Integrated network toxicology, transcriptomics and gut microbiomics reveals hepatotoxicity mechanism induced by benzo[a]pyrene exposure in mice.

Benzo[a]pyrene (BaP) is a ubiquitous environmental pollutant posing various toxicity effects on organisms. Previous studies demonstrated that BaP could induce hepatotoxicity, while the underlying mechanism remains incompletely elucidated. In this study, a comprehensive strategy including network toxicology, transcriptomics and gut microbiomics was applied to investigate the hepatotoxicity and the associated mechanism of BaP exposure in mice. The results showed that BaP induced liver damage, liver oxidative stress and hepatic lipid metabolism disorder. Mechanistically, BaP may disrupt hepatic lipid metabolism through increasing the uptake of free fatty acid (FFA), promoting the synthesis of FA and triglyceride (TG) in the liver and suppressing lipid synthesis in white adipose tissue. Moreover, integrated network toxicology and hepatic transcriptomics revealed that BaP induced hepatotoxicity by acting on several core targets, such as signal transducer and activator of transcription 1 (STAT1), C-X-C motif chemokine ligand 10 (CXCL10) and toll-like receptor 2 (TLR2). Further analysis suggested that BaP inhibited JAK2-STAT3 signaling pathway, as supported by molecular docking and western blot. The 16S rRNA sequencing showed that BaP changed the composition of gut microbiota which may link to the hepatotoxicity based on the correlation analysis. Taken together, this study demonstrated that BaP caused liver injury, hepatic lipid metabolism disorder and gut microbiota dysbiosis, providing novel insights into the hepatotoxic mechanism induced by BaP exposure.

Association of vitamin D intake during pregnancy with small vulnerable newborns: a population-based cohort study.

Maternal vitamin D deficiency is common worldwide and has a significant impact on newborns. However, whether vitamin D intake during pregnancy is related to small vulnerable newborns (SVN) has not been confirmed. Thus, we sought to examine the relationship between maternal vitamin D intake, including vitamin D supplementation and dietary intake, and the risk of SVN. A total of 2980 Chinese mother-infant pairs were included in this study. Information on vitamin D supplementation and dietary intake was prospectively collected through face-to-face interviews. The outcomes assessed included low birth weight (LBW), preterm birth (PTB), small for gestational age (SGA), and SVN (having LBW, PTB, or SGA). Logistic regression models were used to evaluate the association of vitamin D intake with different types of SVN, and a restricted cubic spline function was modeled to explore their dose-response associations. Compared to the lowest total vitamin D intake in the first trimester, the highest total vitamin D intake was associated with a 50.0% decrease in the SGA risk (OR: 0.50, 95% CI: 0.26, 0.96) and a 41.0% decrease in the SVN risk (OR: 0.59, 95% CI: 0.36, 0.95). Similar protective results were observed between vitamin D supplementation in the first trimester and SGA and SVN risks. Moreover, a significant L-shaped relationship was identified for total vitamin D intake, vitamin D supplementation, and dietary intake with the risk of different types of SVN. In conclusion, higher total vitamin D intake and supplementation in the first trimester were associated with a reduced risk of SGA and SVN.

Development and application of a sensitive liquid chromatography-tandem mass spectrometry method for the quantitative analysis of 11 free fatty acids in human serum using a derivatisation strategy.

