Unraveling the causal relationships between depression and brain structural imaging phenotypes: A bidirectional Mendelian Randomization study.

BACKGROUND: Previous studies have revealed structural brain abnormalities in individuals with depression, but the causal relationship between depression and brain structure remains unclear. METHODS: A genetic correlation analysis was conducted using summary statistics from the largest genome-wide association studies for depression (N = 674,452) and 1,265 brain structural imaging-derived phenotypes (IDPs, N = 33,224). Subsequently, a bidirectional two-sample Mendelian Randomization (MR) approach was employed to explore the causal relationships between depression and the IDPs that showed genetic correlations with depression. The main MR results were obtained using the inverse variance weighted (IVW) method, and other MR methods were further employed to ensure the reliability of the findings. RESULTS: Ninety structural IDPs were identified as being genetically correlated with depression and were included in the MR analyses. The IVW MR results indicated that reductions in the volume of several brain regions, including the bilateral subcallosal cortex, right medial orbitofrontal cortex, and right middle-posterior part of the cingulate cortex, were causally linked to an increased risk of depression. Additionally, decreases in surface area of the right middle temporal visual area, right middle temporal cortex, right inferior temporal cortex, and right middle-posterior part of the cingulate cortex were causally associated with a heightened risk of depression. Validation and sensitivity analyses supported the robustness of these findings. However, no evidence was found for a causal effect of depression on structural IDPs. CONCLUSIONS: Our findings reveal the causal influence of specific brain structures on depression, providing evidence to consider brain structural changes in the etiology and treatment of depression.

Employee education, labor protection intensity and auditor risk perception.

Prior literature finds senior executives can influence auditor decision making. However, few studies have discussed the impact of employee's personal characteristics. Our research aims to fill the above research gaps by examining the impact of employee level education on audit costs. Taking A-share listed companies in Shanghai and Shenzhen from 2006 to 2021 as the research object, this paper examines the impact of employee education on audit fees. It is found that highly educated employees can effectively reduce the audit fees borne by the company, but the implementation of the Labor Protection Law weakens this inhibitory effect. In the case of low marketization level and weak Confucian culture intensity, employee education level has a more significant inhibitory effect on audit fees of listed companies. This study provides a basis for empirical research on the impact of employee attributes on auditor decision making, provides a new research perspective on the impact of labor protection law at the corporate micro level, and enriches the theoretical research on corporate governance rooted in traditional Chinese culture. We contribute to the practice that implications for evaluating the effectiveness of adopting labor protection.

Artemisia argyi essential oil alleviates asthma by regulating 5-LOX-CysLTs and IDO-1-KYN pathways: Insights from metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia argyi essential oil (AAEO) is a traditional herbal remedy for asthma. However, the potential effect of AAEO on asthma has not been elucidated. AIM OF THE STUDY: To investigate the protective properties of AAEO upon asthma and elucidate its mechanism. MATERIALS AND METHODS: The effects of AAEO in asthma were assessed by histology and biochemical analysis. Then, we integrated real-time reverse transcription-quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, immunohistochemistry and metabolomics analysis to reveal its mechanism. RESULTS: In vivo, AAEO reduced the counts of white blood cells (WBCs) and cytokines in bronchoalveolar lavage fluid (BALF), ameliorated pathologic alterations in lung tissues, and inhibited secretion of OVA-sIgE and muc5ac. Metabolomics results showed that AAEO can exert therapeutic effects on asthmatic mice by regulating disordered arachidonic acid metabolism and tryptophan metabolism. Further studies shown that AAEO inhibited the expression of 5-LOX and reduced the accumulation of CysLTs in mice. Meanwhile, AAEO promoted the activity of IDO-1, facilitated the conversion of tryptophan to kynurenine, and regulated the imbalance of Treg/Th17 immunity. Immunohistochemical results showed that AAEO promoted the expression of IDO-1. RT-qPCR results showed that AAEO promoted the expression of IL-10 and Foxp3 mRNA, and inhibited the expression of IL-17A and RORγt mRNA, thus regulated the imbalance of Treg/Th17 immunity and exerted its therapeutic effects. CONCLUSION: AAEO treatment not only attenuates the clinical symptoms of asthma but is also involved in regulating lung tissue metabolism. The anti-asthmatic activity of AAEO may be achieved by reprogramming 5-LOX-CysLTs and IDO-1-KYN pathways.

