Gas6/AXL Alleviates Hepatic Ischemia/Reperfusion Injury by Inhibiting Ferroptosis via the PI3K/AKT Pathway.

BACKGROUND: Hepatic ischemia/reperfusion (I/R) injury is a major cause of complications in clinical liver surgery. AXL receptor tyrosine kinase (AXL) is a member of the TAM receptor tyrosine kinase family (TYRO3, AXL, and MERTK). Our previous study has shown that AXL expression was markedly upregulated in liver transplantation patients. However, the underlying mechanism of AXL in hepatic I/R injury remains unclear. METHODS: A mouse liver warm I/R model and a primary hepatocyte hypoxia/reoxygenation model were established to investigate the role of AXL activation and ferroptosis in hepatic I/R injury by pretreating with recombinant mouse growth arrest-specific protein 6 (AXL activator) or R428 (AXL inhibitor). Moreover, we used LY294002 (phosphatidylinositol 3-kinase [PI3K] inhibitor) to evaluate the relationship between the PI3K/AKT (the Ser and Thr kinase AKT) pathway and ferroptosis in hepatic I/R injury. RESULTS: Hepatic I/R injury decreased phosphorylation AXL expression and enhanced ferroptosis in liver transplantation patients and hepatic I/R-subjected mice. AXL activation attenuated lipid peroxidation and ferroptosis in hepatic I/R injury in vivo and in vitro. Inhibition of AXL activation exacerbated liver pathological damage and liver dysfunction, as well as iron accumulation and lipid peroxidation in hepatic I/R injury. Mechanistically, activated growth arrest-specific protein 6/AXL and its downstream PI3K/AKT signaling pathway inhibited ferroptosis during hepatic I/R injury. CONCLUSIONS: AXL activation protects against hepatic I/R injury by preventing ferroptosis through the PI3K/AKT pathway. This study is the first investigation on the AXL receptor and ferroptosis, and activating AXL to mitigate ferroptosis may be an innovative therapeutic strategy to combat hepatic I/R injury.

ZNF397 Deficiency Triggers TET2-driven Lineage Plasticity and AR-Targeted Therapy Resistance in Prostate Cancer.

Cancer cells exhibit phenotypical plasticity and epigenetic reprogramming, which allows them to evade lineage-dependent targeted treatments by adopting lineage plasticity. The underlying mechanisms by which cancer cells exploit the epigenetic regulatory machinery to acquire lineage plasticity and therapy resistance remain poorly understood. We identified Zinc Finger Protein 397 (ZNF397) as a bona fide coactivator of the androgen receptor (AR), essential for the transcriptional program governing AR-driven luminal lineage. ZNF397 deficiency facilitates the transition of cancer cell from an AR-driven luminal lineage to a Ten-Eleven Translocation 2 (TET2)-driven lineage plastic state, ultimately promoting resistance to therapies inhibiting AR signaling. Intriguingly, our findings indicate that a TET2 inhibitor can eliminate the resistance to AR targeted therapies in ZNF397-deficient tumors. These insights uncover a novel mechanism through which prostate cancer acquires lineage plasticity via epigenetic rewiring and offer promising implications for clinical interventions designed to overcome therapy resistance dictated by lineage plasticity.

Role of the GLP2-Wnt1 axis in silicon-rich alkaline mineral water maintaining intestinal epithelium regeneration in piglets under early-life stress.

