Calpain-1 Up-Regulation Promotes Bleomycin-Induced Pulmonary Fibrosis by Activating Ferroptosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal disease. Calpain-1 was shown to be an effective therapeutic target for vascular endothelial dysfunction and pulmonary hypertension. However, the role of calpain-1 in bleomycin (BLM)-induced IPF has not been defined. The aim of this study was to assess the targeting of calpain-1 by activating ferroptosis in BLM-treated knockout mice and murine lung epithelial-12 cells. In this study, the role of calpain-1 in the regulation of IPF was investigated using a BLM-induced IPF mouse model. The results of our study showed that increased expression of calpain-1 was accompanied by increased fibrosis, lipid peroxidation, iron ion accumulation, and YAP levels and decreased levels of p-AMPK in BLM-induced IPF. MDL-28170 (calpain-1 inhibition) treatment and calpain-1 knockdown alleviated ferroptosis and IPF induced by BLM. Overexpression of calpain-1 in murine lung epithelial-12 cells further exacerbated iron accumulation and IPF. Mechanistically, lentivirus-mediated up-regulation of calpain-1 inhibited AMPK activity and promoted the nuclear translocation of YAP, leading to high levels of acyl-CoA synthetase long-chain family 4 -and transferrin receptor protein 1 and triggering a ferroptosis response that ultimately exacerbated BLM-induced lung fibrosis. Calpain-1 inhibition reversed these results and ameliorated BLM-induced IPF. In conclusion, these findings suggest that the calpain-1-acyl-CoA synthetase long-chain family 4-transferrin receptor protein 1-ferroptosis-positive regulatory axis contributes to BLM-induced IPF, which indicates that calpain-1 has potential therapeutic value for the treatment of IPF.

Effects of an inoculation dose of Issatchenkia terricola WJL-G4 on physicochemical properties, active substances, and antioxidant capacity of black, red, and white currant juice.

BACKGROUND: Due to the high level of organic acids - primarily citric acid - black, red, and white currants have an excessively sour taste, making taste adjustment during processing challenging. This study investigated and evaluated the effects of an inoculation dose of the acid-reducing yeast Issatchenkia terricola WJL-G4 on several aspect such as physicochemical properties, chromaticity, active substances, and antioxidant capacity. A sensory evaluation was also conducted. RESULTS: The results indicated that, when the inoculation dose increased from 2% to 12%, the total phenol, total flavonoid, and total anthocyanin content, and antioxidant capacity in currant juice decreased. A low inoculation dose (2-4%) was beneficial for preserving the total phenol and total flavonoid content. Although the levels of most phenolic compounds decreased, the concentrations of caffeic acid, p-coumaric acid, ferulic acid, rutin, and epicatechin were significantly higher than the control after fermentation. Overall acceptability and taste scores of fermented currants improved compared with those of the control group. CONCLUSION: This experiment provided an effective solution, with a theoretical basis, to the problems of the sour taste and harsh flavor of currant juice. © 2024 Society of Chemical Industry.

Bioremediation of environmental organic pollutants by Pseudomonas aeruginosa: Mechanisms, methods and challenges.

The development of the chemical industry has led to a boom in daily consumption and convenience, but has also led to the release of large amounts of organic pollutants, such as petroleum hydrocarbons, plastics, pesticides, and dyes. These pollutants are often recalcitrant to degradation in the environment, whereby the most problematic compounds may even lead to carcinogenesis, teratogenesis and mutagenesis in animals and humans after accumulation in the food chain. Microbial degradation of organic pollutants is efficient and environmentally friendly, which is why it is considered an ideal method. Numerous studies have shown that Pseudomonas aeruginosa is a powerful platform for the remediation of environmental pollution with organic chemicals due to its diverse metabolic networks and its ability to secrete biosurfactants to make hydrophobic substrates more bioavailable, thereby facilitating degradation. In this paper, the mechanisms and methods of the bioremediation of environmental organic pollutants (EOPs) by P. aeruginosa are reviewed. The challenges of current studies are highlighted, and new strategies for future research are prospected. Metabolic pathways and critical enzymes must be further deciphered, which is significant for the construction of a bioremediation platform based on this powerful organism.

Validation and usability of a mobile phone application for epidemiological surveillance of traumatic dental injuries.

