[Retracted] Carnosol inhibits osteoclastogenesis in vivo and in vitro by blocking the RANKL­induced NF­κB signaling pathway.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that one of the data panels in Fig. 3A on p. 6, showing how carnosol inhibits RANKL-induced osteoclastogenesis in the early stage of differentiation,  was strikingly similar to data that had already been submitted for publication in another article in the journal Annals of Translational Medicine written by different authors at different research institutes. Owing to the fact that the contentious data in the above article had already been submitted for publication prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [26: 225, 2022; DOI: 10.3892/mmr.2022.12741].

Pericytes Modulate Third-Generation Tyrosine Kinase Inhibitor Sensitivity in EGFR-Mutated Lung Cancer Cells Through IL32-ß5-Integrin Paracrine Signaling.

EGFR-mutated lung cancer patients sometimes display restricted responses to third-generation tyrosine kinase inhibitors (TKIs), potentially attributable to undervalued input from stromal cells, notably pericytes (PCs). The study shows that PCs isolated from EGFR-mutated patients have a unique secretome profile, notably secreting IL32 and affecting signaling pathways and biological processes linked to TKI sensitivity. Clinical evidence, supported by single-cell RNA sequencing and multiplex immunostaining of tumor tissues, confirms the presence of IL32-expressing pericytes closely interacting with ß5-integrin-expressing cancer cells in EGFR-mutated patients, impacting therapeutic response and prognosis. Co-culture and conditioned medium experiments demonstrate that PCs reduce TKI effectiveness in EGFR-mutated cancer cells, a reversible phenomenon through silencing IL32 expression in PCs or depleting the IL32 receptor ß5-integrin on cancer cells, thereby restoring cancer cell sensitivity. Mechanistically, it is shown that YY1 signaling upregulates IL32 secretion in PCs, subsequently activating the ß5-integrin-Src-Akt pathway in EGFR-mutated cancer cells, contributing to their TKI sensitivity. In animal studies, co-injection of cancer cells with PCs compromises TKI effectiveness, independently of blood vessel functions, while inhibition of ß5-integrin restores tumor cell sensitivity. Overall, the findings highlight direct crosstalk between cancer cells and pericytes, impacting TKI sensitivity via IL32-ß5-integrin paracrine signaling, proposing an enhanced therapeutic approach for EGFR-mutated patients.

Prospective comparative diagnostic performance of quantitative ultrasound parameters for the measurement of hepatic steatosis in a biopsy-proven MASLD cohort.

OBJECTIVES: The aim of this study was to compare the diagnostic performance of attenuation imaging (ATI), shear wave elastography (SWE) and shear wave dispersion (SWD) for detecting and grading hepatic steatosis in patients with metabolic dysfunctionassociated steatotic liver disease (MASLD). METHODS: 66 patients with MASLD (mean age, 41 years ± 12; 36 men, 30 women) confirmed histopathologically and 34 healthy volunteers (mean age, 39 years ± 15; 18 men, 16 women) who were age/sex-matched were prospectively enrolled in this study. ATI, SWE and SWD examinations were performed. Fibrosis stage, necroinflammatory activity and steatosis grade were confirmed histopathologically. Steatosis was graded as follows: S0 (<5%); S1 (5-32%); S2 (33-66%) to S3 (>66%). We compared the diagnostic performance of ATI, SWE and SWD for detecting and grading hepatic steatosis. RESULTS: Both attenuation coefficient (AC) and SWD values were significantly different among the different hepatic steatosis, and both were correlated with hepatic steatosis. SWE could not distinguish hepatic steatosis. ATI had better diagnostic performance than SWD for detecting and grading hepatic steatosis. The area under the receiver operating characteristic (ROC) curve of ATI for detecting ≥ S1, ≥ S2, and = S3 were 0.917 (cut-off value of 0.69 dB/cm/MHz), 0.933 (cut-off value of 0.74 dB/cm/MHz), and 0.870 (cut-off value of 0.82 dB/cm/MHz), respectively. The area under the ROC curve of SWD value was 0.758 (cut-off value of 10.79 m/s/kHz), 0.685 (cut-off value of 12.64 m/s/kHz), and 0.722 (cut-off value of 13.24 m/s/kHz), respectively. CONCLUSIONS: ATI technology is a reliable method for detecting and grading hepatic steatosis in patients with MASLD than SWE and SWD. ADVANCES IN KNOWLEDGE: We compared the diagnostic performance of ATI, SWE, SWD for detecting and grading hepatic steatosis in patients with MASLD in order to find the best diagnostic parameters.

