Ag modified ZnO nanoflower gas sensitive sensor for selective detection of n-butanol.

Ag modified ZnO nanoflowers were successfully prepared by sunlight induced solvent reduction method. The samples were characterized by XRD, FESEM, TEM and EDS, and the results confirmed the presence of Ag nanoparticles on the ZnO nanoflower. The gas sensing performance of the materials was studied at different operating temperatures and different n-butanol concentrations. The results showed that the Ag modified ZnO nanoflower sensor responded to 50 ppm n-butanol up to 147.17 at 280 °C, and the Ag modified ZnO nanoflower sensor exhibited excellent repeatability, stability and response recovery time. In addition, different target gases were employed for the selectivity study of the Ag modified ZnO nanoflower. It can be found that the Ag modified ZnO nanoflower had good selectivity for n-butanol. The improved response of the Ag modified ZnO nanoflower sensor was attributed to the catalytic effect of Ag nanoparticles. The results indicate that the Ag modified ZnO nanoflower will become a very promising sensing material for n-butanol gas detection. .

Loss of Cisd2 Exacerbates the Progression of Age-Related Hearing Loss.

Age-related hearing loss (ARHL) is a disease that impacts human quality of life and contributes to the progression of other neuronal problems. Various stressors induce an increase in free radicals, destroy mitochondria to further contribute to cellular malfunction, and compromise cell viability, ultimately leading to functional decline. Cisd2, a master gene for Marfan syndrome, plays an essential role in maintaining mitochondrial integrity and functions. As shown by our data, specific deletion of Cisd2 in the cochlea exacerbated the hearing impairment of ARHL in C57BL/6 mice. Increased defects in mitochondrial function, potassium homeostasis and synapse activity were observed in the Cisd2-deleted mouse models. These mechanistic phenotypes combined with oxidative stress contribute to cell death in the whole cochlea. Human patients with obviously deteriorated ARHL had low Cisd2 expression; therefore, Cisd2 may be a potential target for designing therapeutic methods to attenuate the disease progression of ARHL.

Effects of ECM protein-coated surfaces on the generation of retinal pigment epithelium cells differentiated from human pluripotent stem cells.

Retinal degeneration diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP), initially manifest as dysfunction or death of the retinal pigment epithelium (RPE). Subretinal transplantation of human pluripotent stem cell (hPSC)-derived RPE cells has emerged as a potential therapy for retinal degeneration. However, RPE cells differentiated from hPSCs using current protocols are xeno-containing and are rarely applied in clinical trials. The development of hPSC-derived RPE cell differentiation protocols using xeno-free biomaterials is urgently needed for clinical applications. In this study, two protocols (the activin A and NIC84 protocols) were selected for modification and use in the differentiation of hiPSCs into RPE cells; the chetomin concentration was gradually increased to achieve high differentiation efficiency of RPE cells. The xeno-free extracellular matrix (ECM) proteins, laminin-511, laminin-521 and recombinant vitronectin, were selected as plate-coating substrates, and a Matrigel (xeno-containing ECM)-coated surface was used as a positive control. Healthy, mature hPSC-derived RPE cells were transplanted into 21-day-old Royal College of Surgeons (RCS) rats, a model of retinal degeneration disease. The visual function of RCS rats was evaluated by optomotor response (qOMR) and electroretinography after transplantation of hPSC-derived RPE cells. Our study demonstrated that hPSCs can be efficiently differentiated into RPE cells on LN521-coated dishes using the NIC84 protocol, and that subretinal transplantation of the cell suspensions can delay the progression of vision loss in RCS rats.

Breast Cancer Screening Using Mammography, Digital Breast Tomosynthesis, and Magnetic Resonance Imaging by Breast Density.