BACKGROUND/AIM: Traumatic dental injuries (TDI) are a public health problem, given their prevalence and consequences. However, their epidemiology is uncertain due to a general lack of quality data capture. The aim of this study was to evaluate the validity and usability of a mobile phone-based application for community-based surveillance of traumatic dental injuries. MATERIALS AND METHODS: A mobile phone-based application, Dental Trauma Tracker (DTT), was developed. This system involves a mobile application for general users to report TDIs and a Web application for researchers to generate epidemiological data. The DTT evaluation used mixed methods and was conducted in three phases: (a) validation of a trauma identification system using preselected TDI images; (b) design evaluation by experts; and (c) usability evaluation measured by the reporting of three fictitious TDI cases and using the System Usability Scale (SUS). RESULTS: In the first phase, 182 participants participated. Most images showed over 95% accuracy, indicating that they adequately represented the type of dentoalveolar trauma being evaluated (κ = 0.75). The design evaluation identified nine usability problems-four of them with a "High priority" to be fixed, four with "Low priority," and one "No fix necessary." A total of 29 volunteers participated in the usability evaluation. The mean time for users to complete all of the reports was 7.8 ± 3.0 minutes. Mean SUS score was 67.4 ± 21.9 (Range: 0-100; worst to best). The global agreement between cases registered with the gold standard was also "Substantial" (κ = 0.71). CONCLUSIONS: This preliminary evaluation confirmed the App's usability, using a sample of potential users, as well as reporting on the results of an expert panel review of the DTT. These are the minimum requirements necessary before further expansion and widespread implementation occurs to confirm these results.

A novel field emission microscopy method to study field emission characteristics of freestanding carbon nanotube arrays.

Field emission (FE) uniformity and the mechanism of emitter failure of freestanding carbon nanotube (CNT) arrays have not been well studied due to the difficulty of observing and quantifying FE performance of each emitter in CNT arrays. Herein a field emission microscopy (FEM) method based on poly(methyl methacrylate) (PMMA) thin film is proposed to study the FE uniformity and CNT emitter failure of freestanding CNT arrays. FE uniformity of freestanding CNT arrays and different levels of FE current contributions from each emitter in the arrays are recorded and visualized. FEM patterns on the PMMA thin film contain the details of the CNT emitter tip shape and whether multiple CNT emitters occur at an emission site. Observation of real-time FE performance and the CNT emitter failure process in freestanding CNT arrays are successfully achieved using a microscopic camera. High emission currents through CNT emitters causes Joule heating and light emission followed by an explosion of the CNTs. The proposed approach is capable of resolving the major challenge of building the relationship between FE performance and CNT morphologies, which can significantly facilitate the study of FE non-uniformity, the emitter failure mechanism and the development of stable and reliable FE devices in practical applications.

Nanotube field electron emission: principles, development, and applications.

There is a growing trend to apply field emission (FE) electron sources in vacuum electronic devices due to their fast response, high efficiency and low energy consumption compared to thermionic emission ones. Carbon nanotubes (CNTs) have been regarded as a promising class of electron field emitters since the 1990s and have promoted the development of FE technology greatly because of their high electrical and thermal conductivity, chemical stability, high aspect ratio and small size. Recent studies have shown that FE from CNTs has the potential to replace conventional thermionic emission in many areas and that it exhibits advanced features in practical applications. Consequently, FE from nanotubes and applications thereof have attracted much attention. This paper provides a comprehensive review of both recent advances in CNT field emitters and issues related to applications of CNT based FE. FE theories and principles are introduced, and the early development of field emitters is related. CNT emitter types and their FE performance are discussed. The current situation for applications based on nanotube FE is reviewed. Although challenges remain, the tremendous progress made in CNT FE over the past ten years indicates the field's development potential.

Ginsenoside Rg1 alleviates vascular remodeling in hypoxia-induced pulmonary hypertension mice through the calpain-1/STAT3 signaling pathway.

Background: Hypoxic pulmonary hypertension (HPH) is the main pathological change in vascular remodeling, a complex cardiopulmonary disease caused by hypoxia. Some research results have shown that ginsenoside Rg1 (Rg1) can improve vascular remodeling, but the effect and mechanism of Rg1 on hypoxia-induced pulmonary hypertension are not clear. The purpose of this study was to discuss the potential mechanism of action of Rg1 on HPH. Methods: C57BL/6 mice, calpain-1 knockout mice and Pulmonary artery smooth muscle cells (PASMCs) were exposed to a low oxygen environment with or without different treatments. The effect of Rg1 and calpain-1 silencing on inflammation, fibrosis, proliferation and the protein expression levels of calpain-1, STAT3 and p-STAT3 were determined at the animal and cellular levels. Results: At the mouse and cellular levels, hypoxia promotes inflammation, fibrosis, and cell proliferation, and the expression of calpain-1 and p-STAT3 is also increased. Ginsenoside Rg1 administration and calpain-1 knockdown, MDL-28170, and HY-13818 treatment showed protective effects on hypoxia-induced inflammation, fibrosis, and cell proliferation, which may be associated with the downregulation of calpain-1 and p-STAT3 expression in mice and cells. In addition, overexpression of calpain 1 increased p-STAT3 expression, accelerating the onset of inflammation, fibrosis and cell proliferation in hypoxic PASMCs. Conclusion: Ginsenoside Rg1 may ameliorate hypoxia-induced pulmonary vascular remodeling by suppressing the calpain-1/STAT3 signaling pathway.

