Improvement of the freezing resistance characteristics of yeast in dough starter.

Improving the freezing resistance of yeast in dough starters is one of the most effective methods to promote the healthy development of frozen dough technology. When the dough starter was composed of yeast, lactic acid bacteria and acetic acid bacteria, the microbial proportion was 10:1:5, and the ratio of wheat flour to corn flour was 1:1. The proline contents of the starters and the survival rates and fermentation capacity of yeast significantly increased compared with those of the starter composed of yeast and wheat flour only (P < 0.05). Laser confocal microscopy observation showed that the cell membrane damage of yeast obviously decreased. Low-field nuclear magnetic resonance method revealed that the water distribution state of starters changed. Adding corn flour and acetic acid bacteria to dough starter in appropriate proportions improves yeast freezing resistance.

The use of transcutaneous electrical acupoint stimulation to reduce opioid consumption in patients undergoing off-pump CABG: a randomized controlled trial.

BACKGROUND: High doses of long-acting opioids were used to facilitate off-pump coronary artery bypass grafting procedure, which may result in opioid-related adverse events after surgery. Transcutaneous electrical acupoint stimulation (TEAS) had been reported to be effective in reducing intraoperative opioids consumption during surgery. The aim of this study is to assess whether TEAS with difference acupoints can reduce the doses of opioid analgesics. METHODS: This was a multicenter, randomized, controlled, double-blind trial. Patients underwent off-pump coronary artery bypass grafting under general anesthesia were enrolled. Eligible patients were randomly and equally grouped into sham acupuncture group (n = 105), regional acupoints combination group (n = 105), or distal-proximal acupoints combination group (n = 105) using a centralized computer-generated randomization system. Transcutaneous electrical acupoint stimulation was applied for 30 min before anesthesia induction. The primary outcome was the doses of sufentanil during anesthesia. Secondary outcomes included the highest postoperative vasoactive-inotropic scores within 24 h, intraoperative propofol consumption, length of mechanical ventilation, duration of cardiac care unit and postoperative hospital stay, incidence of postoperative complications, and mortality within 30 days after surgery. RESULTS: Of the 315 randomized patients, 313 completed the trial. In the modified intention-to-treat analysis, the doses of sufentanil were 303.9 (10.8) µg in the distal-proximal acupoints group, significantly lower than the sham group, and the mean difference was - 34.9 (- 64.9 to - 4.9) µg, p = 0.023. The consumption of sufentanil was lower in distal-proximal group than regional group (303.9 vs. 339.5), and mean difference was - 35.5 (- 65.6 to - 5.5) µg, p = 0.020. The distal-proximal group showed 10% reduction in opioids consumption comparing to both regional and sham groups. Secondary outcomes were comparable among three groups. CONCLUSION: Transcutaneous electrical acupoint stimulation with distal-proximal acupoints combination, compared to regional acupoints combination and sham acupuncture, significantly reduced sufentanil consumption in patients who underwent off-pump coronary artery bypass grafting surgery.

Effect of volatile versus propofol anaesthesia on major complications and mortality after cardiac surgery: a multicentre randomised trial.

BACKGROUND: The comparative effectiveness of volatile anaesthesia and total intravenous anaesthesia (TIVA) in terms of patient outcomes after cardiac surgery remains a topic of debate. METHODS: Multicentre randomised trial in 16 tertiary hospitals in China. Adult patients undergoing elective cardiac surgery were randomised in a 1:1 ratio to receive volatile anaesthesia (sevoflurane or desflurane) or propofol-based TIVA. The primary outcome was a composite of predefined major complications during hospitalisation and mortality 30 days after surgery. RESULTS: Of the 3123 randomised patients, 3083 (98.7%; mean age 55 yr; 1419 [46.0%] women) were included in the modified intention-to-treat analysis. The composite primary outcome was met by a similar number of patients in both groups (volatile group: 517 of 1531 (33.8%) patients vs TIVA group: 515 of 1552 (33.2%) patients; relative risk 1.02 [0.92-1.12]; P=0.76; adjusted odds ratio 1.05 [0.90-1.22]; P=0.57). Secondary outcomes including 6-month and 1-yr mortality, duration of mechanical ventilation, length of ICU and hospital stay, and healthcare costs, were also similar for the two groups. CONCLUSIONS: Among adults undergoing cardiac surgery, we found no difference in the clinical effectiveness of volatile anaesthesia and propofol-based TIVA. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IOR-17013578).