Importance: Information on long-term benefits and harms of screening with digital breast tomosynthesis (DBT) with or without supplemental breast magnetic resonance imaging (MRI) is needed for clinical and policy discussions, particularly for patients with dense breasts. Objective: To project long-term population-based outcomes for breast cancer mammography screening strategies (DBT or digital mammography) with or without supplemental MRI by breast density. Design, Setting, and Participants: Collaborative modeling using 3 Cancer Intervention and Surveillance Modeling Network (CISNET) breast cancer simulation models informed by US Breast Cancer Surveillance Consortium data. Simulated women born in 1980 with average breast cancer risk were included. Modeling analyses were conducted from January 2020 to December 2023. Intervention: Annual or biennial mammography screening with or without supplemental MRI by breast density starting at ages 40, 45, or 50 years through age 74 years. Main outcomes and Measures: Lifetime breast cancer deaths averted, false-positive recall and false-positive biopsy recommendations per 1000 simulated women followed-up from age 40 years to death summarized as means and ranges across models. Results: Biennial DBT screening for all simulated women started at age 50 vs 40 years averted 7.4 vs 8.5 breast cancer deaths, respectively, and led to 884 vs 1392 false-positive recalls and 151 vs 221 false-positive biopsy recommendations, respectively. Biennial digital mammography had similar deaths averted and slightly more false-positive test results than DBT screening. Adding MRI for women with extremely dense breasts to biennial DBT screening for women aged 50 to 74 years increased deaths averted (7.6 vs 7.4), false-positive recalls (919 vs 884), and false-positive biopsy recommendations (180 vs 151). Extending supplemental MRI to women with heterogeneously or extremely dense breasts further increased deaths averted (8.0 vs 7.4), false-positive recalls (1088 vs 884), and false-positive biopsy recommendations (343 vs 151). The same strategy for women aged 40 to 74 years averted 9.5 deaths but led to 1850 false-positive recalls and 628 false-positive biopsy recommendations. Annual screening modestly increased estimated deaths averted but markedly increased estimated false-positive results. Conclusions and relevance: In this model-based comparative effectiveness analysis, supplemental MRI for women with dense breasts added to DBT screening led to greater benefits and increased harms. The balance of this trade-off for supplemental MRI use was more favorable when MRI was targeted to women with extremely dense breasts who comprise approximately 10% of the population.

Discovery of quaternized pyridine-thiazole-ruthenium complexes as potent anti-Staphylococcus aureus agents.

Quaternization of ruthenium complexes may be a promising strategy for the development of new antibiotics. In response to the increasing bacterial resistance, we integrated the quaternary amine structure into the design of ruthenium complexes and evaluated their antibacterial activity. All the ruthenium complexes showed good antibacterial activity against the tested Staphylococcus aureus (S. aureus). Ru-8 was the most effective antibacterial agent that displayed excellent antibacterial activity against S. aureus (MIC = 0.78-1.56 µg/mL). In vitro experiments showed that all nine ruthenium complexes had low hemolytic toxicity to rabbit erythrocytes. Notably, Ru-8 was found to disrupt bacterial cell membranes, alter their permeability, and induce ROS production in bacteria, all the above leading to the death of bacteria without inducing drug resistance. To further explore the antibacterial activity of Ru-8in vivo, we established a mouse skin wound infection model and a G. mellonella larvae infection model. Ru-8 exhibited significant antibacterial efficacy against S. aureus in vivo and low toxicity to mouse tissues. The Ru-8 showed low toxicity to Raw264.7 cells (mouse monocyte macrophage leukemia cells). This study indicates that the ruthenium complex ruthenium quaternary was a promising strategy for the development of new antibacterial agents.

Effect of music-based interventions on anxiety and stress-related vital signs in patients undergoing cardiac catheterization: A systematic review and meta-analysis.

OBJECTIVES: This work aimed to evaluate the effect of music-based intervention (MBI) on anxiety and stress-related vital signs (heart rate, respiratory rate and blood pressure) in patients undergoing cardiac catheterization. DESIGN: A systematic review and meta-analysis. METHODS: This systematic review and meta-analysis was conducted according to PRISMA guidelines. PubMed, Cochrane Library, Embase and CINAHL were systematically searched from inception to October 31, 2023. Two authors independently searched electronic databases, selected literature, extracted data and assessed the risk of bias according to the eligibility criteria. The Review Manager software (RevMan version 5.4.1) was used to perform meta-analysis. RESULTS: Eleven randomized controlled trials (RCTs) with adult patients (n = 1204) (passive music therapy, 8 studies; passive music listening, 3 studies) were enrolled and brought into qualitative assessment. Nine of these RCTs (n = 868) were taken into quantitative analysis. Meta-analysis using the random-effects model revealed that the difference in the pre-post anxiety level in the music group was significantly greater than that in the control group. However, meta-analysis results for heart rate, respiratory rate, systolic blood pressure and diastolic blood pressure did not show significant differences. CONCLUSION: The findings suggested that MBI had a significant effect on reducing anxiety in patients undergoing cardiac catheterization. However, the limited quantity and quality of included studies highlight the need for additional research to comprehensively analyze the influence of MBI on anxiety reduction in this patient population.

