[Clinical diagnosis and treatment analysis of spontaneous cerebrospinal fluid otorrhoea].

Objective:To investigate the clinical features, imaging findings, surgical methods， diagnostic and treatment experience of spontaneous cerebrospinal fluid otorrhoea. Methods:The clinical data of 11 patients with spontaneous cerebrospinal fluid otorrhoea treated surgically at our hospital from May 2018 to May 2023 were retrospectively analyzed. The medical data included medical history, imaging data, leak location, surgical repair method, treatment effect and postoperative follow-up. Results:Among the 11 surgical patients, 4 patients were initially diagnosed with secretory otitis media, 1 was initially diagnosed with purulent otitis media, and 5 patients had a history of meningitis or presented because meningitis as the initial diagnosis. There were 2 cases of cerebrospinal fluid leakage repaired through the ear canal pathway and 9 cases of cerebrospinal fluid leakage repaired through the mastoid pathway. During the operation, leaks were located in the stapes floor plate in 4 cases, sinus meningeal angle in 1 case, posterior cranial fossa combined with middle cranial fossa in 1 case, middle cranial fossa in 4 cases, and labyrinthine segment of the internal auditory canal and facial nerve canal in 1 case. Ten patient was successfully repaired, and another patient developed intracranial hypertension after surgery, with symptoms alleviated by a lateral ventriculoperitoneal shunt. Postoperative follow-up ranged from 6 months to 4 years, and there was no CSF otorrhoea and meningitis recurrence. Conclusion:The incidence of spontaneous cerebrospinal fluid otorrhea is low, the clinical symptoms are atypical, and the rate of delayed diagnosis or missed diagnosis and misdiagnosis is high. Surgery is currently the preferred treatment for spontaneous cerebrospinal fluid otorrhoea, and satisfactory results are usually achieved; During diagnosis and treatment, it is crucial to be vigilant for intracranial hypertension to prevent serious complications and irreversible damage.

Using large language model (LLM) to identify high-burden informal caregivers in long-term care.

BACKGROUND: The rising global elderly population increases the demand for caregiving, yet traditional methods may not fully assess the challenges faced by vital informal caregivers. OBJECTIVE: To investigate the efficacy of Large Language Model (LLM) in detecting overburdened informal caregivers, benchmarking against rule-based and machine learning methods. METHODS: 1,791 eligible informal caregivers from Southern Taiwan and utilized their textual case summary reports for the LLM. We also employed structured questionnaire results for machine learning models. Furthermore, we leveraged the visualization of the LLM's attention mechanisms to enhance our understanding of the model's interpretative capabilities. RESULTS: The LLM achieved an Area Under the Receiver Operating Characteristic (AUROC) curve of 0.84 and an Area Under the Precision-Recall Curve (AUPRC) of 0.70, marking an 8% and 14% improvement over traditional methods. The visualization of the attention mechanism accurately reflected the evaluations of human experts, concentrating on descriptions of high-burden descriptions and the relationships between caregivers and recipients. CONCLUSION: This research demonstrates the notable capability of LLM to accurately identify high-burden caregivers in Long-term Care (LTC) settings. Compared to traditional approaches, LLM offers an opportunity for the future of LTC research and policymaking.

Bacillus suppresses nitrogen efficiency of soybean-rhizobium symbiosis through regulation of nitrogen-related transcriptional and microbial patterns.