The impact of deep-inspiration breath-hold total-body PET/CT imaging on thoracic 18F-FDG avid lesions compared with free-breathing.

OBJECTIVES: To investigate PET/CT registration and quantification accuracy of thoracic lesions of a single 30-second deep-inspiration breath-hold (DIBH) technique with a total-body PET (TB-PET) scanner, and compared with free-breathing (FB) PET/CT. METHODS: 137 of the 145 prospectively enrolled patients finished a routine FB-300 s PET/CT exam and a 30-second DIBH TB-PET with chest to pelvis low dose CT. The total-body FB-300 s, FB-30 s, and DIBH-30 s PET images were reconstructed. Quantitative assessment (SUVmax and SUVmean of lung and other organs), PET/CT registration assessment and lesion analysis (SUVmax, SUVpeak, SUVmean and tumor-background ratio) were compared with Wilcoxon signed-rank tests. RESULTS: The SUVmax and SUVmean of the lung with DIBH-30 s were significantly lower than those with FB. The distances of the liver dome between PET and CT were significantly smaller with DIBH-30 s than with FB. 195 assessable lesions in 106 patients were included, and the detection sensitivity was 97.9 % and 99.0 % in FB-300 s, and DIBH-30 s, respectively. For both small co-identified lesions (n = 86) and larger co-identified lesions with a diameter ≥ 1 cm (n = 91), the lesion SUVs were significantly greater with DIBH-30 s than with FB-300 s. Regarding lesion location, the differences of the SUVs for the lesions in the lower thorax area (n = 97, p < 0.001) were significant between DIBH-30 s and FB-300 s, while these differences were not statistically significant in the upper thorax (n = 80, p > 0.05). The lesion tumor-to-surrounding-background ratio (TsBR) was significantly increased, both in the upper and lower thorax. CONCLUSION: The TB DIBH PET/CT technique is feasible in clinical practice. It reduces the background lung uptake and achieves better registration and lesion quantification, especially in the lower thorax.

Modulating Electron Density of Boron-Oxygen Groups in Borate via Metal Electronegativity for Propane Oxidative Dehydrogenation.

The robust electronegativity of the [BO3]3- structure enables the extraction of electrons from adjacent metals, offering a strategy for modulating oxygen activation in propane oxidative dehydrogenation. Metals (Ni 1.91, Al 1.5, and Ca 1.0) with varying electronegativities were employed to engineer borate catalysts. Metals in borate lacked intrinsic catalytic activity for propane conversion; instead, they modulated [BO3]3- group reactivity through adjustments in electron density. Moderate metal electronegativity favored propane oxidative dehydrogenation to propylene, whereas excessively low electronegativity led to propane overoxidation to carbon dioxide. Aluminum, with moderate electronegativity, demonstrated optimal performance. Catalyst AlBOx-1000 achieved a propane conversion of 47.5%, with the highest propylene yield of 30.89% at 550 °C, and a total olefin yield of 51.51% with a 58.92% propane conversion at 575 °C. Furthermore, the stable borate structure prevents boron element loss in harsh conditions and holds promise for industrial-scale catalysis.

Molecular pharmacology and therapeutic advances of monoterpene perillyl alcohol.