Spatiotemporal expression analysis of jasmonic acid and saponin-related genes uncovers a potential biosynthetic regulation in Panax notoginseng.

BACKGROUND: Sanqi, the root of Panax notoginseng, has long been recognized for its therapeutic effects on cardiovascular diseases. Saponins, including ginsenosides and notoginsenosides, are the main bioactive components of P. notoginseng. The biosynthesis of saponins is closely related to the defense responses orchestrated by endogenous hormones. RESULTS: To provide new insights into the underlying role of phytohormone jasmonic acid (JA) in the synthesis and regulation of saponins, we performed an ultra-performance liquid chromatography analysis of different tissues of P. notoginseng aged 2-4 years. Moreover, by combined evaluation of saponin content and transcriptome profiling of each tissue, the spatial and temporal distribution of saponins was analyzed. N notoginsenoside R1, ginsenoside Rb1 and ginsenoside Rd accumulated in the underground tissues, including the root, tuqi, fibril and rhizome. In agreement with this data, the corresponding genes of the endogenous hormone JAs, especially coronatine insensitive 1 (COI1) and myelocytomatosis proteins 2 (MYC2), were predominantly expressed in the underground tissues. The tissue- and age-specific distribution of saponins was consistent with the expression of genes involved in JA biosynthetic, metabolic and signaling pathways. CONCLUSION: The present study has revealed the temporal and spatial effects of endogenous phtohormones in the synthesis and regulation of notoginsenosides, which will provide a significant impact on improving the ecological planting technology, cultivating new high-quality varieties and protecting the rare resources of medicinal P. notoginseng. © 2024 Society of Chemical Industry.

Label-Free Mapping of Multivalent Binding Pathways with Ligand-Receptor-Anchored Nanopores.

Understanding single-molecule multivalent ligand-receptor interactions is crucial for comprehending molecular recognition at biological interfaces. However, label-free identifications of these transient interactions during multistep binding processes remains challenging. Herein, we introduce a ligand-receptor-anchored nanopore that allows the protein to maintain structural flexibility and favorable orientations in native states, mapping dynamic multivalent interactions. Using a four-state Markov chain model, we clarify two concentration-dependent binding pathways for the Omicron spike protein (Omicron S) and soluble angiotensin-converting enzyme 2 (sACE2): sequential and concurrent. Real-time kinetic analysis at the single-monomeric subunit level reveals that three S1 monomers of Omicron S exhibit a consistent and robust binding affinity toward sACE2 (-13.1 ± 0.2 kcal/mol). These results highlight the enhanced infectivity of Omicron S compared to other homologous spike proteins (WT S and Delta S). Notably, the preceding binding of sACE2 to Omicron S facilitates the subsequent binding steps, which was previously obscured in bulk measurements. Our single-molecule studies resolve the controversy over the disparity between the measured spike protein binding affinity with sACE2 and the viral infectivity, offering valuable insights for drug design and therapies.

Plantago asiatica seed as a protective agent for mitigating metals toxicity on Penaeusvannamei.

Plantago asiatica seeds (PS) are commonly used as a medicinal plant. This study investigates the efficacy of PS against heavy metal toxicity in white shrimp (Penaeus vannamei). After feeding PS diet (5 g/kg) or basal diet (control group) for 7 days, shrimps were exposed to sublethal concentrations of heavy metals in seawater (As: 12 mg/L, Pb: 250 mg/L, Hg: 0.4 mg/L). The 7-day survival observation showed that the survival in groups fed with PS were significantly higher than that in the control group, revealing that dietary PS had the efficacy to mitigate heavy metal toxicity in white shrimp. Under the same feeding condition, white shrimps were exposed to safety dose of heavy metals (1/10 of sublethal concentrations) to understand the mechanism of mitigation. The metal accumulations in haemolymph, gills, hepatopancreas, and muscle tissues as well as the immune, anti-oxidative, stress related gene expressions in haemocytes, gills and hepatopancreas were measured for 14 days. The As accumulation in gills and hepatopancreas of groups fed with PS were significantly lower than those of control group on day 7 and 14, respectively; The Pb concentration in haemolymph of group fed with PS was significantly lower than that of control group on day 7 and 14; The Hg concentration in hepatopancreas of the group fed with PS was significantly lower than that of control group on day 7. Dietary PS could mitigate heavy metal-induced immune suppression, oxidative stress, and stress response by positively regulating immune (proPO I, Toll, IMD), antioxidant (SOD, GST, Trx), and negatively regulating stress response genes (HSP70, MT). The present study demonstrated that dietary PS could protect white shrimp against metal toxicity by reducing metal accumulations and regulating the immune, antioxidant, and stress response gene expressions in specific tissue. Therefore, PS may serve as a beneficial feed additive in the aquaculture.

