Helicobacter pylori infection delays neutrophil apoptosis and exacerbates inflammatory response.

Aim: Understanding molecular mechanisms of Helicobacter pylori (H. pylori)-induced inflammation is important for developing new therapeutic strategies for gastrointestinal diseases. Materials & methods: We designed an H. pylori-neutrophil infection model and explored the effects of H. pylori infection on neutrophils. Results: H. pylori infected neutrophils showed a low level of apoptosis. H. pylori stimulation activated the NACHT/LRR/PYD domain-containing protein 3 (NLRP3)-gasdermin-D (GSDMD) pathway for interleukin (IL)-1ß secretion. However, IL-1ß secretion was not completely dependent on GSDMD, as inhibition of autophagy significantly reduced IL-1ß release, and autophagy-related molecules were significantly upregulated in H. pylori-infected neutrophils. Conclusion: Therefore, H. pylori infection inhibits neutrophils apoptosis and induces IL-1ß secretion through autophagy. These findings may be utilized to formulate therapeutic strategies against H. pylori mediated chronic gastritis.

[Box: see text].

[Cryoprotective effects of deicing micro/nanomaterials with different sizes and shapes on cells].

Extensive studies have been conducted on deicing nanomaterials to improve the cryoprotective effects on cells, tissues, and organs. The nanomaterials with different composition, sizes, and shapes can inhibit the formation and growth of ice crystals, thereby reducing the damage to the cryopreserved samples. In this study, the carbon composite particles (CCPs) with different sizes and shapes were prepared by the hydrothermal method. The results demonstrated that the cryoprotective effect of CCPs enhanced with the decrease in particle size. Compared with spherical CCPs, Janus nanoparticles and WSP nanoflower with special shapes demonstrated improved protective effects on cryopreserved cells. In addition, the combination of deicing micro/nanomaterials at appropriate concentrations with commercial cryoprotectants exerted improved cryoprotective effects on cells. The prepared deicing micro/nanomaterials can improve cell cryopreservation, demonstrating great application potential in biomedical research and cryopreservation.

Molecular-level periodic arrays of long-chain poly(3-hexylthiophene-2,5-diyl) driven by an electric field.

Two-dimensional (2D) periodic arrays of conductive polymers represent attractive platforms for wiring functional molecules into the integrated circuits of molecular electronics. However, the large-scale assembly of polymer periodic arrays at the molecular level faces challenges such as curling, twisting, and aggregation. Here, we assembled the periodic arrays of long-chain poly(3-hexylthiophene-2,5-diyl) (P3HT, Mw = 65 k) at the solid-liquid interface by applying an electric field, within which the charged chain segments were aligned. Atomic force microscopy (AFM) imaging revealed that individual P3HT chains assemble into monolayers featuring face-on orientation, extended chain conformation and isolated packing, which is thermodynamically more stable than folded chains in 2D polycrystals. The assembly process is initiated with the formation of disordered clusters and progresses through voltage-dependent nucleation and growth of extended-chain arrays, wherein continuous conformational adjustments along the nucleation pathway exhibit dependence on the cluster size.

A comparative lipid profile of four fish species: From muscle to industrial by-products based on RPLC-Q-TOF-MS/MS.

Fish are crucial for the fishing industry and essential nutrient provision, including lipids. This study employed a high-throughput lipidomic approach to evaluate and contrast the lipid profiles of three marine fish species (P. crocea, S. fuscens, and C. saira) and one freshwater species (H. molitrix) across head, muscle, and viscera. Over 1000 molecular lipid species across 17 subclasses were identified. Notably, acylated monogalactosyldiacylglycerol (acMGDG) was detected for the first time in these species, with a high prevalence of saturated fatty acids (44.7 %-87.7 %). Glycerolipids (67.7 - 86.3 %) and PLs (10.7 - 31.8 %) were identified as the dominant lipid classes. Marine fish muscles displayed higher PL content than freshwater species, and P. crocea viscera contained over 30 % PLs of total lipids. In particular, ether phosphatidyl ethanolamine incorporated more DHA than ether phosphatidylcholine. The viscera of four fish species also exhibited a significant abundance of diacylglycerol (DG), indicating their potential as functional lipid sources. Multivariate analysis identified triglyceride (TG) (59:13), DG (16:1/22:5), and MGDG (16:0/18:2) as potential biomarkers for differentiating among fish anatomical parts. This study deepens the understanding of the nutritional values of these fish, providing guidance for consumer dietary choices and paving the way for transforming previously underutilized by-products into resources with high-value potential.

