Highly sensitive electrochemical sensing platform for the detection of L-dopa based on electropolymerizing glutathione disulfide and multi-walled carbon nanotube-modified electrodes

Afacile sensing platformfor the detection of L-dopa has been developed by electropolymerizing glutathione disulfide (PGSSG) on the surface of glass carbon electrodes (GCE) which were modified by multi-walled carbon nanotubes (MWCNTs). The electrochemical behaviour of the proposed electrodes were investigated via cyclic voltammetry (CV) and differential pulse voltammetry DPV). The morphology of the PGSSG and PGSSG/MWCNTs were characterized by scanning electron microscopy (SEM). Under the optimized experimental conditions, the sensing platform showed the linear response to L-Dopa in a range from 1.0 × 10–6 to 1.2 × 10–3 M with a detection limit of 3.3 × 10–7M (S/N = 3). Moreover, with the merits of high sensitivity and selectivity, good stability and reproducibility, the sensor was successfully applied for the determination of L-dopa in a real sample.Keywords: L-dopa, glutathione disulfide, multi-walled carbon nanotubes, electropolymerization, electrochemical determinatio

Enhanced Astrocytic Ca\u3csup\u3e2+\u3c/sup\u3e Signals Contribute to Neuronal Excitotoxicity after Status Epilepticus

Status epilepticus (SE), an unremitting seizure, is known to cause a variety of traumatic responses including delayed neuronal death and later cognitive decline. Although excitotoxicity has been implicated in this delayed process, the cellular mechanisms are unclear. Because our previous brain slice studies have shown that chemically induced epileptiform activity can lead to elevated astrocytic Ca2+ signaling and because these signals are able to induce the release of the excitotoxic transmitter glutamate from these glia, we asked whether astrocytes are activated during status epilepticus and whether they contribute to delayed neuronal death in vivo. Using two-photon microscopy in vivo, we show that status epilepticus enhances astrocytic Ca2+ signals for 3 d and that the period of elevated glial Ca2+ signaling is correlated with the period of delayed neuronal death. To ask whether astrocytes contribute to delayed neuronal death, we first administered antagonists which inhibit gliotransmission: MPEP [2-methyl-6-(phenylethynyl)pyridine], a metabotropic glutamate receptor 5 antagonist that blocks astrocytic Ca2+ signals in vivo, and ifenprodil, an NMDA receptor antagonist that reduces the actions of glial-derived glutamate. Administration of these antagonists after SE provided significant neuronal protection raising the potential for a glial contribution to neuronal death. To test this glial hypothesis directly, we loaded Ca2+ chelators selectively into astrocytes after status epilepticus.We demonstrate that the selective attenuation of glial Ca2+ signals leads to neuronal protection. These observations support neurotoxic roles for astrocytic gliotransmission in pathological conditions and identify this process as a novel therapeutic target

Association between salivary microbiota and renal function in renal transplant patients during the perioperative period

IntroductionRenal transplantation is an effective treatment for the end stage renal disease (ESRD). However, how salivary microbiota changes during perioperative period of renal transplant recipients (RTRs) has not been elucidated.MethodsFive healthy controls and 11 RTRs who had good recovery were enrolled. Saliva samples were collected before surgery and at 1, 3, 7, and 14 days after surgery. 16S rRNA gene sequencing was performed.ResultsThere was no significant difference in the composition of salivary microbiota between ESRD patients and healthy controls. The salivary microbiota of RTRs showed higher operational taxonomic units (OTUs) amount and greater alpha and beta diversity than those of ESRD patients and healthy controls, but gradually stabilized over time. At the phylum level, the relative abundance of Actinobacteria, Tenericutes and Spirochaetes was about ten times different from ESRD patients or healthy controls for RTRs overall in time. The relative abundance of Bacteroidetes, Fusobacteria, Patescibacteria, Leptotrichiaceae and Streptococcaceae was correlated with serum creatinine (Scr) after renal transplantation.DiscussionIn short, salivary microbiota community altered in the perioperative period of renal transplantation and certain species of salivary microbiota had the potential to be a biomarker of postoperative recovery

