MYC Drives mRNA Pseudouridylation to Mitigate Proliferation-Induced Cellular Stress during Cancer Development.

Pseudouridylation is a common RNA modification that is catalyzed by the family of pseudouridine synthases (PUS). Pseudouridylation can increase RNA stability and rigidity, thereby impacting RNA splicing, processing, and translation. Given that RNA metabolism is frequently altered in cancer, pseudouridylation may be a functionally important process in tumor biology. Here, we showed that the MYC family of oncoproteins transcriptionally upregulates PUS7 expression during cancer development. PUS7 was essential for the growth and survival of MYC-driven cancer cells and xenografts by promoting adaptive stress responses and amino acid biosynthesis and import. ATF4, a master regulator of stress responses and cellular metabolism, was identified as a key downstream mediator of PUS7 functional activity. Induction of ATF4 by MYC oncoproteins and cellular stress required PUS7, and ATF4 overexpression overcame the growth inhibition caused by PUS7 deficiency. Mechanistically, PUS7 induced pseudouridylation of MCTS1 mRNA, which enhanced its translation. MCTS1, a noncanonical translation initiation factor, drove stress-induced ATF4 protein expression. A PUS7 consensus pseudouridylation site in the 3' untranslated region of ATF4 mRNA was crucial for the induction of ATF4 by cellular stress. These findings unveil a MYC-activated mRNA pseudouridylation program that mitigates cellular stress induced by MYC stimulation of proliferation and biomass production, suggesting that targeting PUS7 could be therapeutic strategy selectively against MYC-driven cancers.

Transport-Friendly Microstructure in SSC-MEA: Unveiling the SSC Ionomer-Based Membrane Electrode Assemblies for Enhanced Fuel Cell Performance.

The significant role of the cathodic binder in modulating mass transport within the catalyst layer (CL) of fuel cells is essential for optimizing cell performance. This investigation focuses on enhancing the membrane electrode assembly (MEA) through the utilization of a short-side-chain perfluoro-sulfonic acid (SSC-PFSA) ionomer as the cathode binder, referred to as SSC-MEA. This study meticulously visualizes the distinctive interpenetrating networks of ionomers and catalysts, and explicitly clarifies the triple-phase interface, unveiling the transport-friendly microstructure and transport mechanisms inherent in SSC-MEA. The SSC-MEA exhibits advantageous microstructural features, including a better-connected ionomer network and well-organized hierarchical porous structure, culminating in superior mass transfer properties. Relative to the MEA bonded by long-side-chain perfluoro-sulfonic acid (LSC-PFSA) ionomer, noted as LSC-MEA, SSC-MEA exhibits a notable peak power density (1.23 W cm-2), efficient O2 transport, and remarkable proton conductivity (65% improvement) at 65 °C and 70% relativity humidity (RH). These findings establish crucial insights into the intricate morphology-transport-performance relationship in the CL, thereby providing strategic guidance for developing highly efficient MEA.

Integration of Motor Unit Filters for Enhanced Surface Electromyogram Decomposition During Varying Force Isometric Contraction.

Muscles generate varying levels of force by recruiting different numbers of motor units (MUs), and as the force increases, the number of recruited MUs gradually rises. However, current decoding methods encounter difficulties in maintaining a stable and consistent growth trend in MU numbers with increasing force. In some instances, an unexpected reduction in the number of MUs can even be observed as force intensifies. To address this issue, in this study, we propose an enhanced decoding method that adaptively reutilizes MU filters. Specifically, in addition to the normal decoding process, we introduced an additional procedure where MU filters are reused to initialize the algorithm. The MU filters are iterated and adapted to the new signals, aiming to decode motor units that were actually activated but cannot be identified due to heavy superimposition. We tested our method on both simulated and experimental surface electromyogram (sEMG) signals. We simulated isometric signals (10%-70%) with known MU firing patterns using experimentally recorded MU action potentials from forearm muscles and compared the decomposition results to two baseline approaches: convolution kernel compensation (CKC) and fast independent component analysis (fastICA). Our method increased the decoded MU number by a rate of 135.4% ± 62.5 % and 63.6% ± 20.2 % for CKC and fastICA, respectively, across different signal-to-noise ratios. The sensitivity and precision for MUs decomposed using the enhanced method remained at the same accuracy level (p <0.001) as those of normally decoded MUs. For the experimental signals, eight healthy subjects performed hand movements at five different force levels (10%-90%), during which sEMG signals were recorded and decomposed. The results indicate that the enhanced process increased the number of decoded MUs by 21.8% ± 10.9 % across all subjects. We discussed the possibility of fully capturing all activated motor units by appropriately reusing previously decoded MU filters and improving the balance of activated motor unit numbers across varying excitation levels.