Exploring the potent hydrolytic activity of chitosan-cerium complex microspheres resin for organophosphorus pesticide degradation.

Chitosan is a biocompatible, non-toxic and renewable natural basic polysaccharide that can be cross-linked and reacted with Ce(IV) to form a physiologically active chitosan-Ce(IV) complex. To investigate this novel complex and its potential to hydrolyze phosphate ester bonds, chitosan-cerium complex microspheres resin (CS-CCMR) was prepared from chitosan and ceric ammonium nitrate by reversed-phase suspension cross-linking polymerization. CS-CCMR was characterized, its ability to hydrolyze disodium p-nitrobenzene phosphate (PNPP2Na) and organophosphorus pesticides was investigated, and the hydrolytic mechanism was explored. CS-CCMR was composed of dark yellow microspheres with smooth surfaces and dense pores. It was found that CS-CCMR contained 4.507 mg/g Ce(IV), indicating that coordination polymerization between Ce(IV) and chitosan was successful. The presence of Ce(IV) in CS-CCMR was confirmed by multiple analytical methods and it was found that coordination of Ce(IV) by chitosan was mediated by the nitrogen atom of the amino group and the oxygen atom of the hydroxyl group of chitosan. It was shown that CS-CCMR efficiently hydrolyzed the phosphate ester bonds of PNPP2Na and five organophosphorus pesticides. Hydrolysis of PNPP2Na is potentially accomplished by charge neutralization and nucleophilic substitution. The mechanism of parathion degradation by CS-CCMR involves modification of the nitro group to give aminoparathion, followed by cleavage of the P-O bond to generate diazinphos. Consequently, the novel chitosan-Ce(IV) complex exhibits great efficiency for hydrolysis of phosphate ester bonds and CS-CCMR is expected to be developed as an agent to reduce the possibility of contamination of fruit and vegetable drinks by organophosphorus pesticides.

Centimeter-Scale Tellurium Oxide Films for Artificial Optoelectronic Synapses with Broadband Responsiveness and Mechanical Flexibility.

Prevailing over the bottleneck of von Neumann computing has been significant attention due to the inevitableness of proceeding through enormous data volumes in current digital technologies. Inspired by the human brain's operational principle, the artificial synapse of neuromorphic computing has been explored as an emerging solution. Especially, the optoelectronic synapse is of growing interest as vision is an essential source of information in which dealing with optical stimuli is vital. Herein, flexible optoelectronic synaptic devices composed of centimeter-scale tellurium dioxide (TeO2) films detecting and exhibiting synaptic characteristics to broadband wavelengths are presented. The TeO2-based flexible devices demonstrate a comprehensive set of emulating basic optoelectronic synaptic characteristics; i.e., excitatory postsynaptic current (EPSC), paired-pulse facilitation (PPF), conversion of short-term to long-term memory, and learning/forgetting. Furthermore, they feature linear and symmetric conductance synaptic weight updates at various wavelengths, which are applicable to broadband neuromorphic computations. Based on this large set of synaptic attributes, a variety of applications such as logistic functions or deep learning and image recognition as well as learning simulations are demonstrated. This work proposes a significant milestone of wafer-scale metal oxide semiconductor-based artificial synapses solely utilizing their optoelectronic features and mechanical flexibility, which is attractive toward scaled-up neuromorphic architectures.

Determining the Minimal Clinically Important Difference (MCID) and Responsiveness of the Chinese Version of Zurich Chronic Middle Ear Inventory (ZCMEI-21-Chn): A Prospective Multicenter Study.

