Current strategies for nonalcoholic fatty liver disease treatment (Review).

Nonalcoholic fatty liver disease (NAFLD), the most common chronic hepatic disease, has become a leading health problem worldwide. The present review summarized the methods and mechanisms to treat NAFLD, including the Mediterranean diet, physical activity and exercise, bariatric surgery and specific therapeutic agents, including statins, peroxisome proliferator­activated receptor agonists, cenicriviroc and farnesoid X receptor agonists. Biologically active substances, such as peptides, alkaloids, polyphenolic compounds, silymarin, antibiotics, fatty acids, vitamins, probiotics, synbiotics and lamiaceae have also demonstrated actions that combat NAFLD. Considering their different mechanisms of action, combining some of them may prove an efficacious treatment for NAFLD. In this light, the present review describes recent progress and future prospects in treating NAFLD.

Dodecylmethylaminoethyl methacrylate inhibits Enterococcus faecalis in a pH-dependent manner.

OBJECTIVES: Considering the correlation between survival microenvironment of E. faecalis and acidic pH value, this study aimed to investigate the potential of utilizing pH-responsive DMAEM monomers and their copolymers with resin-based root canal sealers to inhibit E. faecalis. METHODS: Broth microdilution assay, crystal violet staining and qPCR were performed to evaluate antibacterial effects of DMAEM monomers against E. faecalis at different pH. Methacrylate-resin based root canal sealers were prepared and copolymerized with DMAEM. The flow, solubility, water sorption, apical sealing ability and cytotoxicity of sealers were investigated to optimize formulation. The anti-E. faecalis effects of DMAEM copolymers with sealers were evaluated by direct contact test, colony-forming unit counting and live/dead staining. RESULTS: DMAEM monomers inhibited the growth, biofilm formation and virulence factors expression of E. faecalis in a concentration- and pH-dependent manner. Incorporation of 1.25 % and 2.5 % DMAEM into experimental sealers would not affect the flowability, solubility and periapical sealing ability (P > 0.05), but increased the water sorption of sealers (P < 0.01). Cells viability was higher than 90 % in both 1.25 % and 2.5 % DMAEM groups at pH 7.0. DMAEM copolymers with sealers reduced E. faecalis counts, inhibited biofilm formation and decreased live cells within the biofilm in response to pH values. SIGNIFICANCE: DMAEM monomers and their copolymers with resin-based sealers possessed antibacterial and antibiofilm effects on E. faecalis in response to pH values. DMAEM is promising to inhibit intraradicular E. faecalis in response to its acidic survival environment and maintain low cytotoxicity under neutral conditions, ensuring their biosafety in case of inadvertent entry into periapical tissues.

Impact of peptic ulcer bleeding on the in-hospital outcomes of cirrhotic patients with acute gastrointestinal bleeding: an international multicenter study.

OBJECTIVES: Peptic ulcer is the most common source of non-variceal bleeding. However, it remains controversial whether the outcomes of cirrhotic patients with peptic ulcer bleeding differ from those with variceal bleeding. METHODS: Cirrhotic patients with acute gastrointestinal bleeding (AGIB) who underwent endoscopy and had an identifiable source of bleeding were retrospectively screened from an international multicenter cohort. Logistic regression analyses were performed to explore the impact of peptic ulcer bleeding on in-hospital death and 5-day failure to control bleeding. Propensity score matching (PSM) analysis was performed by matching age, gender, Child-Pugh score, and model for end-stage liver disease score between the peptic ulcer bleeding and variceal bleeding groups. RESULTS: Overall, 1535 patients were included, of whom 73 (4.7%) had peptic ulcer bleeding. Multivariate logistic regression analyses showed that peptic ulcer bleeding was not independently associated with in-hospital death (OR = 2.169, p = 0.126) or 5-day failure to control bleeding (OR = 1.230, p = 0.680). PSM analyses demonstrated that both in-hospital mortality (9.7% vs. 6.3%, p = 0.376) and rate of 5-day failure to control bleeding (6.9% vs. 5.4%, p = 0.787) were not significantly different between the two groups. CONCLUSIONS: The impact of peptic ulcer bleeding on the in-hospital outcomes of cirrhotic patients is similar to that of variceal bleeding.