Effect of bovine colostrum liposomes on the bioavailability of immunoglobulin G and their immunoregulatory function in immunosuppressed BALB/c mice.

Bovine colostrum (BC) has high nutritional value; however, the low bioavailability of immune active substances in BC may affect their immunoregulatory function. Our previous studies indicated that encapsulating bovine colostrum with liposomes could enable the sustained release of immunoglobulin G in vitro; however, the effect of bovine colostrum liposomes (BCLs) on the bioavailability of immunoglobulins in vivo is still unknown. In addition, the immunoregulatory function of BCLs on immunosuppressed mice is still unclear. Therefore, our current study aimed to explore the effect of BCLs on the bioavailability of immunoglobulins, and further explore their immunoregulatory effect on immunosuppressed BALB/c mice. Through metabolic cage experiments, it was shown that BCLs decreased the urine and fecal concentrations of IgG and exhibited a higher bioavailability of IgG in mice than BC (about 2-fold). In addition, by establishing an immunosuppressed animal model, it was found that BCLs could increase the body weight, spleen weight, and thymus weight in immunosuppressed BALB/c mice, which further restored the serum levels of interleukin-4 (IL-4), interleukin-10 (IL-10), tumor necrosis factor α (TNF-α), and interferon γ (IFN-γ). Through histology analysis, it was suggested that BCLs restored the structure of jejunal epithelial cells, which was accompanied by an improvement in intestinal cytokine levels (IL-4, IL-10, TNF-α, and IFN-γ). Finally, BCLs increased serum and intestine concentrations of immunoglobulin G (IgG) and immunoglobulin A (IgA) in immunosuppressed BALB/c mice, which further indicated that BCLs had a sustained-release effect for immunoglobulin G in vivo. Our current research will provide a basis for understanding the role of BCLs on the bioavailability of IgG and their immunoregulatory effect on immunosuppressed mice, which might further provide some reference for the application of BCLs.

Optimizing solvent dipole moment enables PVDF to improve piezoelectric performance.

The all-trans conformation (ß-phase) possesses a significant impact on the piezoelectric polymer polyvinylidene fluoride (PVDF). Inducing more molecular chain [-CH2-CF2-]nto form all-trans conformation is one of the biggest obstacles for manufacturing high-performance piezoelectric sensing devices. Herein, the continuous vacuum technology is used to modulate the polarity of binary solvents by the proportion of the lower solvent. The regulated solvent forms a high dipole moment, an interaction between the dipole ofß-phase and the dipole moment makes the phase reversal in PVDF. Fourier transform infrared spectroscopy, piezoelectric constant test and other characterization results show that when the weakly polar acetone and the strongly polar solvent DMF reach a ratio of 4:6, the pure PVDF film possesses high piezoelectricity (d33∼ -44.8 pC N-1) and strong self-polarization. Additionally, the A4D6device exhibits high sensitivity (S1= 0.182 V/N, 0.5 N ∼ 30 N), driven capability (0.49 mW m-2), and reliability during the electrical tests as a pressure device. This work provides an effective and cost-effective route of optimizing the solvent's polarity to improve the piezoelectric characteristics of the polymer.

Identifying the mediating role of socioeconomic status on the relationship between schizophrenia and major depressive disorder: a Mendelian randomisation analysis.

