Increased straw return promoted soil organic carbon accumulation in China's croplands over the past 40 years.

Quantifying changes in soil organic carbon (SOC) stocks within croplands across a broad spatiotemporal scale in response to anthropogenic and environmental factors offers valuable insights for sustainable agriculture aimed to improve soil health. Using a validated and widely used soil carbon model RothC, we simulated the SOC dynamics across intensive croplands in China that support ∼22 % of the global population using only 7 % of the global cropland area. The modelling results demonstrate that the optimized RothC effectively captures SOC dynamics measured across 29 long-term field trials during 40 years. Between 1980 and 2020, the average SOC at the top 30 cm in croplands increased from 40 Mg C ha-1 to 49 Mg C ha-1, resulting in a national carbon sequestration of 1100 Tg C, with an average carbon sequestration rate of 27 Tg C yr-1. The annual increase rate of SOC (relative to the SOC stock of the previous year), starting at <0.2 % yr-1 in the 1980s, reached around 0.4 % yr-1 in the 1990s and further rose to about 0.8 % yr-1 in the 2000s and 2010s. Notably, the eastern and southern regions, comprising about 40 % of the croplands, contributed about two-thirds of the national SOC gain. In northeast China, SOC slightly decreased from 58 Mg C ha-1 in 1980 to 57 Mg C ha-1 in 2020, resulting in a total decline of 28 Tg C. Increased organic C inputs, particularly from the straw return, was the crucial factor in SOC increase. Future strategies should focus on region-specific optimization of straw management. Specifically, in northeast China, increasing the proportion of straw returned to fields can prevent further SOC decline. In regions with SOC increase, such as the eastern and southern regions, diversified straw utilization (e.g., bioenergy production), could further mitigate greenhouse gas emissions.

Development and validation of a prenatal predictive nomogram for the risk of NICU admission in infants born to Chinese mothers over 35 years of age: a retrospective cohort study.

BACKGROUND: The rising number of women giving birth at advanced maternal age has posed significant challenges in obstetric care in recent years, resulting in increased incidence of neonatal transfer to the Neonatal Intensive Care Unit (NICU). Therefore, identifying fetuses requiring NICU transfer before delivery is essential for guiding targeted preventive measures. OBJECTIVE: This study aims to construct and validate a nomogram for predicting the prenatal risk of NICU admission in neonates born to mothers over 35 years of age. STUDY DESIGN: Clinical data of 4218 mothers aged ≥ 35 years who gave birth at the Department of Obstetrics of the Second Hospital of Shandong University between January 1, 2017 and December 31, 2021 were reviewed. Independent predictors were identified by multivariable logistic regression, and a predictive nomogram was subsequently constructed for the risk of neonatal NICU admission. RESULTS: Multivariate logistic regression demonstrated that the method of prenatal screening, number of implanted embryos, preterm premature rupture of the membranes, preeclampsia, HELLP syndrome, fetal distress, premature birth, and cause of preterm birth are independent predictors of neonatal NICU admission. Analysis of the nomogram decision curve based on these 8 independent predictors showed that the prediction model has good net benefit and clinical utility. CONCLUSION: The nomogram demonstrates favorable performance in predicting the risk of neonatal NICU transfer after delivery by mothers older than 35 years. The model serves as an accurate and effective tool for clinicians to predict NICU admission in a timely manner.

Fucoidan Supplementation Improves Antioxidant Capacity via Regulating the Keap1/Nrf2 Signaling Pathway and Mitochondrial Function in Low-Weaning Weight Piglets.