OBJECTIVES: This study aimed to establish the minimal clinically important difference (MCID) and assess the responsiveness of the Chinese version of Zurich Chronic Middle Ear Inventory (ZCMEI-21-Chn). STUDY DESIGN: Prospective multicenter study. SETTING: Four Chinese tertiary referral centers admitting patients nationwide. PATIENTS: 230 adult patients with chronic otitis media (COM) undergoing tympanoplasty. INTERVENTION: Patients were required to complete the ZCMEI-21-Chn to measure health-related quality of life both preoperatively and postoperatively. An anchor-based method was used to determine the MCID of the derivative cohort by including the Global Rating of Change Questionnaire as an anchor. The generalizability and consistency with functional outcomes of the MCID estimates were externally examined in a validation cohort using a receiver operating characteristic curve analysis. RESULTS: A total of 161 and 69 patients were included in the derivative and validation cohort. The mean preoperative and postoperative ZCMEI-21-Chn total scores were 28.4 (standard deviation [SD] 14.5) and 17.5 (SD 12.6). The mean change in ZCMEI-21-Chn score was 10.9 (SD 14.3, p < 0.001). The MCIDs of the ZCMEI-21-Chn for improvement and deterioration were estimated at 13 (SD 13.0) and -7 (SD 12.9), accordingly. For patients who have reported an improved health-related quality of life, a cutoff value of 15.6 dB HL for elevation of the air-conducted hearing threshold was noticed. However, change of clinical importance judged according to MCID and Japan Otological Society criteria disagreed with each other, notably with a Cohen's kappa ( κ ) of 0.14 ( p = 0.21) in the validation cohort. CONCLUSION: This study is the first to establish the MCID of a COM-specific questionnaire in Chinese. For the COM population undergoing surgical intervention, MCID values of 13 for improvement and -7 for deterioration are recommended. The results were externally validated to be generalizable to nationwide usage, yet distinguishable from the audiological criteria. The availability of the MCID greatly adds to the clinical utility of the ZCMEI-21-Chn by enabling a clinically meaningful interpretation of its score changes.

Self-powered triboelectric-responsive microneedles with controllable release of optogenetically engineered extracellular vesicles for intervertebral disc degeneration repair.

Excessive exercise is an etiological factor of intervertebral disc degeneration (IVDD). Engineered extracellular vesicles (EVs) exhibit excellent therapeutic potential for disease-modifying treatments. Herein, we fabricate an exercise self-powered triboelectric-responsive microneedle (MN) assay with the sustainable release of optogenetically engineered EVs for IVDD repair. Mechanically, exercise promotes cytosolic DNA sensing-mediated inflammatory activation in senescent nucleus pulposus (NP) cells (the master cell population for IVD homeostasis maintenance), which accelerates IVDD. TREX1 serves as a crucial nuclease, and disassembly of TRAM1-TREX1 complex disrupts the subcellular localization of TREX1, triggering TREX1-dependent genomic DNA damage during NP cell senescence. Optogenetically engineered EVs deliver TRAM1 protein into senescent NP cells, which effectively reconstructs the elimination function of TREX1. Triboelectric nanogenerator (TENG) harvests mechanical energy and triggers the controllable release of engineered EVs. Notably, an optogenetically engineered EV-based targeting treatment strategy is used for the treatment of IVDD, showing promising clinical potential for the treatment of degeneration-associated disorders.

Combined UPLC-QqQ-MS/MS and AP-MALDI Mass Spectrometry Imaging Method for Phospholipidomics in Obese Mouse Kidneys: Alleviation by Feeding Sea Cucumber Phospholipids.

Sea cucumber phospholipids have ameliorative effects on various diseases related to lipid metabolism. However, it is unclear whether it can ameliorate obesity-associated glomerulopathy (ORG) induced by a high-fat diet (HFD). The present study applied UPLC-QqQ-MS/MS and atmospheric pressure matrix-assisted laser desorption ionization mass spectrometry imaging (AP-MALDI MSI) to investigate the effects of sea cucumber phospholipids, including plasmalogen PlsEtn and plasmanylcholine PakCho, on phospholipid profiles in the HFD-induced ORG mouse kidney. Quantitative analysis of 135 phospholipids revealed that PlsEtn and PakCho significantly modulated phospholipid levels. Notably, PlsEtn modulated kidney overall phospholipids better than PakCho. Imaging the "space-content" of 9 phospholipids indicated that HFD significantly increased phospholipid content within the renal cortex. Furthermore, PlsEtn and PakCho significantly decreased the expression of transport-related proteins CD36, while elevating the expression of fatty acid ß-oxidation-related protein PPAR-α in the renal cortex. In conclusion, sea cucumber phospholipids reduced renal lipid accumulation, ameliorated renal damage, effectively regulated the content and distribution of renal phospholipids, and improved phospholipid homeostasis, exerting an anti-OGR effect.

Mechanisms of enhancing MgO for stabilization/solidification of Pb-contaminated red clay through CO2 sequestration.

