Targeting Rap1b signaling cascades with CDNF: Mitigating platelet activation, plasma oxylipins and reperfusion injury in stroke.

Cerebral reperfusion injury in stroke, stemming from interconnected thrombotic and inflammatory signatures, often involves platelet activation, aggregation and its interaction with various immune cells, contributing to microvascular dysfunction. However, the regulatory mechanisms behind this platelet activation and the resulting inflammation are not well understood, complicating the development of effective stroke therapies. Utilizing animal models and platelets from hemorrhagic stroke patients, our research demonstrates that human cerebral dopamine neurotrophic factor (CDNF) acts as an endogenous antagonist, mitigating platelet aggregation and associated neuroinflammation. CDNF moderates mitochondrial membrane potential, reactive oxygen species production, and intracellular calcium in activated platelets by interfering with GTP binding to Rap1b, thereby reducing Rap1b activation and downregulating the Rap1b-MAPK-PLA2 signaling pathway, which decreases release of the pro-inflammatory mediator thromboxane A2. In addition, CDNF reduces the inflammatory response in BV2 microglial cells co-cultured with activated platelets. Consistent with ex vivo findings, subcutaneous administration of CDNF in a rat model of ischemic stroke significantly reduces platelet activation, aggregation, lipid mediator production, infarct volume, and neurological deficits. In summary, our study highlights CDNF as a promising therapeutic target for mitigating platelet-induced inflammation and enhancing recovery in stroke. Harnessing the CDNF pathway may offer a novel therapeutic strategy for stroke intervention.

[Mechanism of Huangqi Simiao Decoction in treatment of type 2 diabetes mellitus based on network pharmacology and metabonomics].

This article analyzed the mechanism of Huangqi Simiao Decoction(HSD) for the treatment of type 2 diabetes mellitus(T2DM). The component targets of HSD and the related disease targets of T2DM were screened through network pharmacology. The protein-protein interaction(PPI) network of intersecting targets and the drug-component-intersecting target network were constructed to screen the potential active ingredients and targets. Molecular docking was performed using AutoDock Vina software to verify the interaction between potential components and core targets. The serum was tested by ultra performance liquid chromatography-tandem mass spectrometry, and multivariate statistical analyses, such as principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA), were used to search for the differential metabolites and related metabolic pathways of each group by combining with the MetaboAnalyst database. The same metabolic pathways were analyzed by combining the screened differential metabolites with the intersecting targets screened by network pharmacology. Network pharmacology showed that the nine core components of HSD for the treatment of T2DM were quercetin, kaempferol, stigmasterol, baicalein, ß-sitosterol, flavodoxin, canthaxanthin, canthaxanthin, berberine, and berberine, and the five core targets included AKT1, TP53, TNF, IL6, and VEGFA. Molecular docking showed that the core components bound well to the target genes. Metabolomics showed that a total of 112 common differential metabolites were identified, of which 88 metabolites exhibited increased concentration and 24 metabolites decreased concentration after treatment with HSD. Enrichment analysis showed that HSD regulated the body metabolism of patients with T2DM, mainly related to seven metabolic pathways, such as amino acid metabolism and tricarboxylic acid cycle. The joint analysis of metabolomics and network pharmacology showed that both involved histidine metabolism, arginine and proline metabolic pathways. This study suggests that HSD has a good efficacy for T2DM. Based on the combined analysis of metabolomics and network pharmacology, it was found that the mechanism may be that the pharmacodynamic bases of quercetin, kaempferol, and stigmasterol in HSD enhance the effects on histidine metabolism, arginine and proline metabolic pathways by modulating a variety of metabolites, which provides the basis for further prevention and treatment of T2DM.

Regulation of glycolysis-derived L-lactate production in astrocytes rescues the memory deficits and Aß burden in early Alzheimer's disease models.