Fucoidan (FC) is known for its antioxidant properties, but it has unclear effects and mechanisms on weaned piglets. Two experiments were conducted to determine the optimal FC dosage in piglet diets and its protective effect against lipopolysaccharide (LPS)-induced oxidative stress. In experiment one, 24 low weight weaned piglets were randomly assigned to four dietary treatments: a basal diet (FC 0), or a diet supplemented with 150 (FC 150), 300 (FC 300), or 600 mg/kg FC (FC 600). In experiment two, 72 low-weaning weight piglets were randomly allocated into four treatments: a basal diet (CON), or 300 mg/kg of fucoidan added to a basal diet challenged with LPS (100 µg LPS/kg body weight) or not. The results showed that FC treatments increased the G:F ratio, and dietary FC 300 reduced the diarrhea incidence and increased the plasma IGF-1 concentrations. In addition, FC 300 and FC 600 supplementation increased the plasma SOD activity and reduced the plasma MDA concentration. LPS challenge triggered a strong systemic redox imbalance and mitochondrial dysfunction. However, dietary FC (300 mg/kg) supplementation increased the activity of antioxidant enzymes, including SOD, decreased the MDA concentration in the plasma and liver, down-regulated Keap1 gene expression, and up-regulated Nrf2, CAT, MFN2, SDHA, and UQCRB gene expression in the liver. These results indicated that dietary fucoidan (300 mg/kg) supplementation improved the growth performance and antioxidant capacity of low-weaning weight piglets, which might be attributed to the modulation of the Keap1/Nrf2 signaling pathway and the mitochondrial function in the liver.

Genistein Alleviates Intestinal Oxidative Stress by Activating the Nrf2 Signaling Pathway in IPEC-J2 Cells.

In the weaning period, piglets often face oxidative stress, which will cause increased diarrhea and mortality. Genistein, a flavonoid, which is extracted from leguminous plants, possesses anti-inflammatory and antioxidative bioactivities. However, little is known about whether genistein could attenuate the oxidative stress that occurs in porcine intestinal epithelial cells (IPEC-J2). Herein, this experiment was carried out to investigate the protective effects of genistein in the IPEC-J2 cells oxidative stress model. Our results disclosed that H2O2 stimulation brought about a significant diminution in catalase (CAT) activity and cell viability, as well as an increase in the levels of reactive oxygen species (ROS) in IPEC-J2 cells (p < 0.05), whereas pretreating cells with genistein before H2O2 exposure helped to alleviate the reduction in CAT activity and cell viability (p < 0.05) and the raise in the levels of ROS (p = 0.061) caused by H2O2. Furthermore, H2O2 stimulation of IPEC-J2 cells remarkably suppressed gene level Nrf2 and CAT expression, in addition to protein level Nrf2 expression, but pretreating cells with genistein reversed this change (p < 0.05). Moreover, genistein pretreatment prevented the downregulation of occludin expression at the gene and protein level, and ZO-1 expression at gene level (p < 0.05). In summary, our findings indicate that genistein possesses an antioxidant capacity in IPEC-J2 cells which is effective against oxidative stress; the potential mechanism may involve the Nrf2 signaling pathway. Our findings could offer a novel nutritional intervention strategy to enhance the intestinal health of piglets during the weaning process.

Silybin Alleviated Hepatic Injury by Regulating Redox Balance, Inflammatory Response, and Mitochondrial Function in Weaned Piglets under Paraquat-Induced Oxidative Stress.

Silybin (Si) is the main element of silymarin isolated from the seeds of Silybum marianum L. Gaernt., which has superior antioxidant properties. However, the protective role of Si in maintaining liver health under oxidative stress remains ambiguous. This study aimed to investigate the underlying mechanism of the beneficial effect of dietary Si against hepatic oxidative injury induced by paraquat (PQ) in weaned piglets. A total of 24 piglets were randomly allocated to four treatments with six replicates per treatment and 1 piglet per replicate: the control group; Si group; PQ group; and Si + PQ group. Piglets in the control group and PQ group were given a basal diet, while piglets in the Si and Si + PQ groups were given a Si-supplemented diet. On the 18th day, the pigs in the PQ treatment group received an intraperitoneal injection of PQ, and the others were intraperitoneally injected with the same volume of saline. All piglets were sacrificed on day 21 for plasma and liver sample collection. The results showed that dietary Si supplementation mitigated PQ-induced liver damage, as proven by the reduction in liver pathological changes and plasma activity of alanine transaminase and aspartate transaminase. Si also improved superoxide dismutase and glutathione peroxidase activities and total antioxidant capacity, as well as decreased malondialdehyde and hydrogen peroxide concentration in the liver, which were closely related to the activation of the nuclear factor-erythroid 2-related factor 2 signaling pathway. Meanwhile, Si reduced tumor necrosis factor-α and interleukin-8 production and their transcript levels as well as abrogated the overactivation of nuclear factor-κB induced by PQ. Importantly, Si improved mitochondrial function by maintaining mitochondrial energetics and mitochondrial dynamics, which was indicated by the elevated activity of mitochondrial complexes I and V and adenosine triphosphate content, decreased expression of dynamin 1 protein, and increased expression of mitofusin 2 protein. Moreover, Si inhibited excessive hepatic apoptosis by regulating the B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated-X-protein signaling pathway. Taken together, these results indicated that Si potentially mitigated PQ-induced hepatic oxidative insults by improving antioxidant capacity and mitochondrial function and inhibiting inflammation and cell apoptosis in weaned piglets.

