certain concentrations could improve the resistance of B. striata and increase the content of total phenols at some degree and the trearment of MeJA, H. koningii and T. koningiopsis could promote the growth of seedlings under certain concentrations.

Increase metabolic heat to compensate for low temperature in activated sludge systems.

The efficient operation of activated sludge systems is frequently hindered by low temperatures, and extensive research has been conducted to overcome this difficulty. However, the effect of varying temperatures on heat generation during substrate degradation remains unclear. In this study, results from laboratory-scale reactors show that sludge generated 5.36 ± 0.58 J/mg COD, 4.45 ± 0.24 J/mg COD, and 4.22 ± 0.26 J/mg COD at 10 °C, 20 °C, and 30 °C under aerobic conditions, respectively. Similarly, the sludge generated 4.05 ± 0.31 J/mg COD, 2.37 ± 0.15 J/mg COD, and 2.89 ± 0.18 J/mg COD under anoxic conditions. Despite the decreased respiration rates and hence reduced pollutant removal efficiency, sludge exhibited effective heat generation at low temperatures. Results from the full-scale plant also show a negative correlation between the heat generation capacity of microorganisms and the temperatures. 14.2 °C is considered the critical wastewater temperature for microorganisms' heat generation to offset the investigated plant's heat dissipation. This observation verified that thermal compensation for low temperatures was also significant in the full-scale plant. The mechanism of low-temperature compensation is attributed to non-growth processes being less dependent on temperature than growth processes, resulting in slow microbial growth but high heat generation at low temperatures. These findings provide valuable insights into the design and sustainable operation of wastewater treatment plants.

Patterned graphene oxide via one-step thermal annealing for controlling collective cell migration.

Graphene oxide (GO) is a two-dimensional metastable nanomaterial. Interestingly, GO formed oxygen clusterings in addition to oxidized and graphitic phases during the low-temperature thermal annealing process, which could be further used for biomolecule bonding. By harnessing this property of GO, we created a bio-interface with patterned structures with a common laboratory hot plate that could tune cellular behavior by physical contact. Due to the regional distribution of oxygen clustering at the interface, we refer to it as patterned annealed graphene oxide (paGO). In addition, since the paGO was a heterogeneous interface and bonded biomolecules to varying degrees, arginine-glycine-aspartic acid (RGD) was modified on it and successfully regulated cellular-directed growth and migration. Finally, we investigated the FRET phenomenon of this heterogeneous interface and found that it has potential as a biosensor. The paGO interface has the advantages of easy regulation and fabrication, and the one-step thermal reduction method is suitable for biological applications. We believe that this low-temperature thermal annealing method would make GO interfaces more accessible, especially for the development of nano-interfacial modifications for biological applications, revealing its potential for biomedical applications.

A novel method for identifying aerobic granular sludge state using sorting, densification and clarification dynamics during the settling process.

Aerobic granular sludge is one of the most promising biological wastewater treatment technologies, yet maintaining its stability is still a challenge for its application, and predicting the state of the granules is essential in addressing this issue. This study explored the potential of dynamic texture entropy, derived from settling images, as a predictive tool for the state of granular sludge. Three processes, traditional thickening, often overlooked clarification, and innovative particle sorting, were used to capture the complexity and diversity of granules. It was found that rapid sorting during settling indicates stable granules, which helps to identify the state of granules. Furthermore, a relationship between sorting time and granule heterogeneity was identified, helping to adjust selection pressure. Features of the dynamic texture entropy well correlated with the respirogram, i.e., R2 were 0.86 and 0.91 for the specific endogenous respiration rate (SOURe) and the specific quasi-endogenous respiration rate (SOURq), respectively, providing a biologically based approach for monitoring the state of granules. The classification accuracy of models using features of dynamic texture entropy as an input was greater than 0.90, significantly higher than the input of conventional features, demonstrating the significant advantage of this approach. These findings contributed to developing robust monitoring tools that facilitate the maintenance of stable granular sludge operations.