Rosmarinic Acid Potentiates Cytotoxicity of Cisplatin against Colorectal Cancer Cells by Enhancing Apoptotic and Ferroptosis.

Rosmarinic acid (RA) has demonstrated anticancer effects on several types of malignancies. However, whether RA promotes the anticancer effect of cisplatin on colorectal cancer cells remains sketchy. This study aimed to explore whether RA potentiates the cytotoxicity of cisplatin against colon cancer cells and the underlying mechanism. Cell viability, cell cycle progression, and apoptosis was evaluated using sulforhodamine B (SRB) assay, flow cytometric analysis, and propidium iodide/Annexin V staining, respectively. Western blotting was utilized to analyze signaling pathways. Our findings showed that RA significantly enhanced the inhibitory effect on cell viability and the induction of apoptosis on the colon cancer cell lines DLD-1 and LoVo. Signaling cascade analysis revealed that the combination of RA and cisplatin jointly induced Bax and caspase activation while downregulating Bcl-2, glutathione peroxidase 4 (GPX4), and SLC7A11 in DLD-1 cells. Moreover, caspase inhibitor and ferroptosis inhibitor significantly reversed the inhibition of cell viability in response to RA combined with cisplatin. Collectively, these findings demonstrate that RA enhances the cytotoxicity of cisplatin against colon cancer cells, attributing to the promotion of apoptosis and ferroptosis.

The Gastroprotective Effects of Anisomeles indica against Ethanol-Induced Gastric Ulcer through the Induction of IκB-α and the Inhibition of NF-κB Expression.

Anisomeles indica (L.) Kuntze is a traditional herb with multiple medicinal properties and with potential for preventing or treating various diseases. Acteoside, one of the active ingredients in A. indica, is prepared into commercially available products of A. indica HP813 powder. In this study, the gastroprotective effects of A. indica HP813 powder were evaluated. Wistar rats were treated with A. indica HP813 powder at doses of 0, 207.5, 415, and 830 mg/kg body weight for 28 days. Then, gastric ulcers were induced by the oral administration of 70% ethanol (10 mL/kg body weight) on day 28. The rats were sacrificed at the end of the trial, and stomach tissues were collected. These stomach tissues were then used for macroscopic, microscopic, and immunohistochemical analyses. The results indicated that the area of gastric ulcer was 48.61%, 35.30%, and 27.16% in the ethanol-induced group, 415 mg/kg A. indica HP813 powder group, and 830 mg/kg A. indica HP813 powder group, respectively. In addition, the lesion scores were 2.9, 2.4, and 2.3 in the ethanol-induced group, 415 mg/kg A. indica HP813 powder group, and 830 mg/kg A. indica HP813 powder group, respectively. The immunochemical staining of the gastric tissue revealed that A. indica HP813 powder reduced the expressions of TNF-α and NF-κB proteins in the gastric tissue, which had been induced by ethanol. Finally, A. indica HP813 powder protected the gastric ulcer from ethanol damage through IκB-α induction. The present results demonstrated that A. indica HP813 powder has protective effects against ethanol-induced gastric ulcer.

Preliminary evidence for therapeutic impact of intravesical glucosamine on protamine sulfate and potassium chloride-induced bladder overactivity in rat model.

