Effects of short-term supplementation with DHA-enriched phosphatidylcholine and phosphatidylserine on lipid profiles in the brain and liver of n-3 PUFA-deficient mice in early life after weaning.

BACKGROUND: Lack of n-3 polyunsaturated fatty acids during the period of maternity drastically lowers the docosahexaenoic acid (DHA) level in the brain of offspring and studies have demonstrated that different molecular forms of DHA are beneficial to brain development. The aim of this study was to investigate the effect of short-term supplementation with DHA-enriched phosphatidylserine (PS) and phosphatidylcholine (PC) on DHA levels in the liver and brain of congenital n-3-deficient mice. RESULTS: Dietary supplementation with DHA significantly changed the fatty acid composition of various phospholipid molecules in the cerebral cortex and liver while DHA-enriched phospholipid was more effective than DHA triglyceride (TG) in increasing brain and liver DHA. Both DHA-PS and DHA-PC could effectively increase the DHA levels, but DHA in the PS form was superior to PC in the contribution of DHA content in the brain ether-linked PC (ePC) and liver lyso-phosphatidylcholine molecular species. DHA-PC showed more significant effects on the increase of DHA in liver TG, PC, ePC, phosphatidylethanolamine (PE) and PE plasmalogen (pPE) molecular species and decreasing the arachidonic acid level in liver PC plasmalogen, ePC, PE and pPE molecular species compared with DHA-PS. CONCLUSION: The effect of dietary interventions with different molecular forms of DHA for brain and liver lipid profiles is different, which may provide theoretical guidance for dietary supplementation of DHA for people. © 2024 Society of Chemical Industry.

Distribution, sources and ecological risks of PAHs and n-alkanes in water and sediments of typically polluted estuaries: Insights from the Xiaoqing River.

Seasonal water and sediment samples were collected from the Xiaoqing River estuary and the neighboring sea to study the spatial and temporal distributions, sources and ecological risks of polycyclic aromatic hydrocarbons (PAHs) and n-alkanes. The results showed significant spatial and temporal differences in the concentrations of PAHs and n-alkanes under the influence of precipitation, temperature, and human activities. The concentrations of PAHs in water were lower in the wet season than in the dry season, and those in sediments were higher in the wet season than in the dry season. The concentrations of n-alkanes were higher in the rainy season than in the dry season for both water and sediments. The spatial distributions of PAHs and n-alkanes were estuarine > offshore. The concentration ranges of ∑PAHs in water and sediments were 230.66-599.86 ng/L and 84.51-5548.62 ng/g, respectively, in the wet season and 192.46-8649.55 ng/L and 23.39-1208.92 ng/g, respectively, in the dry season. The proportion of three-ring PAHs in water (57.03% and 78.27% in the wet and dry seasons, respectively) was high, followed by two-ring PAHs (27.31% and 13.59% in the wet and dry seasons, respectively). The proportion of four-ring PAHs was higher in sediments (24.79% and 32.20% in the wet and dry seasons, respectively). The ecological risk of PAHs assessed using the toxicity equivalent quotient and risk quotient was at moderate to moderately high risk levels. The high concentration of n-alkane fraction C16 (611.65-75594.58 ng/L) in the water is indicative of petroleum or other fossil fuel inputs. The main peaks of n-alkanes in river sediments were C27, C29 and C31, indicating higher inputs of plant sources. The sediments in the estuary showed dominance of both short-chain C16 and long-chain C25-C31, indicating a combined input of higher plants and petroleum. The diagnostic ratios of PAHs and n-alkanes indicated that their sources were mainly oil/coal/biomass combustion and petroleum spills attributed to frequent vehicular, vessel and mariculture activities. Given the potential ecological risks of PAHs and n-alkanes in water and sediments, future studies should focus on their bioaccumulation and biotoxicity.

Effects of hydroxyproline supplementation in low fish meal diets on collagen synthesis, myofiber development and muscular texture of juvenile Pacific white shrimp (Litopenaeus vannamei).