Diabetes Mellitus Inhibits Hair Follicle Regeneration by Inducing Macrophage Reprogramming-Mediated Pyroptosis.

Background: Diabetes mellitus (DM) is known to inhibit skin self-renewal and hair follicle stem cell (HFSC) activation, which may be key in the formation of chronic diabetic wounds. This study aimed to investigate the reasons behind the suppression of HFSC activation in DM mice. Methods: Type 1 DM (T1DM) was induced in 6-week-old mice via streptozotocin, and hair follicle growth was subsequently monitored. RNA sequencing, bioinformatics analyses, qRT‒PCR, immunostaining, and cellular experiments were carried out to investigate the underlying mechanisms involved. Results: T1DM inhibited HFSC activation, which correlated with an increase in caspase-dependent programmed cell death. Additionally, T1DM triggered apoptosis and pyroptosis, predominantly in HFSCs and epidermal regions, with pyroptosis being more pronounced in the inner root sheath of hair follicles. Notably, significant cutaneous immune imbalances were observed, particularly in macrophages. Cellular experiments demonstrated that M1 macrophages inhibited HaCaT cell proliferation and induced cell death, whereas high-glucose environments alone did not have the same effect. Conclusion: T1DM inhibits HFSC activation via macrophage reprogramming-mediated caspase-dependent pyroptosis, and there is a significant regional characterization of cell death. Moreover, T1DM-induced programmed cell death in the skin may be more closely related to immune homeostasis imbalance than to hyperglycemia itself. These findings shed light on the pathogenesis of diabetic ulcers and provide a theoretical basis for the use of hair follicle grafts in wound repair.

Agnostic-Specific Modality Learning for Cancer Survival Prediction from Multiple Data.

Cancer is a pressing public health problem and one of the main causes of mortality worldwide. The development of advanced computational methods for predicting cancer survival is pivotal in aiding clinicians to formulate effective treatment strategies and improve patient quality of life. Recent advances in survival prediction methods show that integrating diverse information from various cancer-related data, such as pathological images and genomics, is crucial for improving prediction accuracy. Despite promising results of existing approaches, there are great challenges of modality gap and semantic redundancy presented in multiple cancer data, which could hinder the comprehensive integration and pose substantial obstacles to further enhancing cancer survival prediction. In this study, we propose a novel agnostic-specific modality learning (ASML) framework for accurate cancer survival prediction. To bridge the modality gap and provide a comprehensive view of distinct data modalities, we employ an agnostic-specific learning strategy to learn the commonality across modalities and the uniqueness of each modality. Moreover, a cross-modal fusion network is exerted to integrate multimodal information by modeling modality correlations and diminish semantic redundancy in a divide-and-conquer manner. Extensive experiment results on three TCGA datasets demonstrate that ASML reaches better performance than other existing cancer survival prediction methods for multiple data.

Supplementation of 3'-Sialyllactose During the Growth Period Improves Learning and Memory Development in Mice.