Efficient degradation and enhanced α-glucosidase inhibitory activity of apricot polysaccharides through non-thermal plasma assisted non-metallic Fenton reaction.

Dielectric barrier discharge (DBD) was a commonly used non-thermal plasma (CP) technology. This paper aimed to enhance the biological activity of apricot polysaccharides (AP) by using dielectric barrier discharge (DBD-CP) assisted H2O2-VC Fenton reaction for degradation. The degradation conditions were optimized through response surface methodology. The molecular weight (Mw) of degraded apricot polysaccharides (DAP) was 19.71 kDa, which was 7.25 % of AP. The inhibition rate of DAP (2 mg/mL) was 82.8 ± 3.27 %, which was 106.87 % higher than that of AP. DBD-CP/H2O2-VC degradation changed the monosaccharide composition of AP and improved the linearity of polysaccharide chains. In addition, a novel apricot polysaccharide DAP-2 with a Mw of only 6.60 kDa was isolated from DAP. The repeating units of the main chain of DAP-2 were →4)-α-D-GalpA-(1 →, the branch chain was mainly composed of α-D-GalpA-(1 â†’ 2)-α-L-Rhap-(1→ connected to O-3 position →3,4)-α-D-GalpA-(1→. The complex structure formed by the combination of DAP-2 and α-glucosidase was stable. DAP-2 had a higher α-glucosidase binding ability than the acarbose. These results suggested that DAP-2 had the potential to be developed as a potential hypoglycemic functional food and drug.

Porous Zinc Oxide and Plant Polyphenols as a Replacement for High-Dose Zinc Oxide on Growth Performance, Diarrhea Incidence, Intestinal Morphology and Microbial Diversity of Weaned Piglets.

The aim of this experiment is to evaluate the effects of adding porous zinc oxide, plant polyphenols, and their combination to diets without antibiotics and high-dose zinc oxide on the growth performance, diarrhea incidence, intestinal morphology, and microbial diversity of weaned piglets. A total of 150 Duroc × Landrace × Large White weaned piglets were allocated to one of five diets in a randomized complete block design with six replicates and five piglets per replicate. The experimental period was 42 d, divided into two feeding stages: pre-starter (0-14 d) and starter (14-42 d). In the pre-starter stage, the negative control group (NC) was fed a basal diet, the positive control group (PC) was fed a basal diet with 2000 mg/kg of zinc oxide, the porous zinc oxide group (PZ) was fed a basal diet with 500 mg/kg of porous zinc oxide, the plant polyphenol group (PP) was fed a basal diet with 1500 mg/kg of plant polyphenols, and the combination group (PZ + PP) was fed a basal diet with 500 mg/kg of porous zinc oxide and 1500 mg/kg of plant polyphenols. In the starter stage, the NC, PC, and PZ groups were fed a basal diet, while the PP and PZ + PP groups were fed a basal diet with 1000 mg/kg of plant polyphenols. The results showed that, (1) compared with the PZ group, adding plant polyphenols to the diet showed a trend of increasing the ADFI of weaned piglets from 14 to 28 d (p = 0.099). From days 28 to 42 and days 0 to 42, porous zinc oxide and the combination of porous zinc oxide and plant polyphenols added to the control diet improved the FCR to the level observed in pigs fed the PC diet. (2) Dietary PZ + PP tended to increase the jejunal villus height (VH) of weaned piglets (p = 0.055), and significantly increased the villus-height-to-crypt-depth ratio compared to the NC group (p < 0.05). (3) Compared with the NC group, PZ supplementation decreased the relative abundance of Firmicutes and increased the relative abundance of Bacteroidetes, and the relative abundance of Lactobacillus in the PZ and PZ + PP groups were both increased. In conclusion, porous zinc oxide and plant polyphenols may have synergistic effects in modulating intestinal health in weaned piglets and be a potential alternative to high-dose zinc oxide.