This experiment aimed to evaluate the impact of dietary hydroxyproline (Hyp) supplementation on the muscle quality of juvenile Pacific white shrimp (Litopenaeus vannamei) fed a low fishmeal diet. Six formulated diets included one high fishmeal (HF; 25% fishmeal content) and five low fishmeal diets (10% fishmeal content) with 0%, 0.2%, 0.4%, 0.6% and 0.8% Hyp (LF0, LF2, LF4, LF6 and LF8, respectively). Each diet was assigned to four replicates, and 40 shrimp (0.32 ± 0.00 g) per replicate were fed four times a day for 8 weeks. Dietary Hyp supplementation had little effects on growth performance, but increased the contents of Hyp, prolyl 4-hydroxylases (P4Hs), and collagen. The meat yield, springiness, hardness, chewiness, and cohesiveness of muscle were the highest in the LF4 group among the low fishmeal groups (P < 0.05). Cooking loss and freezing loss of muscle were the lowest in the LF4 group (P < 0.05). Dietary supplementation with 0.4% Hyp increased the myofiber density and decreased the myofiber diameter of muscle (P < 0.05). Supplementation of Hyp in the diet up-regulated the mRNA expression of smyhc5, smyhc15, col1a1, col1a2, igf-1f, tgf-ß and tor and down-regulated the mRNA expression of smyhc 1, smyhc 2, smyhc 6a (P < 0.05). Supplementation of Hyp in the diet up-regulated the protein expression of P-4E-BP1, P-AKT, AKT and P-AKT/AKT (P < 0.05). These results suggested that the addition of 0.4% Hyp to low fishmeal diets improved the muscle quality of L. vannamei.

A preliminary study on brain developmental features of bipolar disorder familial risk and subthreshold symptoms.

BACKGROUND: Risk for Bipolar disorder (BD) is increased among individuals with family history or subthreshold mood symptoms. However, the brain structural developments associated with these BD risks remained unknown. METHODS: This longitudinal cohort study examined the brain grey matter volume (GMV) developmental features of familial and symptomatic risks for BD, and their associations with participants' global function levels. We recruited unaffected BD offspring with (N=26, age=14.9±2.9 years, 14 females) or without (N=35, age=15.3±2.7 years, 19 females) subthreshold manic or depressive symptoms, and unaffected non-BD offspring with (N=49, age=14.5±2.2 years, 30 females) or without (N=68, age=15.0±2.3 years, 37 females) symptoms. The offspring had no mood disorder diagnosis prior to the study. The average follow-up duration was 2.63±1.63 years. RESULTS: We found at baseline, significant interactive effects of familial risk and subthreshold symptoms indicated the symptomatic offspring exhibited markedly large GMV in the brain affective and cognitive circuitries. During follow-up, the combined group of BD offspring (symptomatic and non-symptomatic) displayed accelerated GMV decrease than BD non-offspring, in the hippocampus and anterior cingulate cortex. In contrast, the combined group of symptomatic participants (offspring and non-offspring) displayed slower GMV decrease than non-symptomatic participants, in the ventromedial prefrontal cortex. Larger GMV at baseline, and accelerated GMV decrease during follow-up, prospectively and longitudinally predicted positive global function changes. All results survived multiple-testing correction. CONCLUSIONS: These findings indicated that familial and symptomatic risks of BD are associated with distinct brain structural developments, and unraveled key brain developmental features of particularly vulnerable high-risk individuals to subsequent functional deterioration.

Trimethylamine N-Oxide in Aquatic Foods.

Trimethylamine N-oxide (TMAO), a characteristic nonprotein nitrogen compound, is widely present in seafood, which exhibits osmoregulatory effects for marine organisms in vivo and plays an important role in aquaculture and aquatic product preservation. However, much attention has been focused on the negative effect of TMAO since it has recently emerged as a putative promoter of chronic diseases. To get full knowledge and maximize our ability to balance the positive and negative aspects of TMAO, in this review, we comprehensively discuss the TMAO in aquatic products from the aspects of physiological functions for marine organisms, flavor, quality, the conversion of precursors, the influences on human health, and the seafood ingredients interaction consideration. Though the circulating TMAO level is inevitably enhanced after seafood consumption, dietary seafood still exhibits beneficial health effects and may provide nutraceuticals to balance the possible adverse effects of TMAO.

The validity and reliability of the Chinese version of the biological rhythms interview of assessment in neuropsychiatry in the community: a large Chinese college student population.

