Lutein protects senescent ciliary muscle against oxidative stress through the Keap1/Nrf2/ARE pathway.

BACKGROUND: Aging-induced decline in ciliary muscle function is an important factor in visual accommodative deficits in elderly adults. With this study, we provide an innovative investigation of the interaction between ciliary muscle aging and oxidative stress. METHODS: Tricolor guinea pigs were used for the experiments in vivo and primary guinea pig ciliary smooth muscle cells were used for the experiments in vitro. RESULTS: We enriched for genes associated with muscle-aging-lutein relationship using bioinformatics, including Nuclear factor-erythroid 2-related factor-2 (Nrf2), Glutathione Peroxidase (GPx) gene family, Superoxide Dismutase (SOD) gene family, NAD(P)H: Quinone Oxidoreductase 1 (NQO1) and Heme Oxygenase-1 (HO-1). After gavage to aged guinea pigs, lutein reduced Reactive Oxygen Species (ROS) and P21 levels in senescent ciliary muscle; lutein decreased refractive error and restored accommodation of the eye. In addition, lutein increased GPx, SOD, and Catalase (CAT) levels in serum; lutein increased GPx and CAT levels in ciliary bodies. Lutein regulated the expression of proteins such as Nrf2, Kelch-like ECH-associated protein 1 (Keap1), and downstream proteins in senescent ciliary bodies. Similarly, guinea pig ciliary muscle cell senescence was associated with oxidative stress. In vitro, 100 µM lutein reversed the damage caused by 800 µM H2O2; it reduced Senescence-Associated ß-galactosidase (SA-ß-Gal) and ROS activites, cell apoptosis and cell migration. Also, lutein increased the expression of smooth muscle contractile proteins. Lutein also increased the expression of Nrf2, GPx2, NQO1 and HO-1, decreased the expression of Keap1. A reduction in Nrf2 activity led to a reduction in the ability of lutein to activate antioxidant enzymes in the cells, thus reducing its inhibitory effect on cell senescence. CONCLUSION: lutein improved resistance to oxidative stress in senescent ciliary muscle in vivo and in vitro by regulating the Keap1/Nrf2/Antioxidant Response Element pathway. We have innovatively demonstrated the molecular pharmacological mechanism by which lutein reverse age-related ciliary muscle systolic and diastolic deficits.

Pilocarpine mediated excessive calcium accumulation leads to ciliary muscle cell senescence and apoptosis.

The ciliary muscle constitutes a crucial element in refractive regulation. Investigating the pathophysiological mechanisms within the ciliary muscle during excessive contraction holds significance in treating ciliary muscle dysfunction. A guinea pig model of excessive contraction of the ciliary muscle induced by drops pilocarpine was employed, alongside the primary ciliary muscle cells was employed in in vitro experiments. The results of the ophthalmic examination showed that pilocarpine did not significantly change refraction and axial length during the experiment, but had adverse effects on the regulatory power of the ciliary muscle. The current data reveal notable alterations in the expression profiles of hypoxia inducible factor 1 (HIF-1α), ATP2A2, P53, α-SMA, Caspase-3, and BAX within the ciliary muscle of animals subjected to pilocarpine exposure, alongside corresponding changes observed in cultured cells treated with pilocarpine. Augmented levels of ROS were detected in both tissue specimens and cells, culminating in a significant increase in cell apoptosis in in vivo and in vitro experiments. Further examination revealed that pilocarpine induced an increase in intracellular Ca2+ levels and disrupted MMP, as evidenced by mitochondrial swelling and diminished cristae density compared to control conditions, concomitant with a noteworthy decline in antioxidant enzyme activity. However, subsequent blockade of Ca2+ channels in cells resulted in downregulation of HIF-1α, ATP2A2, P53, α-SMA, Caspase-3, and BAX expression, alongside ameliorated mitochondrial function and morphology. The inhibition of Ca2+ channels presents a viable approach to mitigate ciliary cells damage and sustain proper ciliary muscle function by curtailing the mitochondrial damage induced by excessive contractions.

Dexamethasone-loaded ROS stimuli-responsive nanogels for topical ocular therapy of corneal neovascularization.

