The toxic effects of petroleum pollutants to microalgae in marine environment.

Marine oil pollution is one of the major global environmental pollution problems. Marine microalgae are the foundation of the marine food chain, providing the main primary productivity of the ocean. They not only maintain the energy flow and material cycle of the entire marine ecosystem, but also play an important role in regulating global climate change. Exploring the impact of petroleum pollutants on marine microalgae is extremely important for studying marine environmental pollution. This review first introduced the sources, compositions, and forms of petroleum pollutants and their migration and transformation processes in the ocean. Then, the toxic effects of petroleum pollutants on marine microalgae were summarized. The growth of marine microalgae showed low-concentration promotion and high-concentration inhibition. The population growth and interspecific relationships of marine microalga was changed and the photosynthesis of marine microalgae was influenced. Finally, potential research directions and suggestions for marine microalgae in the future were proposed.

Tetrahedral Framework Nucleic Acids Inhibit Muscular Mitochondria-Mediated Apoptosis and Ameliorate Muscle Atrophy in Sarcopenia.

Sarcopenia is known as age-related muscle atrophy, which influences over a quarter of the elderly population worldwide. It is characterized by a progressive decline in muscle mass, strength, and performance. To date, clinical treatments in sarcopenia are limited to rehabilitative interventions and dietary supplements. Tetrahedral framework nucleic acids (tFNAs) represent a novel kind of DNA-based nanomaterial with superior antiapoptosis capacity in cells, tissues, organs, and systems. In our study, the therapeutic effect of tFNAs treatment on sarcopenia was evaluated both in vivo and in vitro. Results from muscular biophysiological characteristics demonstrated significant improvement in muscle function and endurance in the aged mouse model, and histologic examinations also showed beneficial morphological changes in muscle fibers. In vitro, DEX-induced sarcopenic myotube atrophy was also ameliorated through the inhibition of mitochondria-mediated cell apoptosis. Collectively, tFNAs treatment might serve as an alternative option to deal with sarcopenia in the near future.

Intravascular Intervention Combined with Standard Drug Therapy in Patients with Severe Intracranial Atherosclerotic Stenosis and Plaque Enhancement.

Objective: The purpose of this retrospective cohort study was to evaluate clinical outcomes in high-risk patients with symptomatic intracranial atherosclerotic stenosis (sICAS) resulting from plaque enhancement who underwent balloon dilation or stent implantation. Plaque features were identified based on high-resolution magnetic resonance vessel wall imaging (HRMR-VWI). Methods: A total of 37 patients with sICAS (degree of stenosis ≥70%) were enrolled between January 2018 and March 2022 at a single center. All patients underwent HRMR-VWI and received standard drug treatment after hospital admission. The patients were divided into 2 groups based on whether they underwent interventional treatment (n = 18) or non-interventional treatment (n = 19). The grade of enhancement and enhancement rate (ER) of culprit plaque were evaluated using 3D-HRMR-VWI. The risk of symptom recurrence was compared between the 2 groups during follow-up. Results: There was no statistical difference between the intervention and non-intervention groups in the rate and type of enhancement. Median clinical follow-up time was 17.8 (10.0 to 26.0) months and median follow-up time was 3.6 (3.1 to 6.2) months. In the intervention group, 2 patients had stent restenosis, but no stroke or transient ischemia attacks (TIAs) occurred. In contrast, 1 patient in the non-intervention group had an ischemic stroke and 4 patients had TIAs. The incidence of the primary outcome was lower in the intervention group than in the non-intervention group (0 vs 26.3%; P = .046). Conclusions: High-resolution magnetic resonance intracranial vessel wall imaging (HR MR-IVWI) can be used to identify vulnerable plaque features. It is safe and effective in high-risk patients with sICAS with responsible plaque enhancement to undergo intravascular intervention combined with standard drug therapy. Further studies are needed to analyze the link between plaque enhancement and symptom recurrence in the medication group at baseline.

[Network Meta-analysis of Qi-benefiting and blood-activating Chinese patent medicines against ischemic stroke].