3'-Sialyllactose (3'-SL), a major acidic oligosaccharide found in human milk, has been investigated to improve cognitive-enhancing effects with 3 weeks old C57BL/6 mice by administering 3'-SL orally at a dose of 350 mg/kg/day for 6 weeks. Behavioral tests indicated that supplementation with 3'-SL promoted cognitive and memory development in young mice. Through interaction network and coenrichment analysis, nine differentially expressed genes (DEGs) related to memory and cognition were identified and localized in the hippocampal tissue of mice. The intervention of 3'-SL significantly increased the metabolism of sialic acid in mouse hippocampal tissue and promoted the expression of learning-related genes (p < 0.05). Notably, it increased the expression of genes associated with neural cell adhesion molecule (NCAM, p < 0.05), glutamate receptors, and fibroblast growth factor receptor (FGFR, p < 0.05). This suggests that 3'-SL may elevate polysialylated NCAM (PSA-NCAM) levels, which could subsequently interact with FGFR and glutamate receptors, thereby enhancing synaptic growth and plasticity. Additionally, 3'-SL altered the composition of the mouse intestinal microbiota. The synergistic action of gut microbiota and intestinal sialidase promoted the production of free sialic acid, providing essential nutritional elements for the development of the brain's nervous system. In conclusion, our findings provide new insights into the promoting effect of 3'-SL on cognitive development in growing mice and elucidate its molecular mechanisms.

Macrophage-Targeting and Hydrogen-Peroxide-Responsive Fluorescent Probe for Imaging of Inflammation In Vivo.

An uncontrolled immune response leads to many diseases; therefore, monitoring inflammation is crucial for the diagnosis of subsequent diseases, drug screening, and targeted therapy. Since the inflammatory response mainly occurs in macrophages, there is a need to develop more inflammatory probes with macrophage-targeting ability. Herein, we designed a macrophage-targeted and hydrogen-peroxide-activated fluorescent probe BOH-HCy-Man for real-time imaging of inflammation in vivo and a control probe BOH-HCy without the macrophage-targeting part. The larger rate constant toward H2O2 led to the higher sensitivity of BOH-HCy-Man (19.1-fold) than BOH-HCy (10.2-fold) in vitro. With the help of its macrophage-targeting ability, BOH-HCy-Man possessed an additional 1.6-fold fluorescent enhancement in inflamed RAW 264.7 cells or 1.3-fold fluorescent enhancement in vivo than BOH-HCy. We expected that BOH-HCy-Man will be a powerful tool for early diagnosis of inflammation related diseases.

Exerkine irisin mitigates cognitive impairment by suppressing gut-brain axis-mediated inflammation.

INTRODUCTION: Exercise has been recognized to improve cognitive performance by optimizing gut flora and up-regulating exerkine irisin. OBJECTIVE: Although exercise-induced irisin is beneficial to cognitive improvement, whether this benefit is achieved by optimizing gut microbiota and metabolites is not fully explored. METHODS: After aerobic exercise and exogenous irisin interventions for 12 weeks, the 16S rRNA and metabolites in feces of 21-month-old mice were analyzed. Meanwhile, the differential miRNAs and mRNAs in hippocampal tissues were screened by high-throughput sequencing. Relevant mRNAs and proteins were evaluated by RT-PCR, Western blot, and immunofluorescence. RESULTS: Compared with the young control mice, irisin levels and cognitive capacity of aged mice revealed a significant reduction, while aerobic exercise and intraperitoneal injection of exogenous irisin reversed aging-induced cognitive impairment. Similarly, 147 up-regulated and 173 down-regulated metabolites were detected in aged mice, while 64 and 45 up-regulated and 225 and 187 down-regulated metabolites were detected in aged mice with exercise and irisin interventions, respectively. Moreover, during hippocampal miRNA and mRNA sequencing analysis, 9 differential gut flora and 35 differential genes were identified to be correlated with the inflammatory signaling mediated by the TLR4/MyD88 signal pathway. CONCLUSION: Aging-induced cognitive impairment is due to insulin resistance induced by TLR4/MyD88 signaling activation in hippocampal tissues mediated by gut microbiota and metabolite changes. Myokine irisin may be an important mediator in optimizing gut microbiota and metabolism for an improved understanding of mitigated aging process upon exercise interventions.

Protein disulfide isomerase A4 binds to Brucella BtpB and mediates intracellular NAD+/NADH metabolism in RAW264.7 cells.