Dexamethasone (DEX) has been demonstrated to inhibit the inflammatory corneal neovascularization (CNV). However, the therapeutic efficacy of DEX is limited by the poor bioavailability of conventional eye drops and the increased risk of hormonal glaucoma and cataract associated with prolonged and frequent usage. To address these limitations, we have developed a novel DEX-loaded, reactive oxygen species (ROS)-responsive, controlled-release nanogel, termed DEX@INHANGs. This advanced nanogel system is constructed by the formation of supramolecular host-guest complexes by cyclodextrin (CD) and adamantane (ADA) as a cross-linking force. The introduction of the ROS-responsive material, thioketal (TK), ensures the controlled release of DEX in response to oxidative stress, a characteristic of CNV. Furthermore, the nanogel's prolonged retention on the corneal surface for over 8 h is achieved through covalent binding of the integrin ß1 fusion protein, which enhances its bioavailability. Cytotoxicity assays demonstrated that DEX@INHANGs was not notably toxic to human corneal epithelial cells (HCECs). Furthermore, DEX@INHANGs has been demonstrated to effectively inhibit angiogenesis in vitro. In a rabbit model with chemically burned eyes, the once-daily topical application of DEX@INHANGs was observed to effectively suppress CNV. These results collectively indicate that the nanomedicine formulation of DEX@INHANGs may offer a promising treatment option for CNV, offering significant advantages such as reduced dosing frequency and enhanced patient compliance.

Air-liquid interface exposure of A549 human lung cells to characterize the hazard potential of a gaseous bio-hybrid fuel blend.

Gaseous and semi-volatile organic compounds emitted by the transport sector contribute to air pollution and have adverse effects on human health. To reduce harmful effects to the environment as well as to humans, renewable and sustainable bio-hybrid fuels are explored and investigated in the cluster of excellence "The Fuel Science Center" at RWTH Aachen University. However, data on the effects of bio-hybrid fuels on human health is scarce, leaving a data gap regarding their hazard potential. To help close this data gap, this study investigates potential toxic effects of a Ketone-Ester-Alcohol-Alkane (KEAA) fuel blend on A549 human lung cells. Experiments were performed using a commercially available air-liquid interface exposure system which was optimized beforehand. Then, cells were exposed at the air-liquid interface to 50-2000 ppm C3.7 of gaseous KEAA for 1 h. After a 24 h recovery period in the incubator, cells treated with 500 ppm C3.7 KEAA showed significant lower metabolic activity and cells treated with 50, 250, 500 and 1000 ppm C3.7 KEAA showed significant higher cytotoxicity compared to controls. Our data support the international occupational exposure limits of the single KEAA constituents. This finding applies only to the exposure scenario tested in this study and is difficult to extrapolate to the complex in vivo situation.

Myopia prevalence and ocular biometry in children and adolescents at different altitudes: a cross-sectional study in Chongqing and Tibet, China.