PURPOSE: To investigate the protective effect of intravesical glucosamine in treating overactive bladder (OAB). METHODS: Ninety-two female Sprague-Dawley (SD) rats were divided into 4 groups i.e. protamine sulfate (PS), N-acetylcysteine (NAC), and glucosamine-treated PS (GPS), and normal saline control (NC) were used. We induced hyperactivity in rats via intravesical infusion of PS and potassium chloride (KCl), whereas the NC group underwent a sustained intravesical saline infusion for 1 h. N-acetylcysteine (NAC), a potential antioxidant as well as anti-inflammatory agent was employed as positive control. Cystometrography (CMG) was then conducted to determine urodynamic parameters, i.e., leak point pressure (LPP, n = 48) and inter-contractile interval, the duration between two voids (ICI, n = 32). RESULTS: LPP was significantly elevated in the GPS group (mean ± SD: 110.9 ± 6.2 mmHg) compared to the NC (81.0 ± 32.5 mmHg), PS (40.3 ± 10.9 mmHg), and NAC group (70.3 ± 19.4 mmHg). The cystometrogram data also reveals a prolonged ICI in the GPS group (241.3 ± 40.2 s) compared to the NC group (216.0 ± 41.7 s), PS group (128.8 ± 23.6 s), and NAC group (193.8 ± 28.3 s). CONCLUSION: This preliminary study implies the ameliorative impact of GPS treatment on OAB in terms of improved urodynamic parameters, including LPP and ICI.

Dectin-1 induces TRPV1 sensitization and contributes to visceral hypersensitivity of irritable bowel syndrome in male mice.

BACKGROUND: Visceral hypersensitivity is considered the core pathophysiological mechanism that causes abdominal pain in patients with irritable bowel syndrome (IBS). Fungal dysbiosis has been proved to contribute to visceral hypersensitivity in IBS patients. However, the underlying mechanisms for Dectin-1, a major fungal recognition receptor, in visceral hypersensitivity are poorly understood. This study aimed to explore the role of Dectin-1 in visceral hypersensitivity and elucidate the impact of Dectin-1 activity on the function of transient receptor potential vanilloid type 1 (TRPV1). METHODS: Visceral hypersensitivity model was established by the intracolonic administration of 0.1 mL TNBS (130 µg/mL in 30% ethanol) in the male mice. Fluconazole and nystatin were used as fungicides. Laminarin, a Dectin-1 antagonist and gene knockout (Clec7a-/-) mice were used to interrupt the function of Dectin-1. Colorectal distension-electromyogram recording was performed to assess visceral sensitivity. Immunostaining experiment was performed to determine the localization of Dectin-1 in dorsal root ganglion (DRG) neurons. Calcium imaging study was performed to assay TRPV1-mediated calcium influx in acutely dissociated DRG neurons. RESULTS: Pretreatment with fungicides, administration of laminarin or genetic deletion of Clec7a alleviated TNBS-induced visceral hypersensitivity in male mice. The expression of Dectin-1 was upregulated in the DRG and colon of TNBS-treated mice. Colocalization of Dectin-1 and TRPV1 was observed in DRG neurons. Importantly, pretreatment with curdlan, a Dectin-1 agonist, increased TRPV1-mediated calcium influx. CONCLUSIONS: Dectin-1 contributes to visceral hypersensitivity in IBS or in inflammatory bowel disease in remission and activation of Dectin-1 induces TRPV1 sensitization. SIGNIFICANCE STATEMENT: This work provides direct evidence for the functional regulation of TRPV1 channel by Dectin-1 activity, proposing a new mechanism underlying TRPV1 sensitization. Control of intestinal fungi might be beneficial for the treatment of refractory abdominal pain in patients with IBS or IBD in remission.

Discovery, Synthesis, and Activity Evaluation of Novel Five-Membered Sulfur-Containing Heterocyclic Nucleosides as Potential Anticancer Agents In Vitro and In Vivo.

A series of novel five-membered sulfur-containing heterocyclic nucleoside derivatives were designed, synthesized, and evaluated for their anticancer activities in vitro and in vivo. The structure-activity relationship studies revealed that some of them showed obvious antitumor activities in several cancer cell lines. Among them, compound 22o exhibited remarkable antiproliferative activity against HeLa cells and was more potent than cisplatin (IC50 = 2.80 vs 7.99 µM). Furthermore, mechanism studies indicated that 22o inhibited cell metastasis, induced cell apoptosis, decreased mitochondrial membrane potential, and activated autophagy through the PI3K-Akt-mTOR signaling pathway. Moreover, drug affinity responsive target stability and the cellular thermal shift assay revealed that 22o targeted RPS6 and inhibited its phosphorylation. Importantly, 22o inhibited the growth of the HeLa xenograft mouse model with a low systemic toxicity. These results indicated that 22o may serve as potent anticancer agents that merit further attention in future anticancer drug discovery.

Can an Immersive Virtual Reality 360 Enhancing Students' Self-Directed Learning on Diabetes Knowledge and Self-Efficacy?