Objective: To test the psychometric properties of the Chinese version of the biological rhythms interview of assessment in neuropsychiatry (C-BRIAN) in a group of young adults with and without depressive symptoms. Methods: Three hundred and seventy-eight university students were recruited as participants. Based on the scores from Center for Epidemiological Survey Depression Scale (CES-D), students were divided into the depressed group and healthy group. Explorative factor analysis was applied to assess the construct validity of the C-BRIAN. The Pittsburgh Sleep Quality Index (PSQI) and CES-D were compared with the C-BRIAN to test the convergent validity. The internal consistency of the C-BRIAN was also examined. Results: Three factors were extracted (activities, eating patterns, and sleep factors) explaining 63.9% of the total variance. The internal consistencies were very good with a coefficient of 0.94 (overall) and 0.89-0.91 for three factors. The domains of activities, eating patterns, and sleep were moderately correlated with PSQI (r=0.579) and CES-D (r=0.559) (ps<0.01). Conclusion: Our findings suggest that C-BRIAN has good validity and reliability which can be used to assess the biological rhythm in the young adult population with depressive symptoms. C-BRIAN would be a reliable tool to detect depressive symptoms for timely prevention and intervention in the community.

Projection-TAGs enable multiplex projection tracing and multi-modal profiling of projection neurons.

Single-cell multiomic techniques have sparked immense interest in developing a comprehensive multi-modal map of diverse neuronal cell types and their brain wide projections. However, investigating the spatial organization, transcriptional and epigenetic landscapes of brain wide projection neurons is hampered by the lack of efficient and easily adoptable tools. Here we introduce Projection-TAGs, a retrograde AAV platform that allows multiplex tagging of projection neurons using RNA barcodes. By using Projection-TAGs, we performed multiplex projection tracing of the mouse cortex and high-throughput single-cell profiling of the transcriptional and epigenetic landscapes of the cortical projection neurons. Projection-TAGs can be leveraged to obtain a snapshot of activity-dependent recruitment of distinct projection neurons and their molecular features in the context of a specific stimulus. Given its flexibility, usability, and compatibility, we envision that Projection-TAGs can be readily applied to build a comprehensive multi-modal map of brain neuronal cell types and their projections.

A non-canonical visual cortical-entorhinal pathway contributes to spatial navigation.

Visual information is important for accurate spatial coding and memory-guided navigation. As a crucial area for spatial cognition, the medial entorhinal cortex (MEC) harbors diverse spatially tuned cells and functions as the major gateway relaying sensory inputs to the hippocampus containing place cells. However, how visual information enters the MEC has not been fully understood. Here, we identify a pathway originating in the secondary visual cortex (V2) and directly targeting MEC layer 5a (L5a). L5a neurons served as a network hub for visual processing in the MEC by routing visual inputs from multiple V2 areas to other local neurons and hippocampal CA1. Interrupting this pathway severely impaired visual stimulus-evoked neural activity in the MEC and performance of mice in navigation tasks. These observations reveal a visual cortical-entorhinal pathway highlighting the role of MEC L5a in sensory information transmission, a function typically attributed to MEC superficial layers before.

Gut Microbiota Metabolite TMA May Mediate the Effects of TMAO on Glucose and Lipid Metabolism in C57BL/6J Mice.

SCOPE: Gut microbiota can convert a variety of alkaloids and TMAO into TMA, which is then transported by the blood to the liver, and converted into TMAO. In recent years, TMAO has attracted wide attention as a metabolic risk factor in cardiovascular disease, diabetes, and other diseases. However, it is still unclear about the role of gut microbial metabolite TMA in the adverse health impacts of TMAO. METHODS AND RESULTS: Male C57BL/6J is treated with intraperitoneal (i.p.) or oral TMAO for 8 weeks, the area under the OGTT curve of oral group is significantly increased by about 15% compared to the control and injection groups. Serum triglyceride levels in the oral group are significantly higher by 28.2% and 24.6% than those in the control and injection groups, respectively. Meanwhile, cholesterol content in serum is significantly elevated by 27.6% and 30.7%. Similarly, proinflammatory factors gene expressions are significantly increased with oral but not i.p. TMAO intervention. Furthermore, transformation in HepG2 cells shows that TMAO could not be converted into TMA by hepatocytes. CONCLUSION: The adverse effects of TMAO on glucose and lipid metabolism in C57BL/6J mice may act through gut microbiota metabolite TMA.