The regulation of legume-rhizobia symbiosis by microorganisms has obtained considerable interest in recent research, particularly in the common rhizobacteria Bacillus. However, few studies have provided detailed explanations regarding the regulatory mechanisms involved. Here, we investigated the effects of Bacillus (Bac.B) on Bradyrhizobium-soybean (Glycine max) symbiosis and elucidated the underlying ecological mechanisms. We found that two Bradyrhizobium strains (i.e. Bra.Q2 and Bra.D) isolated from nodules significantly promoted nitrogen (N) efficiency of soybean via facilitating nodule formation, thereby enhanced plant growth and yield. However, the intrusion of Bac.B caused a reverse shift in the synergistic efficiency of N2 fixation in the soybean-Bradyrhizobium symbiosis. Biofilm formation and naringenin may be importantin suppression of Bra.Q2 growth regulated by Bac.B. In addition, transcriptome and microbiome analyses revealed that Bra.Q2 and Bac.B might interact to regulateN transport and assimilation, thus influence the bacterial composition related to plant N nutrition in nodules. Also, the metabolisms of secondary metabolites and hormones associated with plant-microbe interaction and growth regulation were modulated by Bra.Q2 and Bac.B coinoculation. Collectively, we demonstrate that Bacillus negatively affects Bradyrhizobium-soybean symbiosis and modulate microbial interactions in the nodule. Our findings highlight a novel Bacillus-based regulation to improve N efficiency and sustainable agricultural development.

Hunting imaging biomarkers in pulmonary fibrosis: Benchmarks of the AIIB23 challenge.

Airway-related quantitative imaging biomarkers are crucial for examination, diagnosis, and prognosis in pulmonary diseases. However, the manual delineation of airway structures remains prohibitively time-consuming. While significant efforts have been made towards enhancing automatic airway modelling, current public-available datasets predominantly concentrate on lung diseases with moderate morphological variations. The intricate honeycombing patterns present in the lung tissues of fibrotic lung disease patients exacerbate the challenges, often leading to various prediction errors. To address this issue, the 'Airway-Informed Quantitative CT Imaging Biomarker for Fibrotic Lung Disease 2023' (AIIB23) competition was organized in conjunction with the official 2023 International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI). The airway structures were meticulously annotated by three experienced radiologists. Competitors were encouraged to develop automatic airway segmentation models with high robustness and generalization abilities, followed by exploring the most correlated QIB of mortality prediction. A training set of 120 high-resolution computerised tomography (HRCT) scans were publicly released with expert annotations and mortality status. The online validation set incorporated 52 HRCT scans from patients with fibrotic lung disease and the offline test set included 140 cases from fibrosis and COVID-19 patients. The results have shown that the capacity of extracting airway trees from patients with fibrotic lung disease could be enhanced by introducing voxel-wise weighted general union loss and continuity loss. In addition to the competitive image biomarkers for mortality prediction, a strong airway-derived biomarker (Hazard ratio>1.5, p < 0.0001) was revealed for survival prognostication compared with existing clinical measurements, clinician assessment and AI-based biomarkers.

Biomimetic hierarchical porous high entropy alloy for significantly enhancing overall seawater splitting.

Herein, a biomimetic hierarchical porous high entropy alloy (BHP-HEA) is prepared by a strategy combining selective laser melting and selective phase dissolution. It exhibited excellent seawater splitting performance, which only needs a low potential of 1.53 V to realize a current density of 100 mA cm-2, with exceptional stability.

Efficacy and Safety of Adding Ketamine to Lidocaine in Intravenous Regional Anesthesia: A Meta-analysis of Randomized Controlled Trials.

PURPOSE: To systematically evaluate the efficacy and safety of adding ketamine (K) to lidocaine (L) for intravenous regional anesthesia (IVRA). DESIGN: A systematic review and meta-analysis. METHODS: A comprehensive search of the Cochrane library, Embase, PubMed, Web of Science, and ProQuest databases, and the Google Scholar search engine was conducted from inception to March 2023. All retrieved articles were imported into Endnote X20 software and independently screened by two researchers according to predetermined inclusion and exclusion criteria. The data were analyzed using Revman 5.4 software and the assessed outcomes included the time of sensory and motor block onset, time of sensory and motor block recovery, fentanyl consumption, time of tourniquet pain onset, intraoperative and postoperative visual analog scale scores, and complications. FINDINGS: A total of 532 patients from 11 randomized controlled trials were included in the meta-analysis. The results showed that the time of sensory (P < .00001) and motor block onset (P < .00001) were shorter in the L + K group than in the L-only group. The time of sensory (P = .01) and motor block recovery (P = .006) and time of tourniquet pain onset (P < .00001) were longer in the L + K group than in the L-only group. There was a significant reduction in fentanyl consumption (P = .0002) in the L + K group compared to the L-only group. Moreover, the visual analog scale scores in the L + K group were significantly lower than the L-only group 10 minutes (P = .04), 20 minutes (P = .0004), 30 minutes (P < .00001), and 40 minutes (P < .0001) after tourniquet inflation, and 5 minutes (P < .00001), 15 minutes (P = .04), 30 minutes (P = .008), 1 hour (P = .002), 2 hours (P < .00001), and 4 hours (P < .00001) after tourniquet deflation. There was no evidence that the use of K as an adjuvant in IVRA increased adverse effects. CONCLUSIONS: The addition of K to L in IVRA shortened the onset time, prolonged the block time, and reduced intraoperative and postoperative pain without increasing complications.