Effects of Dietary Supplementation of Stimbiotics to Sows on Lactation Performance, Immune Function, and Anti-Inflammatory and Antioxidant Capacities during Late Gestation and Lactation.

Stimbiotic supplementation may provide an innovative feed additive solution to accelerate the proliferation of beneficial fiber-degrading bacteria in the distal intestine and the utilization of dietary fiber. Optimal utilization of dietary fiber has multiple benefits for gut health and nutrient utilization. This study was conducted to evaluate the late gestation and lactation performance, the plasma, colostrum, and milk immunoglobulin (IgA, IgG, and IgM) concentrations, and the anti-inflammatory and antioxidant biomarkers in plasma of sows fed with or without a stimbiotic during the late gestation and lactation phase. A total of 40 sows were allocated to two treatment groups: control (CT) with no supplementation or 100 mg/kg stimbiotic (VP), with 20 sows per treatment. Sows were fed the treatment diets from d 85 of gestation to d 28 of lactation. In the results, the average daily weight gain of piglets during lactation was greater from sows fed in the VP group compared to that in the CT group (p < 0.05). The plasma concentrations of IgM at farrowing and IgG at weaning of the sows fed the diet with the stimbiotic supplementation were much higher than those in the CT sows (p < 0.05), respectively. In addition, the dietary stimbiotic increased the concentrations of IgM in the colostrum and of IgA and IgM in the milk at d 14 of lactation (p < 0.05). Plasma concentrations of malondialdehyde (MDA) on d 0 and d 28 of lactation tended to be lower in sows fed the VP diets compared with those of the sows fed the CT diets. Thus, our study indicated that stimbiotic supplementation could improve the daily weight gain of piglets and the immune function of sows in lactation.

Evaluation of Available Energy and Standardized Ileal Digestibility of Amino Acids in Fermented Flaxseed Meal for Growing Pigs.

Flaxseed meal (FSM) is a byproduct of flaxseed oil extraction which has rich nutritional value and can be used as a high-quality new protein ingredient. However, the anti-nutrient factor (ANF) in FSM restricts its potential application in feed. The strategy of microbial fermentation is a highly effective approach to reducing ANF in FSM and enhancing its feeding value. However, evaluation of the nutritional value of fermented flaxseed meal (FFSM) in growing pigs has not yet been conducted. Thus, the purpose of this study was to investigate the nutritional value of FFSM in growing pigs and comparison of the effect of fermentation treatment on improving the nutritional value of FSM. Two experiments were conducted to determine the available energy value, apparent digestibility of nutrients, and standard ileal digestibility of amino acids of FSM and FFSM in growing pigs. The results showed as follows: (1) Fermentation treatment increased the levels of crude protein (CP), Ca and P in FSM by 2.86%, 9.54% and 4.56%, while decreasing the concentration of neutral detergent fiber (NDF) and acid detergent fiber (ADF) by 34.09% and 12.71%, respectively (p < 0.05); The degradation rate of CGs in FSM was 54.09% (p < 0.05); (2) The digestible energy (DE) and metabolic energy (ME) of FSM and FFSM were 14.54 MJ/kg, 16.68 MJ/kg and 12.85 MJ/kg, 15.24 MJ/kg, respectively; (3) Compared with FSM, dietary FFSM supplementation significantly increased the apparent digestibility of CP, NDF, ADF, Ca, and P of growing pigs (p < 0.05) and significantly increased the standard ileal digestibility of methionine (p < 0.05). These results indicate that fermentation treatment could effectively enhance the nutritional value of FSM and provide basic theoretical data for the application of FFSM in pig production.

Histone deacetylase 9 exacerbates podocyte injury in hyperhomocysteinemia through epigenetic repression of Klotho.

