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, oedema, haemorrhage, 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.

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.

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.

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.

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.

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.

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.

Chinese guideline for the diagnosis and treatment of drug-induced liver injury: an update.

Drug-induced liver injury (DILI) is an important adverse drug reaction that can lead to acute liver failure or even death in severe cases. Currently, the diagnosis of DILI still follows the strategy of exclusion. Therefore, a detailed history taking and a thorough and careful exclusion of other potential causes of liver injury is the key to correct diagnosis. This guideline was developed based on evidence-based medicine provided by the latest research advances and aims to provide professional guidance to clinicians on how to identify suspected DILI timely and standardize the diagnosis and management in clinical practice. Based on the clinical settings in China, the guideline also specifically focused on DILI in chronic liver disease, drug-induced viral hepatitis reactivation, common causing agents of DILI (herbal and dietary supplements, anti-tuberculosis drugs, and antineoplastic drugs), and signal of DILI in clinical trials and its assessment.

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.

Toxic effects and action mechanism of metal-organic framework UiO-66-NH2 in Microcystisaeruginosa.

The zirconium metal-organic framework UiO-66-NH2 has garnered considerable attention for their potentials of removing environmental contaminants from water. The production and application of UiO-66-NH2 make their releases into the aquatic environment inevitable. Nevertheless, little information is available regarding its potential risk to the environment and aquatic organisms, thus limiting the evaluation of its safe and sustainable use. In this study, the ecotoxicity of UiO-66-NH2 was evaluated, specifically its impacts on growth, extracellular organic matter release, and metabolomic changes of the model phytoplankton Microcystis aeruginosa (M. aeruginosa). UiO-66-NH2 exhibited moderate effects on algal physiology including growth, viability, and photosynthetic system. At concentrations below 20 mg/L, UiO-66-NH2 induced negligible inhibition of algal growth, algal viability, and photosynthesis. In contrast, UiO-66-NH2 boosted the release of extracellular organic matter even at concentration as low as 0.02 mg/L. These findings indicated that, while no evident damage to algal cells was observed, UiO-66-NH2 was hazardous to the aquatic environment as it stimulated the release of algal toxins. Moreover, UiO-66-NH2 entered algal cells rather than adhering to the surface of M. aeruginosa as observed by the fluorescence imaging. Based on metabolic analysis, UiO-66-NH2 influenced the cyanobacteria mainly through interference with purine metabolism and ABC transporter. This study sheds light on the potential threat UiO-66-NH2 posing to microalgae, and has potential implications for its safe utilization in the environmental field.

Success of susceptibility-guided eradication of Helicobacter pylori in a region with high secondary clarithromycin and levofloxacin resistance rates.

BACKGROUND: Resistance to clarithromycin (CLA) and levofloxacin (LFX) of Helicobacter pylori (H. pylori) is increasing in severity, and successful eradication is essential. Presently, the eradication success rate has greatly declined, leaving a large number of patients with previous treatment histories. AIM: To investigate secondary resistance rates, explore risk factors for antibiotic resistance, and assess the efficacy of susceptibility-guided therapy. METHODS: We recruited 154 subjects positive for Urea Breath Test who attended The First Affiliated Hospital of China Medical University between July 2022 and April 2023. Participants underwent a string test after an overnight fast. The gastric juice was obtained and transferred to vials containing storage solution. Subsequently, DNA extraction and the specific DNA amplification were performed using quantitative polymerase chain reaction (qPCR). Demographic information was also analyzed as part of the study. Based on these results, the participants were administered susceptibility-guided treatment. Efficacy was compared with that of the empiric treatment group. RESULTS: A total of 132 individuals tested positive for the H. pylori ureA gene by qPCR technique. CLA resistance rate reached a high level of 82.6% (n = 109), LFX resistance rate was 69.7% (n = 92) and dual resistance was 62.1% (n = 82). Gastric symptoms [odds ratio (OR) = 2.782; 95% confidence interval (95%CI): 1.076-7.194; P = 0.035] and rural residence (OR = 5.152; 95%CI: 1.407-18.861; P = 0.013) were independent risk factors for secondary resistance to CLA and LFX, respectively. A total of 102 and 100 individuals received susceptibility-guided therapies and empiric treatment, respectively. The antibiotic susceptibility-guided treatment and empiric treatment groups achieved successful eradication rates of 75.5% (77/102) and 59.0% (59/411) by the intention-to-treat (ITT) analysis and 90.6% (77/85) and 70.2% (59/84) by the per-protocol (PP) analysis, respectively. The eradication rates of these two treatment strategies were significantly different in both ITT (P = 0.001) and PP (P = 0.012) analyses. CONCLUSION: H. pylori presented high secondary resistance rates to CLA and LFX. For patients with previous treatment failures, treatments should be guided by antibiotic susceptibility tests or regional antibiotic resistance profile.

