Epigenetic modification in Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disorder caused by genetic, epigenetic, and environmental factors. Recent advance in genomics and epigenetics have revealed epigenetic mechanisms in PD. These epigenetic modifications include DNA methylation, post-translational histone modifications, chromatin remodeling, and RNA-based mechanisms, which regulate cellular functions in almost all cells. Epigenetic alterations are involved in multiple aspects of neuronal development and neurodegeneration in PD. In this review, we discuss current understanding of the epigenetic mechanisms that regulate gene expression and neural degeneration and then highlight emerging epigenetic targets and diagnostic and therapeutic biomarkers for treating or preventing PD.

Effect of intubation in the lateral position under general anesthesia induction on the position of double-lumen tube placement in patients undergoing unilateral video-assisted thoracic surgery: study protocol for a prospective, single-center, parallel group, randomized, controlled trial.

BACKGROUND: The double-lumen tube (DLT) is an essential equipment for thoracic anesthesia and the precise position of DLT placement is particularly important for anesthesia and surgery. However, the incidence of DLT malposition remains high and it leads to lung isolation failure and hypoxemia during one-lung ventilation. This trial aims to explore the clinical application and efficacy of intubation in the lateral position under general anesthesia induction to reduce the incidence of DLT malposition in patients undergoing unilateral video-assisted thoracic surgery (VATS). METHODS: In this prospective, single-center, parallel group, randomized, controlled trial, we will recruit 108 patients, aged 18-80 years, scheduled for elective unilateral VATS with DLT intubation under general anesthesia, and they will be randomly assigned to two groups: a lateral DLT intubation group (group L) and a conventional supine DLT intubation group (group C). The left-sided DLT will be used to intubate in patients of both groups. The position of DLT will be confirmed and adjusted by using the fiberoptic bronchoscopy (FOB). The primary outcome is the incidence of DLT malposition observed via the FOB, and the secondary outcomes include the time of intubation, the frequency and duration of re-adjustments of DLT placement under FOB, whether to re-intubate, intraoperative vital signs, and postoperative recovery. DISCUSSION: Accurate DLT positioning is crucially important for thoracic surgery, but the incidence of DLT malposition is still high in the present clinical practice of thoracic anesthesia. This trial aims to investigate whether lateral DLT intubation can reduce the incidence of DLT malposition, with more stable intraoperative vital signs and less postoperative complications. TRIAL REGISTRATION: The study protocol was registered at Chinese Clinical Trial Registry ( http://www.chictr.org.cn ) with registration number: ChiCTR2200060794 on June 11, 2022.

Multi-omics analyses reveal stone cell distribution pattern in pear fruit.

Stone cells are the brachysclereid cells in pear (Pyrus) fruit, consisting almost entirely of lignified secondary cell walls. They are distributed mainly near the fruit core and spread radially in the whole fruit. However, the development of stone cells has not been comprehensively characterized, and little is known about the regulation of stone cell formation at the transcriptomic, proteomic, and metabolomic levels. In the present study, we performed phenomic analysis on the stone cells and their associated vascular bundles distributed near the fruit cores. Transcriptomic, proteomic, and metabolomic analyses revealed a significant positive regulation of biological processes which contribute to the lignification and lignin deposition in stone cells near the fruit core, including sucrose metabolism and phenylalanine, tyrosine, tryptophan, and phenylalanine biosynthesis. We found many metabolites generated from the phenylpropanoid pathway contributing to the cell wall formation of stone cells near the fruit core. Furthermore, we identified a key transcription factor, PbbZIP48, which was highly expressed near the fruit core and was shown to regulate lignin biosynthesis in stone cells. In conclusion, the present study provides insight into the mechanism of lignified stone cell formation near the pear fruit core at multiple levels.

Sustainable Self-Cleaning Evaporators for Highly Efficient Solar Desalination Using a Highly Elastic Sponge-like Hydrogel.