OBJECTIVE: To investigate the differences in myopia prevalence and ocular biometry in children and adolescents in Chongqing and Tibet, China. DESIGN: Cross-sectional study. SETTING: The study included children and adolescents aged 6-18 years in Chongqing, a low-altitude region, and in Qamdo, a high-altitude region of Tibet. PARTICIPANTS: A total of 448 participants in Qamdo, Tibet, and 748 participants in Chongqing were enrolled in this study. METHODS: All participants underwent uncorrected visual acuity assessment, non-cycloplegic refraction, axial length (AL) measurement, intraocular pressure (IOP) measurement and corneal tomography. And the participants were grouped according to age (6-8, 9-11, 12-14 and 15-18 years group), and altitude of location (primary school students: group A (average altitude: 325 m), group B (average altitude: 2300 m), group C (average altitude: 3250 and 3170 m) and group D (average altitude: 3870 m)). RESULTS: There was no statistical difference in mean age (12.09±3.15 vs 12.2±3.10, p=0.549) and sex distribution (males, 50.4% vs 47.6%, p=0.339) between the two groups. The Tibet group presented greater spherical equivalent (SE, -0.63 (-2.00, 0.13) vs -0.88 (-2.88, -0.13), p<0.001), shorter AL (23.45±1.02 vs 23.92±1.19, p<0.001), lower prevalence of myopia (39.7% vs 47.6%, p=0.008) and flatter mean curvature power of the cornea (Km, 43.06±1.4 vs 43.26±1.36, p=0.014) than the Chongqing group. Further analysis based on age subgroups revealed that the Tibet group had a lower prevalence of myopia and higher SE in the 12-14, and 15-18 years old groups, shorter AL in the 9-11, 12-14 and 15-18 years old groups, and lower AL to corneal radius of curvature ratio (AL/CR) in all age subgroups compared with the Chongqing group, while Km was similar between the two groups in each age subgroup. Simple linear regression analysis showed that SE decreased with age in both the Tibet and Chongqing groups, with the Tibet group exhibiting a slower rate of decrease (p<0.001). AL and AL/CR increased with age in both the Tibet and Chongqing groups, but the rate of increase was slower in the Tibet group (p<0.001 of both). Multiple linear regression analysis revealed that AL had the greatest effect on SE in both groups, followed by Km. In addition, the children and adolescents in Tibet presented thinner corneal thickness (CCT, p<0.001), smaller white to white distance (WTW, p<0.001), lower IOP (p<0.001) and deeper anterior chamber depth (ACD, p=0.015) than in Chongqing. Comparison of altitude subgroups showed that the prevalence of myopia (p=0.002), SE (p=0.031), AL (p=0.001) and AL/CR (p<0.001) of children at different altitudes was statistically different but the Km (p=0.189) were similar. The highest altitude, Tengchen County, exhibited the lowest prevalence of myopia and greatest SE among children, and the mean AL also decreased with increasing altitude. CONCLUSIONS: Myopia prevalence in Tibet was comparable with that in Chongqing for students aged 6-8 and 9-11 years but was lower and myopia progressed more slowly for students aged 12-14 and 15-18 years than in Chongqing, and AL was the main contributor for this difference, which may be related to higher ultraviolet radiation exposure and lower IOP in children and adolescents at high altitude in Tibet. Differences in AL and AL/CR between Tibet and Chongqing children and adolescents manifested earlier than in SE, underscoring the importance of AL measurement in myopia screening.

Applying metabolic modeling and multi-omics to elucidate the biotransformation mechanisms of marine algal toxin domoic acid (DA) in sediments.

Domoic acid (DA)-producing algal blooms are a global marine environmental issue. However, there has been no previous research addressing the question regarding the fate of DA in marine benthic environments. In this work, we investigated the DA fate in the water-sediment microcosm via the integrative analysis of a top-down metabolic model, metagenome, and metabolome. Results demonstrated that biodegradation is the leading mechanism for the nonconservative attenuation of DA. Specifically, DA degradation was prominently completed by the sediment aerobic community, with a degradation rate of 0.0681 ± 0.00954 d-1. The DA degradation pathway included hydration, dehydrogenation, hydrolysis, decarboxylation, automatic ring opening of hydration, and ß oxidation reactions. Moreover, the reverse ecological analysis demonstrated that the microbial community transitioned from nutrient competition to metabolic cross-feeding during DA degradation, further enhancing the cooperation between DA degraders and other taxa. Finally, we reconstructed the metabolic process of microbial communities during DA degradation and confirmed that the metabolism of amino acid and organic acid drove the degradation of DA. Overall, our work not only elucidated the fate of DA in marine environments but also provided crucial insights for applying metabolic models and multi-omics to investigate the biotransformation of other contaminants.

Marine toxin domoic acid alters nitrogen cycling in sediments.

As a red tide algal toxin with intense neurotoxicity distributed worldwide, domoic acid (DA) has attracted increasing concerns. In this work, the integrative analysis of metagenome and metabolome are applied to investigate the impact of DA on nitrogen cycling in coastal sediments. Here we show that DA can act as a stressor to induce the variation of nitrogen (N) cycling by altering the abundance of functional genes and electron supply. Moreover, microecology theory revealed that DA can increase the role of deterministic assembly in microbial dynamic succession, resulting in the shift of niches and, ultimately, the alteration in N cycling. Notably, denitrification and Anammox, the important process for sediment N removal, are markedly limited by DA. Also, variation of N cycling implies the modification in cycles of other associated elements. Overall, DA is capable of ecosystem-level effects, which require further evaluation of its potential cascading effects.