Aberrant energy metabolism in the brain is a common pathological feature in the preclinical Alzheimer's Disease (AD). Recent studies have reported the early elevations of glycolysis-involved enzymes in AD brain and cerebrospinal fluid according to a large-scale proteomic analysis. It's well-known that astrocytes exhibit strong glycolytic metabolic ability and play a key role in the regulation of brain homeostasis. However, its relationship with glycolytic changes and cognitive deficits in early AD patients is unclear. Here, we investigated the mechanisms by which astrocyte glycolysis is involved in early AD and its potential as a therapeutic target. Our results suggest that Aß-activated microglia can induce glycolytic-enhanced astrocytes in vitro, and that these processes are dependent on the activation of the AKT-mTOR-HIF-1α pathway. In early AD models, the increase in L-lactate produced by enhanced glycolysis of astrocytes leads to spatial cognitive impairment by disrupting synaptic plasticity and accelerating Aß aggregation. Furthermore, we find rapamycin, the mTOR inhibitor, can rescue the impaired spatial memory and Aß burden by inhibiting the glycolysis-derived L-lactate in the early AD models. In conclusion, we highlight that astrocytic glycolysis plays a critical role in the early onset of AD and that the modulation of glycolysis-derived L-lactate by rapamycin provides a new strategy for the treatment of AD.

Optimizing the selection of the endoscopically assisted supracerebellar transtentorial approach to the medial temporo-occipital region: Clinical application of one novel grid coordinate system.

The endoscopically assisted supracerebellar transtentorial (eSCTT) approach is advocated for managing pathologies of the medial temporo-occipital region, but quantitative analysis is currently lacking. The aims of this study were to establish a grid coordinate system on the tentorium to model the anatomical relationship between medial temporo-occipital region pathology and the slope of the tentorium, and then to compare the paramedian eSCTT and extreme-lateral eSCTT approaches quantitatively. Bilateral paramedian and extreme-lateral eSCTT approaches were used to dissect three adult cadaveric heads anatomically. A grid coordinate system was established on the tentorium, and the angles of attack and depth of the surgical corridor of each coordinate point were obtained so that the two eSCTT approaches could be compared statistically. The measurements were then analyzed to determine the condition for selecting each eSCTT approach, and its clinical feasibility was assessed in three patients with large tumors in the medial temporo-occipital region. For coordinate points where the X-coordinate on the grid coordinate system was 1 cm outside the apex of the tentorium, the paramedian eSCTT approach had a significantly wider angle of attack and shorter depth of surgical corridor than the extreme-lateral eSCTT approach. In contrast, the extreme-lateral eSCTT approach was better for coordinate points where the Y-coordinate on the grid coordinate system was 1 cm in front of the apex of the tentorium. The long axis of each patient's tumor was projected on to the tentorium and its corresponding coordinate points were used to match the more appropriate eSCTT approach. Preliminary results for three patients treated with the eSCTT approach for large tumors in the medial temporo-occipital region were encouraging. When the eSCTT approach is applied to manage a large tumor of the medial temporo-occipital region, assessment of the long axis of the tumor and knowledge of the selective condition for each eSCTT approach can help in clinical decision-making.

Transcriptome analysis reveals the molecular mechanism of differences in growth between photoautotrophy and heterotrophy in Chlamydomonas reinhardtii.

Background: The green alga Chlamydomonas reinhardtii can grow photoautotrophically utilizing light and CO2, and heterotrophically utilizing acetate. The physiological and biochemical responses of autotrophy and heterotrophy are different in C. reinhardtii. However, there is no complete understanding of the molecular physiology between autotrophy and heterotrophy. Therefore, we performed biochemical, molecular and transcriptome analysis of C. reinhardtii between autotrophy and heterotrophy. Results: The cell growth characterization demonstrated that heterotrophic cell had enhanced growth rates, and autotrophic cell accumulated more chlorophyll. The transcriptome data showed that a total of 2,970 differentially expressed genes (DEGs) were identified from photoautotrophy 12h (P12h) to heterotrophy 12h (H12h). The DEGs were involved in photosynthesis, the tricarboxylic acid cycle (TCA), pyruvate and oxidative phosphorylation metabolisms. Moreover, the results of qRT-PCR revealed that the relative expression levels of malate dehydrogenase (MDH), succinate dehydrogenase (SDH), ATP synthase (ATPase), and starch synthase (SSS) were increased significantly from P12h and H12h. The protein activity of NAD-malate dehydrogenase (NAD-MDH) and succinate dehydrogenase (SDH) were significantly higher in the H12h group. Conclusion: The above results indicated that the high growth rate observed in heterotrophic cell may be the effects of environmental or genetic regulation of photosynthesis. Therefore, the identification of novel candidate genes in heterotrophy will contribute to the development of microalga strains with higher growth capacity and better performance for biomass production.