MULTI: Multimodal Understanding Leaderboard with Text and Images

Rapid progress in multimodal large language models (MLLMs) highlights the need to introduce challenging yet realistic benchmarks to the academic community, while existing benchmarks primarily focus on understanding simple natural images and short context. In this paper, we present MULTI as a cutting-edge benchmark for evaluating MLLMs on understanding complex tables and images, and reasoning with long context. MULTI provides multimodal inputs and requires responses that are either precise or open-ended, reflecting real-life examination styles. MULTI includes over 18,000 questions and challenges MLLMs with a variety of tasks, ranging from formula derivation to image detail analysis and cross-modality reasoning. We also introduce MULTI-Elite, a 500-question selected hard subset, and MULTI-Extend, with more than 4,500 external knowledge context pieces. Our evaluation indicates significant potential for MLLM advancement, with GPT-4V achieving a 63.7% accuracy rate on MULTI, in contrast to other MLLMs scoring between 28.5% and 55.3%. MULTI serves not only as a robust evaluation platform but also paves the way for the development of expert-level AI.Comment: 16 pages, 9 figures, 10 tables. Details and access are available at: https://OpenDFM.github.io/MULTI-Benchmark

Long Non-Coding RNA MALAT1 Protects Human Osteoblasts from Dexamethasone-Induced Injury via Activation of PPM1E-AMPK Signaling

Background/Aims: Dexamethasone (Dex) induces injuries to human osteoblasts. In this study, we tested the potential role of the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (Lnc-MALAT1) in this process. Materials: Two established human osteoblastic cell lines (OB-6 and hFOB1.19) and primary human osteoblasts were treated with Dex. Lnc-MALAT1 expression was analyzed by quantitative real-time polymerase chain reaction assay. Cell viability, apoptosis, and death were tested by the MTT assay, histone-DNA assay, and trypan blue staining assay, respectively. AMP-activated protein kinase (AMPK) signaling was evaluated by western blotting and AMPK activity assay. Results: Lnc-MALAT1 expression was downregulated by Dex treatment in the established osteoblastic cell lines (OB-6 and hFOB1.19) and primary human osteoblasts. The level of Lnc-MALAT1 was decreased in the necrotic femoral head tissues of Dex-administered patients. In osteoblastic cells and primary human osteoblasts, forced overexpression of Lnc-MALAT1 using a lentiviral vector (LV-MALAT1) inhibited Dex-induced cell viability reduction, cell death, and apoptosis. Conversely, transfection with Lnc-MALAT1 small interfering RNA aggravated Dex-induced cytotoxicity. Transfection with LV-MALAT1 downregulated Ppm1e (protein phosphatase, Mg2+/ Mn2+-dependent 1e) expression to activate AMPK signaling. Treatment of osteoblasts with AMPKα1 short hairpin RNA or dominant negative mutation (T172A) abolished LV-MALAT1-induced protection against Dex-induced cytotoxicity. Furthermore, LV-MALAT1 induced an increase in nicotinamide adenine dinucleotide phosphate activity and activation of Nrf2 signaling. Dex-induced reactive oxygen species production was significantly attenuated by LV-MALAT1 transfection in osteoblastic cells and primary osteoblasts. Conclusion: Lnc-MALAT1 protects human osteoblasts from Dex-induced injuries, possibly via activation of Ppm1e-AMPK signaling

Ocular fundus pathology and chronic kidney disease in a Chinese population

<p>Abstract</p> <p>Background</p> <p>Previous study indicated a high prevalence of ocular fundus pathology among patients with chronic kidney disease (CKD), while the relationship between them has never been explored in a Chinese Population.</p> <p>Methods</p> <p>This cross-sectional study included 9 670 participants enrolled in a medical screening program. Ocular fundus examination was performed by ophthalmologists using ophthalmoscopes. The presence of eGFR less than 60 mL/min/1.73 m²and/or proteinuria was defined as CKD.</p> <p>Results</p> <p>Compared to participants without CKD, participants with CKD had higher prevalence of retinopathy (28.5% vs. 16.3%, P < 0.001), glaucoma suspect (3.1% vs. 1.8%, P = 0.004), age-related macular degeneration (1.7% vs. 0.9%, P = 0.01) and overall eye pathology (32.0% vs. 19.4%, P < 0.001). After adjusting for potential confounders, the odds ratio of proteinuria for overall eye pathology and retinopathy was 1.29 (95% confidence interval [CI] 1.07-1.55) and 1.37 (95% CI 1.12-1.67), respectively. The results were robust after excluding participants with hypertension or with diabetes.</p> <p>Conclusions</p> <p>Ocular fundus pathology is common among Chinese patients with CKD. Regular eye exam among persons with proteinuria is warranted.</p