A stable isotope dilution-liquid chromatography-tandem mass spectrometry method based on a derivatisation strategy involving an N,N'-carbonylimidazole solution (CDI) with 4-(dimethylamino)-benzenemethanamine was developed for the determination of 11 free fatty acids (FFAs) in human blood samples. Serum samples were subjected to liquid‒liquid extraction and centrifuged, and the supernatant was collected for a two-step derivatisation reaction with a CDI and 4-(dimethylamino)-aniline acetonitrile solution. The derivatised solution was separated on a ACQUITY UPLC HSS T3 column (2.1 × 50 mm, 1.8 µm) column with a mobile phase consisting of water-acetonitrile in gradient elution and then detected by tandem mass spectrometry using electrospray ionisation (ESI) and multiple reaction monitoring (MRM) in positive ion mode and quantified using the isotope internal standard method. The effects of the derivatisation reaction time, temperature and concentration of derivatisation reagents on the response values of the analytes were investigated. The optimal conditions were as follows: 1.0 mg mL-1 CDI acetonitrile solution at 25 °C for 25 min, followed by a reaction with a 1.0 mg mL-1 4-(dimethylamino)-benzenemethanamine acetonitrile solution at 70 °C for 30 min. Under the optimal conditions, the limits of detection (LODs) of the 11 FFAs were in the range of 3.0-14.0 ng mL-1; the limits of quantification (LOQs) were in the range of 8.0-45.0 ng mL-1; and the mean recoveries ranged from 83.4 to 112.8%, with intraday and interday precisions ranging from 0.7 to 9.1% and 3.7-9.5%, respectively. The experimental method is simple in terms of the pretreatment operation, accurate and reliable, and can be applied to the sensitive determination of FFAs in human blood samples.

Early change of retinal nerve fiber layer in children with type 1 diabetes mellitus in northern China.

OBJECTIVES: This study aimed to identify discrepancies in the retinal nerve fiber layer (RNFL) between type 1 diabetes mellitus (T1DM) children without retinopathy and healthy subjects in northern China. METHODS: This was a cross-sectional hospital-based study carried out from Jan 2019 until Jul 2021 at the department of pediatrics in Tianjin medical university general hospital. Children with T1DM but no retinal disease were screened. RNFL thickness was obtained via spectral domain optical coherence tomography. Disease duration, HbA1c, 25-hydroxyvitamin D level, insulin regimen, and diet control status were also collected. RESULTS: A total of 20 children with T1DM and 20 matched health participants were enrolled. The mean age in the T1DM group was 10.3 ± 2.8 years, and the median duration of diabetes was 1 (range 1-3) year. Children with T1DM had thinner average RNFL than control subjects (105 ± 6 vs. 110 ± 11 µm, p=0.008), especially in temporal and nasal parts. There was a significant negative association between HbA1c levels and the RNFL thickness in the T1DM group (B (95 % confidence interval): -4.313 (-7.055 to -1.571); p=0.005). CONCLUSIONS: In our study, the decreased thickness of RNFL was negatively associated with elevated HbA1c in children with early stages of T1DM.

Effect of Dietary Protein Intake from Different Sources on Maternal and Umbilical Cord Plasma Amino Acid Levels.

SCOPE: To assess the associations of dietary protein intake from different sources during pregnancy with maternal and umbilical cord plasma amino acid levels. METHODS AND RESULTS: The study includes 216 pregnant women and 39 newborns from the Tongji Birth Cohort in Wuhan, China. The study examines the levels of 21 amino acids in maternal and cord plasma samples using ultra-performance liquid chromatography with tandem mass spectrometry. A significant positive relationship is observed between dietary protein intake from refined grains and maternal plasma cysteine levels. Dietary protein intake from dairy products is positively associated with maternal plasma levels of sulfur amino acid (mainly cystine), but negatively associated with maternal plasma levels of glutamic acid. In addition, the study observes that pre-pregnancy body mass index and parity may be potential determinants of maternal plasma amino acid levels, whereas a history of passive smoking during pregnancy is an important factor influencing cord plasma amino acid levels. CONCLUSIONS: These findings suggest that dietary protein intakes from specific sources during pregnancy may affect maternal plasma levels of amino acids.