Serotonergic Regulation of Synaptic Dopamine Levels Mitigates L-DOPA-Induced Dyskinesia in a Mouse Model of Parkinson's Disease.

Background: The serotonin (5-HT) system can manipulate the processing of exogenous L-DOPA in the DA-denervated striatum, resulting in the modulation of L-DOPA-induced dyskinesia (LID). Objective: To characterize the effects of the serotonin precursor 5-hydroxy-tryptophan (5-HTP) or the serotonin transporter (SERT) inhibitor, Citalopram on L-DOPA-induced behavior, neurochemical signals, and underlying protein expressions in an animal model of Parkinson's disease. Methods: MitoPark (MP) mice at 20 weeks of age, subjected to a 14-day administration of L-DOPA/Carbidopa, displayed dyskinesia, referred to as LID. Subsequent investigations explored the effects of 5-HT-modifying agents, such as 5-HTP and Citalopram, on abnormal involuntary movements (AIMs), locomotor activity, neurochemical signals, serotonin transporter activity, and protein expression in the DA-denervated striatum of LID MP mice. Results: 5-HTP exhibited duration-dependent suppressive effects on developing and established LID, especially related to abnormal limb movements observed in L-DOPA-primed MP mice. However, Citalopram, predominantly suppressed abnormal axial movement induced by L-DOPA in LID MP mice. We demonstrated that 5-HTP could decrease L-DOPA-upregulation of DA turnover rates while concurrently upregulating 5-HT metabolism. Additionally, 5-HTP was shown to reduce the expressions of p-ERK and p-DARPP-32 in the striatum of LID MP mice. The effect of Citalopram in alleviating LID development may be attributed to downregulation of SERT activity in the dorsal striatum of LID MP mice. Conclusions: While both single injection of 5-HTP and Citalopram effectively mitigated the development of LID, the difference in mitigation of AIM subtypes may be linked to the unique effects of these two serotonergic agents on L-DOPA-derived DA and 5-HT metabolism.

Yangonin, one of the kavalactones isolated from Piper methysticum G. Forst, acts through cannabinoid 1 (CB1) receptors to induce an intrathecal anti-hyperalgesia.

ETHNOPHARMACOLOGICAL RELEVANCE: Piper methysticum G. Forst (Piperaceae) is traditionally consumed in Polynesian culture. The roots are used to produce an entheogenic drink and traditional medicine with sedative and anxiolytic properties. There is also evidence that it functions as a pain reliever. Kavalactones, its main active ingredients, exhibit psychoactive effects on the central nervous system. However, the active ingredients and pharmacological mechanisms underlying the analgesic effect of kavalactones are unclear. AIM OF THE STUDY: This study investigated the effects of kavain and yangonin on nociception, inflammatory hyperalgesia, and neuropathic mechanical allodynia at the spinal level. MATERIALS AND METHODS: Male Sprague-Dawley rats were administered kavain and yangonin (27.14 and 19.36 nmol/rat) via intrathecal injection. Tail-flick tests were performed to evaluate the anti-nociceptive properties. The efficacy of kavain and yangonin on inflammatory hyperalgesia was examined using a plantar test in rats with carrageenan-induced paw inflammation. The von Frey test was used to assess mechanical allodynia induced by partial sciatic nerve ligation. RESULTS: Intrathecal injection of yangonin demonstrated a relatively potent anti-nociceptive effect and attenuated carrageenan-induced hyperalgesia. These effects were completely reversed by the co-administration of PF 514273, a cannabinoid 1 (CB1) receptor antagonist. However, yangonin did not affect mechanical allodynia at the spinal level. Kavain, another abundant kavalactone, did not affect nociception, hyperalgesia, or mechanical allodynia at the spinal level. CONCLUSIONS: Overall, our study demonstrated that yangonin exerts anti-nociception and anti-inflammatory hyperalgesia effects via CB1 receptors at the spinal level. We identified a single kavalactone, yangonin, extracted from kava as a promising treatment for pain.