Stress-induced intestinal epithelial injury (IEI) and a delay in repair in infancy are predisposing factors for refractory gut diseases in adulthood, such as irritable bowel syndrome (IBS). Hence, it is necessary to develop appropriate mitigation methods for mammals when experiencing early-life stress (ELS). Weaning, as we all know, is a vital procedure that all mammalian newborns, including humans, must go through. Maternal separation (MS) stress in infancy (regarded as weaning stress in animal science) is a commonly used ELS paradigm. Drinking silicon-rich alkaline mineral water (AMW) has a therapeutic effect on enteric disease, but the specific mechanisms involved have not been reported. Herein, we discover the molecular mechanism by which silicon-rich AMW repairs ELS-induced IEI by maintaining intestinal stem cell (ISC) proliferation and differentiation through the glucagon-like peptide (GLP)2-Wnt1 axis. Mechanistic study showed that silicon-rich AMW activates GLP2-dependent Wnt1/ß-catenin pathway, and drives ISC proliferation and differentiation by stimulating Lgr5+ ISC cell cycle passage through the G1-S-phase checkpoint, thereby maintaining intestinal epithelial regeneration and IEI repair. Using GLP2 antagonists (GLP23-33) and small interfering RNA (SiWnt1) in vitro, we found that the GLP2-Wnt1 axis is the target of silicon-rich AMW to promote intestinal epithelium regeneration. Therefore, silicon-rich AMW maintains intestinal epithelium regeneration through the GLP2-Wnt1 axis in piglets under ELS. Our research contributes to understanding the mechanism of silicon-rich AMW promoting gut epithelial regeneration and provides a new strategy for the alleviation of ELS-induced IEI.

Di (2-ethylhexyl) phthalate induced lipophagy-related renal ferroptosis in quail (Coturnix japonica).

Di(2-ethylhexyl) phthalate (DEHP) is a synthetic chemical applied as a plasticizer. As an environmental toxicant, DEHP poses a serious health threat. Many studies have revealed that DEHP can cause lead to various degrees of damage to the kidney. However, the evidence of DEHP-induced renal ferroptosis has not been reported. The purpose of this work was to probe the specific role of lipophagy in DEHP-induced renal injury and to investigate the relationship between lipophagy and ferroptosis. Quail were treated with DEHP (250 mg/kg BW/day, 500 mg/kg BW/day and 750 mg/kg BW/day) for 45 days. Microstructural and ultrastructural observations showed that DEHP caused damage to glomerular and tubular cells, and autophagy with multilayer structures were observed, suggesting that DEHP can induce lipophagy. The results indicated that the iron homeostasis was abnormal and the lipid peroxidation was increased. SLC7A11 and SLC3A2 were down-regulated. PTGS2, ACSL4 and LPCAT3 were elevated. In conclusion, DEHP could induce lipid peroxidation, lead to ferroptosis, and damage renal cells. Therefore, the relationship between lipophagy and ferroptosis was elucidated, which provided a new basis for intervention and prevention of DEHP increased diseases.

Essential oils improve nursery pigs' performance and appetite via modulation of intestinal health and microbiota.

Optimal intestinal health and functionality are essential for animal health and performance, and simultaneously intestinal nutrient transporters and intestinal peptides are also involved in appetite and feed intake control mechanisms. Given the potential of essential oil (EO) in improving animal performance and improving feed palatability, we hypothesized that dietary supplementation of cinnamaldehyde and carvacrol could improve performance and appetite of nursery pigs by modulating intestinal health and microbiota. Cinnamaldehyde (100 mg/kg), carvacrol (100 mg/kg), and their mixtures (including 50 mg/kg cinnamaldehyde and 50 mg/kg carvacrol) were supplemented into the diets of 240 nursery pigs for 42 d, and data related to performance were measured. Thereafter, the influence of EO on intestinal health, appetite and gut microbiota and their correlations were explored. EO supplementation increased (P < 0.05) the body weight, average daily gain (ADG) and average daily feed intake (ADFI) of piglets, and reduced (P < 0.05) diarrhea rates in nursery pigs. Furthermore, EO increased (P < 0.05) the intestinal absorption area and the abundance of tight junction proteins, and decreased (P < 0.05) intestinal permeability and local inflammation. In terms of intestinal development and the mucus barrier, EO promoted intestinal development and increased (P < 0.05) the number of goblet cells. Additionally, we found that piglets in the EO-supplemented group had upregulated (P < 0.05) levels of transporters and digestive enzymes in the intestine, which were significantly associated with daily gain and feed utilization. In addition, EO supplementation somewhat improved appetite in nursery pigs, increased the diversity of the gut microbiome and the abundance of beneficial bacteria, and there was a correlation between altered bacterial structure and appetite-related hormones. These findings indicate that EO is effective in promoting growth performance and nutrient absorption as well as in regulating appetite by improving intestinal health and bacterial structure.