Zinc(ii)-mediated stereoselective construction of 1,2-cis 2-azido-2-deoxy glycosidic linkage: assembly of Acinetobacter baumannii K48 capsular pentasaccharide derivative.

The capsular polysaccharide (CPS) is a major virulence factor of the pathogenic Acinetobacter baumannii and a promising target for vaccine development. However, the synthesis of the 1,2-cis-2-amino-2-deoxyglycoside core of CPS remains challenging to date. Here we develop a highly α-selective ZnI2-mediated 1,2-cis 2-azido-2-deoxy chemical glycosylation strategy using 2-azido-2-deoxy glucosyl donors equipped with various 4,6-O-tethered groups. Among them the tetraisopropyldisiloxane (TIPDS)-protected 2-azido-2-deoxy-d-glucosyl donor afforded predominantly α-glycoside (α : ß = >20 : 1) in maximum yield. This novel approach applies to a wide acceptor substrate scope, including various aliphatic alcohols, sugar alcohols, and natural products. We demonstrated the versatility and effectiveness of this strategy by the synthesis of A. baumannii K48 capsular pentasaccharide repeating fragments, employing the developed reaction as the key step for constructing the 1,2-cis 2-azido-2-deoxy glycosidic linkage. The reaction mechanism was explored with combined experimental variable-temperature NMR (VT-NMR) studies and mass spectroscopy (MS) analysis, and theoretical density functional theory calculations, which suggested the formation of covalent α-C1GlcN-iodide intermediate in equilibrium with separated oxocarbenium-counter ion pair, followed by an SN1-like α-nucleophilic attack most likely from separated ion pairs by the ZnI2-activated acceptor complex under the influence of the 2-azido gauche effect.

Correlation of resin composite translucency and IOS accuracy: An in-vitro study.

Background: Different restoration materials have different optical characteristics that influence the intraoral scanner's (IOS) image accuracy. The purpose of this in-vitro investigation was to investigate how composite translucency affected the accuracy of IOS. Material and Methods: GC G-aenial Universal Injectable JE composite plates were used for the study at 3 thicknesses (1-2-3mm). A lab scanner (3Shape E1) obtained 1 reference scan, whereas IOS (Trios3) was used to conduct 10 experimental scans per group. After 3D superimposition, deviation values were used to assess the accuracy (trueness and precision) outcomes for the corresponding groups. Using an LS170 V2.0 colorimeter, the translucency parameter (TP) of the plates was determined from L*a*b* values of CIELAB color space. Results: The composite translucency resulted in a decrease in the scale of digital impressions. The 1mm group had the largest scale reduction (0.02mm) significantly, followed by the 2mm and 3mm groups (0.01mm). No difference was found in mean precision. The colorimeter detects the L*a*b* values and showed that 1mm composite plate expressed the highest TP value, then 2mm and 3mm groups (28.90, 14.26 and 6.49 respectively). The thinner composite, the higher translucency and TP were highly positively correlated to IOS trueness of composite plates. Conclusions: Composite translucency has an impact on optical impression accuracy. In correlation, the optical impression becomes less accurate the more translucent the composite is. This implies that in the digital process, the dentist should specify the appropriate optical properties of composite materials concerning both their mechanical and aesthetic qualities. Key words:Accuracy, translucency, resin composite, digital dentistry, intraoral-scanner.

Clinical outcomes of carbapenem-resistant gram-negative bacterial bloodstream infection in patients with end-stage renal disease in intensive care units: a multicenter retrospective observational study.