Gold nanoparticles-anchored peptides enable precise colorimetric estimation of microplastics.

Microplastics (MPs, particle size < 5 mm) are an emerging contaminant in aquatic environment, which have attracted increasing attention worldwide. In this study, a colorimetric method for MPs detection was developed based on gold nanoparticles (AuNPs)-anchored peptides (LCI or TA2), which are able to specifically recognize and adhere to polypropylene (PP) or polystyrene (PS). The AuNPs-anchored peptides accumulated on the surface of MPs, rendering a color change from red to gray-blue and transforming the surface plasmon absorption intensity and wavelength. The designed method presented high selectivity, stability, and reproducibility, with a detection range of 2.5-15 µg/mL. The results demonstrated that the developed approach will be valuable in the precise, facile, and cost-effective estimation of MPs in different matrices, regulating the control over MPs pollution and its hazardous impact on health and ecosystems.

Prognostic value of serum phosphate levels in sepsis: a systematic review and meta-analysis.

Background: There remain controversies over the conclusion of different serum phosphate levels as prognostic predictors of sepsis patients. As such, this study investigated the association between different serum phosphate and the prognosis of sepsis. Methods: Data from PubMed, Embase, Cochrane Library, and Web of Science were systematically retrieved from the inception of databases to June 1, 2023 and independently screened and extracted by two authors. Binary variables in the study were estimated as relative risk ratio (RR) and 95% confidence interval (CI), and continuous variables were estimated as mean and standard deviation. The Newcastle-Ottawa Scale (NOS) was employed to evaluate the quality of the included studies, and subgroup analysis and sensitivity analysis were performed for all outcomes to explore the sources of heterogeneity. Results: Ten studies were included in this study including 38,320 patients with sepsis or septic shock. Against normal serum phosphate levels, a high serum phosphate level was associated with an elevated all-cause mortality risk (RR = 1.46; 95% CI [1.22-1.74]; P = 0.000) and prolonged Intensive Care Unit (ICU) length of stay (LOS) (WMD = 0.63; 95% CI [0.27-0.98]; P = 0.001). However, there was no significant difference in the in-hospital LOS (WMD = 0.22; 95% CI [-0.61-1.05]; P = 0.609). A low serum phosphate level was not significantly associated with the all-cause mortality risk (RR = 0.97; 95% CI [0.86-1.09]; P = 0.588), ICU LOS (WMD = -0.23; 95% CI [-0.75-0.29]; P = 0.394) and in-hospital LOS (WMD = -0.62; 95% CI [-1.72-0.49]; P = 0.274). Conclusion: Sepsis patients with high serum phosphate levels before therapeutic interventions were associated with a significant increase in the all-cause mortality risk, prolonged ICU LOS, and no significant difference in in-hospital LOS. Sepsis patients with low serum phosphate levels before interventions may have a reduced risk of all-cause mortality, shorter ICU LOS, and in-hospital LOS, but the results were not statistically significant.

Applications of Material-Binding Peptides: A Review.

Material-binding peptides (MBPs) are functionalized adhesive materials consisting of a few to several dozen amino acids. This affinity between MBPs and materials is regulated by multiple interactions, including hydrogen bonding, electrostatic, hydrophobic interactions, and π-π stacking. They show selective binding and high affinity to a diverse range of inorganic and organic materials, such as silicon-based materials, metals, metal compounds, carbon materials, and polymers. They are used to improve the biocompatibility of materials, increase the efficiency of material synthesis, and guide the controlled synthesis of nanomaterials. In addition, these can be used for precise targeting of proteins by conjugating to target biomolecules. In this review, we summarize the main designs and applications of MBPs in recent years. The discussions focus on more efficient and functional peptides, including evolution and overall design of MBPs. We have also highlighted the recent applications of MBPs, such as functionalization of material surfaces, synthesis of nanomaterials, drug delivery, cancer therapy, and plastic degradation. Besides, we also discussed the development trend of MBPs. This interpretation will accelerate future investigations to bottleneck the drawbacks of available MBPs, promoting their commercial applications.