BACKGROUND: Perillyl alcohol (POH) is a aroma monoterpene commonly obtained from various plants' essential oil. Recently, increasing researches have demonstrated that POH may be useful, not only as flavor compound, but also as bioactive molecule because of a variety of biological activities. PURPOSE: The aim of this review is to summarize the production, pharmacological activities and molecular mechanism, active derivatives, toxicity and parmacokinetics, and industrial application of POH. METHODS: A systematic search of published articles up to January 2024 in Web of Science, China Knowledge Network, and PubMed databases is conducted using the following keywords: POH, POH derivatives, biological or pharmacological, production or synthesis, pharmacokinetics, toxicity and application. RESULTS: Biotechnological production is considered to be a potential alternative approach to generate POH. POH provides diverse pharmacological benefits, including anticancer, antimicrobial, insecticidal, antioxidant, anti-inflammatory, hypotensive, vasorelaxant, antinociceptive, antiasthmatic, hepatoprotective effects, etc. The underlying mechanisms of action include modulation of NF-κB, JNK/c-Jun, Notch, Akt/mTOR, PI3K/Akt/eNOS, STAT3, Nrf2 and ERS response pathways, mitigation of mitochondrial dysfunction and membrane integrity damage, and inhibition of ROS accumulation, pro-inflammatory cytokines release and NLRP3 activation. What's more, the proteins or genes influenced by POH against diseases refer to Bax, Bcl-2, cyclin D1, CDK, p21, p53, HIF-1α, AP-1, caspase-3, M6P/IGF2R, PARP, VEGF, etc. Some clinical studies report that intranasal delivery of POH is a safe and effective treatment for cancer, but further clinical investigations are needed to confirm other health benefits of POH in human healthy. Depending on these health-promoting properties together with desirable flavor and safety, POH can be employed as dietary supplement, preservative and flavor additive in food and cosmetic fields, as building block in synthesis fields, as anticancer drug in medicinal fields, and as pesticides and herbicides in agricultural fields. CONCLUSION: This review systematically summarizes the recent advances in POH and highlights its therapeutic effects and potential mechanisms as well as the clinical settings, which is helpful to develop POH into functional food and new candidate drug for prevention and management of diseases. Future studies are needed to conduct more biological activity studies of POH and its derivatives, and check their clinical efficacy and potential side effects.

Advantages and Challenges of Total-Body PET/CT at a Tertiary Cancer Center: Insights from Sun Yat-sen University Cancer Center.

In recent decades, researchers worldwide have directed their efforts toward enhancing the quality of PET imaging. The detection sensitivity and image resolution of conventional PET scanners with a short axial field of view have been constrained, leading to a suboptimal signal-to-noise ratio. The advent of long-axial-field-of-view PET scanners, exemplified by the uEXPLORER system, marked a significant advancement. Total-body PET imaging possesses an extensive scan range of 194 cm and an ultrahigh detection sensitivity, and it has emerged as a promising avenue for improving image quality while reducing the administered radioactivity dose and shortening acquisition times. In this review, we elucidate the application of the uEXPLORER system at the Sun Yat-sen University Cancer Center, including the disease distribution, patient selection workflow, scanning protocol, and several enhanced clinical applications, along with encountered challenges. We anticipate that this review will provide insights into routine clinical practice and ultimately improve patient care.

Potential correlations between asymmetric disruption of functional connectivity and metabolism in major depressive disorder.

OBJECTIVE: Previous research has suggested a connection between major depressive disorder (MDD) and certain comorbidities, including gastrointestinal issues, thyroid dysfunctions, and glycolipid metabolism abnormalities. However, the relationships between these factors and asymmetrical alterations in functional connectivity (FC) in adults with MDD remain unclear. METHOD: We conducted a study on a cohort of 42 MDD patients and 42 healthy controls (HCs). Participants underwent comprehensive clinical assessments, including evaluations of blood lipids and thyroid hormone levels, as well as resting-state functional magnetic resonance imaging (Rs-fMRI) scans. Data analysis involved correlation analysis to compute the parameter of asymmetry (PAS) for the entire brain's functional connectome. We then examined the interrelationships between abnormal PAS regions in the brain, thyroid hormone levels, and blood lipid levels. RESULTS: The third-generation ultra-sensitive thyroid stimulating hormone (TSH3UL) level was found to be significantly lower in MDD patients compared to HCs. The PAS score of the left inferior frontal gyrus (IFG) decreased, while the bilateral posterior cingulate cortex (Bi-PCC) PAS increased in MDD patients relative to HCs. Notably, the PAS score of the left IFG negatively correlated with both TSH and total cholesterol (CHOL) levels. However, these correlations lose significance after the Bonferroni correction. CONCLUSION: MDD patients demonstrated abnormal asymmetry in resting-state FC (Rs-FC) within the fronto-limbic system, which may be associated with CHOL and thyroid hormone levels.