Development of a prediction model for exercise tolerance decline in the exercise assessment of patients with acute myocardial infarction undergoing percutaneous coronary intervention revascularization in the acute phase.

Background: Early cardiopulmonary exercise test (CPET) may predict the prognosis of patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI). However, data from CPET to assess the exercise capacity of patients with AMI PCI are still scarce. This study aimed to evaluate the safety of the CPET and assess the predictors and clinical influence of exercise capacity measured by CPET in patients with AMI within 1 week after PCI. Methods: A total of 275 patients with AMI who underwent PCI in the acute phase were selected. Reduced exercise capacity was defined as peak oxygen uptake (VO2peak) <16 mL/kg/min. According to VO2peak, patients were divided into a normal exercise tolerance group and a reduced exercise tolerance group. The general clinical conditions were compared between the 2 groups to investigate the safety of CPET and the influencing factors of exercise tolerance. A nomogram model for predicting patients' exercise capacity was further developed. Clinical outcomes were recorded. Results: The median time of CPET in all patients was 5 days after PCI. Among the 275 patients, exercise tolerance decreased in 90 cases (32.72%). Multivariate logic analysis showed that E/e', age, glycosylated hemoglobin, and estimated glomerular filtration rate (eGFR) were independent predictors of early exercise capacity reduction in these patients. Utilizing the correlation coefficients from pre-assessment clinical and CPET indicators within the logistic regression framework, we constructed a nomogram model to forecast the diminishing exercise tolerance in AMI patients. The predictive accuracy of this model, as indicated by a C-index of 0.771 and an area under the receiver operating characteristic (ROC) curve of 0.771 (95% CI: 0.710-0.832), demonstrates its potential as a robust tool in clinical settings. During a follow-up of 24 months, the incidence of clinical outcomes in patients with low exercise tolerance was significantly higher than that in patients with normal exercise tolerance, among which all-cause mortality and reinfarction were statistically different (P=0.009 and P=0.043). Conclusions: The reduced exercise capacity in patients with AMI after initial PCI is related to age, diastolic dysfunction, renal function, and blood glucose control, which may lead to poor clinical prognosis. The nomogram prediction model performed well in predicting the declining exercise tolerance of patients with AMI.

Three-Dimensional Quantitative Description of the Implantable Collamer Lens in the Ocular Anterior Segment of Patients With Myopia.

PURPOSE: To describe the 3-dimensional (3D) location of the implantable collamer lens (ICL) quantitatively in the posterior ocular chamber of patients with myopia. DESIGN: Cross-sectional study. METHODS: To obtain visualization models before and after mydriasis, an automatic 3D imaging method based on swept-source optical coherence tomography was created. Parameters like the ICL lens volume (ILV), the tilt of the ICL and crystalline lens, the vault distribution index, and topographic maps were evaluated to describe the ICL location. Using a paired sample t test and the Wilcoxon signed rank test, the difference between nonmydriasis and postmydriasis conditions was compared. RESULTS: The study investigated 32 eyes from 20 patients. The 3D central vault did not differ significantly before (P = .994) or after mydriasis (P = .549) compared with the 2D central vault. After mydriasis, the 5-mm ILV decreased by 0.85 mm2 (P = .016), and the vault distribution index increased significantly (P = .001). The ICL and the crystalline lens exhibited tilt (nonmydriasis: ICL total tilt 3.78 ± 1.85 degrees, lens total tilt 4.03 ± 1.53 degrees; postmydriasis: ICL total tilt 3.84 ± 1.56 degrees, lens total tilt 4.09 ± 1.64 degrees). The phenomenon of asynchronous tilt of the ICL and lens was found in 5 eyes, leading to the spatially asymmetric distribution of the ICL-lens distance. CONCLUSION: The 3D imaging technique provided exhaustive and reliable data for the anterior segment. The visualization models offered multiple perspectives on the ICL in the posterior chamber. Before and after mydriasis, the intraocular ICL position was described by the 3D parameters.

Cyclohexanecarboxylic acid degradation with simultaneous nitrate removal by Marinobacter sp. SJ18.