Bisphenol A and its alternatives bisphenol S and F exposure with serum uric acid levels, hyperuricemia, and gout prevalence among US adults: a nationally representative cross-sectional study.

BACKGROUND: Recent studies suggested inconclusive associations between bisphenols exposure and hyperuricemia risk. Our objective was to assess the potential association of bisphenol A (BPA) and its substitutes bisphenol S and F (BPS and BPF) exposure with serum uric acid (SUA) levels, hyperuricemia, and gout prevalence among US adults within the NHANES 2013-2016 datasets. METHODS: Multivariable linear and logistic regression models were used to explore the associations of urinary bisphenols concentrations with SUA levels, hyperuricemia, and gout prevalence, in total population and different sex groups. The restricted cubic spline (RCS) model was used to explore the dose-response relationship. RESULTS: In total population, doubling of urinary BPS and ∑BPs concentrations showed associations with an increase of 2.64 µmol/L (95% CI: 0.54, 4.74) and 3.29 µmol/L (95% CI: 0.59, 5.99) in SUA levels, respectively. The RCS model indicated a significantly "J"-shaped dose-response relationship between BPS exposure and SUA levels. Compared to the reference group of urinary BPS, males in the highest quartile displayed a 13.06 µmol/L (95% CI: 0.75, 25.37) rise in SUA levels. For females, doubling of urinary BPS concentrations was associated with a 3.30 µmol/L (95% CI: 0.53, 6.07) increase in SUA levels, with a significant linear dose-response relationship. In total population, doubling of urinary BPA concentrations showed a 1.05-fold (95% CI: 0.97, 1.14) adjusted risk of having hyperuricemia, with an inverted "U" curve. Doubling of urinary ∑BPs concentrations was associated with a 1.05-fold (95% CI: 0.96, 1.14) adjusted risk of hyperuricemia in total population, with a significant monotonic dose-response relationship. In females, doubling of urinary BPS concentrations was associated with a 1.45-fold (95% CI: 1.01, 2.08) adjusted increased risk of having gout, with a "J" shaped relationship. CONCLUSIONS: BPA and BPS exposure to some extent were associated with elevated SUA levels and increased risk of hyperuricemia, with different dose-response relationships and sex differences.

UBE2J1 is the E2 ubiquitin-conjugating enzyme regulating androgen receptor degradation and antiandrogen resistance.

Prostate cancer (PCa) is primarily driven by aberrant Androgen Receptor (AR) signaling. Although there has been substantial advancement in antiandrogen therapies, resistance to these treatments remains a significant obstacle, often marked by continuous or enhanced AR signaling in resistant tumors. While the dysregulation of the ubiquitination-based protein degradation process is instrumental in the accumulation of oncogenic proteins, including AR, the molecular mechanism of ubiquitination-driven AR degradation remains largely undefined. We identified UBE2J1 as the critical E2 ubiquitin-conjugating enzyme responsible for guiding AR ubiquitination and eventual degradation. The absence of UBE2J1, found in 5-15% of PCa patients, results in disrupted AR ubiquitination and degradation. This disruption leads to an accumulation of AR proteins, promoting resistance to antiandrogen treatments. By employing a ubiquitination-based AR degrader to adeptly restore AR ubiquitination, we reestablished AR degradation and inhibited the proliferation of antiandrogen-resistant PCa tumors. These findings underscore the fundamental role of UBE2J1 in AR degradation and illuminate an uncharted mechanism through which PCa maintains heightened AR protein levels, fostering resistance to antiandrogen therapies.

Nano-selenium alleviates cadmium-induced neurotoxicity in cerebrum via inhibiting gap junction protein connexin 43 phosphorylation.