Effects of soil physicochemical environment on the plasticity of root growth and land productivity in maize soybean relay strip intercropping system.

BACKGROUND: Soil is a key foundation of crop root growth. There are interactions between root system and soil in multiple ways. The present study aimed to further explore the response of root distribution and morphology to soil physical and chemical environment under maize (Zea mays L.) soybean (Glycine Max L. Merr.) relay strip intercropping (MS) An experiment was carried out aiming to examine the effects of nitrogen (N) applications and interspecific distances on root system and soil environment in MS. The two N application levels, referred to as no N application (NN) and conventional N application (CN), were paired with different interspecific distances: 30, 45 and 60 cm (MS30, MS45 and MS60) and 100 cm of monoculture maize and soybean (MM/SS100). RESULTS: The results demonstrated that MS45 increased the distribution of soil aggregates (> 2 mm) near the crop roots and maize soil nutrients status, which increased by 20.3% and 15.6%. Meanwhile, MS reduced soil bulk density, increased soil porosity and improved soil oxygen content. Optimization of the soil environment facilitated root growth. The MS45 achieved a better result on root distribution and morphology than the other configuration and also increased land productivity. CONCLUSION: Relay intercropped soybean with maize in interspecific row spacing of 45 cm, improved soil physicochemical environment, reshaped root architecture and optimized root spatial distribution of crops to achieve greater land productivity. © 2024 Society of Chemical Industry.

Distribution characteristics and migration trends of hexabromocyclododecanes between seawater-sediment system in different seasons of fishing grounds along the Yellow sea and East China sea coasts.

Pollutants in the ecological environment of fishery seawater are harmful to the survival and reproduction of aquatic organisms. Hexabromocyclododecanes (HBCDs) were 42.9% detected within ND-48.89 ng/L in 177 seawater samples and 30.7% within ND-1.07 ng/g dw in 88 sediment samples of the fisheries in the Yellow Sea and East China Sea, respectively. γ-HBCD accounted for 65% of seawater and 89% of sediment samples. HBCDs in seawater in winter (ND-48.89 ng/L) were significantly higher than in summer (ND-4.99 ng/L), possibly because the re-suspension caused by winds and waves could re-migrate HBCDs from the sediment to the seawater in winter. However, seasonal differences of HBCDs in sediment were not significant. The fugacities indicated HBCDs' migrating trend from seawater to sediment due to their hydrophobic nature. There is almost no terrestrial input of HBCDs from the Yangtze and Yellow Rivers, and currently used fishery materials in marine may compose long-lasting sources of HBCDs.

Development and validation of prediction model to estimate vertigo risk after endolymphatic sac decompression in Meniere's disease: a retrospective cohort study.

PURPOSE: To study the efficacy predictors of endolymphatic sac decompression (ESD) in Meniere's disease (MD), and to establish and verify the prediction model of vertigo after ESD in patients with MD. METHODS: The retrospective cohort data of 56 patients with unilateral MD who underwent ESD surgery were recorded. A stepwise regression method was used to select optimal modeling variables, and we established a logistic regression model with the outcome of vertigo after ESD. The bootstrap method was used for internal validation. RESULTS: Potential predictors included sex, age, follow-up duration, disease course, attack duration, frequency of attack, pure-tone threshold average (PTA) of the patient's speech frequency, audiogram type, glycerin test results, MD subtype, and 10-year atherosclerotic cardiovascular disease risk classification. Using the stepwise regression method, we found that the optimal modeling variables were the audiogram type and PTA of the patient's speech frequency. The prediction model based on these two variables exhibited good discrimination [area under the receiver operating characteristic curve: 0.72 (95% confidence interval: 0.57-0.86)] and acceptable calibration (Brier score 0.21). CONCLUSION: The present model based on the audiogram type and PTA of the patient's speech frequency was found to be useful in guidance of ESD efficacy prediction and surgery selection.

BAP18 acting as a novel peroxisome proliferator-activated receptor α co-regulator contributes to hepatocellular carcinoma progression.