Interfacial evaporation using light-absorbing hydrogels offers efficient solar evaporation performance under natural sunlight, ensuring an affordable clean water supply. However, achieving light-absorbing hydrogels with durable and efficient utilization is still a challenge due to inevitable salt accumulation, a difficult-to-control surface morphology, and poor mechanical properties on the surfaces of hydrogel-based evaporators. In this work, a photothermal sponge-like hydrogel with a 3D interconnected porous structure was constructed using low-cost activated carbon as a photothermal material, as well as a double-network polymer chain as the basic skeleton using a simple foaming polymerization strategy. The sponge-like hydrogel evaporator showed tailored surface topography, adequate water transport, excellent elasticity and toughness, good salt rejection, and thermal localization properties. Under the irradiation of simulated sunlight (1.0 kW/m2), a high evaporation rate of 2.33 kg·m-2·h-1 was achieved. Furthermore, efficient salt self-cleaning behavior was achieved due to the fast ion diffusion within the 3D interconnected porous structures. Even in highly concentrated brine of 15 wt %, continuous and efficient water evaporation was still achieved. The excellent evaporation and salt rejection properties of this photothermal sponge-like hydrogel indicated its promising long-term sustainable utilization in seawater desalination.

Aloperine protects human retinal pigment epithelial cells against hydrogen peroxide-induced oxidative stress and apoptosis through activation of Nrf2/HO-1 pathway.

Age-related macular degeneration (AMD) is a complex multifactorial disease associated with the dysfunction of retinal pigment epithelium (RPE). Aloperine is a quinolizidine alkaloid that has been proven to possess broad pharmacological activities. However, the effects of aloperine on AMD remain unclear. In the present study, we used hydrogen peroxide (H2O2) to induce oxidative injury in human RPE cells (ARPE-19 cells). ARPE-19 cells were pretreated with different concentrations of aloperine for 2 h, followed by H2O2 exposure. Cell cytotoxicity was determined using lactate dehydrogenase (LDH) release assay. Cell viability was measured using Cell Counting Kit-8 (CCK-8) assay. The reactive oxygen species (ROS) generation, malondialdehyde (MDA) level, superoxide dismutase (SOD) activity and glutathione peroxidase (GSH-PX) activity were detected to reflect oxidative status. Western blot was performed to detect the expressions of bcl-2, bax, nuclear factor-erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). The activity of caspase-3 was also assessed to indicate cell apoptosis. In addition, ARPE-19 cells were transfected with siNrf2 to knock down Nrf2. Our results showed that pretreatment with aloperine elevated the reduced cell viability of H2O2-induced ARPE-19 cells in a dose-dependent manner. Aloperine greatly decreased the production of ROS and MDA, and increased the activities of SOD and GSH-PX in H2O2-stimulated ARPE-19 cells. H2O2-caused a decrease in bcl-2 expression and increases in bax expression and caspase-3 activity were mitigated by aloperine. Moreover, aloperine treatment enhanced the expression levels of Nrf2 in nuclear fraction and the HO-1 expression in lysates. Knockdown of Nrf2 reversed the protective effects of aloperine on H2O2-induced ARPE-19 cells. In conclusion, these findings demonstrated that aloperine protected ARPE-19 cells from H2O2-induced oxidative stress and apoptosis in part via activating the Nrf2/HO-1 signaling pathway. The findings suggested a therapeutic potential of aloperine for the treatment of ADM.

Antioxidant Effects of Protocatechuic Acid and Protocatechuic Aldehyde: Old Wine in a New Bottle.

Phenolic compounds are naturally present as secondary metabolites in plant-based sources such as fruits, vegetables, and spices. They have received considerable attention for their antioxidant, anti-inflammatory, and anti-carcinogenic properties for protection against many chronic disorders such as neurodegenerative diseases, diabetes, cardiovascular diseases, and cancer. They are categorized into various groups based on their chemical structure and include phenolic acids, flavonoids, curcumins, tannins, and quinolones. Their structural variations contribute to their specific beneficial effects on human health. The antioxidant property of phenolic compounds protects against oxidative stress by up-regulation of endogenous antioxidants, scavenging free radicals, and anti-apoptotic activity. Protocatechuic acid (PCA; 3,4-dihydroxy benzoic acid) and protocatechuic aldehyde (PAL; 3,4-dihydroxybenzaldehyde) are naturally occurring polyphenols found in vegetables, fruits, and herbs. PCA and PAL are the primary metabolites of anthocyanins and proanthocyanidins, which have been shown to possess pharmacological actions including antioxidant activity in vitro and in vivo. This review aims to explore the therapeutic potential of PCA and PAL by comprehensively summarizing their pharmacological properties reported to date, with an emphasis on their mechanisms of action and biological properties.