Depressive disorder prevalence in patients with schizophrenia has been reported to be 40%. People with low socioeconomic status (SES) are more likely to suffer from schizophrenia and major depressive disorder (MDD). However, the causal relationship between schizophrenia and depression and the potential mediating role of SES remains unclear. Two-sample Mendelian randomization (MR) analyses were conducted to explore the bidirectional causal relationship between schizophrenia and MDD with the largest sample size of European ancestry from public genome-wide association studies (sample size ranged from 130,644 to 480,359). Inverse variance weighted (IVW) method was used as the primary analysis, and several canonical MR methods were used as validation analyses. The mediating role of SES (educational years, household income, employment status, and Townsend deprivation index) was estimated by the two-step MR method. MR analyses showed that genetically predicted schizophrenia was associated with an increased risk of MDD (IVW odds ratio [OR] = 1.137 [95% CI 1.095, 1.181]). Reversely, MDD was also associated with an increased risk of schizophrenia (IVW OR = 1.323 [95% CI 1.118, 1.565]). The mediation analysis via the two-step MR method revealed that the causal effect of schizophrenia on MDD was partly mediated by the Townsend deprivation index with a proportion of 10.27%, but no significant mediation effect was found of SES on the causal effect of MDD on schizophrenia. These results suggest a robust bidirectional causal effect between schizophrenia and MDD. Patients with schizophrenia could benefit from the early and effective intervention of the Townsend deprivation index.

Polymorphs of a 1:1 salt of sulfadiazine and piperazine-relative stability, dissolution studies, pharmacokinetics and anti-meningitis efficiency.

Two new salt forms of sulfadiazine (SDZ) and piperazine (PIP) were synthesized and characterized. Out of the two polymorphs (SDZ-PIP Ⅰ and SDZ-PIP II), SDZ-PIP Ⅱ is the more stable form at low temperature, room temperature and high temperature. The solution-mediated phase transformation result shows that SDZ-PIP II can transform into pure SDZ within 15 s in phosphate buffer at 37 °C, which leads to a loss in solubility advantage. The addition of 2 mg/mL PVP K30, a polymeric crystallization inhibitor, maintains the solubility advantage and permits supersaturation for a longer period of time. SDZ-PIP II showed 2.5 times the solubility of SDZ alone. The area under the curve (AUC) of SDZ-PIP II with 2 mg/mL PVP K30 was approximately 165% of that of SDZ alone. Moreover, SDZ-PIP II with PVP K30 was more effective than SDZ alone in treating meningitis. Therefore, the SDZ-PIP II salt improves the solubility, bioavailability, and anti-meningitis activity of SDZ.

Comprehensive quality evaluation of plant-based cheese analogues.

BACKGROUND: In recent years, there has been an increasing demand for plant-based cheese analogues, however, the protein content of plant-based cheeses currently on the market is generally low and cannot meet the nutritional needs of consumers. RESULTS: Based on the ideal value similarity method (TOPSIS) analysis the best recipe for plant-based cheese was 15% tapioca starch, 20% soy protein isolate, 7% gelatine as a quality enhancer and 15% coconut oil. The protein content of this plant-based cheese was170.1 g kg-1 , which was close to commercial dairy-based cheese and significantly higher than commercial plant-based cheese, The fat content was 114.7 g kg-1 , lower than that of commercial dairy-based cheese. The rheology properties show that the viscoelasticity of the plant-based cheese is higher than that of dairy-based cheese and commercial plant-based. The microstructure results show that the type and content of protein has a significant impact on its microstructure. The Fourier-transform infrared (FTIR) spectrum of the microstructure shows a characteristic value at 1700 cm-1 , because the starch was heated and leached to form a complex with lauric acid under the action of hydrogen bond. It can be inferred that in the interaction between plant-based cheese raw materials, fatty acids serve as a bridge between starch and protein. COUCLUSION: This study described the formula of plant-based cheese and the interaction mechanism between the ingredients, providing a basis for the development of subsequent plant-based cheese related products. © 2023 Society of Chemical Industry.

The impact of pre-adulthood urbanicity on hippocampal subfield volumes and neurocognitive abilities in young adults.