Pb-contaminated soil poses significant environmental and health risks as well as soil stability issues. Research on sandy soils highlights CO2-enhanced reactive MgO as a promising solution for improving the solidification of Pb-contaminated soils. However, carbonation effects can differ markedly between soil types owing to varying soil properties. In this study, we evaluated the effects of CO2-enhanced reactive MgO on the engineering and environmental characteristics of Pb-contaminated red clay and explored its mechanism of carbonation solidification. The results showed that CO2-enhanced reactive MgO increased the strength of Pb-contaminated red clay to over 3 MPa within 1 h, which was approximately 25 times the strength of untreated soil (0.2 MPa) and significantly higher than that of reactive MgO-treated, uncarbonated soil (0.8 MPa). The pH of the carbonated soil (9-10) facilitated Pb2+ immobilization, and the increase over the initial parameter elevated the electrical conductivity value. Moreover, CO2-enhanced reactive MgO reduced the Pb2+ leaching concentration to below 0.1 mg/L, even at high Pb concentrations (10,000 mg/kg). Pb2+ transformed into lead carbonates during the carbonation process, with the hydrated magnesium carbonates forming a dense internal structure. This solidification mechanism included chemical precipitation, physical adsorption, and encapsulation. Notably, the carbonation time should be controlled within 1 h to prevent soil expansion. Together, these findings support the potential of CO2-enhanced reactive MgO for efficient and low-carbon application in the solidification of Pb-contaminated red clay.

Odor Fingerprinting of Chitosan and Source Identification of Commercial Chitosan: HS-GC-IMS, Multivariate Statistical Analysis, and Tracing Path Study.

Chitosan samples were prepared from the shells of marine animals (crab and shrimp) and the cell walls of fungi (agaricus bisporus and aspergillus niger). Fourier-transform infrared spectroscopy (FT-IR) was used to detect their molecular structures, while headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) was employed to analyze their odor composition. A total of 220 volatile organic compounds (VOCs), including esters, ketones, aldehydes, etc., were identified as the odor fingerprinting components of chitosan for the first time. A principal component analysis (PCA) revealed that chitosan could be effectively identified and classified based on its characteristic VOCs. The sum of the first three principal components explained 87% of the total variance in original information. An orthogonal partial least squares discrimination analysis (OPLS-DA) model was established for tracing and source identification purposes, demonstrating excellent performance with fitting indices R2X = 0.866, R2Y = 0.996, Q2 = 0.989 for independent variable fitting and model prediction accuracy, respectively. By utilizing OPLS-DA modeling along with a heatmap-based tracing path study, it was found that 29 VOCs significantly contributed to marine chitosan at a significance level of VIP > 1.00 (p < 0.05), whereas another set of 20 VOCs specifically associated with fungi chitosan exhibited notable contributions to its odor profile. These findings present a novel method for identifying commercial chitosan sources, which can be applied to ensure biological safety in practical applications.

Systematic exploration of therapeutic effects and key mechanisms of Panax ginseng using network-based approaches.

Background: Network pharmacology has emerged as a powerful tool to understand the therapeutic effects and mechanisms of natural products. However, there is a lack of comprehensive evaluations of network-based approaches for natural products on identifying therapeutic effects and key mechanisms. Purpose: We systematically explore the capabilities of network-based approaches on natural products, using Panax ginseng as a case study. P. ginseng is a widely used herb with a variety of therapeutic benefits, but its active ingredients and mechanisms of action on chronic diseases are not yet fully understood. Methods: Our study compiled and constructed a network focusing on P. ginseng by collecting and integrating data on ingredients, protein targets, and known indications. We then evaluated the performance of different network-based methods for summarizing known and unknown disease associations. The predicted results were validated in the hepatic stellate cell model. Results: We find that our multiscale interaction-based approach achieved an AUROC of 0.697 and an AUPR of 0.026, which outperforms other network-based approaches. As a case study, we further tested the ability of multiscale interactome-based approaches to identify active ingredients and their plausible mechanisms for breast cancer and liver cirrhosis. We also validated the beneficial effects of unreported and top-predicted ingredients, in cases of liver cirrhosis and gastrointestinal neoplasms. Conclusion: our study provides a promising framework to systematically explore the therapeutic effects and key mechanisms of natural products, and highlights the potential of network-based approaches in natural product research.

Quinoa greens as a novel plant food: a review of its nutritional composition, functional activities, and food applications.