The Toll/interleukin-1 receptor (TIR) signaling domain is distributed widely in mammalian Toll-like receptors and adaptors, plant nucleotide-binding leucine-rich repeat receptors, and specific bacterial virulence proteins. Proteins that possess TIR domain exhibit NADase activity which is distinct from the canonical signaling function of these domains. However, the effects of bacterial TIR domain proteins on host metabolic switches and the underlying mechanism of NADase activity in these proteins remain unclear. Here, we utilized Brucella TIR domain-containing type IV secretion system effector protein, BtpB, to explore the mechanism of NADase activity in host cells. We showed that using ectopic expression BtpB not only generates depletion of NAD+ but also loss of NADH and ATP in RAW264.7 macrophage cells. Moreover, immunoprecipitation-mass spectrometry, co-immunoprecipitation, and confocal microscope assays revealed that BtpB interacted with host protein disulfide isomerase A4 (PDIA4). The Brucella mutant strain deleted the gene for BtpB, significantly decreased PDIA4 expression. Furthermore, our data revealed that PDIA4 played an important role in regulating intracellular NAD+/NADH levels in macrophages, and PDIA4 overexpression restored the decline of intracellular NAD+ and NADH levels induced by Brucella BtpB. The results provide new insights into the metabolic regulatory activity of TIR domain proteins in the critical human and animal pathogen Brucella.

Heterogeneity of SARS-CoV-2 immune responses after the nationwide Omicron wave in China.

It remains unclear how previous infections and vaccinations influenced and shaped heterogeneous immune responses against Omicron and its variants in diverse populations in China. After the national wave of Omicron in early 2023, we evaluated serum levels of neutralizing antibodies (nAbs) against Omicron (B.1.1.529) and its variants (BA.5, BF.7, and CH1.1) in 33 COVID-19 convalescents and 40 uninfected vaccinees, using vesicular stomatitis virus-based pseudovirus neutralizing assay. In addition, we followed 34 Delta convalescent patients to compare their immune responses against Omicron before (late 2021) and after the Omicron wave (early 2023). NAbs at the acute phase of the disease were investigated in 50 Omicron inpatients, including 24 vaccinated and 26 unvaccinated patients. Among them, nasal mucosal IgA levels were measured in 42 subjects. Compared to vaccination, breakthrough infections significantly increased the breadth and magnitude of serum nAbs and mucosal IgA levels against Omicron variants. Exposure to Omicron but not Delta elicited stronger pan-Omicron responses. In Omicron inpatients, nAbs continued to rise as vaccination doses increased. However, in both vaccinees and convalescents, a fourth dose vaccination did not elicit higher nAbs against Omicron. Furthermore, nAbs against Omicron variants lasted longer than nAbs against WT SARS-CoV-2. Breakthrough infections of Omicron variants elicited specific immune responses against Omicron compared to vaccination and Delta infection. Although repeated vaccination revealed limited impacts on serum nAbs, populations at high risk of hospitalization may still benefit from continued vaccination.IMPORTANCEThe study described the specific humoral immunity against Omicron and its variants (BA.5, BF.7, and CH1.1) in diverse populations, including Delta-positive convalescent patients, Omicron-infected patients with a previous or current confirmed Delta infection, Omicron-positive patients, and healthy controls. In addition, we followed Delta convalescents for 1 year to evaluate the effect of a booster vaccine, breakthrough infection, and reinfection. Nasal mucosal IgA levels against SARS-CoV-2 were also examined. The findings of this study demonstrated the varied responses of individuals in different states following the outbreak of Omicron, highlighting the potential advantages of ongoing immunization for groups that are more vulnerable and have a greater likelihood of being hospitalized.

Efficient and simultaneous immobilization of fluoride and lead in water and tea garden soil by bayberry tannin foam loaded zirconium.