Nurses need to be competent in clinical nursing knowledge and skills via engagement in continuing education. The knowledge of nurses should be updated especially in caring for diabetes disease. The potential for immersive experience provision by 360-degree video. This study aims to design an immersive interactive learning experience based on 360° immersive videos and pilot testing on nursing students receiving diabetes education.

Electrochemical Monitoring of Real-Time Vesicle Dynamics Induced by Tau in a Confined Nanopipette.

The microtubule-associated protein tau participates in neurotransmission regulation via its interaction with synaptic vesicles (SVs). The precise nature and mechanics of tau's engagement with SVs, especially regarding alterations in vesicle dynamics, remain a matter of discussion. We report an electrochemical method using a synapse-mimicking nanopipette to monitor vesicle dynamics induced by tau. A model vesicle of ~30 nm is confined within a lipid-modified nanopipette orifice with a comparable diameter to mimic the synaptic lipid environment. Both tau and phosphorylated tau (p-tau) present two-state dynamic behavior in this biomimetic system, showing typical ionic current oscillation, induced by lipid-tau interaction. The results indicate that p-tau has a stronger affinity to the lipid vesicles in the confined environment, blocking the vesicle movement to a higher degree. Taken together, this method bridges a gap for sensing synaptic vesicle dynamics in a confined lipid environment, mimicking vesicle movement near the synaptic membrane. These findings contribute to understanding how different types of tau protein regulate synaptic vesicle motility and to underlying its functional and pathological behaviours in disease.

Influences of Propofol, Ciprofol and Remimazolam on Dreaming During Anesthesia for Gastrointestinal Endoscopy: A Randomized Double-Blind Parallel-Design Trial.

Purpose: To compare the influences of propofol, ciprofol and remimazolam on dreaming during painless gastrointestinal endoscopy. Methods: This study was a single-center, prospective, parallel-design, double-blind, randomized clinical trial. Between May 2023 and October 2023, patients undergoing elective painless gastrointestinal endoscopy were recruited and randomly allocated into one of the three groups. Demographic data, intraoperative information, incidence of dreaming, insufficient anesthesia and intraoperative awareness, type of dream, patient satisfaction score, adverse events, and improvement of sleep quality were collected. Results: The difference in incidence of dreaming among the three groups was not significant (33.33% vs 48.33% vs 41.67%, p=0.061). The number of patients with intraoperative hypotension in the propofol group was larger than that of the remimazolam group (32 vs 12, p=0.001). However, the cases of intraoperative hypotension between propofol group and ciprofol group or ciprofol group and remimazolam group were comparable (32 vs 22, p=0.122; 22 vs 12, p=0.064). The percentage of insufficient anesthesia between propofol group and remimazolam group was significant (13.33% vs 1.67%, p=0.001), while no statistical difference was detected between propofol group and remimazolam group or ciprofol group and remimazolam group (13.33% vs 5.00%, p=0.025; 5.00% vs 1.67%, p=0.150). The ability of propofol to improve sleep quality at 1st post-examination day was significantly better than that of remimazolam (86.21% vs 72.88%, p=0.015), while it was not significant between propofol group and ciprofol group or ciprofol group and remimazolam group (86.21% vs 80.36%, p=0.236; 72.88% vs. 72.88%, p=0.181). Incidence of intraoperative awareness, intraoperative hypoxia, type of dream, satisfaction score, adverse events during recovery, and sleep improvement on the 7th post-examination day was not significant among the groups. Conclusion: Anesthesia with propofol, ciprofol and remimazolam, respectively, for gastrointestinal endoscopy did not induce statistical difference in the incidence of dreaming, despite that all of them are more likely to induce pleasant dreams.

Eye Adult Changes in Thought (Eye ACT) Study: Design and Report on the Inaugural Cohort.