Aurora-A inhibitor synergistically enhances the inhibitory effect of anlotinib on hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly malignant tumor with a global prevalence. In addition to the existing clinical guidelines, the effectiveness of anlotinib and Aurora-A inhibitors in treating HCC has also been demonstrated. However, Anlotinib, as an anti-angiogenesis therapy, has shown significant benefits in clinical trials but is limited by its single-agent treatment and the development of drug resistance. Aurora-A inhibitors are currently being tested in clinical trials but have limited efficacy. Combination therapy may offer clear advantages over monotherapy in this context. METHODS: In this study, we used HCC cell lines to investigate whether the combination of the two drugs could enhance their individual strengths and mitigate their weaknesses, thereby providing greater clinical benefits both in vitro and in vivo. RESULTS: Our findings confirmed that the Aurora-A inhibitor alisertib and anlotinib exhibited a time-dose-dependent inhibitory effect on HCC cells. In vitro cytological experiments demonstrated that the combination of the two drugs synergistically inhibited cell proliferation, invasion, and metastasis, while promoting cell apoptosis. Furthermore, we identified the underlying molecular mechanism by which the combination of the Aurora-A inhibitor alisertib and anlotinib inhibited HCC through the inhibition of the NF-ĸB signaling pathway. CONCLUSIONS: In summary, we have demonstrated the effectiveness of combining anlotinib with an Aurora-A inhibitor, which expands the potential applications of anlotinib in the clinical treatment of HCC in the future.

Effects of Timing and Types of Protein Supplementation on Improving Muscle Mass, Strength, and Physical Performance in Adults Undergoing Resistance Training: A Network Meta-Analysis.

Precise protein supplementation strategies for muscle improvement are still lacking. The timing or type of protein supplementation has been debated as a window of opportunity to improve muscle mass, strength, and physical performance. We conducted a network meta-analysis of randomized controlled trials with protein supplements and resistance training. PubMed, Web of Science, Cochrane Library, and SPORTDiscus databases were searched until May 1, 2023. We included 116 eligible trials with 4,711 participants that reported on 11 timing and 14 types of protein supplementation. Compared with placebo, protein supplementation after exercise (mean difference [MD]: 0.54 kg [95% confidence intervals 0.10, 0.99] for fat-free mass, MD: 0.34 kg [95% confidence intervals 0.10, 0.58] for skeletal muscle mass) and at night (MD: 2.85 kg [0.49, 5.22] for handgrip strength, MD: 12.12 kg [3.26, 20.99] for leg press strength) was most effective in improving muscle mass and strength, respectively (moderate certainty). Milk proteins (milk, whey protein, yogurt, casein, and bovine colostrum), red meat, and mixed protein were effective for gains in both muscle mass and strength (moderate certainty). No timing or type of protein showed a significant enhancement in physical performance (timed up-to-go test, 6-min walk test, and gait speed). Pre/postexercise and Night are key recommended times of protein intake to increase muscle mass and strength, respectively. Milk proteins are the preferred types of protein supplements for improving muscle mass and strength. Future randomized controlled trials that directly compare the effects of protein timing or types are needed. This trial was registered at International Prospective Register of Systematic Reviews as CRD42022358766.

A Healthy, Low-Carbohydrate Diet During Pregnancy Is Associated With a Reduced Risk of Gestational Diabetes Mellitus.

CONTEXT: Evidence on the associations of low-carbohydrate diet (LCD) during pregnancy with gestational diabetes mellitus (GDM) has been limited and inconsistent. OBJECTIVE: We aimed to prospectively evaluate the risk of GDM associated with the LCD considering the quality of macronutrients. METHODS: All participants were from a prospective cohort in Wuhan, China. The overall, healthy LCD (emphasizing low-quality carbohydrates, plant protein, and unsaturated fat), and unhealthy LCD (emphasizing high-quality carbohydrates, animal protein, and saturated fat) scores were calculated according to the percentage of energy intake from carbohydrates, protein, and fat. GDM was screened by a 75-g oral glucose tolerance test between 24 and 28 weeks. Poisson regression models were used to calculate relative risks (RRs) and 95% CIs. RESULTS: Of 2337 pregnant women, 257 (11.0%) were diagnosed with GDM. Overall LCD score was not associated with risk of GDM, but the healthy and unhealthy LCD scores were associated with the risk of GDM. The multivariable-adjusted RRs (95% CI) were 0.68 (0.49-0.94) and 1.52 (1.11-2.08) for healthy and unhealthy LCD scores comparing the highest with the lowest quartile. Substituting high-quality carbohydrates for low-quality carbohydrates and animal protein, and substituting unsaturated fat for saturated fat, were associated with a 13% to 29% lower risk of GDM. CONCLUSION: A healthy LCD during pregnancy characterized by high-quality carbohydrates, plant protein, and unsaturated fat was associated with a lower risk of GDM, whereas an unhealthy LCD consisting of low-quality carbohydrates, animal protein, and saturated fat was associated with a higher risk of GDM.