Nowadays, human activities intensified the combined pollution of fluoride and lead in acidic tea garden soil. The key to eliminating this combined pollution is to immobilize pollutants simultaneously, thus preventing their migration from tea garden soil to tea trees. In this paper, the natural product bayberry tannin was employed as raw material to fabricate functional materials (TF-Zr) for simultaneous adsorption of fluorine (F) and lead (Pb) in water and soil by the reactivity of tannin with Pb2+ and the affinity of Zr with F. SEM-Mapping, EDS, FT-IR, XPS were utilized to probe the immobilization mechanisms. The results showed that TF-Zr could simultaneously and efficiently adsorb F- and Pb2+ from water with the adsorption capacity of 5.02 mg/g (Pb) and 4.55 mg/g (F). The adsorption processes were both in accordance with the proposed secondary kinetic adsorption model. Besides, the presence of F- promoted the adsorption of Pb2+ by TF-Zr. The materials were applied into tea garden soil to explore its effect on the variation of F and Pb forms in the soil. It was found that the proportion of water-soluble fluorine, exchangeable fluorine and exchangeable lead in the tea garden soil decreased significantly, while the proportion of residual fluorine and lead increased evidently, illustrating TF-Zr possessed eximious fixation effect on the highly reactive fluorine and lead in the soil and facilitated their conversion to the more stable residue state. Therefore, TF-Zr can be used for the efficient and simultaneous immobilization of fluorine and lead in water and tea garden soil.

Assembly of Dye Molecules in Covalent Organic Frameworks for Enhanced Colorimetric Biosensing.

Colorimetric assays have been extensively investigated for biosensing applications due to their advantages of visual recognizability, ease of use, and low cost. However, advancing their development is a great challenge due to the inherent limitations of colorimetric dyes. Herein, we report a strategy to assemble dyes in covalent organic frameworks (COFs) to effectively reinforce the applicability of pH-responsive dyes in colorimetric bioassays. Experimental results reveal that three-dimensional COFs can promote the assembly of dyes through hydrogen bonding, resulting in the formation of a dye-supermolecule@COF assembly. Consequently, when sensitized at increased pH levels (e.g., hydroxyl ions), disruption of hydrogen bonds may trigger a rapid transition from their insoluble fixed state within the COFs into soluble, visibly detectable dye anions. This process can also be facilitated by increased hydrophilicity and elevated electrostatic repulsion between the dye anions and COFs, leading to the substantial release of chromogenic dye anions from the COF pores into the solution, thereby amplifying the colorimetric signal output. Therefore, by employing various synthesized dye-supermolecule@COFs as signal tags, we developed a colorimetric bioassay capable of accurately identifying breast cancer cell subtypes. This study not only highlights the effectiveness of dye-supermolecule@COFs in enhancing colorimetric biosensing but also underscores the potential of employing the COF-mediated dye assembly strategy for colorimetric assays.

Targeting Specific Kinase Substrates Rescues Increased Colitis Severity Induced by the Crohn's Disease-Linked LRRK2-N2081D Variant.

LRRK2 contains a kinase domain where both the N2081D Crohn's disease (CD) risk and the G2019S Parkinson's disease (PD)-pathogenic variants are located. The mechanisms by which the N2081D variant increase CD risk, and how these adjacent mutations result in distinct diseases, remain unclear. To investigate the pathophysiology of the CD-linked LRRK2 N2081D variant, we generated a knock-in (KI) mouse model and compared its effects to those of the LRRK2-G2019S mutation. We find that Lrrk2 N 2081 D KI mice demonstrate heightened sensitivity to induced colitis, resulting in more severe inflammation and intestinal damage than Lrrk2 G2019S KI and wild-type mice. Analysis of Colon tissue revealed distinct mutation-dependent LRRK2 RAB substrate phosphorylation, with significantly elevated phosphorylated RAB10 levels in Lrrk2 N2081D mice. In cells, we demonstrate that the N2081D mutation activates LRRK2 through a mechanism distinct from that of LRRK2-G2019S. We further find that proinflammatory stimulation enhances LRRK2 kinase activity, leading to mutation-dependent differences in RAB phosphorylation and inflammatory responses in dendritic cells. Finally, we show that genetic knockout of Rab12 , but not pharmacological LRRK2 kinase inhibition, significantly reduced colitis severity in Lrrk2 N2081D mice. Our study characterizes the pathogenic mechanisms of LRRK2-linked CD, highlights important structural and functional differences between disease-associated LRRK2 variants, and suggests RAB proteins as promising therapeutic targets for modulating LRRK2 activity in CD treatment.