Isoprenoid CARTs: In Vitro and In Vivo mRNA Delivery by Charge-Altering Releasable Transporters Functionalized with Archaea-inspired Branched Lipids.

The delivery of oligonucleotides across biological barriers is a challenge of unsurpassed significance at the interface of materials science and medicine, with emerging clinical utility in prophylactic and therapeutic vaccinations, immunotherapies, genome editing, and cell rejuvenation. Here, we address the role of readily available branched lipids in the design, synthesis, and evaluation of isoprenoid charge-altering releasable transporters (CARTs), a pH-responsive oligomeric nanoparticle delivery system for RNA. Systematic variation of the lipid block reveals an emergent relationship between the lipid block and the neutralization kinetics of the polycationic block. Unexpectedly, iA21A11, a CART with the smallest lipid side chain, isoamyl-, was identified as the lead isoprenoid CART for the in vitro transfection of immortalized lymphoblastic cell lines. When administered intramuscularly in a murine model, iA21A11-mRNA complexes induce higher protein expression levels than our previous lead CART, ONA. Isoprenoid CARTs represent a new delivery platform for RNA vaccines and other polyanion-based therapeutics.

Key Aroma Differences in Volatile Compounds of Aged Feng-Flavored Baijiu Determined Using Sensory Descriptive Analysis and GC×GC-TOFMS.

Sensory descriptive analysis of aged feng-flavored Baijiu liquor indicated notable differences in samples of different ages. The samples of freshly distilled Baijiu and those with shorter storage times exhibit bran and fresh green flavors, whereas, with increasing storage time, honey, sweet, and floral fragrances are gradually enhanced. Samples of feng-flavored Baijiu were prepared using headspace solid-phase microextraction, followed by comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry. A total of 496 compounds were identified in all samples, mainly categorized as 14 groups of substances, including esters and aldehydes. Interestingly, 42 of these substances were found in Feng-flavored Baijiu for the first time. Chemometrics was used to analyze the key differential compounds. First, 143 differential compounds closely related to aging were preliminarily screened, and principal component analysis revealed that these compounds were separated by baijiu age. Then, 65 differential compounds were selected by partial least squares discriminant analysis. Furthermore, 43 key differential compounds were selected by combined analysis with variable importance in projection and Pearson correlation coefficients. Partial least squares regression was used to study the correlation between the sensory properties and key differential compounds, and the results indicated that most compounds were closely related to the aging period of the Baijiu. The results of this study provide a theoretical basis and reference for flavor research on feng-flavored Baijiu.

Organ- and Cell-Selective Delivery of mRNA In Vivo Using Guanidinylated Serinol Charge-Altering Releasable Transporters.

Selective RNA delivery is required for the broad implementation of RNA clinical applications, including prophylactic and therapeutic vaccinations, immunotherapies for cancer, and genome editing. Current polyanion delivery relies heavily on cationic amines, while cationic guanidinium systems have received limited attention due in part to their strong polyanion association, which impedes intracellular polyanion release. Here, we disclose a general solution to this problem in which cationic guanidinium groups are used to form stable RNA complexes upon formulation but at physiological pH undergo a novel charge-neutralization process, resulting in RNA release. This new delivery system consists of guanidinylated serinol moieties incorporated into a charge-altering releasable transporter (GSer-CARTs). Significantly, systematic variations in structure and formulation resulted in GSer-CARTs that exhibit highly selective mRNA delivery to the lung (∼97%) and spleen (∼98%) without targeting ligands. Illustrative of their breadth and translational potential, GSer-CARTs deliver circRNA, providing the basis for a cancer vaccination strategy, which in a murine model resulted in antigen-specific immune responses and effective suppression of established tumors.

Construction of hierarchical porous and polydopamine/salicylaldoxime functionalized zeolitic imidazolate framework-8 via controlled etching for uranium adsorption.