Quinoa (Chenopodium quinoa Willd) is widely regarded as a versatile pseudo-cereal native to the Andes Mountains in South America. It has gained global recognition as a superfood due to its rich nutritional profile. While quinoa grains are well-known, there is an undiscovered potential in quinoa greens, such as sprouts, leaves, and microgreens. These verdant parts of quinoa are rich in a diverse array of essential nutrients and bioactive compounds, including proteins, amino acids, bioactive proteins, peptides, polyphenols, and flavonoids. They have powerful antioxidant properties, combat cancer, and help prevent diabetes. Quinoa greens offer comparable or even superior benefits when compared to other sprouts and leafy greens, yet they have not gained widespread recognition. Limited research exists on the nutritional composition and biological activities of quinoa greens, underscoring the necessity for thorough systematic reviews in this field. This review paper aims to highlight the nutritional value, bioactivity, and health potential of quinoa greens, as well as explore their possibilities within the food sector. The goal is to generate interest within the research community and promote further exploration and wider utilization of quinoa greens in diets. This focus may lead to new opportunities for enhancing health and well-being through innovative dietary approaches.

Comprehensive Lipidomic Analysis of Three Edible Microalgae Species Based on RPLC-Q-TOF-MS/MS.

Microalgae, integral to marine ecosystems for their rich nutrient content, notably lipids and proteins, were investigated by using reversed-phase liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (RPLC-Q-TOF-MS/MS). This study focused on lipid composition in three commonly used microalgae species (Spirulina platensis, Chlorella vulgaris, and Schizochytrium limacinum) for functional food applications. The analysis unveiled more than 700 lipid molecular species, including glycolipids (GLs), phospholipids (PLs), sphingolipids (SLs), glycerolipids, and betaine lipids (BLs). GLs (19.9-64.8%) and glycerolipids (24.1-70.4%) comprised the primary lipid. Some novel lipid content, such as acylated monogalactosyldiacylglycerols (acMGDG) and acylated digalactosyldiacylglycerols (acDGDG), ranged from 0.62 to 9.68%. The analysis revealed substantial GLs, PLs, and glycerolipid variations across microalgae species. Notably, S. platensis and C. vulgaris displayed a predominance of fatty acid (FA) 18:2 and FA 18:3 in GLs, while S. limacinum exhibited a prevalence of FA 16:0, collectively constituting over 60% of the FAs of GLs. In terms of PLs and glycerolipids, S. platensis and C. vulgaris displayed elevated levels of arachidonic acid (AA) and eicosapentaenoic acid (EPA), whereas S. limacinum exhibited a significant presence of docosahexaenoic acid (DHA). Principal component analysis (PCA) revealed MGDG (16:0/18:1), DG (16:0/22:5), Cer (d18:1/20:0), and LPC (16:1) as promising lipid markers for discriminating between these microalgae samples. This study contributes to a comprehensive understanding of lipid profiles in three microalgae species, emphasizing their distinct biochemical characteristics and potentially informing us of their high-value utilization in the food industry.

Evaluating the efficacy of percutaneous puncture biopsy guided by contrast-enhanced ultrasound for peripheral pulmonary lesions.

BACKGROUND: The incidence and mortality of lung cancer have increased annually. Accurate diagnosis can help improve therapeutic efficacy of interventions and prognosis. Percutaneous lung biopsy is a reliable method for the clinical diagnosis of lung cancer. Ultrasound-guided percutaneous lung biopsy technology has been widely promoted and applied in recent years. AIM: To investigate the diagnostic value of contrast-enhanced ultrasound (CEUS)-guided percutaneous biopsy in peripheral pulmonary lesions. METHODS: We retrospectively collected data on 237 patients with peripheral thoracic focal lesions who underwent puncture biopsy at Wuxi People's Hospital. The patients were randomly divided into two groups: The CEUS-guided before lesion puncture group (contrast group) and conventional ultrasound-guided group (control group). Analyze the diagnostic efficacy of the puncture biopsy, impact of tumor size, and number of puncture needles and complications were analyzed and compared between the two groups. RESULTS: Accurate pathological results were obtained for 92.83% (220/237) of peripheral lung lesions during the first biopsy, with an accuracy rate of 95.8% (113/118) in the contrast group and 89.9% (107/119) in the control group. The difference in the area under the curve (AUC) between the contrast and the control groups was not statistically significant (0.952 vs 0.902, respectively; P > 0.05). However, when the lesion diameter ≥ 5 cm, the diagnostic AUC of the contrast group was higher than that of the control group (0.952 vs 0.902, respectively; P < 0.05). In addition, the average number of puncture needles in the contrast group was lower than that in the control group (2.58 ± 0.53 vs 2.90 ± 0.56, respectively; P < 0.05). CONCLUSION: CEUS guidance can enhance the efficiency of puncture biopsy of peripheral pulmonary lesions, especially for lesions with a diameter ≥ 5 cm. Therefore, CEUS guidance has high clinical diagnostic value in puncture biopsy of peripheral focal lung lesions.