This study aimed to compare the efficacy of Qi-benefiting and blood-activating Chinese patent medicines in the treatment of ischemic stroke with network Meta-analysis. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library were searched from database inception to October 2022 for randomized controlled trial(RCT) on 11 Qi-benefiting and blood-activating Chinese patent medicines in the treatment of ischemic stroke. The risk of bias plot was made by RevMan 5.3, and network Meta-analysis and efficacy ranking were performed by Stata 17. Ninety-two RCTs were included, involving 10 608 patients. According to the network Meta-analysis, in terms of the clinical total effective rate, surface under the cumulative ranking curve(SUCRA) as followed: Qilong Capsules+conventional western medicine>Zhishe Tongluo Capsules+conventional western medicine>Longshengzhi Capsules+conventional western medicine>Naoxintong Capsules+conventional western medicine>Tongsaimai Tablets+conventional western medicine>Naoan Capsules+conventional western medicine>Naoluotong Capsules+conventional western medicine>Xiaoshuan Changrong Capsules+conventional western medicine>Dengzhan Shengmai Capsules+conventional western medicine=Tongxinluo Capsules+conventional western medicine>Naomaitai Capsules+conventional western medicine. In terms of the improvement in National Institute of Health stroke scale(NIHSS) score, SUCRA as followed: Longshengzhi Capsules+conventional western medicine>Naomaitai Capsules+conventional western medicine>Naoxintong Capsules+conventional western medicine>Dengzhan Shengmai Capsules+conventional western medicine>Xiaoshuan Changrong Capsules+conventional western medicine>Naoluotong Capsules+conventional western medi-cine>Tongxinluo Capsules+conventional western medicine>Naoan Capsules+conventional western medicine>Qilong Capsules+conventional western medicine. In terms of safety, the overall adverse reactions/events of Qi-benefiting and blood-activating Chinese patent medicines + conventional western medicine were less than those of the control group. Since Qilong Capsules+conventional western medicine and Zhishe Tongluo Capsules+conventional western medicine were preferred to improve the clinical total effective rate. In the aspect of improving NIHSS score, Longshengzhi Capsules+conventional western medicine and Naomaitai Capsules+conventional western medicine were first options. Due to the lack of direct comparisons between drugs, the overall quality of RCT was not high, so more studies are needed to verify the strength of the evidence.

OsPPR939, a nad5 splicing factor, is essential for plant growth and pollen development in rice.

KEY MESSAGE: P-subfamily PPR protein OsPPR939, which can be phosphorylated by OsS6K1, regulates plant growth and pollen development by involving in the splicing of mitochondrial nad5 introns 1, 2, and 3. In land plants, pentatricopeptide repeat (PPR) proteins play key roles in mitochondrial group II intron splicing, but how these nucleus-encoded proteins are imported into mitochondria is unknown. To date, a few PPR proteins have been characterized in rice (Oryza sativa). Here, we demonstrate that the mitochondrion-localized P-subfamily PPR protein OsPPR939 is required for the splicing of nad5 introns 1, 2, and 3 in rice. Complete knockout or partial disruption of OsPPR939 function resulted in different degrees of growth retardation and pollen sterility. The dramatically reduced splicing efficiency of these introns in osppr939-4 and osppr939-5 led to reduced mitochondrial complex I abundance and activity and enhanced expression of alternative respiratory pathway genes. Complementation with OsPPR939 rescued the defective plant morphology of osppr939-4 and restored its decreased splicing efficiency of nad5 introns 1, 2, and 3. Therefore, OsPPR939 plays crucial roles in plant growth and pollen development by splicing mitochondrial nad5 introns 1, 2, and 3. More importantly, the 12th amino acid Ser in the N-terminal targeting sequence of OsPPR939 is phosphorylated by OsS6K1, and truncated OsPPR939 with a non-phosphorylatable S12A mutation in its presequence could not be imported into mitochondria, suggesting that phosphorylation of this amino acid plays an important role in the mitochondrial import of OsPPR939. To our knowledge, the 12th residue Ser on OsPPR939 is the first experimentally proven phosphorylation site in PPR proteins. Our results provide a basis for investigating the regulatory mechanism of PPR proteins at the post-translational level.

Protective effect of Aster tataricus extract on retinal damage on the virtue of its antioxidant and anti-inflammatory effect in diabetic rat.