Origin and evolution of the triploid cultivated banana genome

DATA AVAILABILITY : Genome assemblies of Cavendish, Gros Michel and Zebrina v2.0 have been deposited into NCBI under GenBank numbers JAVVNX000000000, JAVVNW000000000 and JAVVNV000000000 and in the National Genomics Data Center BioProject database (https://ngdc.cncb.ac.cn/bioproject/) under the accession number PRJCA019650. Genome assemblies with annotations and results of ChIP–seq and DNase-seq can be accessed at FigShare (https://figshare.com/projects/Origin_and_evolution_of_the_triploid_cultivated_banana_genome/178041). Raw data used for the assemblies, including PacBio, Illumina and Hi-C data, are available through the Sequence Read Archive of the National Centre for Biotechnology Information (NCBI) under the BioProject PRJNA1017453 with SRA accessions from SRR23425440 to SRR23425472 and from SRR23885547 to SRR23885549. Fifty-eight RNA-seq datasets were downloaded from NCBI BioProject accessions PRJNA381300, PRJNA394594 and PRJNA598018. DNA methylation data were downloaded from NCBI BioProject PRJNA381300.Most fresh bananas belong to the Cavendish and Gros Michel subgroups. Here, we report chromosome-scale genome assemblies of Cavendish (1.48 Gb) and Gros Michel (1.33 Gb), defining three subgenomes, Ban, Dh and Ze, with Musa acuminata ssp. banksii, malaccensis and zebrina as their major ancestral contributors, respectively. The insertion of repeat sequences in the Fusarium oxysporum f. sp. cubense (Foc) tropical race 4 RGA2 (resistance gene analog 2) promoter was identified in most diploid and triploid bananas. We found that the receptor-like protein (RLP) locus, including Foc race 1-resistant genes, is absent in the Gros Michel Ze subgenome. We identified two NAP (NAC-like, activated by apetala3/pistillata) transcription factor homologs specifically and highly expressed in fruit that directly bind to the promoters of many fruit ripening genes and may be key regulators of fruit ripening. Our genome data should facilitate the breeding and super-domestication of bananas.The National Natural Science Foundation of China, Construction of Plateau Discipline of Fujian Province, the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program and from Ghent University (Methusalem funding).http://www.nature.com/ng2024-06-11hj2024BiochemistryGeneticsMicrobiology and Plant PathologySDG-02:Zero Hunge

Polarity Changes in the Transmembrane Domain Core of HIV-1 Vpu Inhibits Its Anti-Tetherin Activity

Tetherin (BST-2/CD317) is an interferon-inducible antiviral protein that restricts the release of enveloped viruses from infected cells. The HIV-1 accessory protein Vpu can efficiently antagonize this restriction. In this study, we analyzed mutations of the transmembrane (TM) domain of Vpu, including deletions and substitutions, to delineate amino acids important for HIV-1 viral particle release and in interactions with tetherin. The mutants had similar subcellular localization patterns with that of wild-type Vpu and were functional with respect to CD4 downregulation. We showed that the hydrophobic binding surface for tetherin lies in the core of the Vpu TM domain. Three consecutive hydrophobic isoleucine residues in the middle region of the Vpu TM domain, I15, I16 and I17, were important for stabilizing the tetherin binding interface and determining its sensitivity to tetherin. Changing the polarity of the amino acids at these positions resulted in severe impairment of Vpu-induced tetherin targeting and antagonism. Taken together, these data reveal a model of specific hydrophobic interactions between Vpu and tetherin, which can be potentially targeted in the development of novel anti-HIV-1 drugs