Cadmium (Cd) as a ubiquitous toxic heavy metal is reported to affect the nervous system. Selenium (Se) has been shown to have antagonistic effects against heavy metal toxicity. In addition, it shows potential antioxidant and anti-inflammatory properties. Thus, the purpose of this study was to determine the possible mechanism of brain injury after high Cd exposure and the mitigation of Nano-selenium (Nano-Se) against Cd-induced brain injury. In this study, the Cd-treated group showed a decrease in the number of neurons in brain tissue, swelling of the endoplasmic reticulum and mitochondria, and the formation of autophagosomes. Nano-Se intervention restored Cd-caused alterations in neuronal morphology, endoplasmic reticulum, and mitochondrial structure, thereby reducing neuronal damage. Furthermore, we found that some differentially expressed genes were involved in cell junction and molecular functions. Subsequently, we selected eleven (11) related differentially expressed genes for verification. The qRT-PCR results revealed the same trend of results as determined by RNA-Seq. Our findings also showed that Nano-Se supplementation alleviated Cx43 phosphorylation induced by Cd exposure. Based on immunofluorescence colocalization it was demonstrated that higher expression of GFAP and lower expressions of Cx43 were restored by Nano-Se supplementation. In conclusion, the data presented in this study establish a direct association between the phosphorylation of Cx43 and the occurrence of autophagy and neuroinflammation. However, it is noteworthy that the introduction of Nano-Se supplementation has been observed to mitigate these alterations. These results elucidate the relieving effect of Nano-Se on Cd exposure-induced brain injury.

Antihyperuricemic activity and inhibition mechanism of xanthine oxidase inhibitory peptides derived from whey protein by virtual screening.

Xanthine oxidase (XO), a rate-limiting enzyme in uric acid production, is the pivotal therapeutic target for gout and hyperuricemia. In this study, 57 peptides from α-lactalbumin and ß-lactoglobulin were obtained via virtual enzymatic hydrolysis, and 10 XO inhibitory peptides were virtually screened using molecular docking. Then toxicity, allergenicity, solubility, and isoelectric point of the obtained 10 novel peptides were evaluated by in silico tools. The XO activity of these synthetic peptides was tested using an in vitro assay by high-performance liquid chromatography. Their inhibitory mechanism was further explored by molecular docking. The results showed that 4 peptides GL, PM, AL, and AM exhibited higher inhibitory activity, and their half maximal inhibitory concentration in vitro was 10.20 ± 0.89, 23.82 ± 0.94, 34.49 ± 0.89, and 40.45 ± 0.92 mM, respectively. The peptides fitted well with XO through hydrogen bond, hydrophobic interaction, and van der Waals forces, and amino acid residues Glu802, Leu873, Arg880, and Pro1076 played an important role in this process. Overall, this study indicated 4 novel peptides GL, PM, AL, and AM from whey protein exhibited XO inhibitory activity, and they might be useful and safe XO inhibitors for hyperuricemia prevention and treatment.

ZNF397 Loss Triggers TET2-driven Epigenetic Rewiring, Lineage Plasticity, and AR-targeted Therapy Resistance in AR-dependent Cancers.

Cancer cells exhibit phenotypical plasticity and epigenetic reprogramming, which allows them to evade lineage-dependent targeted treatments by adopting lineage plasticity. The underlying mechanisms by which cancer cells exploit the epigenetic regulatory machinery to acquire lineage plasticity and therapy resistance remain poorly understood. We identified Zinc Finger Protein 397 (ZNF397) as a bona fide co-activator of the androgen receptor (AR), essential for the transcriptional program governing AR-driven luminal lineage. ZNF397 deficiency facilitates the transition of cancer cell from an AR-driven luminal lineage to a Ten-Eleven Translocation 2 (TET2)-driven lineage plastic state, ultimately promoting resistance to therapies inhibiting AR signaling. Intriguingly, our findings indicate that TET2 inhibitor can eliminate the AR targeted therapies resistance in ZNF397-deficient tumors. These insights uncover a novel mechanism through which prostate and breast cancers acquire lineage plasticity via epigenetic rewiring and offer promising implications for clinical interventions designed to overcome therapy resistance dictated by lineage plasticity. Statement of Significance: This study reveals a novel epigenetic mechanism regulating tumor lineage plasticity and therapy response, enhances understanding of drug resistance and unveils a new therapeutic strategy for prostate cancer and other malignancies. Our findings also illuminate TET2's oncogenic role and mechanistically connect TET2-driven epigenetic rewiring to lineage plasticity and therapy resistance.