BACKGROUND: Urbanicity refers to the conditions that are particular to urban areas and is a growing environmental challenge that may affect hippocampus and neurocognition. This study aimed to investigate the effects of the average pre-adulthood urbanicity on hippocampal subfield volumes and neurocognitive abilities as well as the sensitive age windows of the urbanicity effects. PARTICIPANTS AND METHODS: We included 5,390 CHIMGEN participants (3,538 females; age: 23.69 ± 2.26 years, range: 18-30 years). Pre-adulthood urbanicity of each participant was defined as the average value of annual night-time light (NL) or built-up% from age 0-18, which were extracted from remote-sensing satellite data based on annual residential coordinates of the participants. The hippocampal subfield volumes were calculated based on structural MRI and eight neurocognitive measures were assessed. The linear regression was applied to investigate the associations of pre-adulthood NL with hippocampal subfield volumes and neurocognitive abilities, mediation models were used to find the underlying pathways among urbanicity, hippocampus and neurocognition, and distributed lag models were used to identify sensitive age windows of urbanicity effect. RESULTS: Higher pre-adulthood NL was associated with greater volumes in the left (ß = 0.100, 95%CI: [0.075, 0.125]) and right (0.078, [0.052, 0.103]) fimbria and left subiculum body (0.045, [0.020, 0.070]) and better neurocognitive abilities in information processing speed (-0.212, [-0.240, -0.183]), working memory (0.085, [0.057, 0.114]), episodic memory (0.107, [0.080, 0.135]), and immediate (0.094, [0.065, 0.123]) and delayed (0.087, [0.058, 0.116]) visuospatial recall, and hippocampal subfield volumes and visuospatial memory showed bilateral mediations for the urbanicity effects. Urbanicity effects were greatest on the fimbria in preschool and adolescence, on visuospatial memory and information processing from childhood to adolescence and on working memory after 14 years. CONCLUSION: These findings improve our understanding of the impact of urbanicity on hippocampus and neurocognitive abilities and will benefit for designing more targeted intervention for neurocognitive improvement.

Occurrence of microplastics pollution in the Yangtze River: Distinct characteristics of spatial distribution and basin-wide ecological risk assessment.

The widespread presence of microplastics (MPs) in the Yangtze River, the third longest river in the world, has drawn increasing attention. Although numerous studies have been conducted recently to investigate and analyze the MPs exposure to the surface water of the river, most merely focus on a certain part of the Yangtze River, and knowledge of MPs based on the basin-wide is still scattered. This article reveals the spatial distribution characteristics of MPs in the Yangtze River from the whole watershed scale. Among the five areas in the basin, the upstream and the midstream were demonstrated to contain more MPs (3598.6 particles/m3 and 3226.8 particles/m3). The obtained results suggested the MP presented in the entire watersheds was uneven and the 'hotspots' occurred, where the MPs concentrations were relatively higher than the surrounding. The discharging of the wastewater treatment plants along the river, the locations of dams, and the stability and fragment of MPs, were demonstrated to be the important driving factors in the spatial distribution of MPs and leading to the appearance of the MP 'hotspots' in the Yangtze River, but were previously overlooked. It is the first study to evaluate the ecological risk of MPs exposure to the surface water of the Yangtze River with multiple assessment methods, taking not only abundance but also morphological characteristics, polymer composition and toxic effect into account. More importantly, based on the multiple individual MPs risk assessment methods, we developed the BetaMP method which achieves a comprehensive assessment of MP risk in basin-wide by taking multiple MP characteristics into account for the first time. This is conducive to better understanding the environmental impacts of MPs pollution in the different regions of the river.

Transcriptional signatures of the cortical morphometric similarity network gradient in first-episode, treatment-naive major depressive disorder.