New insight into PAH4 induced hepatotoxicity and the dose-response assessment in rats model.

PAH4 (sum of benzo[a]pyrene, chrysene, benz[a]anthracene and benzo[b]fluoranthene) has been proposed as better marker than benzo[a]pyrene to assess total PAHs exposure in foodstuffs. However, the toxicological behaviors of PAH4 combined exposure remain unclear. This study aimed to investigate PAH4 toxicity effects with non-targeted metabolomics approach and evaluate the external and internal dose-response relationships based on benchmark dose (BMD) analysis. Male Sprague-Dawley rats were treated by gavage with vehicle (corn oil) or four doses of PAH4 (10, 50, 250, 1000 µg/kg·bw) for consecutive 30 days. After the final dose, the liver, blood and urine samples of rats were subsequently collected for testing. The concentrations of urinary mono-hydroxylated PAHs metabolites (OH-PAHs) including 3-hydroxybenzo[a]pyrene (3-OHB[a]P), 3-hydroxychrysene (3-OHCHR) and 3-hydroxybenz[a]anthracene (3-OHB[a]A) were determined to reflect internal PAH4 exposure. Our results showed PAH4 exposure increased relative liver weight and serum aspartate aminotransferase (AST) activity and caused hepatocyte swelling and degeneration, implying hepatotoxicity induced by PAH4. Serum metabolomics suggested PAH4 exposure perturbed lipid metabolism through upregulating the expression of glycerolipids metabolites, which was evidenced by markedly increased serum triglyceride (TG) level and hepatic TG content. Additionally, urinary OH-PAHs concentrations presented strong positive correlations with the external dose, indicating they were able to reflect PAH4 exposure. Furthermore, PAH4 exposure led to a dose-response increase of hepatic TG content, based on which the 95% lower confidence value of BMDs for external and internal doses were estimated as 5.45 µg/kg·bw and 0.11 µmol/mol·Cr, respectively. In conclusion, this study suggested PAH4 exposure could induce hepatotoxicity and lipid metabolism disorder, evaluating the involved dose-response relationships and providing a basis for the risk assessment of PAHs.

Cholesterol-rich dietary pattern during early pregnancy and genetic variations of cholesterol metabolism genes in predicting gestational diabetes mellitus: a nested case-control study.