Enhancing traumatic brain injury emergency care: the impact of grading and zoning nursing management.

OBJECTIVE: This research aimed to evaluate the impact of grading and zoning nursing management on traumatic brain injury (TBI) patients' emergency treatment outcomes. METHODS: This randomized controlled trial included 200 TBI patients. They were treated with a conventional care (control group, n = 100) and a novel grading and zoning approach (study group, n = 100), respectively. This innovative model organized care into levels based on urgency and complexity, facilitating targeted medical response and resource allocation. Key metrics compared included demographic profiles, consultation efficiency (time metrics and emergency treatment rates), physiological parameters (HR, RR, MAP, SpO2, RBS), and patient outcomes (hospital and ICU stays, complication rates, and emergency outcomes). RESULTS: The study group demonstrated significantly improved consultation efficiency, with reduced times for physician visits, examinations, emergency stays, and specialist referrals (all p < 0.001), alongside a higher emergency treatment rate (93% vs. 79%, p = 0.004), notably better physiological stability, improved HR, RR, MAP, SpO2 and RBS (p < 0.001), shorter hospital and ICU stays, fewer complications, and superior emergency outcomes. CONCLUSION: Grading and zoning nursing management substantially enhances TBI patients' emergency care efficiency and clinical outcomes, suggesting a viable model for improving emergency treatment protocols.

Understanding and alleviating informal caregiver burden through the development and validation of a caregiver strain index-based model in Taiwan.

BACKGROUND: Quantifying the informal caregiver burden is important for understanding the risk factors associated with caregiver overload and for evaluating the effectiveness of services provided in Long-term Care (LTC). OBJECTIVE: This study aimed to develop and validate a Caregiver Strain Index (CSI)-based score for quantifying the informal caregiver burden, while the original dataset did not fully cover evaluation items commonly included in international assessments. Subsequently, we utilized the CSI-based score to pinpoint key caregiver burden risk factors, examine the initial timing of LTC services adoption, and assess the impact of LTC services on reducing caregiver burden. METHODS: The study analyzed over 28,000 LTC cases in Southern Taiwan from August 2019 to December 2022. Through multiple regression analysis, we identified significant risk factors associated with caregiver burden and examined changes in this burden after utilizing various services. Survival analysis was employed to explore the relationship between adopting the first LTC services and varying levels of caregiver burden. RESULTS: We identified 126 significant risk factors for caregiver burden. The most critical factors included caregiving for other disabled family members or children under the age of three (ß = 0.74, p < 0.001), the employment status of the caregiver (ß = 0.30-0.53, p < 0.001), the frailty of the care recipient (ß = 0.28-0.31, p < 0.001), and the behavioral symptoms of dementia in care recipients (ß = 0.28-2.60, p < 0.05). Generally, caregivers facing higher burdens sought LTC services earlier, and providing home care services alleviated the caregiver's burden. CONCLUSION: This comprehensive study suggests policy refinements to recognize high-risk caregivers better early and provide timely support to improve the overall well-being of both informal caregivers and care recipients.

Evaluating the role of DNA methyltransferases in trophoblast fusion and preeclampsia development: Insights from methylation-regulated genes.