Attenuating mitochondrial dysfunction and morphological disruption with PT320 delays dopamine degeneration in MitoPark mice.

BACKGROUND: Mitochondria are essential organelles involved in cellular energy production. Changes in mitochondrial function can lead to dysfunction and cell death in aging and age-related disorders. Recent research suggests that mitochondrial dysfunction is closely linked to neurodegenerative diseases. Glucagon-like peptide-1 receptor (GLP-1R) agonist has gained interest as a potential treatment for Parkinson's disease (PD). However, the exact mechanisms responsible for the therapeutic effects of GLP-1R-related agonists are not yet fully understood. METHODS: In this study, we explores the effects of early treatment with PT320, a sustained release formulation of the GLP-1R agonist Exenatide, on mitochondrial functions and morphology in a progressive PD mouse model, the MitoPark (MP) mouse. RESULTS: Our findings demonstrate that administration of a clinically translatable dose of PT320 ameliorates the reduction in tyrosine hydroxylase expression, lowers reactive oxygen species (ROS) levels, and inhibits mitochondrial cytochrome c release during nigrostriatal dopaminergic denervation in MP mice. PT320 treatment significantly preserved mitochondrial function and morphology but did not influence the reduction in mitochondria numbers during PD progression in MP mice. Genetic analysis indicated that the cytoprotective effect of PT320 is attributed to a reduction in the expression of mitochondrial fission protein 1 (Fis1) and an increase in the expression of optic atrophy type 1 (Opa1), which is known to play a role in maintaining mitochondrial homeostasis and decreasing cytochrome c release through remodeling of the cristae. CONCLUSION: Our findings suggest that the early administration of PT320 shows potential as a neuroprotective treatment for PD, as it can preserve mitochondrial function. Through enhancing mitochondrial health by regulating Opa1 and Fis1, PT320 presents a new neuroprotective therapy in PD.

Mechanically Tunable Circularly Polarized Luminescence of Liquid Crystal-Templated Chiral Perovskite Quantum Dots.

Endowing perovskite quantum dots (PQDs) with circularly polarized luminescence (CPL) offers great promise for innovative chiroptical applications, but the existing strategies are inefficient in acquiring stimuli-responsive flexible chiral perovskite films with large, tunable dissymmetry factor (glum) and long-term stability. Here, we report a strategy for the design and synthesis of luminescent cholesteric liquid crystal elastomer (Lumin-CLCE) films with mechanically tunable CPL, which is enabled by liquid crystal-templated chiral self-assembly and in situ covalent cross-linking of judiciously designed photopolymerizable CsPbX3 (X=Cl, Br, I) PQD nanomonomers into the elastic polymer networks. The resulting Lumin-CLCE films showcase circularly polarized structural color in natural light and noticeable CPL with a maximum glum value of up to 1.5 under UV light. The manipulation of CPL intensity and rotation direction is achieved by controlling the self-assembled helicoidal nanostructure and the handedness of soft helices. A significant breakthrough lies in the achievement of a reversible, mechanically tunable perovskite-based CPL switch activated by biaxial stretching, which enables flexible, dynamic anti-counterfeiting labels capable of decrypting preset information in specific polarization states. This work can provide new insights for the development of advanced chiral perovskite materials and their emerging applications in information encryption, flexible 3D displays, and beyond.

Nanoparticles transfected with plasmid-encoded lncRNA-OIP5-AS1 inhibit renal ischemia-reperfusion injury in mice via the miR-410-3p/Nrf2 axis.