Efficient uranium extraction from seawater is critical for the development of the nuclear industry. Herein, a polydopamine/salicylaldoxime decorated hierarchical zeolitic imidazolate framework-8 (H-PDA/SA-ZIF-8) is constructed by using a controlled etching process. Benefiting from the combination of PDA/SA and the zeolitic imidazolate framework-8 (ZIF-8), as well as a controlled etching process, the H-PDA/SA-ZIF-8 possesses multiaffinity sites, excellent specific surface area (1234.92 m2 g-1), and a hierarchical pore structure. The H-PDA/SA-ZIF-8 exhibits excellent adsorption capacity (Qm = 869.6 mg g-1), selectivity, and reusability in uranium adsorption. The adsorption process of H-PDA/SA-ZIF-8 fits very well with the Langmuir isotherm model and pseudo-second-order models, and the adsorption process equilibrates within 20 min (C0 = 20 mg L-1). Furthermore, the H-PDA/SA-ZIF-8 shows remarkable antibacterial ability. Impressively, the adsorption capacity of H-PDA/SA-ZIF-8 to uranium in natural seawater reaches 6.9 mg g-1 after circulation for 15 days. Therefore, the H-PDA/SA-ZIF-8 is a promising and fascinating material for uranium extraction from natural seawater.

Joint genotypic and phenotypic outcome modeling improves base editing variant effect quantification.

CRISPR base editing screens enable analysis of disease-associated variants at scale; however, variable efficiency and precision confounds the assessment of variant-induced phenotypes. Here, we provide an integrated experimental and computational pipeline that improves estimation of variant effects in base editing screens. We use a reporter construct to measure guide RNA (gRNA) editing outcomes alongside their phenotypic consequences and introduce base editor screen analysis with activity normalization (BEAN), a Bayesian network that uses per-guide editing outcomes provided by the reporter and target site chromatin accessibility to estimate variant impacts. BEAN outperforms existing tools in variant effect quantification. We use BEAN to pinpoint common regulatory variants that alter low-density lipoprotein (LDL) uptake, implicating previously unreported genes. Additionally, through saturation base editing of LDLR, we accurately quantify missense variant pathogenicity that is consistent with measurements in UK Biobank patients and identify underlying structural mechanisms. This work provides a widely applicable approach to improve the power of base editing screens for disease-associated variant characterization.

Aristolochic acid induces acute kidney injury through ferroptosis.

Aristolochic acid (AA)-induced acute kidney injury (AKI) presents with progressive decline in renal function and rapid progression to end-stage renal disease. Among the multiple mechanisms identified in AKI, ferroptosis has been shown to be involved in various forms of AKI. But few studies have elucidated the role of ferroptosis in AA-induced AKI. In this study, we investigated the role of ferroptosis in AA-induced acute renal tubular injury in vivo and in vitro. Mice with acute aristolochic acid nephropathy showed increased malondialdehyde levels, aggravated lipid peroxidation, decreased superoxide dismutase activity, and glutathione depletion. The expression of glutathione peroxidase 4 was decreased and the expression of acyl-CoA synthetase long-chain family member 4 was increased. Inhibition of ferroptosis by ferrostatin-1 significantly improved the renal function, reduced histopathological lesions, partially alleviated lipid peroxidation, and restored the antioxidant capacity. In vitro studies also revealed that AA significantly reduced cell viability, induced reactive oxygen species production, increased intracellular iron level and decreased ferroptosis-related protein expression. Inhibition of ferroptosis significantly increased cell viability and attenuated AA-induced renal tubular epithelial cell injury. It is suggested that ferroptosis plays an important role in AA-induced acute tubular injury. And inhibition of ferroptosis may exert renoprotective effects possibly by preventing lipid peroxidation, restoring the antioxidant activity or regulating iron metabolism.

Protein neddylation and its role in health and diseases.