The etiology of preeclampsia (PE), a complex and multifactorial condition, remains incompletely understood. DNA methylation, which is primarily regulated by three DNA methyltransferases (DNMTs), DNMT1, DNMT3A, and DNMT3B, plays a vital role in early embryonic development and trophectoderm differentiation. Yet, how DNMTs modulate trophoblast fusion and PE development remains unclear. In this study, we found that the DNMTs expression was downregulated during trophoblast cells fusion. Downregulation of DNMTs was observed during the reconstruction of the denuded syncytiotrophoblast (STB) layer of placental explants. Additionally, overexpression of DNMTs inhibited trophoblast fusion. Conversely, treatment with the DNA methylation inhibitor 5-aza-CdR decreased the expression of DNMTs and promoted trophoblast fusion. A combined analysis of DNA methylation data and gene transcriptome data obtained from the primary cytotrophoblasts (CTBs) fusion process identified 104 potential methylation-regulated differentially expressed genes (MeDEGs) with upregulated expression due to DNA demethylation, including CD59, TNFAIP3, SDC1, and CDK6. The transcription regulation region (TRR) of TNFAIP3 showed a hypomethylation with induction of 5-aza-CdR, which facilitated CREB recruitment and thereby participated in regulating trophoblast fusion. More importantly, clinical correlation analysis of PE showed that the abnormal increase in DNMTs may be involved in the development of PE. This study identified placental DNA methylation-regulated genes that may contribute to PE, offering a novel perspective on the role of epigenetics in trophoblast fusion and its implication in PE development.

Assembly of Copper Alkynyl Clusters into Dimensionally Diverse Coordinated Polymers Mediated by Pyridine Ligands.

Surface ligands play crucial roles in modifying the properties of metal nanoclusters and stabilizing atomically precise structures, and also serve as vital linkers for constructing cluster-based coordination polymers. In this study, we present the results of the solvothermal synthesis of eight novel copper alkynyl clusters incorporating pyridine ligands using a one-pot method. The resulting compounds underwent characterization through elemental analysis, Fourier transform infrared (FT-IR) spectroscopy, powder X-ray diffraction (PXRD), and single-crystal X-ray diffraction (SCXRD). Our observations revealed that distinct pyridine ligands with varying lengths and coordination sites exert significant influence on the structure and dimensionality of the clusters. The structural diversity of these clusters led to the formation of one-dimensional (1D), two-dimensional (2D), or dimer arrangements linked by seven pyridine bridging ligands. Remarkably, these complexes exhibited unique UV-vis absorption and photoluminescence properties, which were influenced by the specific bridging ligand and structural framework. Furthermore, density functional theory (DFT) calculations demonstrated the capability of the conjugated system in the pyridine ligand to impact the band gap of clusters. This study not only unveils the inherent structural diversity in coordination polymers based on copper alkynyl clusters but also offers valuable insights into harnessing ligand engineering for structural and property modulation.

Nurse-Led Care at Home Visit Versus Standard Care in Patients with Mild Acute Pancreatitis: A Retrospective Analysis.

BACKGROUNDS: Frequent hospitalization and the costs of hospitalization are the main burdens in China for patients with acute pancreatitis. Most admitted patients have mild disease conditions that do not require hospitalization. AIMS: Here, we compare some health and economic aspects of patients with mild acute pancreatitis who received nurse-led care at home visits against those who were hospitalized on follow-up. METHODS: Patients discharged from the hospital after treatment for mild acute pancreatitis received (NC cohort, n = 104) or did not receive (HN cohort, n = 141) regular home visits by nurses for treatment and care. Patients were rehospitalized by caregivers with or without help of nurse. RESULTS: Hospital readmission events occurred in both cohorts at a follow-up care time of 2 months. Compared with the time of discharge from the hospital, unwanted effects were higher in follow-up care in all patients (p < 0.001 for all). Patients in the NC cohort had less time to resolution of pain, less time to resumption of oral solid food intake, smaller number of patients with hospital readmissions, less average time of hospitalization, lower cost of care, and lower occurrence of unwanted effects than those of patients in the HN cohort during 2 months of follow-up care (p < 0.05 for all). CONCLUSIONS: Patients with mild acute pancreatitis who undergo treatment require nurse-led nontreatment intervention(s) for rehabilitation in follow-up. Nurse-led follow-up care at-home visits increase recovery, are beneficial and cost-effective, and decrease unwanted adverse effects in patients receiving treatment for mild acute pancreatitis. LEVEL OF EVIDENCE: IV. TECHNICAL EFFICACY: Stage 5.