Nanostructures composed of liposomes and polydopamine (PDA) have demonstrated efficacy as carriers for delivering plasmids, effectively alleviating renal cell carcinoma. However, their role in acute kidney injury (AKI) remains unclear. This study aimed to investigate the effects of the plasmid-encoded lncRNA-OIP5-AS1@PDA nanoparticles (POP-NPs) on renal ischemia/reperfusion (RI/R) injury and explore the underlying mechanisms. RI/R or OGD/R models were established in mice and HK-2 cells, respectively. In vivo, vector or POP-NPs were administered (10 nmol, IV) 48 h after RI/R treatment. In the RI/R mouse model, the OIP5-AS1 and Nrf2/HO-1 expressions were down-regulated, while miR-410-3p expression was upregulated. POP-NPs treatment effectively reversed RI/R-induced renal tissue injury, restoring altered levels of blood urea nitrogen, creatinine, malondialdehyde, inflammatory factors (IL-8, IL-6, TNF-α), ROS, apoptosis, miR-410-3p, as well as the suppressed expression of SOD and Nrf2/HO-1 in the model mice. Similar results were obtained in cell models treated with POP-NPs. Additionally, miR-410-3p mimics could reverse the effects of POP-NPs on cellular models, partially counteracted by Nrf2 agonists. The binding relationship between OIP5-AS1 and miR-410-3p, alongside miR-410-3p and Nrf2, has been substantiated by dual-luciferase reporter and RNA pull-down assays. The study revealed that POP-NPs can attenuate RI/R-induced injury through miR-410-3p/Nrf2 axis. These findings lay the groundwork for future targeted therapeutic approaches utilizing nanoparticles for RI/R-induced AKI.

Intrathecal injections of angiotensin IV and oxytocin conjugates induce antihyperalgesia and antiallodynia in both sexes of rats.

Our previous studies have established that intrathecal oxytocin (OT) and angiotensin IV (Ang IV) injections induce antihyperalgesia and antiallodynia in rodents. Ang IV, a renin-angiotensin system hexapeptide, acts as an endogenous inhibitor that inhibits the oxytocin-degrading enzyme insulin-regulated aminopeptidase (IRAP). The pain inhibitory effects by Ang IV were found to be through its inhibition on IRAP to potentiate the effect of OT. However, these effects were found to be with a significant sex difference, which could be partially due to the higher expression of IRAP at the spinal cords of female. Therefore, we synthesized Ang IV and OT conjugates connected with a peptide bond and tested for their effects on hyperalgesia and allodynia. Carrageenan-induced hyperalgesia and partial sciatic nerve ligation (PSNL) were performed using rat models. Conjugates Ang IV-OT (Ang IV at the N-terminal) and OT-Ang IV (OT at the N-terminal) were synthesized and intrathecally injected into male and female rats. Our results showed that Ang IV-OT exhibited prominent antihyperalgesia in male rats, particularly during hyperalgesia recovery, whereas OT-Ang IV was more effective during development stage. Ang IV-OT showed clear antihyperalgesia in female rats, but OT-Ang IV had no significant effect. Notably, both conjugates alleviated neuropathic allodynia in male rats; however, OT-Ang IV had no effect in female rats, whereas Ang IV-OT induced significant antiallodynia. In conclusion, Ang IV-OT has greater therapeutic potential for treating hyperalgesia and allodynia than OT-Ang IV. Its effects were not affected by sex, unlike those of OT and OT-Ang IV, extending its possible clinical applications.

Endoscopic transorbital decompression for traumatic superior orbital fissure syndrome: from cadaveric study to clinical application.

PURPOSE: The endoscopic endonasal approach (EEA) is a minimally invasive and promising modality for treating traumatic superior orbital fissure (SOF) syndrome (tSOFS). Recently, the endoscopic transorbital approach (ETOA) has been considered an alternative method for reaching the anterolateral skull base. This study accessed the practicality of using the ETOA to treat SOF decompression using both cadaveric dissection and clinical application. METHODS: Bilateral anatomic dissections were performed on four adult cadaveric heads using the ETOA and EEA to address SOF decompression. The ETOA procedure for SOF decompression is described, and the extent of SOF decompression was compared between the ETOA and EEA. The clinical feasibility of the ETOA for treating SOF decompression was performed in two patients diagnosed with tSOFS. RESULTS: ETOA allowed for decompression over the lateral aspect of the SOF, from the meningo-orbital band superolaterally to the maxillary strut inferomedially. By contrast, the EEA allowed for decompression over the medial aspect of the SOF, from the lateral opticocarotid recess superiorly to the maxillary strut inferiorly. In both patients treated using the ETOA and SOF decompression, the severity of ophthalmoplegia got obvious improvement. CONCLUSIONS: Based on the cadaveric findings, ETOA provided a feasible access pathway for SOF decompression with reliable outcomes, and our patients confirmed the clinical efficacy of the ETOA for managing tSOFS.