NEDD8 (Neural precursor cell expressed developmentally downregulated protein 8) is an ubiquitin-like protein that is covalently attached to a lysine residue of a protein substrate through a process known as neddylation, catalyzed by the enzyme cascade, namely NEDD8 activating enzyme (E1), NEDD8 conjugating enzyme (E2), and NEDD8 ligase (E3). The substrates of neddylation are categorized into cullins and non-cullin proteins. Neddylation of cullins activates CRLs (cullin RING ligases), the largest family of E3 ligases, whereas neddylation of non-cullin substrates alters their stability and activity, as well as subcellular localization. Significantly, the neddylation pathway and/or many neddylation substrates are abnormally activated or over-expressed in various human diseases, such as metabolic disorders, liver dysfunction, neurodegenerative disorders, and cancers, among others. Thus, targeting neddylation becomes an attractive strategy for the treatment of these diseases. In this review, we first provide a general introduction on the neddylation cascade, its biochemical process and regulation, and the crystal structures of neddylation enzymes in complex with cullin substrates; then discuss how neddylation governs various key biological processes via the modification of cullins and non-cullin substrates. We further review the literature data on dysregulated neddylation in several human diseases, particularly cancer, followed by an outline of current efforts in the discovery of small molecule inhibitors of neddylation as a promising therapeutic approach. Finally, few perspectives were proposed for extensive future investigations.

Effects of acidification by traditional Jiaozi starter and neutralization with alkali (Na2CO3) on whole wheat dough properties.

BACKGROUND: Whole wheat steamed bread has been recommended for its potential nutritional benefits to human health. Given the positive role of both organic acid and alkali in improving dough development and product quality, the present study investigated the effects of neutralization by addition of alkali (Na2CO3) after dough acidification with traditional Jiaozi starter on the properties of whole wheat dough. RESULTS: The population of yeast and lactic acid bacteria and the acidification level of the dough increased significantly after fermentation with Jiaozi. Incorporation of alkali greatly improved the leavening capacity of the remixed dough and the quality of steamed bread. Jiaozi fermentation and alkali addition changed the water distribution patterns (T2) and affected the secondary structures of gluten protein, starch crystallinity and pasting properties. The storage modulus (G') of the dough increased significantly with the alkali addition, which could be attributed to the promoted cross-linking of the gluten structure and the altered hydration state of the macromolecules. CONCLUSION: The results of the present study indicate that a combination of Jiaozi fermentation and alkali addition could improve the technological properties of whole wheat dough and the quality of steamed bread. The results will help us to further explore the potential application of moderate acidification and alkali addition in the production of leavened whole wheat products. © 2024 Society of Chemical Industry.

Serum fibroblast growth factor 23 concentration and the risk of mortality in patients undergoing peritoneal dialysis.

BACKGROUND: Fibroblast growth factor 23 (FGF23) is a phosphate-regulating hormone that is secreted in large amounts early in chronic kidney disease. In this cohort, we aimed to investigate the association between serum FGF23 concentration and mortality in patients undergoing peritoneal dialysis (PD). METHODS: Serum FGF23 level was determined by enzyme-linked immunosorbent assay (ELISA) in a large 15-year prospective cohort study of PD patients with stored serum samples at baseline. Kaplan-Meier survival curves and Cox proportional hazards models were performed to characterise the relationship of FGF23 with mortality. RESULTS: A total of 737 incident PD patients were analysed. The baseline median FGF23 concentration was 683.2 (518.5-896.2) pg/mL. Age, serum phosphorus, high-density lipoprotein cholesterol and high-sensitivity C-reactive protein were independently correlated with serum FGF23 concentration. During a median follow-up of 66.7 (41.1-95.4) months, 171 of the 737 participants (23.2%) died, including 84 (49.1%) cardiovascular disease-related and 50 (29.2%) infection-related deaths. Multivariable Cox regression analysis showed that the adjusted hazard ratios of the highest tertile of serum FGF23 compared with those in the lowest tertile were 1.36 (95% confidence interval (CI): 0.89-2.07; p = 0.154), 0.75 (95% CI: 0.40-1.38; p = 0.353) and 2.66 (95% CI: 1.15-6.15; p = 0.022) for all-cause, cardiovascular disease-related and infection-related mortality, respectively. CONCLUSION: High serum FGF23 concentration is associated with a higher risk of infection-related death for incident PD patients.

Evaluation of the hepatotoxicity of Psoralea corylifolia L. based on a zebrafish model.