Risk of Systemic Inflammatory Response Syndrome Following Preoperative Glucocorticoids Administration in Patients After Percutaneous Nephrolithotomy: A Retrospective Cohort Study.

INTRODUCTION: Systemic inflammatory response syndrome (SIRS) is one of the most serious complications in patients undergoing percutaneous nephrolithotomy (PCNL). Although glucocorticoids are increasingly used during PCNL, few studies have been concerned about the association between glucocorticoids and postoperative SIRS. The study aims to explore whether preoperative use of glucocorticoids is associated with SIRS after PCNL. METHODS: A total of 1259 patients who underwent PCNL between January 2015 and April 2021 were enrolled in the retrospective cohort study. Risk factors for post-PCNL SIRS were identified by univariate and multivariate regression analysis. To further explore the association between preoperative administration of glucocorticoids and SIRS, 113 pairs of patients were matched for the confounding factors using propensity score matching (PSM) analysis. The odds ratios (OR) and 95 % confidence intervals (CI) for the above variables were analyzed. RESULTS: The incidence of SIRS after PCNL was 9.6 % (121/1259) and the patients who suffered from postoperative SIRS had longer hospital stays and higher hospital costs (all p < 0.05). Multivariate logistic regression analysis indicated that female, preoperative leukocyte count, insertion of central vein catheter, serum albumin, preoperative high-sensitive C-reactive protein/albumin ratio, preoperative transfusion, preoperative administration of glucocorticoids were independent risk factors for SIRS (all p < 0.05). After minimization, the effects of confounding factors by PSM, preoperative administration of glucocorticoids was significantly correlated with SIRS in patients after PCNL (OR=2.44, 95 %CI: 1.31-4.55, p = 0.005). CONCLUSION: Preoperative administration of glucocorticoids is an independent risk factor for SIRS in patients undergoing PCNL.

Systemic inflammatory response syndrome (SIRS) is a frequent and severe complication in patients underwent percutaneous nephrolithotomy (PCNL), which can be challenging to diagnose early, potentially leading to delayed treatment. Identifying SIRS risk factors and promptly treating high-risk patients is crucial. Glucocorticoids are commonly used to prevent SIRS in clinical practice, and this study aims to investigate whether preoperative glucocorticoid administration is associated with SIRS after PCNL. In total, 1259 patients underwent PCNL and were enrolled in the study. The study utilized both propensity score matching (PSM) analysis and regression analysis to identify risk factors for post-PCNL SIRS. The incidence of SIRS after PCNL was 9.6 % in the study and patients with postoperative SIRS had longer hospital stays and higher hospital costs. After minimizing the potential influence of confounding factors through the use of PSM, we found a significant association between the preoperative use of glucocorticoids and the occurrence of SIRS in patients undergoing PCNL. Based on our analysis, we can conclude that the preoperative administration of glucocorticoids represents an independent risk factor for the development of SIRS in these patients.

[Research progress on the organ-protective effect of Maresin-1 in sepsis].

Sepsis is a fatal organ dysfunction caused by the uncontrolled inflammatory response of the host to infection. Excessive inflammatory reaction is the core factor in the occurrence and development of sepsis, the degree of organ dysfunction is directly related to the prognosis of sepsis. Timely intervention of excessive inflammatory response and alleviation of organ function damage are essential to improve the prognosis of sepsis. Maresin-1 (MaR-1) is a newly discovered endogenous specific pro-inflammatory resolution mediator, which plays a role of anti-inflammatory, pro-inflammatory regression and organ protection in sepsis, and may be a new target for the treatment of sepsis. This article reviews the research progress of the role of MaR-1 in the regulation of inflammation and organ protection in sepsis, in order to provide reference for the clinical development of new drugs for the treatment of sepsis.

Efficacy of H2O2 inactivated bovine virus diarrhoea virus (BVDV) type 1 vaccine in mice.