Naphthenic acid (NA) is a toxic pollutant with potential threat to human health. However, NA transformations in marine environments are still unclear. In this study, the characteristics and pathways of cyclohexanecarboxylic acid (CHCA) biodegradation were explored in the presence of nitrate. The results showed that CHCA was completely degraded with pseudo-first-order kinetic reaction under aerobic and anaerobic conditions, accompanied by nitrate removal rates exceeding 70%, which was positively correlated with CHCA degradation (P < 0.05). In the proposed CHCA degradation pathways, cyclohexane is dehydrogenated to form cyclohexene, followed by ring-opening by dioxygenase to generate fatty acid under aerobic conditions or cleavage of cyclohexene through ß-oxidation under anaerobic conditions. Whole genome analysis indicated that nitrate was removed via assimilation and dissimilation pathways under aerobic conditions and via denitrification pathway under anaerobic conditions. These results provide a basis for alleviating combined pollution of NA and nitrate in marine environments with frequent anthropogenic activities.

A new pathway for anaerobic biotransformation of marine toxin domoic acid.

Domoic acid (DA) is a harmful algal toxin produced by marine diatom Pseudo-nitzschia and seriously threatens ecosystem and human health. However, the current knowledge on its biotransformation behavior in coastal anaerobic environment is lacking. This study investigated the anaerobic biotransformation of DA by a new marine consortium GH1. The results demonstrated that 90% of DA (1 mg L-1) was cometabolically biotransformed under sulfate-reducing condition. A new anaerobic biotransformation pathway involving DA hydration, dehydrogenation, and C-C bond cleavage was proposed, where the conjugated double-bond of DA was interrupted, resulting in the corresponding alcohols and ketones, subsequently cleaved hydrolytically, and yielding the lower molecular weight products. Desulfovibrio and Clostridiales were markedly enriched in the anaerobic biotransformation of DA, which might jointly contribute to the elevated bacterial consortium resistance and degradation to DA. This study could deepen understanding of behavior and fate for DA in marine environments.

Human Vascular Endothelial Cells Promote the Secretion of Vascularization Factors and Migration of Human Skin Fibroblasts under Co-Culture and Its Preliminary Application.

The good treatment of skin defects has always been a challenge in the medical field, and the emergence of tissue engineering skin provides a new idea for the treatment of injured skin. However, due to the single seed cells, the tissue engineering skin has the problem of slow vascularization at the premonitory site after implantation into the human body. Cell co-culture technology can better simulate the survival and communication environment of cells in the human body. The study of multicellular co-culture hopes to bring a solution to the problem of tissue engineering. In this paper, human skin fibroblasts (HSFs) and human vascular endothelial cells (HVECs) were co-cultured in Transwell. The Cell Counting Kit 8 (CCK8), Transwell migration chamber, immunofluorescence, Western blot (WB), and real time quantitative PCR (RT-qPCR) were used to study the effects of HVECs on cell activity, migration factor (high mobility group protein 1, HMGB1) and vascularization factor (vascular endothelial growth factor A, VEGFA and fibroblast growth factor 2, FGF2) secretion of HSFs after co-cultured with HVECs in the Transwell. The biological behavior of HSFs co-cultured with HVECs was studied. The experimental results are as follows: (1) The results of cck8 showed that HVECS could promote the activity of HSFs. (2) HVECs could significantly promote the migration of HSFs and promote the secretion of HMGB1. (3) HVECs could promote the secretion of VEGFA and FGF2 of HSFs. (4) The HVECs and HSFs were inoculated on tissue engineering scaffolds at the ratio of 1:4 and were co-cultured and detected for 7 days. The results showed that from the third day, the number of HSFs was significantly higher than that of the control group without HVECs.

HMGB1/RAGE axis accelerates the repair of HUVECs injured by pathological mechanical stretching via promoting bFGF expression.