Objective: Psoralea corylifolia L. (FP) has received increasing attention due to its potential hepatotoxicity. Methods: In this study, zebrafish were treated with different concentrations of an aqueous extract of FP (AEFP; 40, 50, or 60 µg/mL), and the hepatotoxic effects of tonicity were determined by the mortality rate, liver morphology, fluorescence area and intensity of the liver, biochemical indices, and pathological tissue staining. The mRNA expression of target genes in the bile acid metabolic signaling pathway and lipid metabolic pathway was detected by qPCR, and the mechanism of toxicity was initially investigated. AEFP (50 µg/mL) was administered in combination with FXR or a peroxisome proliferator-activated receptor α (PPARα) agonist/inhibitor to further define the target of toxicity. Results: Experiments on toxic effects showed that, compared with no treatment, AEFP administration resulted in liver atrophy, a smaller fluorescence area in the liver, and a lower fluorescence intensity (p < 0.05); alanine transaminase (ALT), aspartate transaminase (AST), and γ-GT levels were significantly elevated in zebrafish (p < 0.01), and TBA, TBIL, total cholesterol (TC), TG, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were elevated to different degrees (p < 0.05); and increased lipid droplets in the liver appeared as fatty deposits. Molecular biological validation revealed that AEFP inhibited the expression of the FXR gene, causing an increase in the expression of the downstream genes SHP, CYP7A1, CYP8B1, BSEP, MRP2, NTCP, peroxisome proliferator-activated receptor γ (PPARγ), ME-1, SCD-1, lipoprotein lipase (LPL), CPT-1, and CPT-2 and a decrease in the expression of PPARα (p < 0.05). Conclusion: This study demonstrated that tonic acid extracts are hepatotoxic to zebrafish through the inhibition of FXR and PPARα expression, thereby causing bile acid and lipid metabolism disorders.

Molecular insights into inhibiting effects of lignin on cellulase investigated by molecular dynamics simulation.

The hydrolysis of lignocellulose into fermentable monosaccharides using cellulases represents a critical stage in lignocellulosic bioconversion. However, the inactivation of cellulase in the presence of lignin is attributed to the high cost of biofinery. To address this challenge, a comprehensive investigation into the structure-function relationship underlying lignin-driven cellulase inactivation is essential. In this study, molecular docking and molecular dynamics (MD) simulations were employed to explore the impacts of lignin fragments on the catalytic efficiency of cellulase at the atomic level. The findings revealed that soluble lignin fragments and cellulose could spontaneously form stable complexes with cellulase, indicating a competitive binding scenario. The enzyme's structure remained unchanged upon binding to lignin. Furthermore, specific amino acid residues have been identified as involved in interactions with lignin and cellulose. Hydrophobic interactions were found to dominate the binding of lignin to cellulase. Based on the mechanisms underlying the interactions between lignin fragments and cellulase, decreased hydrophobicity and change in the charge of lignin may mitigate the inhibition of cellulase. Furthermore, site mutations and chemical modification are also feasible to improve the efficiency of cellulase. This study may contribute valuable insights into the design of more lignin-resistant enzymes and the optimization of lignocellulosic pretreatment technologies.Communicated by Ramaswamy H. Sarma.

The enhanced hepatotoxicity of isobavachalcone in depigmented zebrafish due to calcium signaling dysregulation and lipid metabolism disorder.

Isobavachalcone (IBC) is a flavonoid component derived from Psoraleae Fructus that can increase skin pigmentation and treat vitiligo. However, IBC has been reported to be hepatotoxic. Current studies on IBC hepatotoxicity are mostly on normal organisms but lack studies on hepatotoxicity in patients. This study established the depigmented zebrafish model by using phenylthiourea (PTU) and investigated the difference in hepatotoxicity between normal and depigmented zebrafish caused by IBC and the underlying mechanism. Morphological, histological, and ultrastructural examination and RT-qPCR verification were used to evaluate the effects of IBC on the livers of zebrafish larvae. IBC significantly decreased liver volume, altered lipid metabolism, and induced pathological and ultrastructural changes in the livers of zebrafish with depigmentation compared with normal zebrafish. The RNA-sequencing and RT-qPCR results showed that the difference in hepatotoxicity between normal and depigmented zebrafish caused by IBC was closely related to the calcium signaling pathway, lipid decomposition and metabolism, and oxidative stress. This work delved into the mechanism of the enhanced IBC-induced hepatotoxicity in depigmented zebrafish and provided a new insight into the hepatotoxicity of IBC.