Hepatocellular carcinoma (HCC) is a common malignancy worldwide with a poor prognosis. The therapeutic outcomes of HCC patients are urgently needed to be improved, and predictive biomarkers for the optimal treatment selection remains to be further defined. In the present study, our results showed that BPTF-associated protein of 18 KDa (BAP18) was highly expressed in HCC tissues. In cultured HCC cells, BAP18 regulated a subset of down-stream genes involved in different functions, particularly including peroxisome proliferator-activated receptor (PPAR) pathway and lipid metabolism. Furthermore, BAP18 co-activated PPARα-mediated transactivation and facilitated the recruitment of nucleosome acetyltransferase of H4 (NuA4)/tat interacting protein 60 (TIP60) complex, thereby increasing histone H4 acetylation on stearoyl-CoA desaturase 1 (SCD1) loci. In addition, BAP18 promoted HCC cell proliferation, increased intracellular lipid levels and enhanced cell survival under the metabolic stress conditions, such as glucose limitation or tyrosine kinase inhibitors (TKIs) treatment. Importantly, higher BAP18 expression was positively correlated with the postoperative recurrence and the poor disease-free survival in clinical patients receiving sorafenib treatment. Altogether, we discovered that BAP18 plays an oncogenic role in the survival and proliferation of HCC cells, and BAP18 may serve as a predictive biomarker for adjunct TKIs treatment in patients with HCC, and further facilitate the precise treatment.

Fine mapping identifies independent HLA associations in autoimmune hepatitis type 1.

Background & Aims: Association studies have greatly refined the important role of the major histocompatibility complex (MHC) region in autoimmune hepatitis (AIH). However, the effects of human leucocyte antigen (HLA) polymorphisms on AIH are not well established. The aim of this study is to systematically characterise the association of MHC variants with AIH in our well-defined cohort of patients. Methods: We performed an imputation-based analysis on the extensive association observed within the MHC region using the Han-MHC reference panel, and tested the comprehensive associations of HLA polymorphisms with AIH in 1622 Chinese AIH type 1 patients and 10,466 population controls. Results: A total of 588 HLA variants were significantly associated with AIH, with HLA-B∗35:01 (p = 8.17 × 10-304; odds ratio [OR] = 7.32) contributing the strongest signal. Stepwise conditional analysis revealed additional independent signals at HLA-B∗08:01 (p = 1.35 × 10-33; OR = 4.26) and rs7765379 (p = 5.08 × 10-18; OR = 1.66). A strong link between the lead HLA variant and clinical phenotypes of AIH was observed: patients with HLA-B∗35:01 were less frequently positive for ANA and tended to have higher serum AST and ALT levels at diagnosis, but lower serum IgG levels. Conclusions: Our study reveals three novel and independent variants at HLA-B∗35:01, HLA-B∗08:01, and rs7765379 associated with AIH across the whole MHC region in the Han Chinese population. The findings illustrate the value of the MHC region in AIH and provide a new perspective for the immunogenetics of AIH. Impact and implications: This study revealed three novel and independent variants associated with autoimmune hepatitis across the whole major histocompatibility complex region in the Han Chinese population. These findings are significant in identifying autoantigens, providing insights into the activation of the autoimmune processes, and further advancing our understanding of the immunogenetic basis underlying autoimmune hepatitis.

Synthetic Antioxidants as Contaminants of Emerging Concern in Indoor Environments: Knowns and Unknowns.

Synthetic antioxidants, including synthetic phenolic antioxidants (SPAs), amine antioxidants (AAs), and organophosphite antioxidants (OPAs), are essential additives for preventing oxidative aging in various industrial and consumer products. Increasing attention has been paid to the environmental contamination caused by these chemicals, but our understanding of synthetic antioxidants is generally limited compared to other emerging contaminants such as plasticizers and flame retardants. Many people spend a significant portion (normally greater than 80%) of their time indoors, meaning that they experience widespread and persistent exposure to indoor contaminants. Thus, this Perspective focuses on the problem of synthetic antioxidants as indoor environmental contaminants. The wide application of antioxidants in commercial products and their demonstrated toxicity make them an important family of indoor contaminants of emerging concern. However, significant knowledge gaps still need to be bridged: novel synthetic antioxidants and their related transformation products need to be identified in indoor environments, different dust sampling strategies should be employed to evaluate human exposure to these contaminants, geographic scope and sampling scope of research on indoor contamination should be broadened, and the partition coefficients of synthetic antioxidants among different media need to be investigated.