AIM: During hypertension-induced endothelial dysfunction, periodic mechanical stretching (MS) activates related inflammatory pathways and leads to endothelial damage, but the underlying mechanisms remain unknown. The present study aimed to determine the injury of HUVECs caused by overstretching and the role of HMGB1-RAGE pathway in HUVECs after injury. MAIN METHODS AND KEY FINDINGS: Human umbilical vein endothelial cells (HUVECs) were cultured and seeded in BioFlex™ plates (six wells). Cells were exposed to 5% (physiological state) and 20% (pathological state) mechanical stretch at 1 Hz for 12 or 24 h in a Flexcell-5000™, with unstretched cells serving as controls. It was found that excessive MS can inhibit cell viability, proliferation, and tube-forming ability resulting in disordered cell arrangement and orientation, slowing cell migration. All these changes cause endothelial damage compared to physiological MS. Endothelial cells (ECs) promote cell migration and self-repair after injury by increasing the High-mobility group box 1 (HMGB1) expression. Experiments and protein prediction networks have shown that HMGB1 can also promote the expression of downstream protein bFGF by binding to receptor for advanced glycation end products (RAGE). Interestingly, VEGF protein expression did not change significantly during this repair process, implying that bFGF replaces the role of VEGF in vascular endothelial repair. SIGNIFICANCE: The present study demonstrates that in the context of endothelial injury caused by excessive MS, the HMGB1/RAGE/bFGF pathway is activated and promotes endothelial repair after injury. Therefore, understanding these mechanisms will help find new therapies for diseases such as hypertension, atherosclerosis, and aneurysm formation.

The Effectiveness and Rotational Stability of Vertical Implantation of the Implantable Collamer Lens for the Treatment of Myopia.

PURPOSE: To explore the effectiveness and rotational stability of vertical implantation of the Implantable Collamer Lens (ICL) (STAAR Surgical) to treat myopia. METHODS: This was a prospective, randomized, controlled study, including 78 eyes from 46 patients with myopia who underwent ICL implantation. The patients were randomly divided into vertical and horizontal implantation groups. At 1 day, 1 week, 1 month, and 3 months after surgery, rotational stability was evaluated using the postoperative axis deviation from the intended axis by the digital anterior segment photograph. The vault, crystalline lens rise, anterior chamber depth, manifest refraction spherical equivalent, intraocular pressure, and visual acuity values were obtained before and after surgery. RESULTS: A 3-month follow-up period showed significant differences between the efficacy indexes in the horizontal (1.11 ± 0.02) and vertical (1.13 ± 0.02) groups (P = .455). No significant difference was observed in the postoperative manifest refraction spherical equivalent between the horizontal (-0.27 ± 0.18 diopters) and vertical (0.01 ± 0.08 diopters) groups (P = .151). Also, no statistically significant difference was observed in the corneal endothelial cells and intraocular pressure between groups (P = .555, P = .464). The rotation angle of the horizontal group was greater at 1 week, 1 month, and 3 months (3.14° ± 2.13°, 2.97° ± 2.01°, 3.27° ± 2.12°, respectively) compared to that of the vertical group (1.30° ± 1.29°, 1.85° ± 1.60°, 1.74° ± 1.33°, respectively) (P < .001 for all). From 1 week to 3 months, the changing angle of horizontal (0.31° ± 1.86°) and vertical (0.49° ± 1.33°) ICL rotation displayed a positive correlation with the changing vault of horizontal (48.41 ± 86.02 mm) and vertical (39.64 ± 78.43 mm) ICL rotation (r = 0.242, 0.335, P = .033, .037). CONCLUSIONS: The study supports great efficacy and safety in both vertical and horizontal implantation, with the vertical implantation group displaying better stability. [J Refract Surg. 2022;38(10):641-647.].

Response mechanism of microbial community during anaerobic biotransformation of marine toxin domoic acid.