Online joint localization without user interactions.

Wi-Fi fingerprinting has been a popular indoor localization due to the widespread layout of indoor WLAN. However, the signal fluctuations in the complex environments make it difficult to maintain high accuracy localization for the received signal strength (RSS) fingerprinting. Various positioning solutions have emerged to address this challenge, either working in stand-alone mode or in collaborative mode. In the former case, the user only utilizes his own RSS observation to request location service, while the latter usually requires information transfer between users. Considering the spatial correlation of wireless signal distribution, we propose an online joint localization scheme (JointLoc) that does not require direct interaction between users. The fact that the signals observed by users in physical proximity characterize the surroundings is used by JointLoc to identify neighboring users for joint localization. Besides this, JointLoc further integrates a novel subset-based localization scheme, thus the influence of anomalous RSS signals is eliminated before making the final location decision. We have fully evaluated the performance of JointLoc in two RSS datasets collected in real environments. Compared with conventional algorithms and the latest ones, results show that JointLoc is robust against signal fluctuations, and achieves good localization accuracy.

Adherence to the Diabetes Risk Reduction Diet and Bladder Cancer Risk in the Prostate, Lung, Colorectal, Ovarian (PLCO) Cohort.

BACKGROUND: This study aimed to explore the relationship between diabetes risk reduction diet (DRRD) and bladder cancer risk in Prostate, Lung, Colorectal, Ovarian (PLCO) cohort. METHODS: Data from 99,001 participants in the PLCO Cancer Screening Trial were analyzed using Cox proportional hazards regression models to estimate HRs and 95% confidence intervals (CI) for the association between DRRD score and bladder cancer incidence. Subgroup analyses were conducted to assess whether variables such as age, sex, body mass index, cigarette smoking status, and history of diabetes influenced the observed association. The DRRD score was formulated on the basis of nine nutrient intake indicators derived from the Dietary History Questionnaire. RESULTS: During the median follow-up of 11.7 years, 761 new bladder cancer cases were identified. Participants with highest DRRD scores exhibited a reduced risk of bladder cancer compared with those in the lowest quartile (unadjusted analysis, HR, 0.65; 95% CI, 0.53-0.82); multivariable adjusted analysis, HR, 0.79; 95% CI, 0.64-0.98; Ptrend = 0.007). A similar risk reduction was seen solely in transitional cell carcinoma (HR, 0.79; 95% CI, 0.64-0.99; P = 0.007). In addition, the significant negative association between DRRD scores and bladder cancer risk persisted even after excluding participants with unique characteristics. CONCLUSIONS: This large prospective population-based study suggests that adherence to a DRRD may contribute to the prevention of bladder cancer. IMPACT: The DRRD could potentially mitigate bladder cancer risk, which warrants further validation in diverse populations.

Transorbital transposition of the temporoparietal fascia flap to reconstruct the skull base defects: A preclinical study with comparison to the transpterygoid transposition.

BACKGROUND: Transpterygoid transposition of the temporoparietal fascia flap (TPFF) is a feasible selection for ventral skull base defect (VSBD) reconstruction, but not anterior skull base defect (ASBD) reconstruction, after expanded endoscopic endonasal approach (EEEA). The goal of this study is to introduce the transorbital transposition of the TPFF for skull base defects reconstruction after EEEA, and make quantitative comparison between the transpterygoid transposition and transorbital transposition. METHODS: Cadaveric dissections were performed in five adult cadaveric heads with creating three transporting corridors bilaterally, encompassing superior transorbital corridor, inferior transorbital corridor, and transpterygoid corridor. For each transporting corridor, the minimum necessary length of the TPFF for skull base defects reconstruction was measured. RESULTS: The areas of ASBD and VSBD were 1019.63 ± 176.32 mm2 and 572.99 ± 126.21 mm2 . The length of the harvested TPFF was 149.38 ± 6.21 mm. In contrast to the transpterygoid transposition with incomplete coverage, transorbital transposition of the TPFF allowed full coverage of ASBD with a minimum necessary length of 109.75 ± 8.31 mm. For VSBD reconstruction, transorbital transposition of the TPFF needs shorter minimum necessary length (123.88 ± 4.49 mm) than transpterygoid transposition (138.00 ± 6.28 mm). CONCLUSIONS: Transorbital corridor is a novel pathway for transporting the TPFF into the sinonasal cavity for skull base defects reconstruction after EEEA. In comparison with transpterygoid transposition, transorbital transposition provides wider coverage of skull base defects with a fixed length of the TPFF.