Background: Conflicting research on retinal biomarkers of Alzheimer's disease and related dementias (AD/ADRD) is likely related to limited sample sizes, study design, and protocol differences. Objective: The prospective Eye Adult Changes in Thought (Eye ACT) seeks to address these gaps. Methods: Eye ACT participants are recruited from ACT, an ongoing cohort of dementia-free, older adults followed biennially until AD/ADRD, and undergo visual function and retinal imaging assessment either in clinic or at home. Results: 330 participants were recruited as of 03/2023. Compared to ACT participants not in Eye ACT (N = 1868), Eye ACT participants (N = 330) are younger (mean age: 70.3 versus 71.2, p = 0.014), newer to ACT (median ACT visits since baseline: 3 versus 4, p < 0.001), have more years of education (17.7 versus 16.2, p < 0.001) and had lower rates of visual impairment (12% versus 22%, p < 0.001). Compared to those seen in clinic (N = 300), Eye ACT participants seen at home (N = 30) are older (77.2 versus 74.9, p = 0.015), more frequently female (60% versus 49%, p = 0.026), and have significantly worse visual acuity (71.1 versus 78.9 Early Treatment Diabetic Retinopathy Study letters, p < 0.001) and contrast sensitivity (-1.9 versus -2.1 mean log units at 3 cycles per degree, p = 0.002). Cognitive scores and retinal imaging measurements are similar between the two groups. Conclusions: Participants assessed at home had significantly worse visual function than those seen in clinic. By including these participants, Eye ACT provides a unique longitudinal cohort for evaluating potential retinal biomarkers of dementia.

A distinct dimer configuration of a diatom Get3 forming a tetrameric complex with its tail-anchored membrane cargo.

BACKGROUND: Most tail-anchored (TA) membrane proteins are delivered to the endoplasmic reticulum through a conserved posttranslational pathway. Although core mechanisms underlying the targeting and insertion of TA proteins are well established in eukaryotes, their role in mediating TA protein biogenesis in plants remains unclear. We reported the crystal structures of algal arsenite transporter 1 (ArsA1), which possesses an approximately 80-kDa monomeric architecture and carries chloroplast-localized TA proteins. However, the mechanistic basis of ArsA2, a Get3 (guided entry of TA proteins 3) homolog in plants, for TA recognition remains unknown. RESULTS: Here, for the first time, we present the crystal structures of the diatom Pt-Get3a that forms a distinct ellipsoid-shaped tetramer in the open (nucleotide-bound) state through crystal packing. Pulldown assay results revealed that only tetrameric Pt-Get3a can bind to TA proteins. The lack of the conserved zinc-coordination CXXC motif in Pt-Get3a potentially leads to the spontaneous formation of a distinct parallelogram-shaped dimeric conformation in solution, suggesting a new dimer state for subsequent tetramerization upon TA targeting. Pt-Get3a nonspecifically binds to different subsets of TA substrates due to the lower hydrophobicity of its α-helical subdomain, which is implicated in TA recognition. CONCLUSIONS: Our study provides new insights into the mechanisms underlying TA protein shielding by tetrameric Get3 during targeting to the diatom's cell membrane.

Effects of Taiwanese indigenous cinnamon (Cinnamomum osmophloeum) leaf hot-water extract on nonspecific immune responses, resistance against Vibrio parahaemolyticus, nonviable cells, and haemocyte subpopulations in white shrimp (Penaeusvannamei).

This study investigated the effects of Cinnamomum osmophloeum leaf hot-water extract (CLWE) on nonspecific immune responses and resistance to Vibrio parahaemolyticus in white shrimp (Penaeus vannamei). Firstly, a cell viability assay demonstrated that the CLWE is safe to white shrimp heamocytes in the concentration of 0-500 mg L-1. Haemocytes incubated in vitro with 10 and 50 mg L-1 of CLWE showed significantly higher response in superoxide anion production, PO activity, and phagocytic activity. In the in vivo trials, white shrimp were fed with 0, 0.5, 1, 5, and 10 g kg-1 CLWE supplemented feeds (designated as CLWE 0, CLWE 0.5, CLWE 1, CLWE 5, and CLWE 10, respectively) over a period of 28 days. In vivo experiments demonstrated that CLWE 0.5 feeding group resulted in the highest total haemocyte count, superoxide anion production, phenoloxidase activity, and phagocytic activity. Moreover, CLWE 0.5 supplemented feed significantly upregulated the clotting system, antimicrobial peptides, pattern recognition receptors, pattern recognition proteins, and antioxidant defences in white shrimp. Furthermore, the shrimp were infected with V. parahaemolyticus injections after 14 days of feeding as challenge test. Based on the challenge test result, both CLWE 0.5 and CLWE 5 demonstrated a strong resistance to V. parahaemolyticus. These two dosages effectively reduced the number of nonviable cells and activated different haemocyte subpopulations. These findings indicated that treatment with CLWE 0.5 could promote nonspecific immune responses, immune-related gene expression, and resistance to V. parahaemolyticus in white shrimp.