Current treatment strategies for COVID­19 (Review).

The spread of the novel severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) emerged suddenly at the end of 2019 and the disease came to be known as coronavirus disease 2019 (COVID­19). To date, there is no specific therapy established to treat COVID­19. Identifying effective treatments is urgently required to treat patients and stop the transmission of SARS­CoV­2 in humans. For the present review, >100 publications on therapeutic agents for COVID­19, including in vitro and in vivo animal studies, case reports, retrospective analyses and meta­analyses were retrieved from PubMed and analyzed, and promising therapeutic agents that may be used to combat SARS­CoV­2 infection were highlighted. Since the outbreak of COVID­19, different drugs have been repurposed for its treatment. Existing drugs, including chloroquine (CQ), its derivative hydroxychloroquine (HCQ), remdesivir and nucleoside analogues, monoclonal antibodies, convalescent plasma, Chinese herbal medicine and natural compounds for treating COVID­19 evaluated in experimental and clinical studies were discussed. Although early clinical studies suggested that CQ/HCQ produces antiviral action, later research indicated certain controversy regarding their use for treating COVID­19. The molecular mechanisms of these therapeutic agents against SARS­CoV2 have been investigated, including inhibition of viral interactions with angiotensin­converting enzyme 2 receptors in human cells, viral RNA­dependent RNA polymerase, RNA replication and the packaging of viral particles. Potent therapeutic options were reviewed and future challenges to accelerate the development of novel therapeutic agents to treat and prevent COVID­19 were acknowledged.

Physiological responses of Agriophyllum squarrosum and Setaria viridis to drought and re-watering.

Drought resistance of psammophyte determines survival and growth, but their responses to drought are not well understood. We conducted a pot experiment to study how physiological characteristics respond to drought and rehydration. We found that watering to 60-65% of field capacity (the control) provided more water than was required by Agriophyllum squarrosum and its leaves became yellow and slightly wilted. The total chlorophyll content and Fm (maximum fluorescence after dark adaptation) in control were lower than in the drought treatment, and both decreased after rehydration. With increasing drought duration and intensity, the relative water content (RWC), chlorophyll content, Fm, and the quantum efficiency of photosystem II (Fv/Fm) of Setaria viridis decreased, but malondialdehyde and membrane permeability increased. During the late drought, the activities of three antioxidant enzymes in A. squarrosum increased to prevent membrane lipid peroxidation; for S. viridis, only peroxidase and superoxide dismutase activities increased. After rehydration, RWC of both species increased, but Fv/Fm of A. squarrosum and Fm of S. viridis did not recover under severe drought. Our research illustrated that A. squarrosum is better adapted to arid environment than S. viridis, but the high soil moisture content is not conducive to normal growth of A. squarrosum.

Generation of integration-free human iPSC line LCPHi001-A from a Parkinson's disease patient carrying the RecNciI mutation in GBA gene.

Parkinson's disease (PD) is a neurodegenerative disease caused by environmental and genetic factors. The identified PD genes include SNCA, LRRK2, Parkin, DJ-1, PINK1, and ATP13A2. Mutations in the glucocerebrosidase (GBA) gene were reported to be associated with PD in different ethnic populations. Here we generated a novel induced pluripotent stem cell (iPSC) line LCPHi001-A from a PD patient carrying RecNciI mutation (c.1448 T > C, c.1483G > C, and c.1497G > C) in GBA by non-integrative episomal plasmids. The LCPHi001-A line expressed pluripotency markers, displayed differentiation capacity to three germ layers in vivo, and had the normal karyotype.