The Stylo Cysteine-Rich Peptide SgSnakin1 Is Involved in Aluminum Tolerance through Enhancing Reactive Oxygen Species Scavenging.

Stylo (Stylosanthes spp.) is an important pasture legume with strong aluminum (Al) resistance. However, the molecular mechanisms underlying its Al tolerance remain fragmentary. Due to the incomplete genome sequence information of stylo, we first conducted full-length transcriptome sequencing for stylo root tips treated with and without Al and identified three Snakin/GASA genes, namely, SgSnakin1, SgSnakin2, and SgSnakin3. Through quantitative RT-PCR, we found that only SgSnakin1 was significantly upregulated by Al treatments in stylo root tips. Histochemical localization assays further verified the Al-enhanced expression of SgSnakin1 in stylo root tips. Subcellular localization in both tobacco and onion epidermis cells showed that SgSnakin1 localized to the cell wall. Overexpression of SgSnakin1 conferred Al tolerance in transgenic Arabidopsis, as reflected by higher relative root growth and cell vitality, as well as lower Al concentration in the roots of transgenic plants. Additionally, overexpression of SgSnakin1 increased the activities of SOD and POD and decreased the levels of O2·- and H2O2 in transgenic Arabidopsis in response to Al stress. These findings indicate that SgSnakin1 may function in Al resistance by enhancing the scavenging of reactive oxygen species through the regulation of antioxidant enzyme activities.

Replacing soybean meal with fermented rapeseed meal in diets: potential effects on growth performance, antioxidant capacity, and liver and intestinal health of juvenile tilapia (Oreochromis niloticus).

This study aims to evaluate the effects of substituting soybean meal with fermented rapeseed meal (FRM) on growth, antioxidant capacity, and liver and intestinal health of the genetically improved farmed tilapia (GIFT, Oreochromis niloticus). A total of 450 tilapia (7.22 ± 0.15 g) were fed with five experimental diets, including a basal diet containing 40% soybean meal (CP0), which was subsequently replaced by 25% (CP25), 50% (CP50), 75% (CP75), and 100% (CP100) FRM in a recirculated aquiculture system for 9 weeks (30 fish per tank in triplicates). The results showed that the weight gain, specific growth rate, feed intake, feed efficiency, hepatosomatic index, and viscerosomatic index of fish in both CP75 and CP100 groups were significantly lower than those in CP0 group (P < 0.05). The fish in CP100 group had the lower content of muscle crude protein while the higher level of muscle crude lipid (P < 0.05). Activities of serum aspartate aminotransferase, alanine aminotransferase along with total triglyceride in CP100 group were significantly higher than those in CP0 group (P < 0.05). There were no significant differences in the contents of liver protease, amylase, and lipase among five groups (P > 0.05). The activities of liver total antioxidant capacity and superoxide dismutase exhibited the increased tendency with the increase of FRM replacement levels from 25 to 50% (P < 0.05), while then significantly decreased from 75 to 100% (P < 0.05). Histological morphology indicated that the fish in between CP75 and CP100 groups had poor liver and intestine health. Intestinal microbial diversity analysis showed that the relative abundance of Cetobacterium and Alcaligenaceae in both CP75 and CP100 groups were lower than that in other three groups. In conclusion, the maximum replacement level of soybean meal with FRM in the diet was determined to be 50% without compromising the growth performance, antioxidant status, and liver and intestinal health of tilapia under the current experimental conditions. The observed decrease in food intake and subsequent retarded growth performance in the CP75 and CP100 groups can be attributed directly to a reduction in feed palatability caused by FRM.