BACKGROUND: Higher dietary cholesterol intake during pregnancy increases risk of gestational diabetes mellitus (GDM). However, no studies have investigated interindividual variability in cholesterol metabolism and the association of genetics and diet on GDM. OBJECTIVE: ; To prospectively evaluate the joint association of cholesterol-rich dietary patterns and polymorphisms of genes coding for cholesterol metabolism pathway proteins with GDM. METHODS: A total of 1116 pregnant females from the Tongji Birth Cohort were enrolled. GDM was diagnosed according to a 75-g 2-h oral glucose tolerance test at 24-28 wk of gestation. Dietary data were collected by a validated food frequency questionnaire. The reduced-rank regression method was used to identify dietary patterns using dietary cholesterol as the response variable. Time-of-flight mass spectrometry was used for genotyping. The genetic risk score (GRS) for GDM was constructed with genetic variants in 28 cholesterol metabolism-related single-nucleotide polymorphisms (SNPs). Conditional logistic regression models were used to assess the odds ratio (OR) for GDM. RESULTS: The cholesterol-rich dietary pattern was rich in livestock and poultry meat and eggs but lower in cereals. The multivariable-adjusted ORs for GDM were 1.24 (95% confidence interval: 1.06-1.44) per SD increment of cholesterol-rich pattern scores and 1.28 (1.09-1.49) per tertile GRS. The variants of the CYP7A1 rs3808607 G→T/rs8192871 G→A/rs7833904 A→T, as well as AGGG and TTGA haplotypes of 4 CYP7A1-spanning SNPs, were significantly associated with GDM. For the joint effect, the OR was 3.53 (1.71-7.31) in the highest categories of both dietary pattern scores and GRS compared with individuals with the lowest strata without significant interaction (P for interaction = 0.101). CONCLUSIONS: Both a cholesterol-rich dietary pattern and genetic variants of cholesterol metabolism genes are associated with risk of GDM. Adherence to a cholesterol-rich dietary pattern during early pregnancy promotes the chance of GDM, especially in women with higher GRS. CLINICAL TRIAL REGISTRY: This trial was registered at http://www.chictr.org.cn (Registration number: ChiCTR1800016908). URL: =https://www.chictr.org.cn/showprojEN.html?proj=28081.

Pregnancy Cholesterol Metabolism Markers and the Risk of Gestational Diabetes Mellitus: A Nested Case-Control Study.

This study aims to determine the association of pregnancy cholesterol metabolism markers with gestational diabetes mellitus (GDM) risk. We performed a nested case-control study in the Tongji Birth Cohort. GDM was diagnosed according to the 75 g 2 h oral glucose tolerance test (OGTT) at 24-28 gestational weeks. Nine cholesterol metabolism markers were detected using gas chromatography-mass spectrometry. Conditional logistic regression models were conducted. A total of 444 pregnant women were matched in a 1:2 ratio. The cholestanolTC and ß-sitosterolTC in cholesterol absorption markers presented negative associations with the risks of GDM (adjusted OR: 0.77, 95% CI: 0.61-0.96; adjusted OR: 0.80, 95% CI: 0.64-1.00). The desmosterolTC in cholesterol synthesis markers were positively associated with the risks of GDM (adjusted OR: 1.25, 95% CI: 1.00-1.56), similar in the ratios of cholesterol synthesis to absorption markers. After adjustment for insulin or HOMA-IR, these effects were reduced. In conclusion, higher cholesterol synthesis and lower cholesterol absorption marker levels in the first pregnancy are associated with a higher risk of GDM, and insulin resistance may play a vital role in this association.

Deoxynivalenol Exposure Induced Colon Damage in Mice Independent of the Gut Microbiota.

SCOPE: To investigate whether deoxynivalenol (DON) can induce intestinal damage through gut microbiota in mice. METHODS AND RESULTS: Mice are orally administered DON (1 mg kg-1 bw day-1 ) for 4 weeks, and then recipient mice receive fecal microbiota transplantation (FMT) from DON-exposed mice after antibiotic treatment. Furthermore, the mice are orally treated with DON (1 mg kg-1 bw day-1 ) for 4 weeks after antibiotic treatment. Histological damage, disruption of tight junction protein expression, and increased oxidative stress and apoptosis in the colon as well as higher serum lipopolysaccharides are observed after DON exposure. Moreover, DON exposure changes the composition and diversity of the gut microbiota as well as the contents of fecal metabolites (mainly bile acids). Differential metabolic pathways may be related to mitochondrial metabolism, apoptosis, and inflammation following DON exposure. However, only a decrease in mRNA levels of occludin and claudin-3 is observed in the colon of recipient mice after FMT. After depleting the gut microbiota in mice, DON exposure can also cause histological damage, disorders of tight junction protein expression, and increased oxidative stress and apoptosis in the colon. CONCLUSIONS: DON exposure can induce colon damage in mice independent of the gut microbiota.

Magnesium Status, Genetic Variants of Magnesium-Related Ion Channel Transient Receptor Potential Membrane Melastatin 6 (TRPM6) and the Risk of Gestational Diabetes Mellitus in Chinese Pregnant Women: A Nested Case-Control Study.