Bioinspired fine-tuning of the mechanical rigidity of SNEDDS for the efficient crossing of multiple gastrointestinal barriers.

Nanoproperties, such as size, charge, and rigidity, have been demonstrated to be crucial for nanovehicles to overcome numerous gastrointestinal obstacles. However, the facile approach of modifying the rigidity of nanovehicles remains scarce, limiting understanding of how rigidity impacts their oral delivery. Inspired by the fact that cellular phospholipid content regulates plasma membrane rigidity, the rigidity of self-nanoemulsifiying drug delivery system (SNEDDS) could be fine-tuned via phosphocholine content while their size and zeta potential remain unchanged, using insulin as a model drug. Notably, soft SNEDDS exerted longer gastrointestinal transit time, higher drug release rate, stronger gastrointestinal stability and relatively lower mucus permeation but superior epithelial transcytosis than their hard counterparts in a macropinocytosis-dependent manner. The rigidity-related enhanced transcytosis was attributed to improved endocytosis, lysosome escape capability and exocytosis. Rats with type 1 diabetes exhibited greater oral insulin absorption and blood glucose lowering effect with soft SNEDDS. This study demonstrated the regulatory role of phospholipids in nanovehicle rigidity, which could help develop mechanically optimized nanomedicines in the future.

Loss of SYNCRIP unleashes APOBEC-driven mutagenesis, tumor heterogeneity, and AR-targeted therapy resistance in prostate cancer.

Tumor mutational burden and heterogeneity has been suggested to fuel resistance to many targeted therapies. The cytosine deaminase APOBEC proteins have been implicated in the mutational signatures of more than 70% of human cancers. However, the mechanism underlying how cancer cells hijack the APOBEC mediated mutagenesis machinery to promote tumor heterogeneity, and thereby foster therapy resistance remains unclear. We identify SYNCRIP as an endogenous molecular brake which suppresses APOBEC-driven mutagenesis in prostate cancer (PCa). Overactivated APOBEC3B, in SYNCRIP-deficient PCa cells, is a key mutator, representing the molecular source of driver mutations in some frequently mutated genes in PCa, including FOXA1, EP300. Functional screening identifies eight crucial drivers for androgen receptor (AR)-targeted therapy resistance in PCa that are mutated by APOBEC3B: BRD7, CBX8, EP300, FOXA1, HDAC5, HSF4, STAT3, and AR. These results uncover a cell-intrinsic mechanism that unleashes APOBEC-driven mutagenesis, which plays a significant role in conferring AR-targeted therapy resistance in PCa.

Identification of High Tolerance to Jujube Witches' Broom in Indian Jujube (Ziziphus mauritiana Lam.) and Mining Differentially Expressed Genes Related to the Tolerance through Transcriptome Analysis.

The jujube witches' broom (JWB) disease is a severe threat to jujube trees, with only a few cultivars being genuinely tolerant or resistant to phytoplasma. The defense mechanism of jujube trees against phytoplasma is still unclear. In this study, we aimed to investigate the tolerance mechanism of Indian jujube 'Cuimi' to JWB and identify the key genes that contribute to JWB high tolerance. Based on the symptoms and phytoplasma concentrations after infection, we confirmed the high tolerance of 'Cuimi' to JWB. Comparative transcriptome analysis was subsequently performed between 'Cuimi' and 'Huping', a susceptible cultivar of Chinese jujube. Unique gene ontology (GO) terms were identified in 'Cuimi', such as protein ubiquitination, cell wall biogenesis, cell surface receptor signaling pathway, oxylipin biosynthetic process, and transcription factor activity. These terms may relate to the normal development and growth of 'Cuimi' under phytoplasma infection. We identified 194 differential expressed genes related to JWB high tolerance, involved in various processes, such as reactive oxygen species (ROS), Ca2+ sensors, protein kinases, transcription factors (TFs), lignin, and hormones. Calmodulin-like (CML) genes were significantly down-regulated in infected 'Cuimi'. We speculated that the CML gene may act as a negative regulatory factor related to JWB high tolerance. Additionally, the cinnamoyl-CoA reductase-like SNL6 gene was significantly up-regulated in infected 'Cuimi', which may cause lignin deposition, limit the growth of phytoplasma, and mediate immune response of 'Cuimi' to phytoplasma. Overall, this study provides insights into the contribution of key genes to the high tolerance of JWB in Indian jujube 'Cuimi'.