A phase I, randomized study to evaluate the safety, tolerability, and pharmacokinetics of mefunidone in healthy subjects.

Background: Mefunidone is a novel synthetic compound and is better when compared to pirfenidone for the anti-fibrotic treatment of renal fibrosis in end-stage renal disease. We conducted this first-in-human, phase I clinical trial to determine the safety, tolerability, and pharmacokinetic (PK) (including food effect) profiles of mefunidone administered orally as single and multiple ascending doses in healthy subjects. Methods: Part A assessed single ascending doses of mefunidone from 25 mg to 800 mg or placebo once daily in the fasting state. Part A also assessed the effect of food on tolerability and PK in the 100 mg cohort. Part B consisted of three treatment groups who received 100 mg, 200 mg, or 400 mg of mefunidone or placebo twice daily (BID, bis in die) on days 1-6 and once in the morning on day 7. Results: Single oral doses of mefunidone up to 800 mg and multiple doses of mefunidone up to 400 mg BID were all well-tolerated. Mefunidone behaved with ideal dose proportionality within the single-dose range of 50 mg-600 mg and the multiple-dose range of 100 mg BID to 400 mg BID by day 7. High-fat fed conditions led to a delay in Tmax by approximately 1 h and a slight reduction of approximately 20% in Cmax compared to that in fasting conditions, but it did not significantly affect systemic exposure. Conclusion: Mefunidone exhibited favorable pharmacokinetics and safety profiles. The present study informed and supported further developmental clinical studies of mefunidone. Clinical Trial Registration: clinicaltrials.gov, identifier CXHL1900206.

Dietary cholesterol intervention could alleviate the intestinal injury of Oreochromis niloticus induced by plant-based diet via the intestinal barriers.

This study aims to explore the effects of supplementing cholesterol in plant-based feed on intestinal barriers (including physical barrier, chemical barrier, immune barrier, biological barrier) of GIFT strain tilapia (Oreochromis niloticus). Four isonitrogenous and isolipidic diets were prepared as follows: plant-based protein diet (Con group) containing corn protein powder, soybean meal, cottonseed meal, and rapeseed meal, with the addition of cholesterol at a level of 0.6 % (C0.6 % group), 1.2 % (C1.2 % group), and 1.8 % (C1.8 % group), respectively. A total of 360 fish (mean initial weight of (6.08 ± 0.12) g) were divided into 12 tanks with 30 fish per tank, each treatment was set with three tanks and the feeding period lasted 9 weeks. Histological analysis revealed that both the C0.6 % and C1.2 % groups exhibited a more organized intestinal structure, with significantly increased muscle layer thickness compared to the Con group (P < 0.05). Furthermore, in the C1.2 % group, there was a significant up-regulation of tight junction-related genes (claudin-14, occludin, zo-1) compared to the Con group (P < 0.05). 5-ethynyl-2'-deoxyuridine staining results also demonstrated a notable enhancement in intestinal cell proliferation within the C1.2 % group (P < 0.05). Regarding the intestinal chemical barrier, trypsin and lipase activities were significantly elevated in the C1.2 % group (P < 0.05), while hepcidin gene expression was considerably down-regulated in this group but up-regulated in the C1.8 % group (P < 0.05). In terms of the intestinal immune barrier, inflammation-related gene expression levels (tnf-α, il-1ß, caspase 9, ire1, perk, atf6) were markedly reduced in the C1.2 % group (P < 0.05). Regarding the intestinal biological barrier, the composition of the intestinal microbiota indicated that compared to the Con group, both the 0.6 % and 1.2 % groups showed a significant increase in Shannon index (P < 0.05). Additionally, there was a significant increase in the abundance of Firmicutes and Clostridium in the C1.2 % group (P < 0.05). In summary, supplementation of 1.2 % cholesterol in the plant-based diet exhibits the potential to enhance intestinal tight junction function and improve the composition of intestinal microbiota, thereby significantly promoting tilapia's intestinal health.