Effect of Aster tataricus (AT) was estimated on the retinal injury in diabetic rats by its antioxidant and anti-inflammatory activity. Streptozotocin (STZ) was used to induce diabetes at a dose of 60mg/kg, i.p. and blood glucose was estimated to confirm the diabetic rats. All the animals were separated in to 5 different groups (n=10) such as control, diabetic retinopathy (DR) receives saline solution, and AT treated group receives AT (100, 200 and 400mg/kg) for the duration of 8 week. After treatment protocol period blood glucose and HbA1c% was estimated in the blood sample of diabetic rats. Retinal tissue was isolated for the fundus photography and retinal vessel diameter, retinal vascular permeability and leukocytosis were estimated. Moreover in the retinal tissue homogenate oxidative stress parameters such as superoxide dismutase (SOD), glutathione peroxidase (GSH) and catalase (CAT) and concentration of cytokines (TNFα, IL10) was estimated. Result of the study suggested that root extract of AT contain rich amount of polyphenol in it which significantly reduces the body weight and concentration of glucose in blood in diabetic rats. Fundus photography suggested that AT extract attenuates the structure and functional abnormalities that develops due to diabetes. Retinal leukocytosis and vascular permeability was significantly decreases in AT treated group than DR group. There was significant increase in the activity of GSH, CAT and SOD in AT treated group than DR group. Moreover AT also attenuates the altered concentration of TNFα, IL10 and NF-κB in the retina of STZ induced diabetic rat. Thus present study concludes that root extract of AT effectively manages the diabetic retinopathy by controlling the blood glucose and also by attenuating the altered oxidative stresss and inflammatory mediators such as TNFα, IL10 and NF-κB in the retina of STZ induced diabetic rat.

Engineering Yarrowia lipolytica for Campesterol Overproduction.

Campesterol is an important precursor for many sterol drugs, e.g. progesterone and hydrocortisone. In order to produce campesterol in Yarrowia lipolytica, C-22 desaturase encoding gene ERG5 was disrupted and the heterologous 7-dehydrocholesterol reductase (DHCR7) encoding gene was constitutively expressed. The codon-optimized DHCR7 from Rallus norvegicus, Oryza saliva and Xenapus laevis were explored and the strain with the gene DHCR7 from X. laevis achieved the highest titer of campesterol due to D409 in substrate binding sites. In presence of glucose as the carbon source, higher biomass conversion yield and product yield were achieved in shake flask compared to that using glycerol and sunflower seed oil. Nevertheless, better cell growth rate was observed in medium with sunflower seed oil as the sole carbon source. Through high cell density fed-batch fermentation under carbon source restriction strategy, a titer of 453±24.7 mg/L campesterol was achieved with sunflower seed oil as the carbon source, which is the highest reported microbial titer known. Our study has greatly enhanced campesterol accumulation in Y. lipolytica, providing new insight into producing complex and desired molecules in microbes.

Phosphatase Inhibitors Function as Novel, Broad Spectrum Botulinum Neurotoxin Antagonists in Mouse and Human Embryonic Stem Cell-Derived Motor Neuron-Based Assays.

There is an urgent need to develop novel treatments to counter Botulinum neurotoxin (BoNT) poisoning. Currently, the majority of BoNT drug development efforts focus on directly inhibiting the proteolytic components of BoNT, i.e. light chains (LC). Although this is a rational approach, previous research has shown that LCs are extremely difficult drug targets and that inhibiting multi-serotype BoNTs with a single LC inhibitor may not be feasible. An alternative approach would target neuronal pathways involved in intoxication/recovery, rather than the LC itself. Phosphorylation-related mechanisms have been implicated in the intoxication pathway(s) of BoNTs. However, the effects of phosphatase inhibitors upon BoNT activity in the physiological target of BoNTs, i.e. motor neurons, have not been investigated. In this study, a small library of phosphatase inhibitors was screened for BoNT antagonism in the context of mouse embryonic stem cell-derived motor neurons (ES-MNs). Four inhibitors were found to function as BoNT/A antagonists. Subsequently, we confirmed that these inhibitors protect against BoNT/A in a dose-dependent manner in human ES-MNs. Additionally, these compounds provide protection when administered in post-intoxication scenario. Importantly, the inhibitors were also effective against BoNT serotypes B and E. To the best of our knowledge, this is the first study showing phosphatase inhibitors as broad-spectrum BoNT antagonists.