SCOPE: Magnesium plays an important role in regulating glucose metabolism. The study attempts to explore association between magnesium status and single nucleotide polymorphisms (SNPs) of gene involved in magnesium absorption-transient receptor potential membrane melastatin 6 (TRPM6) and gestational diabetes mellitus (GDM) risk METHODS AND RESULTS: A nested case-control study including 170 GDM cases and matched 340 controls is conducted based on Tongji Birth Cohort. Dietary, serum, and urine magnesium are evaluated before the diagnosis of GDM. Compared to the lowest tertile, women in the highest tertile of serum magnesium are at a lower risk of GDM (adjusted odds ratio [aOR] 0.42, 95% confidence intervals [CI] 0.21-0.84). Serum magnesium is inversely associated with insulin and homeostatic model assessment of insulin resistance (ß = -0.05, p = 0.002; ß = -0.04, p = 0.001, respectively). The aOR for GDM in carriers of the CT or CC genotypes of TRPM6 rs2274924 compared with carriers of the TT genotype is 2.76 (95% CI 1.78-4.26). Dietary magnesium is positively associated with serum magnesium (ß = 0.02, p = 0.004), but not with GDM risk. CONCLUSION: Serum magnesium and the TRPM6 rs2274924 polymorphism are associated with the risk of GDM.

Adverse associations between maternal deoxynivalenol exposure and birth outcomes: a prospective cohort study in China.

BACKGROUND: Deoxynivalenol (DON), one of the most prevalent mycotoxins, has been found to cause fetal growth retardation in animals. However, limited evidence exists regarding its effects on pregnant women. METHODS: Maternal urinary concentration of total DON (tDON) and free DON (fDON) in the second trimester was measured using liquid chromatography with tandem mass spectrometry. Provisional daily intake (PDI) of DON was calculated based on tDON concentration. Linear and logistic regression models were used to evaluate the association between DON exposure levels and birth weight, birth length, and the risk of small for gestational age (SGA). RESULTS: Among 1538 subjects, the median concentrations of tDON and fDON were 12.1 ng/mL and 5.1 ng/mL, respectively. The PDI values revealed that the median DON intake was 0.7 µg/kg bw, and 35.9% of the total population exceeded the provisional maximum tolerable daily intake (PMTDI) of 1 µg/kg bw. Compared with the lowest tertile, birth weight decreased by 81.11 g (95% CI: -127.00, -35.23) for tDON (P-trend < 0.001) and 63.02 g (95% CI: -108.72, -17.32) for fDON (P-trend = 0.004) in the highest tertile. Each unit increase in Ln-tDON and Ln-fDON was also inversely associated with birth weight. Furthermore, compared to those who did not exceed PMTDI, pregnant women whose PDI exceeded PMTDI had lower birth weight (ß = -79.79 g; 95% CI: -119.09, -40.49) and birth length (ß = -0.21 cm; 95% CI: -0.34, -0.07), and a higher risk of SGA (OR = 1.48; 95% CI: 1.02, 2.15) in their offspring. Similar associations with birth weight, birth length, and SGA were found when comparing the highest tertile of PDI to the lowest tertile (all P-trend < 0.05). CONCLUSIONS: Maternal DON exposure is related to decreased birth weight. Our findings implicate that DON exposure during pregnancy may cause fetal growth faltering, and measures should be taken to reduce DON exposure in pregnant women.

Association between Nutrition and Health Knowledge and Multiple Chronic Diseases: A Large Cross-Sectional Study in Wuhan, China.