BACKGROUND: Carbapenem-resistant gram-negative bacteria (CRGNB) present a considerable global threat due to their challenging treatment and increased mortality rates, with bloodstream infection (BSI) having the highest mortality rate. Patients with end-stage renal disease (ESRD) undergoing renal replacement therapy (RRT) face an increased risk of BSI. Limited data are available regarding the prognosis and treatment outcomes of CRGNB-BSI in patients with ESRD in intensive care units (ICUs). METHODS: This multi-center retrospective observational study included a total of 149 ICU patients with ESRD and CRGNB-BSI in Taiwan from January 2015 to December 2019. Clinical and microbiological outcomes were assessed, and multivariable regression analysis was used to evaluate the independent risk factors for day-28 mortality and the impact of antimicrobial therapy regimen on treatment outcomes. RESULTS: Among the 149 patients, a total of 127 patients (85.2%) acquired BSI in the ICU, with catheter-related infections (47.7%) and pneumonia (32.2%) being the most common etiologies. Acinetobacter baumannii (49.0%) and Klebsiella pneumoniae (31.5%) were the most frequently isolated pathogens. The day-28 mortality rate from BSI onset was 52.3%, and in-hospital mortality was 73.2%, with survivors experiencing prolonged hospital stays. A higher Sequential Organ Failure Assessment (SOFA) score (adjusted hazards ratio [aHR], 1.25; 95% confidence interval [CI] 1.17-1.35) and shock status (aHR, 2.12; 95% CI 1.14-3.94) independently predicted day-28 mortality. Colistin-based therapy reduced day-28 mortality in patients with shock, a SOFA score of ≥ 13, and Acinetobacter baumannii-related BSI. CONCLUSIONS: CRGNB-BSI led to high mortality in critically ill patients with ESRD. Day-28 mortality was independently predicted by a higher SOFA score and shock status. In patients with higher disease severity and Acinetobacter baumannii-related BSI, colistin-based therapy improved treatment outcomes.

Sex-specific association of peripheral blood cell indices and inflammatory markers with depressive symptoms in early adolescence.

BACKGROUND: Previous studies have reported the correlation of dysregulated blood cell indices and peripheral inflammatory markers with depression in adults but limited studies have examined this correlation in early adolescents. METHODS: This study used data from the Chinese Early Adolescents Cohort Study, which was conducted in Anhui, China. Students' depression symptoms were repeatedly measured using the Chinese version of the Center for Epidemiological Studies Depression Scale for Children. Students' blood samples were collected in September 2019 and September 2021. The peripheral blood cell counts and inflammatory marker levels were determined using routine blood tests. Multivariable regression models were used to explore the associations between blood cell indices and adolescent depressive symptoms in both the whole sample and the sex-stratified samples. RESULTS: The white blood cell (WBC) count, neutrophil count (NC), platelet (PLT) count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, and systemic immune inflammation index (SII) were positively correlated with the severity of depressive symptoms during follow-up. The mean corpuscular volume (MCV), mean hemoglobin (HGB) volume (MCH), and mean corpuscular HGB concentration (MCHC) exhibited negative temporal correlations with depressive symptoms. Additionally, several sex-specific blood cell markers were correlated with depression. Male adolescents with increased red blood cell (RBC) and female adolescents with decreased HGB levels and upregulated WBC, NC, NLR, and SII levels exhibited severe depressive symptoms at follow-up. CONCLUSIONS: These findings suggested the potential usefulness of peripheral blood cell indices in the assessment of depression in early adolescents.

Sensitive fluorescence detection of miRNA-124 in cardiomyocytes under oxidative stress using a nucleic acid probe.