Enhanced Carotenoid Production in Chlamydomonas reinhardtii by Overexpression of Endogenousand Exogenous Beta-Carotene Ketolase (BKT) Genes.

Chlamydomonas reinhardtii is a unicellular green alga that can grow heterotrophically by using acetate as a carbon source. Carotenoids are natural pigments with biological activity and color, which have functions such as antioxidant, anti-inflammatory, vision protection, etc., and have high commercial value and prospects. We transformed Chlamydomonas reinhardtii with the BKT genes from Phaffia rhodozyma (PrBKT) and Chlamydomonas reinhardtii (CrBKT) via plasmid vector, and screened out the stable transformed algal strains C18 and P1. Under the condition that the cell density of growth was not affected, the total carotenoid content of C18 and P1 was 2.13-fold and 2.20-fold higher than that of the WT, respectively. CrBKT increased the levels of ß-carotene and astaxanthin by 1.84-fold and 1.21-fold, respectively, while PrBKT increased them by 1.11-fold and 1.27-fold, respectively. Transcriptome and metabolome analysis of C18 and P1 showed that the overexpression of CrBKT only up-regulated the transcription level of BKT and LCYE (the gene of lycopene e-cyclase). However, in P1, overexpression of PrBKT also led to the up-regulation of ZDS (the gene of ζ-carotene desaturase) and CHYB (the gene of ß-carotene hydroxylase). Metabolome results showed that the relative content of canthaxanthin, an intermediate metabolite of astaxanthin synthesis in C18 and P1, decreased. The overall results indicate that there is a structural difference between CrBKT and PrBKT, and overexpression of PrBKT in Chlamydomonas reinhardtii seems to cause more genes in carotenoid pathway metabolism to be up-regulated.

Light-driven dandelion-inspired microfliers.

In nature, many plants have evolved diverse flight mechanisms to disperse seeds by wind and propagate their genetic information. Inspired by the flight mechanism of the dandelion seeds, we demonstrate light-driven dandelion-inspired microfliers based on ultralight and super-sensitive tubular-shaped bimorph soft actuator. Like dandelion seeds in nature, the falling velocity of the as-proposed microflier in air can be facilely controlled by tailoring the degree of deformation of the "pappus" under different light irradiations. Importantly, the resulting microflier is able to achieve a mid-air flight above a light source with a sustained flight time of ~8.9 s and a maximum flight height of ~350 mm thanks to the unique dandelion-like 3D structures. Unexpectedly, the resulting microflier is found to exhibit light-driven upward flight accompanied by autorotating motion, and the rotation mode can be customized in either a clockwise or counterclockwise direction by engineering the shape programmability of bimorph soft actuator films. The research disclosed herein can offer new insights into the development of untethered and energy-efficient artificial aerial vehicles that are of paramount significance for many applications from environmental monitoring and wireless communication to future solar sail and robotic spacecraft.

Wireless Power Transfer to Electrothermal Liquid Crystal Elastomer Actuators.

Wireless actuation of electrically driven soft actuators is of paramount importance for the development of bioinspired soft robotics without physical connection or on-board batteries. Here, we demonstrate untethered electrothermal liquid crystal elastomer (LCE) actuators based on emerging wireless power transfer (WPT) technology. We first design and fabricate electrothermal LCE-based soft actuators that consist of an active LCE layer, a conductive liquid metal-filled polyacrylic acid (LM-PA) layer, and a passive polyimide layer. LM can function not only as an electrothermal transducer to endow resulting soft actuators with electrothermal responsiveness but also as an embedded sensor to track the resistance changes. Various shape-morphing and locomotive modes such as directional bending, chiral helical deformation, and inchworm-inspired crawling can be facilely obtained through appropriately controlling the molecular alignment direction of monodomain LCEs, and the reversible shape-deformation behaviors of resulting soft actuators can be monitored in real-time through resistance changes. Interestingly, untethered electrothermal LCE-based soft actuators have been achieved by designing a closed conductive LM circuit within the actuators and combining it with inductive-coupling WPT technology. When the resulting soft actuator approaches a commercially available wireless power supply system, an induced electromotive force can be generated within the closed LM circuit, which results in Joule heating and wireless actuation. As proof-of-concept illustrations, wirelessly driven soft actuators that can exhibit programmable shape-morphing behaviors are demonstrated. The research disclosed herein can provide insights into the development of bioinspired somatosensory soft actuators, battery-free wireless soft robots, and beyond.