Community carbon and water exchange responses to warming and precipitation enhancement in sandy grassland along a restoration gradient.

Temperature increasing and precipitation alteration are predicted to occur in arid and semiarid lands; however, the response mechanism of carbon and water exchange at community level is still unclear in semiarid sandy land. We investigated the responses of carbon and water exchanges to warming and precipitation enhancement along a sand dune restoration gradient: mobile sand dunes (MD), semifixed sand dunes (SFD), and fixed sand dunes (FD). The average net ecosystem productivity (NEP) and evapotranspiration (ET) between May and August increased by 98% and 59%, respectively, from MD to SFD, while they had no significant differences between FD and the other two habitats. Warming inhibited ecosystem NEP, ET, and water use efficiency (WUE) by 69%, 49% (p < .001), and 80%, respectively, in SFD, while it nearly had no significant effects in MD and FD. However, precipitation addition by 30% nearly had no significant effects on community NEP, ET, and WUE, except for warming treatment in FD. In general, precipitation addition of 30% may still not be enough to prevent drought stress for growth of plants, due to with low water holding capacity and high evaporation rates in sandy land. Temperature increase magnified drought stress as it increased evapotranspiration rates especially in summer. In addition, community NEP, ET, and WUE were usually influenced by interactions between habitats and temperature, as well as the interactions among habitats, temperature, and precipitation. Species differences in each habitat along the restoration gradient may alter climate sensitivity of sandy land. These results will support in understanding and the prediction of the impacts of warming and precipitation change in semiarid sandy grassland.

Growth and Physiology of Two Psammophytes to Precipitation Manipulation in Horqin Sandy Land, Eastern China.

The availability of water is the critical factor driving plant growth, physiological responses, population and community succession in arid and semiarid regions, thus a precipitation addition-reduction platform with five experimental treatments, was established to explore the growth and physiology of two psammophytes (also known as psammophiles) to precipitation manipulation in Horqin Sandy Land. Changes in coverage and density were measured, and antioxidant enzymes and osmoregulatory substances in both of the studied species were determined. Investigation results showed that the average vegetation coverage increased with an increasing precipitation, and reached a maximum in July. Under the -60% precipitation treatment, Tribulus terrestris accounted for a large proportion of the area, but Bassia dasyphylla was the dominant species in the +60% treatment. T. terrestris was found to have higher a drought stress resistance than B. dasyphylla. From days 4 to 7 after rainfall, B. dasyphylla under precipitation reduction showed obvious water stress. The malondialdehyde (MDA) content of B. dasyphylla was higher than that of T. terrestris, but that of B. dasyphylla had the lower relative water content (RWC). The MDA content in the precipitation reduction treatments of the two studied species was higher than that in the precipitation addition treatments from days 4 to 10. Peroxidase (POD) and superoxide dismutase (SOD) activity and the soluble proteins and free proline content of T. terrestris were higher than those of B. dasyphylla. The free proline content of T. terrestris and B. dasyphylla increased with increasing drought stress. Our data illustrated that T. terrestris had a higher drought stress resistance than B. dasyphylla, which was correlated with the augmentation of some antioxidant enzymes and osmoregulatory substance. The adaptive mechanism provides solid physiological support for an understanding of psammophyte adaptation to drought stress, and of community succession or species manipulation for desertified land restoration.

Sipeimine-producing endophytic fungus isolated from Fritillaria ussuriensis.

Ten strains of endophytic fungi were isolated from the bulbs of the traditional Chinese medicinal plant Fritillaria ussuriensis. The extract from one of them, Fu7, showed a positive reaction with Dragendorff's reagent and the same Rf value in thin-layer chromatography (TLC) analysis as authentic sipeimine. A further TLC scan and high-performance liquid chromatography-evaporative light-scattering detection (HPLC-ELSD) showed that one ingredient of the extract of strain Fu7 had a similar absorption curve in the range 200-700 nm and the same retention time as authentic sipeimine. Thus, the fungus produces the bioactive ingredient sipeimine, as does its host plant, and could be used for the production of sipeimine by fermentation.