Recent studies have shown that major depressive disorder (MDD) is accompanied by alterations in functional and structural network gradients. However, whether changes are present in the cortical morphometric similarity (MS) network gradient, and the relationship between alterations of the gradient and gene expression remains largely unknown. In this study, the MS network was constructed, and its gradient was calculated in 71 patients with first-episode, treatment-naive MDD, and 69 demographically matched healthy controls. Between-group comparisons were performed to investigate abnormalities in the MS network gradient, and partial least squares regression analysis was conducted to explore the association between gene expression profiles and MS network gradient-based alternations in MDD. We found that the gradient was primarily significantly decreased in sensorimotor regions in patients with MDD compared with healthy controls, and increased in visual-related regions. In addition, the altered principal MS network gradient in the left postcentral cortex and right lingual cortex exhibited significant correlations with symptom severity. The abnormal gradient pattern was spatially correlated with the brain-wide expression of genes enriched for neurobiologically relevant pathways, downregulated in the MDD postmortem brain, and preferentially expressed in different cell types and cortical layers. These results demonstrated alterations of the principal MS network gradient in MDD and suggested the molecular mechanisms for structural alternations underlying MDD.

Spontaneous brain activity abnormalities in migraine: A meta-analysis of functional neuroimaging.

Neuroimaging studies have demonstrated that migraine is accompanied by spontaneous brain activity alterations in specific regions. However, these findings are inconsistent, thus hindering our understanding of the potential neuropathology. Hence, we performed a quantitative whole-brain meta-analysis of relevant resting-state functional imaging studies to identify brain regions consistently involved in migraine. A systematic search of studies that investigated the differences in spontaneous brain activity patterns between migraineurs and healthy controls up to April 2022 was conducted. We then performed a whole-brain voxel-wise meta-analysis using the anisotropic effect size version of seed-based d mapping software. Complementary analyses including jackknife sensitivity analysis, heterogeneity test, publication bias test, subgroup analysis, and meta-regression analysis were conducted as well. In total, 24 studies that reported 31 datasets were finally eligible for our meta-analysis, including 748 patients and 690 controls. In contrast to healthy controls, migraineurs demonstrated consistent and robust decreased spontaneous brain activity in the angular gyrus, visual cortex, and cerebellum, while increased activity in the caudate, thalamus, pons, and prefrontal cortex. Results were robust and highly replicable in the following jackknife sensitivity analysis and subgroup analysis. Meta-regression analyses revealed that a higher visual analog scale score in the patient sample was associated with increased spontaneous brain activity in the left thalamus. These findings provided not only a comprehensive overview of spontaneous brain activity patterns impairments, but also useful insights into the pathophysiology of dysfunction in migraine.

PI-NLOS: polarized infrared non-line-of-sight imaging.

Passive non-line-of-sight (NLOS) imaging is a promising technique to enhance visual perception for the occluded object hidden behind the wall. Here we present a data-driven NLOS imaging framework by using polarization cue and long-wavelength infrared (LWIR) images. We design a dual-channel input deep neural network to fuse the intensity features from polarized LWIR images and contour features from polarization degree images for NLOS scene reconstruction. To train the model, we create a polarized LWIR NLOS dataset which contains over ten thousand images. The paper demonstrates the passive NLOS imaging experiment in which the hidden people is approximate 6 meters away from the relay wall. It is an exciting finding that even the range is further than that in the prior works. The quantitative evaluation metric of PSNR and SSIM show that our method as an advance over state-of-the-art in passive NLOS imaging.

Disrupted local functional connectivity in schizophrenia: An updated and extended meta-analysis.