Endoscopically assisted presigmoid retrolabyrinthine approach to the lateral mesencephalic sulcus: a cadaveric study with comparison to the variant supracerebellar infratentorial approaches.

The supracerebellar infratentorial (SCIT) approach is commonly used to gain access to the lateral mesencephalic sulcus (LMS), which has been established as a safe entry point into the posterolateral midbrain. This study describes a lateral variant of the SCIT approach, the supreme-lateral SCIT approach, for accessing the LMS through the presigmoid retrolabyrinthine craniectomy and quantitatively compares this approach with the paramedian and extreme-lateral SCIT approaches. Anatomical dissections were performed in four cadaveric heads. In each head, the supreme-lateral SCIT approach was established on one side, following a detailed description of each step, whereas the paramedian and supreme-lateral SCIT approaches were established on the other side. Quantitative measurements of the exposed posterolateral midbrain, the angles of LMS entry, and the depth of surgical corridors were recorded and compared between the three SCIT approach variants. The supreme-lateral (67.70 ± 23.14 mm2) and extreme-lateral (70.83 ± 24.99 mm2) SCIT approaches resulted in larger areas of exposure anterior to the LMS than the paramedian SCIT approach (38.61 ± 9.84 mm2); the supreme-lateral SCIT approach resulted in a significantly smaller area of exposure posterior to the LMS (65.24 ± 6.81 mm2) than the other two variants (paramedian = 162.75 ± 31.98 mm2; extreme-lateral = 143.10 ± 23.26 mm2; both P < .001). Moreover, the supreme-lateral SCIT approach resulted in a surgical corridor with a shallower depth and a smaller angle relative to the horizontal plane than the other two variants. The supreme-lateral SCIT approach is a more lateral approach than the extreme-lateral SCIT approach, providing a subtemporal approach with direct LMS visualization. The supreme-lateral SCIT offers the benefits of both subtemporal and SCIT approaches and represents a suitable option for the management of selected midbrain pathologies.

PT320, a Sustained-Release GLP-1 Receptor Agonist, Ameliorates L-DOPA-Induced Dyskinesia in a Mouse Model of Parkinson's Disease.

To determine the efficacy of PT320 on L-DOPA-induced dyskinetic behaviors, and neurochemistry in a progressive Parkinson's disease (PD) MitoPark mouse model. To investigate the effects of PT320 on the manifestation of dyskinesia in L-DOPA-primed mice, a clinically translatable biweekly PT320 dose was administered starting at either 5 or 17-weeks-old mice. The early treatment group was given L-DOPA starting at 20 weeks of age and longitudinally evaluated up to 22 weeks. The late treatment group was given L-DOPA starting at 28 weeks of age and longitudinally observed up to 29 weeks. To explore dopaminergic transmission, fast scan cyclic voltammetry (FSCV) was utilized to measure presynaptic dopamine (DA) dynamics in striatal slices following drug treatments. Early administration of PT320 significantly mitigated the severity L-DOPA-induced abnormal involuntary movements; PT320 particularly improved excessive numbers of standing as well as abnormal paw movements, while it did not affect L-DOPA-induced locomotor hyperactivity. In contrast, late administration of PT320 did not attenuate any L-DOPA-induced dyskinesia measurements. Moreover, early treatment with PT320 was shown to not only increase tonic and phasic release of DA in striatal slices in L-DOPA-naïve MitoPark mice, but also in L-DOPA-primed animals. Early treatment with PT320 ameliorated L-DOPA-induced dyskinesia in MitoPark mice, which may be related to the progressive level of DA denervation in PD.