Enhancing growth, liver health, and bile acid metabolism of tilapia (Oreochromis niloticus) through combined cholesterol and bile acid supplementation in plant-based diets.

The present study aimed to compare the nutritional effects of cholesterol, bile acids, and combination of cholesterol with bile acids in plant-based diets on juvenile genetically improved farmed tilapia (GIFT; Oreochromis niloticus). The isonitrogenous (321 g/kg crude protein) and isolipidic (76 g/kg crude fat) diets (Con diet) were based on plant protein sources, which included corn gluten meal, soybean meal, cottonseed meal and rapeseed meal. The Con diet was supplemented with 12 g/kg cholesterol (CHO diet), 0.2 g/kg bile acids (BAs diet), a combination of 12 g/kg cholesterol and 0.2 g/kg bile acids (CHO-BAs diet), respectively. Each diet was fed to three tanks in an indoor recirculating aquaculture system for 9 weeks. Results showed that compared to the Con group, fish had a higher weight gain rate, hepatosomatic index, and a lower feed conversion ratio in the CHO-BAs group. The highest levels of whole-fish fat and ash were found in the Con group. Serum parameters, including activities of alanine aminotransferase (ALT) and aspartate transaminase (AST), along with levels of glucose (GLU) and triglyceride (TG) except for total cholesterol (TCHO), were lower in the CHO, BAs, and CHO-BAs groups than those in the Con group (P < 0.001). Histological examination revealed that fish in the Con group exhibited severe hepatocyte vacuolization and diminished hepatocyte proliferation. Gene expression analysis indicated that the transcriptional levels of bile acid metabolism-related genes (including fxr, fgf19, bsep) were up-regulated in the CHO-BAs group (P < 0.05), whereas cholesterol metabolism-related genes (acly and hmgcr) were down-regulated in both CHO and CHO-BAs groups (P < 0.001). Moreover, UPLC-MS/MS analysis revealed that the higher taurine-conjugated bile acids (T-BAs), followed by free bile acids (Free-BAs) and glycine (G-BAs) were determined in tilapia bile. Among these, taurochenodeoxycholic bile acid was the predominant bile acid. Dietary bile acids supplementation also increased the proportion of T-BAs (tauro ß-muricholic acid and taurodehydrocholic acid) while decreasing Free-BAs in the fish bile. In conclusion, the incorporation of cholesterol with bile acids into plant-based diets can effectively reduce cholesterol uptake, suppress bile acids synthesis, enhance bile acids efflux, and promote hepatocyte proliferation, which is helpful for maintaining the normal liver morphology in tilapia, and thus improving its growth performance.

Metformin induction of heat shock factor 1 activation and the mitochondrial unfolded protein response alleviate cardiac remodeling in spontaneously hypertensive rats.

Heart failure and cardiac remodeling are both characterized by mitochondrial dysfunction. Healthy mitochondria are required for adequate contractile activity and appropriate regulation of cell survival. In the mammalian heart, enhancement of the mitochondrial unfolded protein response (UPRmt) is cardioprotective under pressure overload conditions. We explored the UPRmt and the underlying regulatory mechanism in terms of hypertension-induced cardiac remodeling and the cardioprotective effect of metformin. Male spontaneously hypertensive rats and angiotensin II-treated neonatal rat cardiomyocytes were used to induce cardiac hypertrophy. The results showed that hypertension induced the formation of aberrant mitochondria, characterized by a reduced mtDNA/nDNA ratio and swelling, as well as lower levels of mitochondrial complexes I to V and inhibition of the expression of one protein subunit of each of complexes I to IV. Such changes eventually enlarged cardiomyocytes and increased cardiac fibrosis. Metformin treatment increased the mtDNA/nDNA ratio and regulated the UPRmt, as indicated by increased expression of activating transcription factor 5, Lon protease 1, and heat shock protein 60, and decreased expression of C/EBP homologous protein. Thus, metformin improved mitochondrial ultrastructure and function in spontaneously hypertensive rats. In vitro analyses revealed that metformin reduced the high levels of angiotensin II-induced mitochondrial reactive oxygen species in such animals and stimulated nuclear translocation of heat shock factor 1 (HSF1). Moreover, HSF1 small-interfering RNA reduced the metformin-mediated improvements in mitochondrial morphology and the UPRmt by suppressing hypertrophic signals and cardiomyocyte apoptosis. These results suggest that HSF1/UPRmt signaling contributes to the beneficial effects of metformin. Metformin-mediated targeting of mitochondrial protein homeostasis and modulation of HSF1 levels have potential therapeutic implications in terms of cardiac remodeling.