Experimental evaluation of an artificial anal sphincter based on biomechanical compatibility.

BACKGROUND: The artificial anal sphincter is a device used to treat patients with fecal incontinence who are unable to control their bowel movements on their own. Long-term morphological changes in the tissue surrounding the artificial anal sphincter can cause biomechanical compatibility problems, which seriously affect the clinical application of the artificial anal sphincter. METHODS: In this paper, the superelasticity of shape memory alloys was utilized to design and fabricate a biomechanically compatible constant force clamping artificial anal sphincter. An in vitro simulation system was constructed to verify the effectiveness, safety, and constant force characteristics of the artificial anal sphincter. RESULTS: The experimental results demonstrated that the artificial anal sphincter could be effectively closed with no leakage of the liquid-like intestinal contents, which are most likely to leak. The pressure of the artificial anal sphincter on the intestinal tube gradually increased and eventually became constant during closure, and the pressure value was always less than the intestinal blood supply pressure threshold. CONCLUSIONS: In this paper, we designed an artificial anal sphincter based on biomechanical compatibility and the corresponding in vitro simulation experimental program and preliminarily verified the effectiveness, safety, and constant force characteristics of the artificial anal sphincter.

Mapping the Research on Periocular Basal Cell Carcinoma in the Past 20 Years: A Bibliometric Network Analysis.

PURPOSE: This study aims to analyze the literature on periocular basal cell carcinoma, identify research trends, and offer insights into future research areas in this field to assist clinicians and researchers. METHODS: 903 publications on periocular basal cell carcinoma were collected from the Web of Science Core Collection database. We assessed the contributions from various countries, institutions, journals, and authors, and performed network analysis using Excel, VOSviewer, and R Studio to represent the prominent areas of research visually. RESULTS: The country with the highest number of publications and citations in this study was the United States of America, with 250 publications, 5917 citations, and the highest H-index of 44. Ophthalmic Plastic and Reconstructive Surgery is the leading journal. The UTMD Anderson Cancer Center had the highest number of publications, accounting for 43, or 4.76% of the total. Selva D from the University of Adelaide, Australia, is the top author with 26 publications, and 751 citations. Targeted therapy for PBCC-related pathways has been a hot topic in recent years. CONCLUSIONS: This study using bibliometrics seeks to explore the patterns and focal points of research and analyzes publication patterns, key research areas, influential authors, and prominent journals in periocular basal cell carcinoma during the last 2 decades.

Arsenic trioxide and p97 inhibitor synergize against acute myeloid leukemia by targeting nascent polypeptides and activating the ZAKα-JNK pathway.

Arsenic trioxide (ATO) has exhibited remarkable efficacy in treating acute promyelocytic leukemia (APL), primarily through promoting the degradation of the PML-RARα fusion protein. However, ATO alone fails to confer any survival benefit to non-APL acute myeloid leukemia (AML) patients and exhibits limited efficacy when used in combination with other agents. Here, we explored the general toxicity mechanisms of ATO in APL and potential drugs that could be combined with ATO to exhibit synergistic lethal effects on other AML. We demonstrated that PML-RARα degradation and ROS upregulation were insufficient to cause APL cell death. Based on the protein synthesis of different AML cells and their sensitivity to ATO, we established a correlation between ATO-induced cell death and protein synthesis. Our findings indicated that ATO induced cell death by damaging nascent polypeptides and causing ribosome stalling, accompanied by the activation of the ZAKα-JNK pathway. Furthermore, ATO-induced stress activated the GCN2-ATF4 pathway, and ribosome-associated quality control cleared damaged proteins with the assistance of p97. Importantly, our data revealed that inhibiting p97 enhanced the effectiveness of ATO in killing AML cells. These explorations paved the way for identifying optimal synthetic lethal drugs to enhance ATO treatment on non-APL AML.