Daphnetin alleviates allergic airway inflammation by inhibiting T-cell activation and subsequent JAK/STAT6 signaling.

Allergic asthma is a major health burden on society as a chronic respiratory disease characterized by inflammation and muscle tightening around the airways in response to inhaled allergens. Daphne kiusiana Miquel is a medicinal plant that can suppress allergic airway inflammation; however, its specific molecular mechanisms of action are unclear. In this study, we aimed to elucidate the mechanisms by which D. kiusiana inhibits allergic airway inflammation. We evaluated the anti-inflammatory effects of the ethyl acetate (EA) fraction of D. kiusiana and its major compound, daphnetin, on murine T lymphocyte EL4 cells stimulated with phorbol 12-myristate 13-acetate and ionomycin in vitro and on asthmatic mice stimulated with ovalbumin in vivo. The EA fraction and daphnetin inhibited T-helper type 2 (Th2) cytokine secretion, serum immunoglobulin E production, mucus secretion, and inflammatory cell recruitment in vivo. In vitro, daphnetin suppressed intracellular Ca2+ mobilization (a critical regulator of nuclear factor of activated T cells) and functions of the activator protein 1 transcription factor to reduce interleukin (IL)-4 and IL-13 expression. Daphnetin effectively suppressed the IL-4/-13-induced activation of Janus kinase (JAK)/signal transducer and activator of transcription 6 (STAT6) signaling in vitro and in vivo, thereby inhibiting the expression of GATA3 and PDEF, two STAT6-target genes responsible for producing Th2 cytokines and mucins. These findings indicate that daphnetin suppresses allergic airway inflammation by stabilizing intracellular Ca2+ levels and subsequently inactivating the JAK/STAT6/GATA3/PDEF pathway, suggesting that daphnetin is a promising alternative to existing asthma treatments.

Improving Aerobic Digestion of Food Waste by Adding a Personalized Microbial Inoculum.

In the context of China's garbage classification policy, on-site aerobic food waste (FW) digestion is crucial for reducing transportation and disposal costs. The efficiency of this process is largely determined by the microbial community structure and its functions. Therefore, this study aimed to analyze the impact of a personalized microbial consortium (MCM) on the efficiency of aerobic FW digestion and to reveal the underlying mechanisms. An MCM, sourced from naturally degrading FW, was selected to enrich degrading bacteria with relatively high hydrolyzing ability. The functionality of the MCM was evaluated by tracing the successions of microbial communities, and comparing the differences in the forms of organic compounds, metabolic functions, and hydrolase activities. X-ray photoelectron spectroscopy demonstrated that the MCM metabolized faster, and produced more acidic metabolites. Metagenomic analysis indicated that FW inoculated with the personalized MCM increased abundance of Bacillaceae producing hydrolysis enzymes and promoted glycolysis metabolic pathways, enhancing energy generation for metabolism, compared to the commercial effective bacterial agent. This paper provides both theoretical and practical evidence for the improvement of biochemical processor of FW with the personalized MCM, which has promising application prospects and economic value.

Key factor screening in mouse NASH model using single-cell sequencing combined with machine learning.