Nanoselenium Alleviates Cadmium-Induced Cerebral Injury via Regulating Cerebral Metal Transporters and Metal-Regulatory Transcription Factor 1.

Cadmium (Cd) is a hazardous environmental metal that poses a global public health concern due to its high toxic potential. Nanoselenium (Nano-Se) is a nanoform of elemental Se that is widely used to antagonize heavy metal toxicity owing to its high safety margin with low doses. However, the role of Nano-Se in relieving Cd-induced brain damage is unclear. For this study, Cd-exposure-induced cerebral damage was established by using a chicken model. Administration of Nano-Se with Cd significantly decreased the Cd-mediated elevation of cerebral ROS, MDA, and H2O2 levels as well as markedly increased the Cd-mediated reduced activities of antioxidant biomarkers (GPX, T-SOD, CAT, and T-AOC). Accordingly, co-treatment with Nano-Se significantly reduced Cd-mediated increased Cd accumulation and recovered the Cd-induced biometal imbalance, notably Se and Zn. Nano-Se downregulated the Cd-induced upregulation of ZIP8, ZIP10, ZNT3, ZNT5, and ZNT6 and upregulated the Cd-mediated decreased expressions of ATOX1 and XIAP. Nano-Se also increased the Cd-mediated decreased mRNA levels of MTF1 and its target genes MT1 and MT2. Surprisingly, co-treatment with Nano-Se regulated the Cd-induced increased total protein level of MTF1 by reducing its expression. Moreover, altered selenoproteins regulation was recovered after co-treatment with Nano-Se as evidenced by increased expression levels of antioxidant selenoproteins (GPx1-4 and SelW) and Se transport-related selenoproteins (SepP1 and SepP2). The histopathological evaluation and Nissl staining of the cerebral tissues also supported that Nano-Se markedly reduced the Cd-induced microstructural alterations and well preserved the normal histological architectures of the cerebral tissue. Overall, the results of this research reveal that Nano-Se may be beneficial in mitigating Cd-induced cerebral injury in the brains of chickens. This present study provides a basis for preclinical research for its usefulness as a potential therapeutic for the treatment of neurodegeneration in the heavy-metal-induced neurotoxicity.

Bioaccumulation of pharmaceuticals and personal care products (PPCPs) in freshwater pearl mussels Hyriopsis cumingii in Poyang Lake.

Thirty-five PPCPs were measured in representative freshwater pearl mussels (Hyriopsis cumingii) in Poyang Lake, the largest lake of China, as well as their responses to sedimentary PPCPs. We observed 32 PPCPs in soft tissues of mussels at a total concentration of 2721.5 ± 929.3 ng·g-1 dry weight (dw), much higher than those in sediments (21 PPCPs, 273.2 ± 89.4 ng·g-1 dw). Anti-inflammatories were the primary contaminants detected in both sediments and mussels. PPCP concentrations in mussels exhibited significant organ-specific characteristics, and gonads were identified as a hotspot for these contaminants. Correlation analysis showed that gonads were more likely to assimilate triclosan from sediments. Biochemical analysis revealed a higher physiological sensitivity of glutathione synthesis in gonads to sedimentary PPCPs, suggesting the long-term oxidative damage. Our findings highlight the concern on the potential effects of sedimentary PPCPs to propagation of mussels, and emphasize the necessity to formulate strategies for sedimentary PPCPs control targeting a healthy lake.