A neural decoding algorithm that generates language from visual activity evoked by natural images.

Transforming neural activities into language is revolutionary for human-computer interaction as well as functional restoration of aphasia. Present rapid development of artificial intelligence makes it feasible to decode the neural signals of human visual activities. In this paper, a novel Progressive Transfer Language Decoding Model (PT-LDM) is proposed to decode visual fMRI signals into phrases or sentences when natural images are being watched. The PT-LDM consists of an image-encoder, a fMRI encoder and a language-decoder. The results showed that phrases and sentences were successfully generated from visual activities. Similarity analysis showed that three often-used evaluation indexes BLEU, ROUGE and CIDEr reached 0.182, 0.197 and 0.680 averagely between the generated texts and the corresponding annotated texts in the testing set respectively, significantly higher than the baseline. Moreover, we found that higher visual areas usually had better performance than lower visual areas and the contribution curve of visual response patterns in language decoding varied at successively different time points. Our findings demonstrate that the neural representations elicited in visual cortices when scenes are being viewed have already contained semantic information that can be utilized to generate human language. Our study shows potential application of language-based brain-machine interfaces in the future, especially for assisting aphasics in communicating more efficiently with fMRI signals.

Development and feasibility testing of an online virtual reality platform for delivering therapeutic group singing interventions for people living with spinal cord injury.

People with quadriplegia have a high risk for respiratory illness, social isolation and depression. Previous research has demonstrated that therapeutic singing interventions can not only improve breathing function and speech loudness, but also improve mood and social connectedness for people with quadriplegia. Face-to-face group attendance is difficult for this population due to difficulties with distance and travel. Online environments offer an accessible and cost-effective solution for people to connect with others without leaving their home. In a two-phase iterative design, we explored and tested different approaches for delivering online music therapy sessions with 12 patients from an inpatient spinal cord injury rehabilitation service. Six participants in Phase 1 trialled different virtual reality headsets and completed a short interview about their experience of the equipment and online singing trials. Outcomes from Phase 1 testing led to the development of a custom-built virtual reality application for online group music therapy sessions with low-latency audio. We tested the acceptability and feasibility of this platform in comparison to face-to-face and teleconference options for music therapy with six different patients. These participants completed three validated questionnaires: System Usability Scale, Quebec User Evaluation of Satisfaction with assistive Technology, and Psychosocial Impact of Assistive Devices Scale, and an interview about their experience. Questionnaire scores were good with mean ratings of 4.4 for Quebec User Evaluation of Satisfaction with assistive Technology, 53 for System Usability Scale and positive mean Psychosocial Impact of Assistive Devices Scale scores of 1.5 for competence, 2 for adaptability and 1.5 for self-esteem. Thematic analysis of post-session qualitative interviews revealed five themes: virtual reality was a positive experience, virtual reality was immersive and transportative, virtual reality reduced inhibitions about singing in front of others, virtual reality may reduce social cues, and the virtual reality equipment was comfortable, accessible and easy to use. Telehealth options, including a custom-designed virtual reality program, with low-latency audio are an acceptable and feasible mode of delivery for therapeutic singing interventions for people with spinal cord injury. Future non-inferiority research is needed to test online delivery modes for music therapy in comparison to face-to-face treatment.

An efficient strategy for the synthesis of polysubstituted chromeno[4,3-b]pyrrolidine derivatives.

A powerful cascade reaction was developed for the synthesis of chromeno[4,3-b]pyrrolidines with high yields and excellent stereoselectivities. This efficient cascade reaction expeditiously established two fused rings which bear three contiguous stereogenic centers including one quaternary stereocenter in a single operation with low catalyst loading under mild conditions.

Organocatalytic asymmetric multicomponent cascade reaction via 1,3-proton shift and [3+2] cycloaddition: an efficient strategy for the synthesis of oxindole derivatives.

An efficient and powerful organocatalytic cascade reaction was achieved for the synthesis of biologically important chiral spiro[pyrrolidin-3,2'-oxindoles] using very simple and readily available starting materials. Three C-C bonds and four contiguous stereogenic centers including one quaternary stereocenter were established in a single operation with reasonable yields and good stereoselectivity.