The role of volatile organic compounds for assessing characteristics and severity of non-cystic fibrosis bronchiectasis: an observational study.

Background: Hypoxic conditions and Pseudomonas aeruginosa (P. aeruginosa) infection are significant factors influencing the prognosis and treatment of patients with bronchiectasis. This study aimed to explore the potential for breath analysis to detect hypoxic conditions and P. aeruginosa infection in bronchiectasis patients by analyzing of volatile organic compounds (VOCs) in exhaled breath condensate (EBC). Methods: EBC samples were collected from stable bronchiectasis patients and analyzed using solid phase microextraction-gas chromatography-mass spectrometry (SPME-GCMS). The association of VOCs with bronchiectasis patients' phenotypes including hypoxic conditions and P. aeruginosa isolation was analyzed, which may relate to the severity of bronchiectasis disease. Results: Levels of 10-heptadecenoic acid, heptadecanoic acid, longifolene, and decanol in the hypoxia group were higher compared to the normoxia group. Additionally, the levels of 13-octadecenoic acid, octadecenoic acid, phenol, pentadecanoic acid, and myristic acid were increased in P. aeruginosa (+) group compared to the P. aeruginosa (-) group. Subgroup analysis based on the bronchiectasis severity index (BSI)reveled that the levels of 10-heptadecenoic acid, heptadecanoic acid, decanol, 13-octadecenoic acid, myristic acid, and pentadecanoic acid were higher in the severe group compared to the moderate group. Multivariate linear regression showed that 10-heptadecenoic acid and age were independent prognostic factors for bronchiectasis patients with hypoxia. Furthermore, octadecenoic acid, phenol and gender were identified as independent prognostic factors for bronchiectasis patients with P. aeruginosa isolation. Conclusion: The study provides evidence that specific VOCs in EBC are correlated with the severity of bronchiectasis, and 10-heptadecenoic acid is shown to be a predictive marker for hypoxia condition in bronchiectasis patients.

Patient-Derived Organoids as Therapy Screening Platforms in Cancer Patients.

Patient-derived organoids (PDOs) developed ex vivo and in vitro are increasingly used for therapeutic screening. They provide a more physiologically relevant model for drug discovery and development compared to traditional cell lines. However, several challenges remain to be addressed to fully realize the potential of PDOs in therapeutic screening. This paper summarizes recent advancements in PDO development and the enhancement of PDO culture models. This is achieved by leveraging materials engineering and microfabrication technologies, including organs-on-a-chip and droplet microfluidics. Additionally, this work discusses the application of PDOs in therapy screening to meet diverse requirements and overcome bottlenecks in cancer treatment. Furthermore, this work introduces tools for data processing and analysis of organoids, along with their microenvironment. These tools aim to achieve enhanced readouts. Finally, this work explores the challenges and future perspectives of using PDOs in drug development and personalized screening for cancer patients.

Quality-of-Life Bronchiectasis Respiratory Symptom Scale Predicts the Risk of Exacerbations in Adults with Bronchiectasis: A Prospective Observational Study.