Neuroimaging studies have shown that schizophrenia is associated with disruption of resting-state local functional connectivity. However, these findings vary considerably, which hampers our understanding of the underlying pathophysiological mechanisms of schizophrenia. Here, we performed an updated and extended meta-analysis to identify the most consistent changes of local functional connectivity measured by regional homogeneity (ReHo) in schizophrenia. Specifically, a systematic search of ReHo studies in patients with schizophrenia in PubMed, Embase, and Web of Science identified 18 studies (20 datasets), including 652 patients and 596 healthy controls. In addition, we included three whole-brain statistical maps of ReHo differences calculated based on independent datasets (163 patients and 194 controls). A voxel-wise meta-analysis was then conducted to investigate ReHo alterations and their relationship with clinical characteristics using the newly developed seed-based d mapping with permutation of subject images (SDM-PSI) meta-analytic approach. Compared with healthy controls, patients with schizophrenia showed significantly higher ReHo in the bilateral medial superior frontal gyrus, while lower ReHo in the bilateral postcentral gyrus, right precentral gyrus, and right middle occipital gyrus. The following sensitivity analyses including jackknife analysis, subgroup analysis, heterogeneity test, and publication bias test demonstrated that our results were robust and highly reliable. Meta-regression analysis revealed that illness duration was negatively correlated with ReHo abnormalities in the right precentral/postcentral gyrus. This comprehensive meta-analysis not only identified consistent and reliably aberrant local functional connectivity in schizophrenia but also helped to further deepen our understanding of its pathophysiology.

Total Brain Volumetric Measures and Schizophrenia Risk: A Two-Sample Mendelian Randomization Study.

Schizophrenia (SCZ) is an idiopathic psychiatric disorder with a heritable component and a substantial public health impact. Although abnormalities in total brain volumetric measures (TBVMs) have been found in patients with SCZ, it is still unknown whether these abnormalities have a causal effect on the risk of SCZ. Here, we performed a Mendelian randomization (MR) study to investigate the possible causal associations between each TBVM and SCZ risk. Specifically, genome-wide association study (GWAS) summary statistics of total gray matter volume, total white matter volume, total cerebrospinal fluid volume, and total brain volume were obtained from the United Kingdom Biobank database (33,224 individuals), and SCZ GWAS summary statistics were provided by the Psychiatric Genomics Consortium (150,064 individuals). The main MR analysis was conducted using the inverse variance weighted method, and other MR methods, including MR-Egger, weighted median, simple mode, and weighted mode methods, were performed to assess the robustness of our findings. For pleiotropy analysis, we employed three approaches: MR-Egger intercept, MR-PRESSO, and heterogeneity tests. No TBVM was causally associated with SCZ risk according to the MR results, and no significant pleiotropy or heterogeneity was found for instrumental variables. Taken together, this study suggested that alterations in TBVMs were not causally associated with the risk of SCZ.

Abnormal Regional Spontaneous Brain Activities in White Matter in Patients with Autism Spectrum Disorder.

Previous studies have demonstrated patients with autism spectrum disorder (ASD) are accompanied by alterations of spontaneous brain activity in gray matter. However, whether the alterations of spontaneous brain activity exist in white matter remains largely unclear. In this study, 88 ASD patients and 87 typical controls (TCs) were included and regional homogeneity (ReHo) was calculated to characterize spontaneous brain activity in white matter. Voxel-wise two-sample t-tests were performed to investigate ReHo alterations, and cluster-level analyses were conducted to examine structural-functional coupling changes. Compared with TCs, the ASD group showed significantly decreased ReHo in the left superior corona radiata and left posterior limb of internal capsule, and decreased ReHo in the left anterior corona radiata with a trend level of significance. In addition, significantly weaker structural-functional coupling was observed in the left superior corona radiata and left posterior limb of internal capsule in ASD patients. Taken together, these findings highlighted abnormalities of white matter's regional spontaneous brain activity in ASD, which may provide new insights into the pathophysiological mechanisms of this disorder.

Isolation and structure elucidation of a new flavonol glycoside from Sabia Parviflora.

A new flavonol glycoside named Sabiapside A (1), along with four known compounds, quercetin-3-O-gentiobioside (2), camellianoside (3), isobariclisin-3-O- rutinoside (4), tsubakioside A (5), was isolated from Sabia parviflora. Their structures were elucidated by extensive spectroscopic analysis including MS, UV, IR and NMR data. The antioxidant activities of these glycosides evaluated by ABTS+ and DPPH radical scavenging reaction was higher than that of vitamin C used as the reference antioxidant.

[Study on HPLC fingerprint of Sabia parviflora].