In this international multicenter study, we included 1535 patients with acute gastrointestinal bleeding (AGIB) and divided them into peptic ulcer bleeding and variceal bleeding groups. We found that only a minority of AGIB episodes in cirrhotic patients was attributed to peptic ulcer. Additionally, after adjusting for the severity of liver dysfunction, the in-hospital mortality and the rate of 5-day failure to control bleeding should be similar between cirrhotic patients with peptic ulcer bleeding and those with variceal bleeding.

Carvedilol to prevent decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by liver stiffness: study protocol for a randomied, double-blind, placebo-controlled, multicentre trial in China.

INTRODUCTION: Patients with clinically significant portal hypertension (CSPH) are recommended to be treated with non-selective beta-blockers (ie, carvedilol) to prevent the first hepatic decompensation event by the renewing Baveno VII consensus. CSPH is defined by hepatic venous pressure gradient (HVPG)≥10 mm Hg; however, the HVPG measurement is not widely adopted due to its invasiveness. Liver stiffness (LS)≥25 kPa can be used as a surrogate of HVPG≥10 mm Hg to rule in CSPH with 90% of the positive predicting value in majority aetiologies of patients. A compelling argument is existing for using LS≥25 kPa to diagnose CSPH and then to initiate carvedilol in patients with compensated cirrhosis, and about 5%-6% of patients under this diagnosis criteria may not be benefited from carvedilol and are at risk of lower heart rate and mean arterial pressure. Randomised controlled trial on the use of carvedilol to prevent liver decompensation in CSPH diagnosed by LS remains to elucidate. Therefore, we aimed to investigate if compensated cirrhosis patients with LS≥25 kPa may benefit from carvedilol therapy. METHODS AND ANALYSIS: This study is a randomised, double-blind, placebo-controlled, multicentre trial. We will randomly assign 446 adult compensated cirrhosis patients with LS≥25 kPa and without any previous decompensated event and without high-risk gastro-oesophageal varices. Patients are randomly divided into two groups, with 223 subjects in group A and 223 subjects in group B. Group A is a carvedilol intervention group, while group B is a placebo group. All patients in both groups will receive aetiology therapies and are followed up at an interval of 6 months. The 3-year incidences of decompensated events of cirrhosis-related and liver-related death are the primary outcome. The secondary outcomes include development of each complication of portal hypertension individually (ascites, variceal bleeding or overt hepatic encephalopathy), development of spontaneous bacterial peritonitis and other bacterial infections, development of new varices, growth of small varices to large varices, delta changes in LS and spleen stiffness, change in hepatic dysfunction assessed by Child-Pugh and model for end-stage liver disease score, change in platelet count, development of hepatocellular carcinoma, development of portal vein thrombosis and adverse events with a 3-year follow-up. A predefined interim analysis will be performed to ensure that the calculation is reasonable. ETHICS AND DISSEMINATION: The study protocol has been approved by the ethics committees of the Sixth People's Hospital of Shenyang (2023-05-003-01) and independent ethics committee for clinical research of Zhongda Hospital, affiliated to Southeast University (2023ZDSYLL433-P01). The results from this trial will be submitted for publication in peer-reviewed journals and will be presented at international conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300073864.

Effects of N levels on land productivity and N2O emissions in maize-soybean relay intercropping.