Although hyperhomocysteinemia (hHcys) has been recognized as an important independent risk factor in the progression of end-stage renal disease and the development of cardiovascular complications related to end-stage renal disease, the mechanisms triggering pathogenic actions of hHcys are not fully understood. The present study was mainly designed to investigate the role of HDACs in renal injury induced by hHcys. Firstly, we identified the expression patterns of HDACs and found that, among zinc-dependent HDACs, HDAC9 was preferentially upregulated in the kidney from mice with hHcys. Deficiency or pharmacological inhibition of HDAC9 ameliorated renal injury in mice with hHcys. Moreover, podocyte-specific deletion of HDAC9 significantly attenuated podocyte injury and proteinuria. In vitro, gene silencing of HDAC9 attenuated podocyte injury by inhibiting apoptosis, reducing oxidative stress and maintaining the expressions of podocyte slit diaphragm proteins. Mechanically, we proved for the first time that HDAC9 reduced the acetylation level of H3K9 in the promoter of Klotho, then inhibited gene transcription of Klotho, finally aggravating podocyte injury in hHcys. In conclusion, our results indicated that targeting of HDAC9 might be an attractive therapeutic strategy for the treatment of renal injury induced by hHcys.

The Effects of Dietary Silybin Supplementation on the Growth Performance and Regulation of Intestinal Oxidative Injury and Microflora Dysbiosis in Weaned Piglets.

Oxidative stress is the major incentive for intestinal dysfunction in weaned piglets, which usually leads to growth retardation or even death. Silybin has caught extensive attention due to its antioxidant properties. Herein, we investigated the effect of dietary silybin supplementation on growth performance and determined its protective effect on paraquat (PQ)-induced intestinal oxidative damage and microflora dysbiosis in weaned piglets. In trial 1, a total of one hundred twenty healthy weaned piglets were randomly assigned into five treatments with six replicate pens per treatment and four piglets per pen, where they were fed basal diets supplemented with silybin at 0, 50, 100, 200, or 400 mg/kg for 42 days. In trial 2, a total of 24 piglets were randomly allocated to two dietary treatments with 12 replicates per treatment and 1 piglet per pen: a basal diet or adding 400 mg/kg silybin to a basal diet. One-half piglets in each treatment were given an intraperitoneal injection of paraquat (4 mg/kg of body weight) or sterile saline on day 18. All piglets were euthanized on day 21 for sample collection. The results showed that dietary supplementation with 400 mg/kg silybin resulted in a lower feed conversion ratio, diarrhea incidence, and greater antioxidant capacity in weaned piglets. Dietary silybin enhanced intestinal antioxidant capacity and mitochondrial function in oxidative stress piglets induced by PQ. Silybin inhibited mitochondria-associated endogenous apoptotic procedures and then improved the intestinal barrier function and morphology of PQ-challenged piglets. Moreover, silybin improved intestinal microbiota dysbiosis induced by the PQ challenge by enriching short-chain fatty-acid-producing bacteria, which augmented the production of acetate and propionate. Collectively, these findings indicated that dietary silybin supplementation linearly decreased feed conversion ratio and reduced diarrhea incidence in normal conditions, and effectively alleviated oxidative stress-induced mitochondrial dysfunction, intestinal damage, and microflora dysbiosis in weaned piglets.

Rosa laevigata Michx. Polysaccharide Ameliorates Diabetic Nephropathy in Mice through Inhibiting Ferroptosis and PI3K/AKT Pathway-Mediated Apoptosis and Modulating Tryptophan Metabolism.

Diabetic nephropathy (DN) is a metabolic disease wherein chronic hyperglycemia triggers various renal cell dysfunctions, eventually leading to progressive kidney failure. Rosa laevigata Michx. is a traditional Chinese herbal medicine. Many studies have confirmed its antioxidative, anti-inflammatory, and renoprotective effects. However, the effects and mechanisms of Rosa laevigata Michx. polysaccharide (RLP) in DN remain unclear. In this study, a DN mouse model was established to investigate the therapeutic effect of RLP on DN mice. Then, nontargeted metabolomics was used to analyze the potential mechanism of RLP in the treatment of DN. Finally, the effects of RLP on ferroptosis and the PI3K/AKT pathway were investigated. The results demonstrated that RLP effectively alleviated renal injury and reduced inflammation and oxidative stress in the kidney. In addition, nontargeted metabolomic analysis indicated that RLP could modulate riboflavin metabolism and tryptophan metabolism in DN mice. Notably, ferroptosis and PI3K/AKT pathway-mediated apoptosis in the kidney were also ameliorated following RLP treatment. In conclusion, this study confirmed that RLP had a significant therapeutic effect on DN mice. Furthermore, RLP treatment modulated tryptophan metabolism and inhibited ferroptosis and PI3K/AKT pathway-mediated apoptosis in the kidney.