Nutrition and health knowledge (NHK) is linked to people's dietary behavior and health outcomes. However, studies on the associations between NHK and chronic diseases are limited. This study aimed to examine the association of NHK with five specific chronic diseases (diabetes/hyperglycemia, hypertension, dyslipidemia, coronary heart disease (CHD), and stroke) in central China. Individual NHK and disease status were investigated using a self-reporting questionnaire. We further added up the number of chronic diseases and used this as a secondary outcome. A total of 21,559 adults were enrolled in this cross-sectional study. NHK score was significantly inversely associated with diabetes/hyperglycemia, hypertension, CHD, and stroke (all p-trends < 0.001). Moreover, an inverse association was found between NHK and the number of chronic diseases, especially among responders with three or more chronic diseases. Stratified analyses showed that the above association was more likely to be stronger among younger, female, highly educated, and inner-city residents. However, NHK was negatively associated with dyslipidemia in less educated people and positively correlated with dyslipidemia in highly educated people. NHK showed an inverse relationship with specific chronic diseases and the number of chronic diseases. Improving NHK might be a key strategy for easing the global burden of chronic diseases.

Mycorrhizae enhance reactive minerals but reduce mineral-associated carbon.

Soil organic carbon (C) is the largest active C pool of Earth's surface and is thus vital in sustaining terrestrial productivity and climate stability. Arbuscular mycorrhizal fungi (AMF) form symbioses with most terrestrial plants and critically modulate soil C dynamics. Yet, it remains unclear whether and how AMF-root associations (i.e., mycorrhizae) interact with soil minerals to affect soil C cycling. Here we showed that the presence of both roots and AMF increased soil dissolved organic C and reactive Fe minerals, as well as litter decomposition and soil CO2 emissions. However, it reduced mineral-associated C. Also, high-resolution nanoscale secondary ion mass spectrometry images showed the existence of a thin coating (0.5-1.0 µm thick) of 56 Fe16 O- (Fe minerals) on the surface of 12 C14 N- (fungal biomass), illustrating the close physical association between fungal hyphae and soil Fe minerals. In addition, AMF genera were divergently related to reactive Fe minerals, with Glomus being positively but Paraglomus and Acaulospora negatively correlated with reactive Fe minerals. Moreover, the presence of roots and AMF, particularly when combined with litter addition, enhanced the abundances of several critical soil bacterial genera that are associated with the formation of reactive minerals in soils. A conceptual framework was further proposed to illustrate how AMF-root associations impact soil C cycling in the rhizosphere. Briefly, root exudates and the inoculated AMF not only stimulated the decomposition of litter and SOC and promoted the production of CO2 emission, but also drove soil C persistence by unlocking mineral elements and promoting the formation of reactive minerals. Together, these findings provide new insights into the mechanisms that underlie the formation of reactive minerals and have significant implications for understanding and managing soil C persistence.

Association of maternal dietary patterns derived by multiple approaches with gestational diabetes mellitus: a prospective cohort study.

We used two a priori diet scores [Mediterranean diet (aMed) and Diet Balance Index (DBI)] and two a posteriori approaches [principal components analysis (PCA) and reduced-rank regression (RRR)] to examine the association of maternal dietary patterns with risk of gestational diabetes mellitus (GDM) and blood glucose among 2202 pregnant women in the Tongji Birth Cohort. Compared to the highest quartile of the aMed and legumes-vegetables-fruits (derived by PCA) scores, the fasting blood glucose (FBG) levels were higher in the lower quartiles (p-trend < 0.05). Lower scores of the meats-eggs-dairy (derived by PCA) and eggs-fish patterns (derived by RRR; characterised by higher intakes of freshwater fish, eggs, and lower intakes of leafy and cruciferous vegetables and fruits) were associated with decreased FBG levels (p-trend < 0.05). Similarities were found across approaches that some dietary patterns were associated with FBG, but not with postprandial glucose and GDM risk.

Nox4 as a novel therapeutic target for diabetic vascular complications.