Genomic dynamics of the Lower Yellow River Valley since the Early Neolithic.

The Yellow River Delta played a vital role in the development of the Neolithic civilization of China. However, the population history of this region from the Neolithic transitions to the present remains poorly understood due to the lack of ancient human genomes. This especially holds for key Neolithic transitions and tumultuous turnovers of dynastic history. Here, we report genome-wide data from 69 individuals dating to 5,410-1,345 years before present (BP) at 0.008 to 2.49× coverages, along with 325 present-day individuals collected from 16 cities across Shandong. During the Middle to Late Dawenkou period, we observed a significant influx of ancestry from Neolithic Yellow River farmers in central China and some southern Chinese ancestry that mixed with local hunter-gatherers in Shandong. The genetic heritage of the Shandong Longshan people was found to be most closely linked to the Dawenkou culture. During the Shang to Zhou Dynasties, there was evidence of genetic admixture of local Longshan populations with migrants from the Central Plain. After the Qin to Han Dynasties, the genetic composition of the region began to resemble that of modern Shandong populations. Our genetic findings suggest that the middle Yellow River Basin farmers played a role in shaping the genetic affinity of neighboring populations in northern China during the Middle to Late Neolithic period. Additionally, our findings indicate that the genetic diversity in the Shandong region during the Zhou Dynasty may be linked with their complex ethnicities.

Near-Infrared Fluorescent Probe for the Detection of Cysteine.

Hemicyanine dyes are an ideal structure for building near-infrared fluorescent probes due to their excellent emission wavelength properties and biocompatibility in biological imaging field. Developing a near-infrared fluorescent probe capable of detecting cysteine (Cys) was the aim of this study. A novel developed fluorescent probe P showed high selectivity and sensitivity to Cys in the presence of various analytes. The detection limit of P was found to be 0.329 µM. The MTT assay showed that the probe was essentially non-cytotoxic. Furthermore, the probe was successfully used as cysteine imaging in living cells and mice.

Dietary bile acids supplementation decreases hepatic fat deposition with the involvement of altered gut microbiota and liver bile acids profile in broiler chickens.

BACKGROUND: High-fat diets (HFD) are known to enhance feed conversion ratio in broiler chickens, yet they can also result in hepatic fat accumulation. Bile acids (BAs) and gut microbiota also play key roles in the formation of fatty liver. In this study, our objective was to elucidate the mechanisms through which BA supplementation reduces hepatic fat deposition in broiler chickens, with a focus on the involvement of gut microbiota and liver BA composition. RESULTS: Newly hatched broiler chickens were allocated to either a low-fat diet (LFD) or HFD, supplemented with or without BAs, and subsequently assessed their impacts on gut microbiota, hepatic lipid metabolism, and hepatic BA composition. Our findings showed that BA supplementation significantly reduced plasma and liver tissue triglyceride (TG) levels in 42-day-old broiler chickens (P < 0.05), concurrently with a significant decrease in the expression levels of fatty acid synthase (FAS) in liver tissue (P < 0.05). These results suggest that BA supplementation effectively diminishes hepatic fat deposition. Under the LFD, BAs supplementation increased the BA content and ratio of Non 12-OH BAs/12-OH BAs in the liver and increased the Akkermansia abundance in cecum. Under the HFD, BA supplementation decreased the BAs and increased the relative abundances of chenodeoxycholic acid (CDCA) and cholic acid (CA) in hepatic tissue, while the relative abundances of Bacteroides were dramatically reduced and the Bifidobacterium, Escherichia, and Lactobacillus were increased in cecum. Correlation analyses showed a significant positive correlation between the Akkermansia abundance and Non 12-OH BA content under the LFD, and presented a significant negative correlation between the Bacteroides abundance and CA or CDCA content under the HFD. CONCLUSIONS: The results indicate that supplementation of BAs in both LFD and HFD may ameliorate hepatic fat deposition in broiler chickens with the involvement of differentiated microbiota-bile acid profile pathways.