Aims: To identify and analyze genes closely related to the progression of nonalcoholic steatohepatitis (NASH) by employing a combination of single-cell RNA sequencing and machine-learning algorithms. Main methods: Single-cell RNA sequencing (scRNA-seq) analysis was performed to find the cell population with the most significant differences between the Chow and NASH groups. This approach was used to validate the developmental trajectory of this cell population and investigate changes in cellular communication and important signaling pathways among these cells. Subsequently, high dimensional Weighted Gene Co-expression Network Analysis (hdWGCNA) was used to find the key modules in NASH. Machine learning analyses were performed to further identify core genes. Deep learning techniques were applied to elucidate the correlation between core genes and immune cells. The accuracy of this correlation was further confirmed using deep learning techniques, specifically Convolutional Neural Networks. Key findings: By comparing scRNA-seq data between the Chow and NASH groups, we have observed a notable distinction existing in the Kupffer cell population. Signaling interactions between hepatic macrophages and other cells were significantly heightened in the NASH group. Through subsequent analysis of macrophage subtypes and key modules, we identified 150 genes tightly associated with NASH. Finally, we highlighted the 16 most significant core genes using multiple iterations of machine learning. Furthermore, we pointed out the close relationship between core genes and immune cells. Significances: Using scRNA-seq analysis and machine learning, we can distinguish NASH-related genes from large genetic datasets, providing theoretical support in finding potential targets for the development of novel therapies.

Association of exposure to a mixture of phenols, parabens, and phthalates with altered serum thyroid hormone levels and the roles of iodine status and thyroid autoantibody status: A study among American adults.

BACKGROUND: Toxicological and epidemiological studies have shown that environmental endocrine disruptors interfere with hormonal homeostasis. However, there is limited research on the effects of mixed exposure to nonpersistent endocrine disruptors on thyroid hormones and the factors (e.g., presence status of thyroid autoantibodies or nutritional status of organismal iodine) that may influence this association. METHODS: Data were collected from the National Health and Nutrition Examination Survey (NHANES) 2007-2008 and 2011-2012. Relationships between single pollutants and thyroid hormone and thyroid autoantibody levels were assessed using generalized linear (GLM) and restricted cubic spline (RCS) regression models. Weighted quantile sum regression (WQS), group-weighted quantile sum regression (GWQS), quantile-based g-computation (qgcomp), and adaptive elasticity network (AENET) were applied to assess the mixed exposure effect. Next, subgroup analyses were performed on the basis of the urinary iodine concentration or thyroid autoantibody status to assess the modifying role of urinary iodine and thyroid autoantibodies. RESULTS: A total of 2385 study participants were included in this study. Both the single-pollutant model and the multipollutant mixed model revealed that parabens and bis(2-ethylhexyl) phthalate (DEHP) metabolites were significantly and negatively associated with serum thyroxine (T4) levels. However, no associations were found between the target pollutants and thyroid autoantibodies (thyroglobulin antibodies (TgAb) and thyroid peroxidase antibodies (TPOAb)). In addition, this study revealed that urinary iodine or thyroid autoantibody status altered the associations of some of the target pollutants with thyroid hormones. WQS and qgcomp analyses, revealed that the associations of mixed pollutants with hormones differed depending on the urinary iodine or antibody status, especially T4 and thyroid-stimulating hormone (TSH). CONCLUSION: Significant associations were found between phenols, parabens, and phthalates and serum thyroid hormone levels, with parabens and DEHP metabolites playing major roles. Urinary iodine and thyroid autoantibody status act as modifiers between environmental endocrine-disrupting pollutants and thyroid hormones.

A mitochondria-targeted fluorescent sensor for imaging endogenous peroxynitrite changes in acute lung injury.

Acute lung injury (ALI) is a serious pulmonary inflammatory disease resulting from excessive reactive oxygen species (ROS) which could cause the damage of the alveolar epithelial cells and capillary endothelial cells. Peroxynitrite, as one of short-lived reactive oxygen species, is closely related to the process of ALI. Thus, it is important to monitor the fluctuation of peroxynitrite in living system for understanding the process of ALI. Herein, the novel mitochondria-targeted fluorescent probe BHMT was designed to respond to peroxynitrite and pH with distinct fluorescence properties respectively. The absorption spectrum of the probe BHMT exhibited a notable red shift as the pH value declined from 8.8 to 2.6. Upon reaction with peroxynitrite, BHMT had a significant increase of fluorescence intensity (63-fold) with maintaining a detection limit of only 43.7 nM. Furthermore, BHMT could detect the levels of endogenous peroxynitrite and image the intracellular pH in ratiometric channels utilizing cell imaging. In addition, BHMT was successfully applied to revealing the relationship between the peroxynitrite and the extent of ALI. Thus, these results indicated the probe BHMT could be a potential tool for diagnosing the early stage of ALI and revealed the peroxynitrite was likely to be a crucial therapeutic target in ALI treatment.