MicroRNAs (miRNAs) are small noncoding RNAs of 18-25 bases. miRNAs are also important new biomarkers that can be used for disease diagnosis in the future. Studies have shown that miR-124 levels are significantly elevated during acute myocardial infarction (AMI) and play a key role in the cardiovascular system. A variety of methods have been established to detect myocardial infarction-related miRNAs. However, most require complex miRNA extraction and isolation, and these methods are virtually undetectable when RNA levels are low in the sample. It may lead to biased results. Thus, it is necessary to develop a technique that can detect miRNA without extracting it, which means that intracellular detection is of great significance. Here, we improved the traditional silicon spheres and obtained a biosensor that could effectively capture and detect specific noncoding nucleic acids through the layer-by-layer assembly method. The sensor is protected by hyaluronic acid so it can successfully escape the lysosome into the cell and achieve detection. With the help of a full-featured microplate reader, we determined that the detection limit of the biosensor could reach 1 fM, meeting the needs of intracellular detection. At the same time, we prepared an oxidative stress cardiomyocyte infarction model and successfully captured the overexpressed miR-124 in the infarcted cells to achieve in situ detection. This study could provide a new potential tool to develop miRNAs for sensitive diagnosis in AMI, and the proposed strategy implies its potential for biomedical research.

Esterification and Etherification of Aliphatic Alcohols Enabled by Catalytic Strain-Release of Donor-Acceptor Cyclopropane.

We herein disclose a highly efficient protocol for the esterification and etherification of alcohols, leveraging a Sc(OTf)3-catalyzed ring-strain release event in the meticulously designed, chromatographically stable mixed anhydrides or benzyl esters that incorporate an intramolecular donor-acceptor cyclopropane (DAC). This versatile method facilitates the straightforward functionalization of sugar, terpene, and steroid alcohols under mild acidic conditions, as showcased by the single-catalyst-driven, dual protection of sugar diol.

Nicotinamide Riboside Promotes the Proliferation of Endogenous Neural Stem Cells to Repair Spinal Cord Injury.

Activation of endogenous neural stem cells (NSC) is one of the most potential measures for neural repair after spinal cord injury. However, methods for regulating neural stem cell behavior are still limited. Here, we investigated the effects of nicotinamide riboside promoting the proliferation of endogenous neural stem cells to repair spinal cord injury. Nicotinamide riboside promotes the proliferation of endogenous neural stem cells and regulates their differentiation into neurons. In addition, nicotinamide riboside significantly restored lower limb motor dysfunction caused by spinal cord injury. Nicotinamide riboside plays its role in promoting the proliferation of neural stem cells by activating the Wnt signaling pathway through the LGR5 gene. Knockdown of the LGR5 gene by lentivirus eliminates the effect of nicotinamide riboside on the proliferation of endogenous neural stem cells. In addition, administration of Wnt pathway inhibitors also eliminated the proliferative effect of nicotinamide riboside. Collectively, these findings demonstrate that nicotinamide promotes the proliferation of neural stem cells by targeting the LGR5 gene to activate the Wnt pathway, which provides a new way to repair spinal cord injury.

Tailoring Stress-Strain Curves of Flexible Snapping Mechanical Metamaterial for On-Demand Mechanical Responses via Data-Driven Inverse Design.

By incorporating soft materials into the architecture, flexible mechanical metamaterials enable promising applications, e.g., energy modulation, and shape morphing, with a well-controllable mechanical response, but suffer from spatial and temporal programmability towards higher-level mechanical intelligence. One feasible solution is to introduce snapping structures and then tune their responses by accurately tailoring the stress-strain curves. However, owing to the strongly coupled nonlinearity of structural deformation and material constitutive model, it is difficult to deduce their stress-strain curves using conventional ways. Here, a machine learning pipeline is trained with the finite element analysis data that considers those strongly coupled nonlinearities to accurately tailor the stress-strain curves of snapping metamaterialfor on-demand mechanical response with an accuracy of 97.41%, conforming well to experiment. Utilizing the established approach, the energy absorption efficiency of the snapping-metamaterial-based device can be tuned within the accessible range to realize different rebound heights of a falling ball, and soft actuators can be spatially and temporally programmed to achieve synchronous and sequential actuation with a single energy input. Purely relying on structure designs, the accurately tailored metamaterials increase the devices' tunability/programmability. Such an approach can potentially extend to similar nonlinear scenarios towards predictable or intelligent mechanical responses.

SH-Alb inhibits phenotype remodeling of pro-fibrotic macrophage to attenuate liver fibrosis through SIRT3-SOD2 axis.