Integrated 16S rRNA sequencing and nontargeted metabolomics analysis to reveal the mechanisms of Yu-Ye Tang on type 2 diabetes mellitus rats.

Introduction: Yu-Ye Tang (YYT) is a classical formula widely used in treatment of type 2 diabetes mellitus (T2DM). However, the specific mechanism of YYT in treating T2DM is not clear. Methods: The aim of this study was to investigate the therapeutic effect of YYT on T2DM by establishing a rat model of T2DM. The mechanism of action of YYT was also explored through investigating gut microbiota and serum metabolites. Results: The results indicated YYT had significant therapeutic effects on T2DM. Moreover, YYT could increase the abundance of Lactobacillus, Candidatus_Saccharimonas, UCG-005, Bacteroides and Blautia while decrease the abundance of and Allobaculum and Desulfovibrio in gut microbiota of T2DM rats. Nontargeted metabolomics analysis showed YYT treatment could regulate arachidonic acid metabolism, alanine, aspartate and glutamate metabolism, arginine and proline metabolism, glycerophospholipid metabolism, pentose and glucuronate interconversions, phenylalanine metabolism, steroid hormone biosynthesis, terpenoid backbone biosynthesis, tryptophan metabolism, and tyrosine metabolism in T2DM rats. Discussion: In conclusion, our research showed that YYT has a wide range of therapeutic effects on T2DM rats, including antioxidative and anti-inflammatory effects. Furthermore, YYT corrected the altered gut microbiota and serum metabolites in T2DM rats. This study suggests that YYT may have a therapeutic impact on T2DM by regulating gut microbiota and modulating tryptophan and glycerophospholipid metabolism, which are potential key pathways in treating T2DM.

Gallic acid improves the metformin effects on diabetic kidney disease in mice.

OBJECTIVES: Metformin is an antidiabetic agent that is used as the first-line treatment of type 2 diabetes mellitus. Gallic acid is a type of phenolic acid that has been shown to be a potential drug candidate to treat diabetic kidney disease, an important complication of diabetes. We aimed to test whether a combination of gallic acid and metformin can exert synergetic effect on diabetic kidney disease in diabetic mice model. METHODS: Streptozotocin (65 mg/kg) intraperitoneal injection was used to induce diabetic kidney disease in mice. The diabetic mice were treated with saline (Vehicle), gallic acid (GA) (30 mg/kg), metformin (MET) (200 mg/kg), or the combination of gallic acid (30 mg/kg) and metformin (200 mg/kg) (GA + MET). RESULTS: Our results demonstrated that compared to the untreated diabetic mice, all three strategies (GA, MET, and GA + MET) exhibited various effects on improving renal morphology and functions, reducing oxidative stress in kidney tissues, and restoring AMP-activated protein kinase (AMPK)/silent mating type information regulation 2 homolog 1 (SIRT1) signaling in kidney tissues of diabetic mice. Notably, the combination strategy (GA + MET) provided the most potent renal protection effects than any single strategies (GA or MET). CONCLUSION: Our results support the hypothesis that gallic acid might serve as a potential supplement to metformin to enhance the therapeutical effect of metformin.

Dietary Supplementation with Different Types of Potassium and Magnesium during Late Gestation and Lactation Modulates the Reproductive Performance, Antioxidant Capacity, and Immune Function of Sows.