Exportin XPO6 upregulation activates the TLR2/MyD88/NF-κB signaling by facilitating TLR2 mRNA nuclear export in COPD pulmonary monocytes.

Chronic obstructive pulmonary disease (COPD) poses a significant health threat characterized by lung inflammation primarily triggered by pulmonary monocytes. Despite the centrality of inflammation in COPD, the regulatory mechanisms governing this response remain elusive, presenting a challenge for anti-inflammatory interventions. In this study, we assessed the expression of exportins in COPD mouse models, revealing a notable upregulation of XPO6 in the mouse lung (P = 0.0011). Intriguingly, we observed a consistent upregulation of XPO6 in pulmonary monocytes from both human and mouse COPD subjects (P < 0.0001). Furthermore, in human lung tissue, XPO6 expression exhibited a positive correlation with TLR2 expression (P = 0). In vitro investigations demonstrated that XPO6 enhances TLR2 expression, activating the MyD88/NF-κB inflammatory signaling pathway. This activation, in turn, promotes the secretion of pro-inflammatory cytokines such as TNFα, IL-6, and IL-1ß in monocytes. Mechanistically, XPO6 facilitates the nuclear export of TLR2 mRNA, ensuring its stability and subsequent protein expression in monocytes. In conclusion, our findings unveil that the upregulation of XPO6 in COPD pulmonary monocytes activates the MyD88/NF-κB inflammatory signaling pathway by facilitating the nuclear export of TLR2 mRNA, thereby identifying XPO6 as a promising therapeutic target for anti-inflammatory interventions in COPD.

Genome-wide CNV analysis reveals candidate genes associated with milk production traits in water buffalo (Bubalus bubalis).

Buffaloes are vital contributors to the global dairy industry. Understanding the genetic basis of milk production traits in buffalo populations is essential for breeding programs and improving productivity. In this study, we conducted whole-genome resequencing on 387 buffalo genomes from 29 diverse Asian breeds, including 132 river buffaloes, 129 swamp buffaloes, and 126 crossbred buffaloes. We identified 36,548 copy number variant (CNVs) spanning 133.29 Mb of the buffalo genome, resulting in 2,100 copy number variant regions (CNVRs), with 1,993 shared CNVRs being found within the studied buffalo types. Analyzing CNVRs highlighted distinct genetic differentiation between river and swamp buffalo subspecies, verified by evolutionary tree and principal component analyses. Admixture analysis grouped buffaloes into river and swamp categories, with crossbred buffaloes displaying mixed ancestry. To identify candidate genes associated with milk production traits, we employed 3 approaches. First, we used Vst-based population differentiation, revealing 11 genes within CNVRs that exhibited significant divergence between different buffalo breeds, including genes linked to milk production traits. Second, expression quantitative loci (eQTL) analysis revealed differential expression of CNVR-driven genes (DECGs) associated with milk production traits. Notably, known milk production-related genes were among these DECGs, validating their relevance. Last, a genome-wide association study (GWAS) identified 3 CNVRs significantly linked to peak milk yield. Our study provides comprehensive genomic insights into buffalo populations and identifies candidate genes associated with milk production traits. These findings facilitate genetic breeding programs aimed at increasing milk yield and improving quality in this economically important livestock species.