BACKGROUND: Relay intercropping of maize and soybean can improve land productivity. However, the mechanism behind N2O emissions in this practice remains unclear. A two-factor randomized block field trial was conducted to reveal the mechanism of N2O emissions in a full additive maize-soybean relay intercropping. Factor A was three cropping systems - that is, monoculture maize (Zea mays L.), monoculture soybean (Glycine max L. Merr.) and maize-soybean relay intercropping. Factor B was different N supply, containing no N, reduced N and conventional N. Differences in N2O emissions, soil properties, rhizosphere bacterial communities and yield advantage were evaluated. RESULTS: The land equivalent ratio was 1.55-2.44, and the cumulative N2O emission ( C E N 2 O $$ \mathrm{C}{\mathrm{E}}_{{\mathrm{N}}_2\mathrm{O}} $$ ) was notably lower by 60.2% in intercropping than in monoculture, respectively. Reduced N declined C E N 2 O $$ \mathrm{C}{\mathrm{E}}_{{\mathrm{N}}_2\mathrm{O}} $$ without penalty on the yield advantages. The relay intercropping shifted soil properties - for example, soil organic matter, total N, NH 4 + $$ {\mathrm{NH}}_4^{+} $$ and protease activity - and improved the soil microorganism community - for example, Proteobacteria and Acidobacteria. Intercropping reduced C E N 2 O $$ \mathrm{C}{\mathrm{E}}_{{\mathrm{N}}_2\mathrm{O}} $$ by directly suppressing nirS- and amoA-regulated N2O generation during soil N cycling, or nirS- and amoA-mediated soil properties shifted to reduce C E N 2 O $$ \mathrm{C}{\mathrm{E}}_{{\mathrm{N}}_2\mathrm{O}} $$ indirectly. Reduced N directly reduced C E N 2 O $$ \mathrm{C}{\mathrm{E}}_{{\mathrm{N}}_2\mathrm{O}} $$ by decreasing soil N content and reducing soil microorganism activities to alleviate N2O produced in soil N cycling. CONCLUSION: Conducting a full additive maize-soybean relay intercropping with reduced nitrogen supply provides a way to alleviate N2O emissions without the penalty on the yield advantage by changing rhizosphere bacterial communities and soil N cycling. © 2024 Society of Chemical Industry.

A retrospective study of 29 fatal cases of insulin overdose.

PURPOSE: To summarize recent cases of fatal insulin poisoning both domestically and internationally, thereby offering valuable insights for the forensic identification of insulin overdose cases. METHODS: Literature published since 2000 on fatal insulin overdose were systematically searched and screened. Data encompassing variables such as year, age, sex, cause of death, scene conditions, occupations, medical histories of victims and perpetrators, autopsy timing, dosage and administration methods, forensic pathology, and toxicological analysis, were compiled for rigorous statistical analysis. RESULTS: Among the 29 fatal cases of insulin poisoning, suicides and homicides accounted for 55.2 % and 41.4 %, respectively. Precisely 34.5 % of victims or perpetrators were associated with the medical industry, 27.6 % had diabetes, and 24.1 % had mental illnesses such as depression. Intravenous injection resulted in quicker death than did subcutaneous injection. In some cases, immunohistochemical staining of insulin and protamine at injection sites yielded positive results. The average molar ratio of insulin to C-peptide in post-mortem blood was 13.76 ± 5.167, indicating a significant diagnostic value for insulin poisoning. CONCLUSION: Assessment of cases of fatal insulin overdose should be thorough, incorporating case investigation, scene examination, medical records review, autopsy findings, pathological examinations, and laboratory tests, alongside considering the condition of the body and timing of death autopsy. Using mass spectrometry to detect insulin proves valuable, particularly in cases of poor body preservation.

Review of the lethal mechanism of insulin poisoning and the characteristic of forensic identification.

Insulin, as the only hypoglycemic hormone in the body, plays a key role in blood sugar control. However, excessive insulin intake can lead to insulin poisoning and even death, which often occurs in clinical and forensic work. At present, some researches on insulin poisoning have been carried out at home and abroad, however, it seems that the mechanism and forensic characteristics of insulin poisoning are not clear and complete. Therefore, in this paper, we reviewed the potential mechanism of insulin poisoning, the methods of insulin detection and the forensic identification of poisoning cases, aiming at providing services for the forensic identification of insulin poisoning.

Rapid fluorescent nucleic acid sensing with ultra-thin gold nanosheets.