The objective of this study was to investigate the effects of dietary supplementation with different types of potassium and magnesium on the reproductive performance, antioxidant capacity, and immunity of sows. Forty-five Landrace × Yorkshire sows at the late gestation stage (85 d) were randomly assigned to three groups (n = 15). Sows in the control group (CON), potassium chloride and magnesium sulfate group (PM), and potassium-magnesium sulfate group (PMS) were fed with a basal diet, a basal diet supplemented with magnesium sulfate (0.20%) and potassium chloride (0.15%), or a basal diet supplemented with potassium-magnesium sulfate (0.45%), respectively. The results showed that dietary supplementation with PMS did not yield significant effects on the reproductive performance compared with the CON group (p > 0.05). However, it significantly elevated the level of insulin-like growth factor 1 (IGF-1) in plasma and immunoglobulin A (IgA) in colostrum (p < 0.05). Furthermore, PMS significantly augmented the activities of catalase (CAT) and superoxide dismutase (SOD) while reducing the levels of malondialdehyde (MDA) in comparison to the CON group (p < 0.05). Compared with the PM group, the PMS group significantly reduced the incidence rate of intrauterine growth restriction (IUGR) (p < 0.05) and significantly decreased the concentration of the proinflammatory cytokine (TNF-α) level in plasma (p < 0.05). These results indicated that dietary supplementation with PMS during late gestation could enhance sows' antioxidant capacity and the IgA level in colostrum. These findings will provide a theoretical reference for the use of magnesium and potassium in sow production to improve sows' health.

San-Huang-Yi-Shen capsule ameliorates diabetic nephropathy in mice through inhibiting ferroptosis.

Diabetic nephropathy (DN) is one of the main complications of diabetes. However, effective therapy to block or slow down the progression of DN is still lacking. San-Huang-Yi-Shen capsule (SHYS) has been shown to significantly improve renal function and delay the progression of DN. However, the mechanism of SHYS on DN is still unclear. In this study, we established a mouse model of DN. Then, we investigated the anti-ferroptotic effects of SHYS including the reduction of iron overload and the activation of cystine/GSH/GPX4 axis. Finally, we used a GPX4 inhibitor (RSL3) and ferroptosis inhibitor (ferrostatin-1) to determine whether SHYS ameliorates DN through inhibiting ferroptosis. The results showed that SHYS treatment was effective for mice with DN in terms of improving renal function, and reducing inflammation and oxidative stress. Besides, SHYS treatment reduced iron overload and upregulated the expression of cystine/GSH/GPX4 axis-related factors in kidney. Moreover, SHYS exhibited similar therapeutic effect on DN as ferrostatin-1, RSL3 could abolish the therapeutic and anti- ferroptotic effects of SHYS on DN. In conclusion, SHYS can be used to treat mice with DN. Furthermore, SHYS could inhibit ferroptosis in DN through reducing iron overload and upregulating the expression of cystine/GSH/GPX4 axis.

Targeting Squalene Epoxidase Confers Metabolic Vulnerability and Overcomes Chemoresistance in HNSCC.

Cisplatin resistance poses a substantial hurdle in effectively treating head and neck squamous cell carcinoma (HNSCC). Utilizing multiple tumor models and examining an internal HNSCC cohort, squalene epoxidase (SQLE) is pinpointed as a key driver of chemoresistance and tumorigenesis, operating through a cholesterol-dependent pathway. Comprehensive transcriptomic analysis reveals that SQLE is essential for maintaining c-Myc transcriptional activity by stabilizing the c-Myc protein and averting its ubiquitin-mediated degradation. Mechanistic investigation demonstrates that SQLE inhibition diminishes Akt's binding affinity to lipid rafts via a cholesterol-dependent process, subsequently deactivating lipid raft-localized Akt, reducing GSK-3ß phosphorylation at S9, and increasing c-Myc phosphorylation at T58, ultimately leading to c-Myc destabilization. Importantly, employing an Sqle conditional knockout mouse model, SQLE's critical role in HNSCC initiation and progression is established. The preclinical findings demonstrate the potent synergistic effects of combining terbinafine and cisplatin in arresting tumor growth. These discoveries not only provide novel insights into the underlying mechanisms of SQLE-mediated cisplatin resistance and tumorigenesis in HNSCC but also propose a promising therapeutic avenue for HNSCC patients unresponsive to conventional cisplatin-based chemotherapy.