BACKGROUND: Bovine viral diarrhea (BVD) is an acute febrile infectious disease caused by the bovine viral diarrhea virus (BVDV), which has brought huge economic losses to the world's cattle industry. At present, commercial inactivated BVDV vaccines may cause some adverse reactions during use. This study aims to develop a safer and more efficient inactivated BVDV vaccine. METHODS: Here, we described the generation and preclinical efficacy of a hydrogen peroxide (H2O2) inactivated BVDV type 1 vaccine in mice, and administered it separately with commercial vaccine (formaldehyde inactivated) in mice to study its efficacy. RESULTS: The BVDV type 1 IgG, IFN- γ, IL-4 and neutralizing antibody in the serum of the H2O2 inactivated vaccine group can be maintained in mice for 70 days. The IgG level reached its maximum value of 0.67 on the 42nd day, significantly higher than the commercial formaldehyde inactivated BVDV type 1 vaccine. IFN- γ and IL-4 reached their maximum values on the 28th day after immunization, at 123.16 pg/ml and 143.80 pg/ml, respectively, slightly higher than commercial vaccines, but the effect was not significant. At the same time the BVDV-1 neutralizing antibody titer reached a maximum of 12 Nu on the 42nd day post vaccination. CONCLUSIONS: The H2O2 inactivated BVDV vaccine has good safety and immunogenicity, which provides a potential solution for the further development of an efficient and safe BVDV vaccine.

High life satisfaction reported among small-scale societies with low incomes.

Global polls have shown that people in high-income countries generally report being more satisfied with their lives than people in low-income countries. The persistence of this correlation, and its similarity to correlations between income and life satisfaction within countries, could lead to the impression that high levels of life satisfaction can only be achieved in wealthy societies. However, global polls have typically overlooked small-scale, nonindustrialized societies, which can provide an alternative test of the consistency of this relationship. Here, we present results from a survey of 2,966 members of Indigenous Peoples and local communities among 19 globally distributed sites. We find that high average levels of life satisfaction, comparable to those of wealthy countries, are reported for numerous populations that have very low monetary incomes. Our results are consistent with the notion that human societies can support very satisfying lives for their members without necessarily requiring high degrees of monetary wealth.

LC-MS/MS method for the quantification of cortisol of hepatocellular carcinoma.

The imbalance of steroid hormones is closely related to the occurrence and development of hepatocellular carcinoma (HCC). However, most research has focused on steroid hormone receptors, and reports about the relationship between the serum concentration of cortisol and the development of HCC are rare. The aim of this research was to establish a simple, specific, sensitive and reliable liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method for the quantitation of cortisol in human serum and to compare the level of cortisol in serum between 221 HCC patients and 183 healthy volunteers. The results showed that the correlation coefficients of the linear regression with a weighing factor of 1/x2 ranged from 0.9933 to 0.9984 over the range of 2-1,000 ng/ml. The inter- and intra-day precision and accuracy were <10%. The matrix effect and recovery of cortisol were 94.9-102.5% and 96.3-99.8%, respectively. The concentration of cortisol in HCC patients was significantly higher than that in healthy volunteers (p < 0.05) and was not affected by sex, age, menopause or α-fetoprotein (AFP) level. The present study reveals that elevated cortisol might promote the progression of HCC.

Effects of Lycium barbarum polysaccharide on cytokines in adolescents with subthreshold depression: a randomized controlled study.

JOURNAL/nrgr/04.03/01300535-202409000-00036/figure1/v/2024-01-16T170235Z/r/image-tiff Strong evidence has accumulated to show a correlation between depression symptoms and inflammatory responses. Moreover, anti-inflammatory treatment has shown partial effectiveness in alleviating depression symptoms. Lycium barbarum polysaccharide (LBP), derived from Goji berries, exhibits notable antioxidative and anti-inflammatory properties. In our recent double-blinded randomized placebo-controlled trial, we found that LBP significantly reduced depressive symptoms in adolescents with subthreshold depression. It is presumed that the antidepressant effect of LBP may be associated with its influence on inflammatory cytokines. In the double-blinded randomized controlled trial, we enrolled 29 adolescents with subthreshold depression and randomly divided them into an LBP group and a placebo group. In the LBP group, adolescents were given 300 mg/d LBP. A 6-week follow up was completed by 24 adolescents, comprising 14 adolescents from the LBP group (15.36 ± 2.06 years, 3 men and 11 women) and 10 adolescents from the placebo group (14.9 ± 1.6 years, 2 men and 8 women). Our results showed that after 6 weeks of treatment, the interleukin-17A level in the LBP group was lower than that in the placebo group. Network analysis showed that LBP reduced the correlations and connectivity between inflammatory factors, which were associated with the improvement in depressive symptoms. These findings suggest that 6-week administration of LBP suppresses the immune response by reducing interleukin-17A level, thereby exerting an antidepressant effect.