Effects of dietary supplementation with a carvacrol-cinnamaldehyde-thymol blend on growth performance and intestinal health of nursery pigs.

BACKGROUND: Stress, herd transfer, and food changes experienced by nursery and fattening pigs can lead to reduced performance, reduced digestion and absorption, and impaired intestinal health. Given the role of essential oils in relieving stress and improving animal welfare, we hypothesized that essential oils may improve pig performance via promoting gut health and gut homeostasis laid by EOs supplementation during nursery continuously impacts performance in fattening pigs. RESULTS: A total of 100 piglets (Landrace × Large White; weighted 8.08 ± 0.34 kg, weaned at d 28) were randomly selected and divided into 2 treatments: (1) basal diet (Con); (2) basal diet supplement with 0.1% complex essential oils (CEO). The experiment period was 42 days. Then weaned piglets' growth performance and indications of intestinal health were assessed. Compared to the Con group, dietary supplemented CEO enhanced BW at 14 d (P < 0.05), and increased ADG during 1 ~ 14 d and 1 ~ 42 d (P < 0.05). Furthermore, CEO group had lower FCR during 1 ~ 42 d (P < 0.05). The CEO group also showed higher VH and VH:CD in duodenum and ileum (P < 0.05). Additionally, dietary CEO supplementation improved gut barrier function, as manifested by increased the mRNA expression of tight-junction protein and decreased serum DAO, ET and D-LA levels (P < 0.05). Finally, CEO supplementation alleviated gut inflammation, increased the activity of digestive enzymes. Importantly, piglets supplemented with CEOs during nursery also had better performance during fattening, suggesting that the establishment of intestinal health will also continuously affect subsequent digestion and absorption capacity. In short, dietary supplemented CEO improved performance and gut health via modulating increased intestine absorptive area, barrier integrity, digestive enzyme activity, and attenuating intestine inflammation. Meanwhile, essential oil supplementation during the nursery period also had a favorable effect on the performance of growing pigs. CONCLUSIONS: Therefore, the strategy of adding CEO to pig diets as a growth promoter and enhancing intestinal health is feasible.

Association between blood manganese levels and depressive symptoms among US adults: A nationally representative cross-sectional study.

BACKGROUND: Recent studies indicated that manganese (Mn) levels were inconsistently associated with the prevalence of depression. We aimed to evaluate whether blood Mn concentrations were associated with the risk of depression among US adults. METHODS: Using the NHANES 2011-2019 datasets, we conducted a cross-sectional study in 16,572 eligible participants with complete data on blood Mn concentrations and depression diagnosis. A weighted multivariable logistic model and restricted cubic spline model were applied to explore the association and dose-response relationship of blood Mn concentrations with depression risk in the total population and subgroups. RESULTS: In the total population, compared with the lowest reference group of blood Mn, participants in the second, third, and fourth quartile had an OR of 0.84 (95%CI: 0.66, 1.07), 0.93 (95%CI: 0.73, 1.19) and 0.91 (95%CI: 0.71, 1.15) for depression (ptrend = 0.640). In subgroup analyses, doubling of blood Mn concentrations was associated with a 0.83-fold (95%CI: 0.67, 1.02), 0.30 -fold (0.14, 0.65) decreased risk of depression in females and other ethnic groups, respectively. Significant modification effects of ethnicity on the association of blood Mn concentrations with depression risk were observed. LIMITATIONS: cross-sectional study design and self-reported depressive symptoms. CONCLUSIONS: Elevated blood Mn concentrations were associated with decreased depression risk in females and other specific subgroups. Mn supplementation could be a potential pathway for intervention and prevention of depression.

Cadmium aggravates the blood-brain barrier disruption via inhibition of the Wnt7A/ß-catenin signaling axis.