Fluorescently labeled DNA oligonucleotides and gold nanospheres have been frequently utilized in biosensors, providing efficient nucleic acid detection. Nevertheless, the restricted loading capacity of gold nanospheres undermines overall sensitivity. In this study, we employed four-atom-thick ultrathin gold nanosheets (AuNSs), utilizing a "pre-mix model" for rapid target nucleic acid detection. In this approach, fluorescently labeled DNA probes were pre-incubated with the target nucleic acid, followed by the addition of AuNSs for probe adsorption and fluorescence quenching. With the developed method, we efficiently and rapidly detected the SARS-CoV-2 N gene sequence within 30 min, involving a brief 15-min target pre-incubation and a subsequent 15-min adsorption of free probes and fluorescence quenching by AuNSs. This method exhibited heightened sensitivity compared to gold nanospheres, boasting a limit of detection (LOD) of 0.808 nM. Furthermore, exceptional recovery was achieved in simulated biological samples. The study introduces an effective strategy for nucleic acid sensing characterized by rapidity, heightened sensitivity, ease of operation, and robustness. These findings encourage further development of rapid biomarker sensing methods employing 2D nanomaterials.

CD63 + tumor-associated macrophages drive the progression of hepatocellular carcinoma through the induction of epithelial-mesenchymal transition and lipid reprogramming.

BACKGROUND: Tumor-associated macrophages (TAMs) constitute a substantial part of human hepatocellular carcinoma (HCC). The present study was devised to explore TAM diversity and their roles in HCC progression. METHODS: Through the integration of multiple 10 × single-cell transcriptomic data derived from HCC samples and the use of consensus nonnegative matrix factorization (an unsupervised clustering algorithm), TAM molecular subtypes and expression programs were evaluated in detail. The roles played by these TAM subtypes in HCC were further probed through pseudotime, enrichment, and intercellular communication analyses. Lastly, vitro experiments were performed to validate the relationship between CD63, which is an inflammatory TAM expression program marker, and tumor cell lines. RESULTS: We found that the inflammatory expression program in TAMs had a more obvious interaction with HCC cells, and CD63, as a marker gene of the inflammatory expression program, was associated with poor prognosis of HCC patients. Both bulk RNA-seq and vitro experiments confirmed that higher TAM CD63 expression was associated with the growth of HCC cells as well as their epithelial-mesenchymal transition, metastasis, invasion, and the reprogramming of lipid metabolism. CONCLUSIONS: These analyses revealed that the TAM inflammatory expression program in HCC is closely associated with malignant tumor cells, with the hub gene CD63 thus representing an ideal target for therapeutic intervention in this cancer type.

Synergistic Effects of Nutrients on Musculoskeletal Health in Gerontology: Understanding the Combined Impact of Macronutrients and Micronutrients.

With the global aging population, addressing prevalent age-related conditions such as osteoporosis and sarcopenia is crucial. Traditional nutritional strategies focusing on single nutrients like calcium, vitamin D, or protein have limitations, prompting a nuanced exploration of the relationship between aging, nutrition, and musculoskeletal health. This cross-sectional study examines the complex interplay between dietary intake of macronutrients, common micronutrients, and water, as well as their association with musculoskeletal health in adults aged 50 to 80 years, using U.S. National Health and Nutrition Examination Survey data (NHANES). Employing multiple linear regression, restricted cubic splines, weighted quantile sum (WQS), and quantile-based g-computation (QGC) regression models, our initial analysis using the WQS model revealed that a one-quartile increase in mixed macronutrient intake was associated with a significant 0.009 unit increase in bone mineral density (BMD) and a 0.670 unit increase in grip strength, while a similar increase in mixed micronutrient intake showed a 0.007 unit increase in BMD and a 0.442 unit increase in grip strength. Our findings highlight the importance of a balanced dietary approach in promoting musculoskeletal health in the elderly, offering holistic strategies for overall well-being.

Zinc-associated phospholipid metabolic alterations and their impacts on ALT levels in workers.