Domoic acid (DA) is a potent neurotoxin produced by toxigenic Pseudo-nitzschia blooms and quickly transfers to the benthic anaerobic environment by marine snow particles. DA anaerobic biotransformation is driven by microbial interactions, in which trace amounts of DA can cause physiological stress in marine microorganisms. However, the underlying response mechanisms of microbial community to DA stress remain unclear. In this study, we utilized an anaerobic marine DA-degrading consortium GLY (using glycine as co-substrate) to systematically investigate the global response mechanisms of microbial community during DA anaerobic biotransformation.16S rRNA gene sequencing and metatranscriptomic analyses were applied to measure microbial community structure, function and metabolic responses. Results showed that DA stress markedly changed the composition of main species, with increased levels of Firmicutes and decreased levels of Proteobacteria, Cyanobacteria, Bacteroidetes and Actinobacteria. Several genera of tolerated bacteria (Bacillus and Solibacillus) were increased, while, Stenotrophomonas, Sphingomonas and Acinetobacter were decreased. Metatranscriptomic analyses indicated that DA stimulated the expression of quorum sensing, extracellular polymeric substance (EPS) production, sporulation, membrane transporters, bacterial chemotaxis, flagellar assembly and ribosome protection in community, promoting bacterial adaptation ability under DA stress. Moreover, amino acid metabolism, carbohydrate metabolism and lipid metabolism were modulated during DA anaerobic biotransformation to reduce metabolic burden, increase metabolic demands for EPS production and DA degradation. This study provides the new insights into response of microbial community to DA stress and its potential impact on benthic microorganisms in marine environments.

Prenatal Morphine Exposure Differentially Alters Addictive and Emotional Behavior in Adolescent and Adult Rats in a Sex-Specific Manner.

The effects of prenatal opioid exposure in adult animals has been widely studied, but little is known about the effects of prenatal opioid on adolescents. Most of the risk behaviors associated with drug abuse are initiated during adolescence. The developmental state of the adolescent brain makes it vulnerable to initiate drug use and susceptible to drug-induced brain changes. In this study, pregnant rats were subcutaneously injected with an increasing dose of morphine (5 mg/kg, 7 mg/kg, 10 mg/kg) for 9 days since the gestation day 11. The effects of prenatal morphine (PNM) on learning and memory, anxiety- and depressive- like behavior, morphine induced conditioned place preference (CPP) as well as locomotor sensitization were tested in both adolescent and adult rats. The results showed that: (1) PNM decreased anxiety-like behavior in both adolescent and adult female rats, but not males; (2) PNM decreased depressive-like behavior in adolescent but increased depressive -like behavior in adult females; (3) PNM increased low dose morphine induced locomotor sensitization in females; (4) PNM decreased tyrosine hydroxylase (TH) expression in the prefrontal cortex but decreased dopamine D1 receptor expression in the nucleus-accumbens (NAc) in female rats. These results suggested that PNM altered the emotional and addictive behavior mainly in female rats, with female rats being less anxiety and depressive during adolescence, but more depressive in adult, and more sensitive to low dose morphine induced locomotor activity sensitization, which might be mediated in part by the differential expression of the TH, dopamine D1 receptors in the female brain.

Serine active site containing protein 1 depletion alters lipid metabolism and protects against high fat diet-induced obesity in mice.

OBJECTIVE: Although the serine active site containing 1 (SERAC1) protein is essential for cardiolipin remodeling and cholesterol transfer, its physiological role in whole-body energy metabolism remains unclear. Thus, we investigated the role of SERAC1 in lipid distribution and metabolism in mice. METHODS: CRISPR/Cas9 was used to create homozygous Serac1 knockout mice. A range of methods, including electron microscopy, histological analysis, DNA sequencing, glucose and insulin tolerance tests, and biochemical analysis of serum lipid levels, were used to assess lipid distribution and rates of lipid synthesis in mice. RESULTS: We found that Serac1 depletion in mice prevented high-fat diet-induced obesity but did not affect energy expenditure. The liver was affected by Serac1 depletion, but adipose tissues were not. Serac1 depletion was shown to impair cholesterol transfer from the liver to the serum and led to an imbalance in cholesterol distribution. The livers from mice with Serac1 depletion showed increased cholesterol synthesis because the levels of cholesterol synthesis enzymes were upregulated. Moreover, the accumulation of hepatic lipid droplets in mice with Serac1 depletion were decreased, suggesting that SERAC1 depletion may decrease the risk for hepatic steatosis in high fat diet-induced mice. CONCLUSION: Our findings demonstrate that SERAC1 can serve as a potential target for the treatment or prevention of diet-induced hepatic lipid metabolic disorders.

SERAC1 is a component of the mitochondrial serine transporter complex required for the maintenance of mitochondrial DNA.