Cadmium (Cd) is a non-biodegradable widespread environmental pollutant, which can cross the blood-brain barrier (BBB) and cause cerebral toxicity. However, the effect of Cd on the BBB is still unclear. In this study, a total of 80 (1-day-old) Hy-Line white variety chicks (20 chickens/group) were selected and randomly divided into four (4) groups: the control group (Con group) (fed with a basic diet, n = 20), the Cd 35 group (basic diet with 35 mg/kg CdCl2, n = 20), the Cd 70 group (basic diet with 70 mg/kg CdCl2, n = 20) and the Cd 140 group (basic diet with 140 mg/kg CdCl2, n = 20), and fed for 90 days. The pathological changes, factors associated with the BBB, oxidation level and the levels of Wingless-type MMTV integration site family, member 7 A (Wnt7A)/Wnt receptor Frizzled 4 (FZD4)/ß-catenin signaling axis-related proteins in brain tissue were detected. Cd exposure induced capillary damage and neuronal swelling, degeneration and loss of neurons. Gene Set Enrichment Analysis (GSEA) showed the weakened Wnt/ß-catenin signaling axis. The protein expression of the Wnt7A, FZD4, and ß-catenin was decreased by Cd expusure. Inflammation generation and BBB dysfunction were induced by Cd, as manifested by impaired tight junctions (TJs) and adherens junctions (AJs) formation. These findings underscore that Cd induced BBB dysfunction via disturbing Wnt7A/FZD4/ß-catenin signaling axis.

Mitocytosis Is Critical for Phthalate-Induced Injury to the Ovarian Granulosa Cell Layer in Quail (Coturnix japonica).

Phthalates are widely used synthetic chemicals that determine endocrine disruption effects on female reproductivity and oviposition. Our study demonstrated that the mitochondrial quality in ovarian granulosa cells (GCs) is associated with a poor prognosis in female reproduction. However, the molecular mechanism of di-(2-ethylhexyl) phthalate (DEHP) exposure on the quail ovarian GC layer is still unknown. To validate the effects of DEHP on the GC layer, 8 days' old 150 female Japanese quail were treated orally with DEHP (250, 500, and 750 mg/kg BW/day) for 45 days to explore the toxic effects of DEHP on the ovarian GC layer. Histopathological assessment and ultrastructure observation found that DEHP decreased the thickness of the GC layer, resulted in mitochondrial damage, and activated mitocytosis. Additionally, the results further suggested that DEHP impacted the secretion of steroid hormones (reduced FSH, E2, and T levels and boosted Prog, PRL, and LH levels) by triggering mitocytosis (enhanced transcription of MYO19 and protein of KIF5B levels), mitochondrial dynamics (increasing mRNA and protein levels of OPA1, DRP1, MFN1, and MFN2), mitophagy (increasing mRNA and protein levels of Parkin, LC3B, and P62), and inducing GC function disorder. In conclusion, our research provided a new idea to explain the mechanism of DEHP toxicity of the ovarian GC layer in quail and presented insights into the role of mitocytosis in DEHP-induced ovarian GC layer injury.

Interpretable machine learning assisted spectroscopy for fast characterization of biomass and waste.

The combination of machine learning and infrared spectroscopy was reported as effective for fast characterization of biomass and waste (BW). However, this characterization process is lack of interpretability towards its chemical insights, leading to less satisfactory recognition for its reliability. Accordingly, this paper aimed to explore the chemical insights of the machine learning models in the fast characterization process. A novel dimensional reduction method with significant physicochemical meanings was thus proposed, where the high loading spectral peaks of BW were selected as input features. Combined with functional groups attribution of these spectral peaks, the machine learning models established based on the dimensionally reduced spectral data could be explained with clear chemical insights. The performance of classification and regression models between the proposed dimensional reduction method and principal component analysis method was compared. The influence mechanism of each functional group on the characterization results were discussed. CH deformation, CC stretch & CO stretch and ketone/aldehyde CO stretch played essential roles in C, H/ LHV and O prediction, respectively. The results of this work demonstrated the theoretical fundamentals of the machine learning and spectroscopy based BW fast characterization method.