Zinc (Zn) is an essential trace element that is required for various biological functions, but excessive exposure to Zn is associated with many disorders and even diseases. However, the health effects and underlying mechanisms of long-term and high concentration exposure of Zn remain to be unclear. In the present study, we investigated the association between occupational exposure to Zn and liver function indicators (like alanine aminotransferase (ALT)) in workers. We found a positive association between Zn exposure and ALT level in workers. Workers having higher blood Zn (7735.65 (1159.15) µg/L) shows a 30.4 % increase in ALT level compared to those with lower blood Zn (5969.30 (989.26) µg/L). Furthermore, we explored the effects of phospholipids (PLs) and their metabolism on ALT level and discovered that Zn exposure in workers was associated with changes in PL levels and metabolism, which had further effects on increased ALT levels in workers. The study provides insights into the relationship between occupational Zn exposure and liver function, highlights the risk of long-term exposure to high concentrations of Zn, and paves the way for understanding the underlying mechanisms of Zn exposure on human health.

Deep Learning Model for Predicting Proliferative Hepatocellular Carcinoma Using Dynamic Contrast-Enhanced MRI: Implications for Early Recurrence Prediction Following Radical Resection.

RATIONALE AND OBJECTIVES: The proliferative nature of hepatocellular carcinoma (HCC) is closely related to early recurrence following radical resection. This study develops and validates a deep learning (DL) prediction model to distinguish between proliferative and non-proliferative HCCs using dynamic contrast-enhanced MRI (DCE-MRI), aiming to refine preoperative assessments and optimize treatment strategies by assessing early recurrence risk. MATERIALS AND METHODS: In this retrospective study, 355 HCC patients from two Chinese medical centers (April 2018-February 2023) who underwent radical resection were included. Patient data were collected from medical records, imaging databases, and pathology reports. The cohort was divided into a training set (n = 251), an internal test set (n = 62), and external test sets (n = 42). A DL model was developed using DCE-MRI images of primary tumors. Clinical and radiological models were generated from their respective features, and fusion strategies were employed for combined model development. The discriminative abilities of the clinical, radiological, DL, and combined models were extensively analyzed. The performances of these models were evaluated against pathological diagnoses, with independent and fusion DL-based models validated for clinical utility in predicting early recurrence. RESULTS: The DL model, using DCE-MRI, outperformed clinical and radiological feature-based models in predicting proliferative HCC. The area under the curve (AUC) for the DL model was 0.98, 0.89, and 0.83 in the training, internal validation, and external validation sets, respectively. The AUCs for the combined DL and clinical feature models were 0.99, 0.86, and 0.83 in these sets, while the AUCs for the combined DL, clinical, and radiological model were 0.99, 0.87, and 0.8, respectively. Among models predicting early recurrence, the DL plus clinical features model showed superior performance. CONCLUSION: The DL-based DCE-MRI model demonstrated robust performance in predicting proliferative HCC and stratifying patient risk for early postoperative recurrence. As a non-invasive tool, it shows promise in enhancing decision-making for individualized HCC management strategies.

Construction and validation of a rat model of acute necrotizing pancreatitis-associated intestinal injury.

Acute pancreatitis (AP) is an acute inflammatory reaction of the pancreatic tissue, which involves auto-digestion, edema, hemorrhage, and necrosis. AP can be categorized into mild, moderately severe, and severe AP, with severe pancreatitis also referred to as acute necrotizing pancreatitis (ANP). ANP is characterized by the accumulation of necrotic material in the peritoneal cavity. This can result in intestinal injury. However, the mechanism of ANP-associated intestinal injury remains unclear. We established an ANP-associated intestinal injury rat model (ANP-IR model) by injecting pancreatitis-associated ascites fluid (PAAF) and necrotic pancreatic tissue at various proportions into the triangular area formed by the left renal artery and ureter. The feasibility of the ANP-IR model was verified by comparing the similar changes in indicators of intestinal inflammation and barrier function between the two rat models. In addition, we detected changes in apoptosis levels and YAP protein expression in the ileal tissues of rats in each group and validated them in vitro in rat epithelial crypt cells (IEC-6) to further explore the potential injury mechanisms of ANP-associated intestinal injury. We also collected clinical data from patients with ANP to validate the effects of PAAF and pancreatic necrosis on intestinal injury. Our findings offer a theoretical basis for restricting the buildup of peritoneal necrosis in individuals with ANP, thus promoting the restoration of intestinal function and enhancing treatment efficacy. The use of the ANP-IR model in further studies can help us better understand the mechanism and treatment of ANP-associated intestinal injury.NEW & NOTEWORTHY We constructed a rat model of acute necrotizing pancreatitis-associated intestinal injury and verified its feasibility. In addition, we identified the mechanism by which necrotic pancreatic tissue and pancreatitis-associated ascites fluid (PAAF) cause intestinal injury through the HIPPO signaling pathway.