Molecular mechanism of circHIPK3 in mitochondrial function in septic acute kidney injury.

Cell senescence, glycolysis, and mitochondrial deficit jointly regulate the development of septic acute kidney injury (SAKI). This study aimed to explore the role of circular RNA HIPK3 (circHIPK3) in mitochondrial function in SAKI. The SAKI mouse model was established by Candida albicans infection, followed by Western blot assay, measurements of serum lactate, and adenosine triphosphate (ATP), 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimi-dazolylcarbocyanine iodide (JC-1) staining and flow cytometry. Human renal tubular epithelial cells were treated with lipopolysaccharide to establish the SAKI cell model, followed by cell counting kit-8 assay, tests of hexokinase activity, lactate production, oxygen consumption rate, extracellular acidification rate, ATP, and JC-1 staining, and Western blot assay. The roles of mitochondrial pyruvate carrier 1 (MPC1) were validated by kidney function tests, hematoxylin and eosin staining, periodic acid-Schiff staining, and SA-ß-gal staining. circHIPK3 downregulation reduced glycolysis and mitochondrial dysfunction both in vivo and in vitro through the microRNA (miR)-148b-3p/DNMT1/3a/Klotho axis. Inhibition of miR-148b-3p or Klotho increased glycolysis and mitochondrial dysfunction. Knockdown of MPC1 increased lactate content and decreased ATP levels and MMP both in vivo and in vitro. Collectively, circHIPK3, in concert with the miR-148b-3p/DNMT1/3a/Klotho axis, increased glycolysis, and inhibited the negative regulation of lactate production by MPC1, and aggravated mitochondrial dysfunction and cell senescence in SAKI.

Tuning Blood-Material Interactions to Generate Versatile Hemostatic Powders and Gels.

Polymer-based hemostatic materials/devices have been increasingly exploited for versatile clinical scenarios, while there is an urgent need to reveal the rational design/facile approach for procoagulant surfaces through regulating blood-material interactions. In this work, degradable powders (PLPS) and thermoresponsive gels (F127-PLPS) are readily developed as promising hemostatic materials for versatile clinical applications, through tuning blood-material interactions with optimized grafting of cationic polylysine: the former is facilely prepared by conjugating polylysine onto porous starch particle, while F127-PLPS is prepared by the simple mixture of PLPS and commercial thermosensitive polymer. In vitro and in vivo results demonstrate that PLPS2 with the optimal-/medium content of polylysine grafts achieve the superior hemostatic performance. The underlying procoagulant mechanism of PLPS2 surface is revealed as the selective fibrinogen adsorption among the competitive plasma-protein-adsorption process, which is the foundation of other blood-material interactions. Moreover, in vitro results confirm the achieved procoagulant surface of F127-PLPS through optimal PLPS2 loading. Together with the tunable thermoresponsiveness, F127-PLPS exhibits outstanding hemostatic utilization in both femoral-artery-injury and renal-artery-embolization models. The work thereby pioneers an appealing approach for generating versatile polymer-based hemostatic materials/devices.

LncRNA MALAT1-targeting antisense oligonucleotide ameliorates the AngII-induced vascular smooth muscle cell proliferation and migration via Nrf2/GPX4 antioxidant pathway.