Diabetic vascular complications can affect both microvascular and macrovascular. Diabetic microvascular complications, such as diabetic nephropathy, diabetic retinopathy, diabetic neuropathy, and diabetic cardiomyopathy, are believed to be caused by oxidative stress. The Nox family of NADPH oxidases is a significant source of reactive oxygen species and plays a crucial role in regulating redox signaling, particularly in response to high glucose and diabetes mellitus. This review aims to provide an overview of the current knowledge about the role of Nox4 and its regulatory mechanisms in diabetic microangiopathies. Especially, the latest novel advances in the upregulation of Nox4 that aggravate various cell types within diabetic kidney disease will be highlighted. Interestingly, this review also presents the mechanisms by which Nox4 regulates diabetic microangiopathy from novel perspectives such as epigenetics. Besides, we emphasize Nox4 as a therapeutic target for treating microvascular complications of diabetes and summarize drugs, inhibitors, and dietary components targeting Nox4 as important therapeutic measures in preventing and treating diabetic microangiopathy. Additionally, this review also sums up the evidence related to Nox4 and diabetic macroangiopathy.

Curcumin protects against rotenone-induced Parkinson's disease in mice by inhibiting microglial NLRP3 inflammasome activation and alleviating mitochondrial dysfunction.

Parkinson's disease (PD) is a common neurodegenerative disorder worldwide. Currently, treatment options can only relieve symptoms but cannot prevent, slow, or halt the neurodegenerative process of PD. Much evidence has suggested that microglia-mediated neuroinflammation is involved in the pathophysiology of PD. As an anti-inflammatory agent, curcumin may exert a neuroprotective effect on PD. However, its mechanism has yet to be demonstrated clearly. Our results indicated that curcumin alleviated rotenone-induced behavioral defects, dopamine neuron loss, and microglial activation. Besides, the NF-κB signaling pathway, the NLRP3 inflammasome, and pro-inflammatory cytokines, including IL-18 and IL-1ß, contributed to the microglia-mediated neuroinflammation in PD. Furthermore, Drp1-mediated mitochondrial fission causing mitochondrial dysfunction also had an etiological role in the process. This study suggests that curcumin protects against rotenone-induced PD by inhibiting microglial NLRP3 inflammasome activation and alleviating mitochondrial dysfunction in mice. Thus, curcumin may be a neuroprotective drug with promising prospects in PD.

Metabolism and elimination kinetics of mono-hydroxylated PAHs metabolites following single exposure to different combinations of PAH4 in rats.

The metabolism of polycyclic aromatic hydrocarbons (PAHs) and the elimination kinetics of their mono-hydroxylated metabolites (OH-PAHs) following single exposure to different combinations of four PAHs (PAH4) were studied. Male Sprague-Dawley rats were orally exposed to a single dose of benzo[a]pyrene (B[a]P) or PAH2 (B[a]P + chrysene), PAH3 (B[a]P + chrysene + benz[a]anthracene), and PAH4 (B[a]P + chrysene + B[a]A + benzo[b]fluoranthene) with each combination adjusted to the same dose of individual compound. OH-PAHs including 3-hydroxybenzo[a]pyrene, 3-hydroxychrysene, 3-hydroxybenz[a]anthracene, and 1-hydroxypyrene (1-OHP) were detected in serum and urine samples collected at six intervals over a 72-h period post-dosing. The hepatic mRNA levels of cytochrome P450 (CYPs) were determined to ascertain the expression induction of PAHs metabolic enzymes. Results showed OH-PAHs (except 1-OHP) peaked within 8 h in serum and were excreted from urine within 24-48 h. The serum and urinary concentration of 3-hydroxybenzo[a]pyrene was significantly increased after PAH4 exposure compared with other PAHs combinations. Inversely, urinary concentration of 3-hydroxychrysene was decreased after PAH4 exposure, and the kinetics of 3-hydroxybenz[a]anthracene or 1-OHP were not different depending on the PAHs combinations. Also, CYPs were markedly induced by PAHs. Notably, the induction levels of CYP1A1 and CYP1B1 were significantly higher after PAH4 exposure compared with B[a]P exposure. The results indicated the metabolism of B[a]P was accelerated after PAH4 exposure which might be partly due to the induction of CYPs. These results confirmed PAHs are rapidly metabolized and suggested potential interactions of PAHs may happen among PAH4 mixture.