This research was performed to establish the HPLC fingerprint of Sabia parviflora. HPLC method was carried out on a Thermo Accucore-C18(4. 6 mm×150 mm,2. 6 µm) column by 30% tetrahydrofuran in methyl alcohol-acetonitrile-0. 1% phosphate solution as mobile phase at a flow rate of 1. 0 m L·min-1,the column temperature was 30 ℃ and the detection wavelength was 360 nm. The fingerprints were further evaluated by chemometrics methods including similarity analysis,hierarchical clustering analysis,and principal component analysis. In HPLC fingerprint,15 common peaks were selected as the common peaks,and 6 contents of them were identified. The similarity degrees of 38 batches of the samples was more than 0. 710,and the samples were divided into 6 clusters by their quality difference. The method was precision,repeatable,stable,simple and reliable,which could be used for quality control and evaluation of S. parviflora.

Rhodosporidium toruloides sir2-like genes remodelled the mitochondrial network to improve the phenotypes of ageing cells.

It is known that mitochondria are associated with the ageing process, and the eukaryotic sir2 family of genes significantly affects cellular lifespan. The mammalian sir2 family affects mitochondrial function by regulating targets in different pathways, including oxidative stress, oxidative phosphorylation, and mitochondrial biosynthesis. This study reports that Rt-sirtuin2 and Rt-sirtuin4 genes transfections significantly impacted the lifespan of Rhodosporidium toruloides, and they can significantly improve cellular responses to H2O2 treatment, which induces cell senescence, and restore mitochondrial function. The Rt-sirtuin2 and Rt-sirtuin4 genes increase the expression of the mitochondria-associated proteins Mfn1, Mfn2, and Drp1 and the autophagy-associated proteins LC3-II, LC3-I, Beclin-1 and Parkin and reconstitute mitochondrial networks. Overall, the phenotypic reversal of senescent cells is achieved by regulating mitochondrial viability and mitochondrial autophagy. In vivo experiments with animals also confirmed the improvement of various ageing indexes by the Rt-sirtuin2 and Rt-sirtuin4 genes. Strategies for remodelling mitochondria and improving mitochondrial quality and function can reverse the state of human cells from an ageing phenotype to an active metabolic phenotype. The R. toruloides Sir2 genes can be used to prevent and treat diseases of ageing or mitochondrial dysfunction.

Oral engineered Bifidobacterium longum expressing rhMnSOD to suppress experimental colitis.

In recent years, using genetic engineering and bioengineering techniques, Bifidobacterium as a carrier to express specific functions of the protein or polypeptide, has become a new treatment for disease. Ulcerative colitis (UC) is a type of inflammatory bowel diseases (IBD). Although the cause of this inflammatory disorder is still unknown, a large amount of evidence suggests that ulcerative colitis is associated with increased activity of reactive oxygen species (ROS), manganese superoxide dismutase (MnSOD) is a kind of superoxide dismutase (SOD) has been demonstrated to play a key role in the pathophysiology of colitis. Here, we explored the Bifidobacterium as a drug delivery system to orally deliver a potent anti-inflammatory but poor penetration and stability antioxidant enzymes human MnSOD, transported into cells by a penetratin PEP-1. We constructed an expression vector expressing PEP-1-hMnSOD fusion protein, and successfully expressed hMnSOD fusion protein in engineered Bifidobacterium. Then we identified the bioactivity of engineered Bifidobacterium in LPS-induced inflammatory cell model. Finally, we used Bifidobacterium expressing PEP-1-hMnSOD fusion protein against DSS-induced ulcerative colitis mice. B. longum-PEP-1-rhMnSOD can successfully express rhMnSOD in the colon. We found that levels of inflammatory cytokines TNF-α, IL-1ß, IL-6 and IL-8 as well as histological damage in colonic tissues showed that engineered Bifidobacterium effectively reduced dextran sulfate sodium(DSS)-induced ulcerative colitis, we also tested the MPO, verified the above conclusions. These results suggest that oral Bifidobacterium expressing PEP-1-hMnSOD fusion protein can be treated as a new method of UC treatment.