ABSTRACT: The high level of oxidative stress induced by angiotensin II (AngII) is the main pathophysiological process that promotes the proliferation and migration of vascular smooth muscle cells (VSMCs) and induces vascular remodeling. LncRNA Metastasis-related lung adenocarcinoma transcript 1 (MALAT1) has been determined to play an important role in the modulation of oxidative stress and the development of cardiovascular diseases. Nevertheless, the function and underlying mechanism of MALAT1 in restenosis induced by hypertensive angioplasty remain unclear. AngII increased the expression of MALAT1 in VSMCs. We found that anti-sense oligonucleotide lncRNA MALAT1 (ASO-MALAT1) could inhibit AngII induced reactive oxygen species (ROS) production and VSMCs proliferation and migration by inducing the expression of glutathione peroxidase 4 (GPX4), which can be reversed by siRNA-GPX4. And GPX4 overexpression can inhibit the proliferation and migration of VSMCs induced by AngII. In addition, we found that the process by which MALAT1 knockdown induces GPX4 expression involves nuclear factor erythrocyte 2 related factor 2 (Nrf2). Overexpression of Nrf2 can increase the expression of GPX4, and down-regulation of GPX4 by ML385 (Nrf2 inhibitor) blocked the protective effect of ASO-MALAT1 on AngII-induced proliferation and migration of VSMCs. Ferrostatin-1 (Fer-1, ip 5mg/kg per day for 2 weeks), a GPX4 agonist, significantly inhibited neointimal formation in spontaneously hypertensive rat (SHR) by the inhibition of oxidative stress. In conclusion, these data imply that ASO-MALAT1 suppresses the AngII-induced oxidative stress, proliferation and migration of VSMCs by activating Nrf2/GPX4 antioxidant signaling. GPX4 may be a potential target for the therapeutic intervention of hypertensive vascular restenosis.

Evaluation of bioequivalence and safety analysis of capecitabine tablets and Xeloda® under postprandial dosing conditions in Chinese patients with solid tumor.

OBJECTIVES: To compare the pharmacokinetic and safety of the test group capecitabine tablets (0.5 g) and the reference group capecitabine tablets (0.5 g). METHODS: This study was registered at www.chinadrugtrials.org.cn under the registration number CTR20220138. 48 subjects with solid tumor were recruited and randomized to receive either the test group or the reference group at a dose of 2 g per cycle for three cycles of the entire trial. RESULTS: The point estimate of the geometric mean ratio of Cmax for the subject and reference groups was 1.0670, which was in the range of 80.00%-125.00%. And the upper limit of 95% confidence interval was -0.0450 < 0. The statistics of geometric mean ratio of AUC0-t and AUC0-∞ (test group/reference group) and their 90% confidence intervals were in the range of 80.00%-125.00%, thus the test group was bioequivalent to the reference group under the conditions of this postprandial test. There were no major or serious adverse events. Conclusion: The pharmacokinetic profiles of capecitabine under postprandial conditions were consistent between the two groups. The two groups were bioequivalent and had a similar favorable safety profile in Chinese patients with solid tumor.

Isolation and functional analysis of acid-producing bacteria from bovine rumen.

Ruminants such as cattle rely mainly on microbes in the rumen to digest cellulose and hemicellulose from forage, and the digestion products are mainly absorbed and utilized by the host in the form of short chain fatty acids (SCFAs). This study aimed to isolate acid-producing strains from the cattle rumen and investigate their functions. A total of 980 strains of acid-producing bacteria were isolated from cattle rumen contents using a medium supplemented with bromocresol green. Combined with the test of acid production ability and 16S rRNA amplicon sequencing technology, five strains were selected based on their ability to produce relatively high levels of acid, including Bacillus pumillus, Enterococcus hirae, Enterococcus faecium, and Bacillus subtilis. Sheep were treated by gavage with a mixed bacterial suspension. The results showed that mixed bacteria significantly increased the body weight gain and feed conversion rate of sheep. To investigate the function of acid-producing bacteria in sheep, we used 16S rDNA sequencing technology to analyze the rumen microbes of sheep. We found that mixed bacteria changed the composition and abundance of sheep rumen bacteria. Among them, the abundance of Bacteroidota, Actinobacteriota, Acidobacteriota, and Proteobacteria was significantly increased, and the abundance of Firmicutes was significantly decreased, indicating that the changes in gut microbiota changed the function of the sheep rumen. The acid-producing bacteria isolated in this study can effectively promote the growth of ruminants, such as cattle and sheep, and can be used as additives to improve breeding efficiency, which lays a foundation for subsequent research on probiotics.