Tumor Microenvironment-Activatable Phototheranostic: Leveraging Nitric Oxide and Weak Acidity as Dual Biomarkers for Ratiometric Fluorescence, Photoacoustic Imaging, and Photothermal Therapy.

Tumor microenvironment-responsive phototheranostic agents are highly sought after for their ability to improve diagnostic accuracy and treatment specificity. Here, we introduce a novel single-molecule probe, POZ-NO, which is activated by nitric oxide (NO) and weak acidity, enabling dual-mode imaging and photothermal therapy (PTT) of tumors. In acidic environments with elevated NO levels, POZ-NO exhibits a distinctive ratiometric fluorescence signal shift from the red to near-infrared, accompanied by a 700 nm photoacoustic signal. Additionally, POZ-NO demonstrated potent photothermal effects upon NO and acidity activation, achieving an impressive conversion efficiency of 74.3% under 735 nm laser irradiation. In vivo studies confirm POZ-NO's ability to accurately image tumors through ratiometric fluorescence and photoacoustic modes while selectively treating tumors with PTT.

Light recovery after maize harvesting promotes soybean flowering in a maize-soybean relay strip intercropping system.

Moving from sole cropping to intercropping is a transformative change in agriculture, contributing to yield. Soybeans adapt to light conditions in intercropping by adjusting the onset of reproduction and the inflorescence architecture to optimize reproductive success. Maize-soybean strip intercropping (MS), maize-soybean relay strip intercropping (IS), and sole soybean (SS) systems are typical soybean planting systems with significant differences in light environments during growth periods. To elucidate the effect of changes in the light environment on soybean flowering processes and provide a theoretical basis for selecting suitable varieties in various planting systems to improve yields, field experiments combining planting systems (IS, MS, and SS) and soybean varieties (GQ8, GX7, ND25, and NN996) were conducted in 2021 and 2022. Results showed that growth recovery in the IS resulted in a balance in the expression of TERMINAL FLOWER 1 (TFL1) and FLOWERING LOCUS T (FT) in the meristematic tissues of soybeans, which promoted the formation of new branches or flowers. IS prolonged the flowering time (2-7 days) and increased the number of forming flowers compared with SS (93.0 and 169%) and MS (67.3 and 103.3%) at the later soybean flowering stage. The higher carbon and nitrogen content in the middle and bottom canopies of soybean contributed to decreased flower abscission by 26.7 and 30.2%, respectively, compared with SS. Canopy light environment recovery promoted branch and flower formation and transformation of flowers into pods with lower flower-pod abscission, which contributed to elevating soybean yields in late-maturing and multibranching varieties (ND25) in IS.

Alterations in gut microbiota contribute to cognitive deficits induced by chronic infection of Toxoplasma gondii.