Rationale: The relationship between symptoms, measured using a validated disease-specific questionnaire, and longitudinal exacerbation risk has not been demonstrated in bronchiectasis. Objectives: The aim of this study is to investigate whether baseline symptoms, assessed using the Quality-of-Life Bronchiectasis Respiratory Symptom Scale (QoL-B-RSS) and its individual component scores, could predict future exacerbation risk in patients with bronchiectasis. Methods: The study included 436 adults with bronchiectasis from three tertiary hospitals. Symptoms were measured using the QoL-B-RSS, with scores ranging from 0 to 100, where lower scores indicated more severe symptoms. We examined whether symptoms as continuous measures were associated with the risk of exacerbation over 12 months. The analysis was also repeated for individual components of the QoL-B-RSS score. Results: The baseline QoL-B-RSS score was associated with an increased risk of exacerbations (rate ratio, 1.25 for each 10-point decrease; 95% confidence interval [CI], 1.15-1.35; P < 0.001), hospitalizations (rate ratio, 1.24; 95% CI, 1.05-1.43; P = 0.02), and reduced time to the first exacerbation (hazard ratio, 1.12; 95% CI, 1.03-1.21; P = 0.01) over 12 months, even after adjusting for relevant confounders, including exacerbation history. The QoL-B-RSS score was comparable to exacerbation history in its association with future frequent exacerbations (defined as three or more exacerbations per year) and hospitalization (area under the curve, 0.86 vs. 0.84; P = 0.46; and area under the curve, 0.81 vs. 0.83; P = 0.41, respectively). Moreover, patients with more severe symptoms in the majority of individual components of the QoL-B-RSS were more likely to experience exacerbations. Conclusions: Symptoms can serve as useful indicators for identifying patients at increased risk of exacerbation in bronchiectasis. Beyond relying solely on exacerbation history, a comprehensive assessment of symptoms could facilitate timely and cost-effective implementation of interventions for exacerbation prevention.

[Near infrared distance sensing method for Chang'e-3 alpha particle X-ray spectrometer].

Alpha particle X-ray spectrometer (APXS) is one of the payloads of Chang'E-3 lunar rover, the scientific objective of which is in-situ observation and off-line analysis of lunar regolith and rock. Distance measurement is one of the important functions for APXS to perform effective detection on the moon. The present paper will first give a brief introduction to APXS, and then analyze the specific requirements and constraints to realize distance measurement, at last present a new near infrared distance sensing algorithm by using the inflection point of response curve. The theoretical analysis and the experiment results verify the feasibility of this algorithm. Although the theoretical analysis shows that this method is not sensitive to the operating temperature and reflectance of the lunar surface, the solar infrared radiant intensity may make photosensor saturation. The solutions are reducing the gain of device and avoiding direct exposure to sun light.

Engineered Vesicles and Hydrogel Technologies for Myocardial Regeneration.

Increased prevalence of cardiovascular disease and potentially life-threatening complications of myocardial infarction (MI) has led to emerging therapeutic approaches focusing on myocardial regeneration and restoration of physiologic function following infarction. Extracellular vesicle (EV) technology has gained attention owing to the biological potential to modulate cellular immune responses and promote the repair of damaged tissue. Also, EVs are involved in local and distant cellular communication following damage and play an important role in initiating the repair process. Vesicles derived from stem cells and cardiomyocytes (CM) are of particular interest due to their ability to promote cell growth, proliferation, and angiogenesis following MI. Although a promising candidate for myocardial repair, EV technology is limited by the short retention time of vesicles and rapid elimination by the body. There have been several successful attempts to address this shortcoming, which includes hydrogel technology for the sustained bioavailability of EVs. This review discusses and summarizes current understanding regarding EV technology in the context of myocardial repair.

Enhanced Probe Bonding and Fluorescence Properties through Annealed Graphene Oxide Nanosheets.

Graphene oxide (GO) has been widely used in biological sensing studies because of its excellent physical and chemical properties. In particular, the rich functional groups on the surface of GO can effectively enhance the bonding of biomolecules and serve as an efficient sensing substrate. However, when biomolecules are labeled with fluorescence, the GO interface affects the biomolecules by reducing the fluorescence properties and limiting their applications in biosensing. Here, we establish an annealed GO (aGO) substrate through the annealing process, which can effectively increase the bonding amount of a DNA probe because of the accumulation of oxygen atoms on the surface without significantly damaging the nanosheet structure. Furthermore, we prove that the aGO substrate can effectively maintain its fluorescence performance and stability by exposing more graphic domains. Overall, this study successfully verifies that GO's interface annealing modification can be used as an alternative innovative interface application in biosensing.