SERAC1 deficiency is associated with the mitochondrial 3-methylglutaconic aciduria with deafness, (hepatopathy), encephalopathy, and Leigh-like disease [MEGD(H)EL] syndrome, but the role of SERAC1 in mitochondrial physiology remains unknown. Here, we generated Serac1-/- mice that mimic the major diagnostic clinical and biochemical phenotypes of the MEGD(H)EL syndrome. We found that SERAC1 localizes to the outer mitochondrial membrane and is a protein component of the one-carbon cycle. By interacting with the mitochondrial serine transporter protein SFXN1, SERAC1 facilitated and was required for SFXN1-mediated serine transport from the cytosol to the mitochondria. Loss of SERAC1 impaired the one-carbon cycle and disrupted the balance of the nucleotide pool, which led to primary mitochondrial DNA (mtDNA) depletion in mice, HEK293T cells, and patient-derived immortalized lymphocyte cells due to insufficient supply of nucleotides. Moreover, both in vitro and in vivo supplementation of nucleosides/nucleotides restored mtDNA content and mitochondrial function. Collectively, our findings suggest that MEGD(H)EL syndrome shares both clinical and molecular features with the mtDNA depletion syndrome, and nucleotide supplementation may be an effective therapeutic strategy for MEGD(H)EL syndrome.

Research on the coordinated development of ecosystem services and well-being in agricultural and pastoral areas.

Payment for Ecosystem Services (PES) has been widely accepted as a policy tool for promoting ecological and social progress. However, PES development and implementation in traditional agricultural and pastoral areas are often more challenging than in other areas. The contradiction between ecological protection and people's livelihood development in traditional agricultural and pastoral areas is related to developing country's sustainable development strategy. Based on this, we evaluate the PES (ERCCP: the Ecological Relocation and Capital Compensation Program) program in Tianzhu County, as a case study to investigated the impact of ERCCP on the local natural and social ecosystems on a 20-year scale. The results of indicated that ERCCP has achieved "win-win" gains of restoring environment and promoting socioeconomic development: in the 10 years since ERCCP was implemented, the area of forest land and grassland increased significantly, increasing by 1135.6 ha and 919.62 ha, respectively. 57.5% of farmland was converted to grassland and 30.8% to forest, respectively. In addition, 92.2% and 7.5% of bare land were replaced by grassland and forest, respectively, indicating a gradual recovery of green land during this period. We also analyzed the effects of ERCCP on social systems, and found that the change of agro-pastoralists' attitude towards ERCCP promoted the transfer of labor force from the primary industry to the tertiary industry, accelerated the development of urbanization, and made the poor population completely out of poverty by 2020. In addition, we predict that the income level of households, the PES return on investment of local governments, and the value of regional ecosystem services will increase significantly after 2025. In this context, We establish a theoretical model to explain the win-win plan for the coordinated development of ecosystem services and regional well-being to explore the sustainability of PES and provided a typical case for the similar research area in the world, especially in the areas with the ecological fragility and poverty problems.

A novel degradation mechanism of naphthenic acids by marine Pseudoalteromonas sp.

Naphthenic acids (NAs) are a persistent toxic organic pollutant that occur in different environment worldwide and cause serious threat to the ecosystem and public health. However, knowledge on the behavior and fate of NAs in marine environments still remains unknown. In this study, the degradation mechanism of NAs (cyclohexylacetic acid, CHAA) was investigated using an common indigenous marine Pseudoalteromonas sp. The results showed that CHAA could be degraded completely under aerobic condition, but could not be utilized directly under anaerobic condition. Interestingly, transcriptome and key enzyme activity results showed the CHAA degradation pathway induced under aerobic condition could still work in anaerobic condition. The degradation was activated by acetyl-CoA transferase and sequentially formed the corresponding cyclohexene, alcohol, and ketone with the assistance of related enzymes, and finally cleaved by hydroxymethylglutarate-CoA lyase. Besides, there was a positive correlation between chemotaxis and aerobic degradation genes (r = 0.976, P < 0.05), the chemotaxis would enhance bacterium movement and NAs biodegradation. It is proposed that bacterium could translocate to NAs and accomplish biodegradation from aerobic to anaerobic environments, which was a new anaerobic degradation pathway of NAs. This study provides new insights into the fate of NAs and other organic contaminants in marine environment.