Chronic infection with Toxoplasma gondii (T. gondii) emerges as a risk factor for neurodegenerative diseases in animals and humans. However, the underlying mechanisms are largely unknown. We aimed to investigate whether gut microbiota and its metabolites play a role in T. gondii-induced cognitive deficits. We found that T. gondii infection induced cognitive deficits in mice, which was characterized by synaptic ultrastructure impairment and neuroinflammation in the hippocampus. Moreover, the infection led to gut microbiota dysbiosis, barrier integrity impairment, and inflammation in the colon. Interestingly, broad-spectrum antibiotic ablation of gut microbiota attenuated the adverse effects of the parasitic infection on the cognitive function in mice; cognitive deficits and hippocampal pathological changes were transferred from the infected mice to control mice by fecal microbiota transplantation. In addition, the abundance of butyrate-producing bacteria and the production of serum butyrate were decreased in infected mice. Interestingly, dietary supplementation of butyrate ameliorated T. gondii-induced cognitive impairment in mice. Notably, compared to the healthy controls, decreased butyrate production was observed in the serum of human subjects with high levels of anti-T. gondii IgG. Overall, this study demonstrates that gut microbiota is a key regulator of T. gondii-induced cognitive impairment.

Phthalate acid esters: A review of aquatic environmental occurrence and their interactions with plants.

The increasing use of phthalate acid esters (PAEs) in various applications has inevitably led to their widespread presence in the aquatic environment. This presents a considerable threat to plants. However, the interactions between PAEs and plants in the aquatic environment have not yet been comprehensively reviewed. In this review, the properties, occurrence, uptake, transformation, and toxic effects of PAEs on plants in the aquatic environment are summarized. PAEs have been prevalently detected in the aquatic environment, including surface water, groundwater, seawater, and sediment, with concentrations ranging from the ng/L or ng/kg to the mg/L or mg/kg range. PAEs in the aquatic environment can be uptake, translocated, and metabolized by plants. Exposure to PAEs induces multiple adverse effects in aquatic plants, including growth perturbation, structural damage, disruption of photosynthesis, oxidative damage, and potential genotoxicity. High-throughput omics techniques further reveal the underlying toxicity molecular mechanisms of how PAEs disrupt plants on the transcription, protein, and metabolism levels. Finally, this review proposes that future studies should evaluate the interactions between plants and PAEs with a focus on long-term exposure to environmental PAE concentrations, the effects of PAE alternatives, and human health risks via the intake of plant-based foods.

Design, synthesis, and biological application of A-D-A-type boranil fluorescent dyes.

For the first time, three acceptor-donor-acceptor (A-D-A)-type boranil fluorescent dyes, CSU-BF-R (R = H, CH3, and OCH3), featuring phenothiazine as the donor, were designed and synthesized. CSU-BF-R exhibited remarkable photophysical characteristics, including large Stokes shifts (>150 nm), high fluorescence quantum yields (up to 40%), long-wavelength emissions, and strong red solid-state fluorescence. Moreover, these CSU-BF-R fluorescent dyes were demonstrated to function as highly selective and sensitive ratiometric fluorescent probes for detecting hypochlorous acid (HClO). The preliminary biological applications of CSU-BF-OCH3 for sensing intracellular HClO in living cells and zebrafish were demonstrated. Therefore, CSU-BF-R possess the potential to further explore the physiological and pathological functions associated with HClO and provide valuable insights into the design of high-performance A-D-A-type fluorescent dyes.

Phocaeicola vulgatus alleviates diet-induced metabolic dysfunction-associated steatotic liver disease progression by downregulating histone acetylation level via 3-HPAA.

Diet-induced metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent metabolic disorder with limited effective interventions available. A novel approach to address this issue is through gut microbiota-based therapy. In our study, we utilized multi-omics analysis to identify Phocaeicola vulgatus (P. vulgatus) as a potential probiotic for the treatment of MASLD. Our findings from murine models clearly illustrate that the supplementation of P. vulgatus mitigates the development of MASLD. This beneficial effect is partly attributed to the metabolite 3-Hydroxyphenylacetic acid (3-HPAA) produced by P. vulgatus, which reduces the acetylation levels of H3K27 and downregulates the transcription of Squalene Epoxidase (SQLE), a rate-limiting enzyme in steroid biosynthesis that promotes lipid accumulation in liver cells. This study underscores the significant role of P. vulgatus in the development of MASLD and the critical importance of its metabolite 3-HPAA in regulating lipid homeostasis. These findings offer a promising avenue for early intervention therapy in the context of MASLD.