Albumin has a variety of biological functions, such as immunomodulatory and antioxidant activity, which depends largely on its thiol activity. However, in clinical trials, the treatment of albumin by injection of commercial human serum albumin (HSA) did not achieve the desired results. Here, we constructed reduced modified albumin (SH-Alb) for in vivo and in vitro experiments to investigate the reasons why HSA did not achieve the expected effects. SH-Alb was found to delay the progression of liver fibrosis in mice by alleviating liver inflammation and oxidative stress. Although R-Alb also has some of the above roles, the effect of SH-Alb is more remarkable. Mechanism studies have shown that SH-Alb reduces the release of pro-inflammatory and pro-fibrotic cytokine through the mitogen-activated protein kinase (MAPK) signaling pathway. In addition, SH-Alb deacetylates SOD2, a key enzyme of mitochondrial reactive oxygen species (ROS) production, by promoting the expression of SIRT3, thereby reducing the accumulation of ROS. Finally, macrophages altered by R-Alb or SH-Alb can inhibit the activation of hepatic stellate cells and endothelial cells, further delaying the progression of liver fibrosis. These results indicate that SH-Alb can remodel the phenotype of macrophages, thereby affecting the intrahepatic microenvironment and delaying the process of liver fibrosis. It provides a good foundation for the application of albumin in clinical treatment.

Endoscopic Endonasal Internal Carotid Artery Transposition Technique in Tumor With Parasellar Extension: A Single-Center Experience.

BACKGROUND AND OBJECTIVES: Lateralization or mobilization of the internal carotid artery (ICA) during a midline approach is required to expose lesions behind or lateral to the ICA. However, there have been no published data regarding the surgical outcomes of the endoscopic endonasal internal carotid transposition technique (EEITT). This study aimed to analyze the relevant surgical anatomy around the ICA and propose a grading scheme of EEITT. METHODS: A retrospective review of patients who underwent EEITT at a single institution was performed. Based on structures that limited the ICA and intraoperative findings, an anatomically surgical grading scheme of EEITT was proposed. RESULTS: Forty-two patients (mean age 45.6 years, 57.1% female patients) were included. Of them, 29 cases (69.0%) were Knosp grade 4 pituitary adenoma, 6 cases (14.3%) were chordoma, 6 cases (14.3%) were meningioma, and a single case (2.4%) was meningeal IgG4-related disease. The EEITT was categorized into Grades 1, 2 and 3, which was used in 24 (57.1%), 12 (28.6%), and 6 (14.3%) cases, respectively. The most common symptom was visual disturbance (45.2%). The gross total resection rate in Grade 1 (79.2%) and Grade 2 (83.3%) was much higher than that in Grade 3 (66.6%). The overall rate of visual function improvement, preoperative cranial nerve (CN) palsy improvement, and postoperative hormonal remission was 89.4%, 85.7%, and 88.9%, respectively. The rate for the following morbidities was cerebrospinal fluid leakage, 2.4%; permanent diabetes insipidus, 4.8%; new transient CN palsy, 9.5%; permanent CN palsy, 4.7%; panhypopituitarism, 7.1%; and ICA injury, 2.4%. CONCLUSION: The EEITT is technically feasible and could be graded according to the extent of disconnection of limiting structures. For complex tumor with parasellar extensions, the distinction into Grades 1, 2, and 3 will be of benefit to clinicians in predicting risks, avoiding complications, and generating tailored individualized surgical strategies.

l-2-Hydroxyglutarate remodeling of the epigenome and epitranscriptome creates a metabolic vulnerability in kidney cancer models.

Tumor cells are known to undergo considerable metabolic reprogramming to meet their unique demands and drive tumor growth. At the same time, this reprogramming may come at a cost with resultant metabolic vulnerabilities. The small molecule l-2-hydroxyglutarate (l-2HG) is elevated in the most common histology of renal cancer. Similarly to other oncometabolites, l-2HG has the potential to profoundly impact gene expression. Here, we demonstrate that l-2HG remodels amino acid metabolism in renal cancer cells through combined effects on histone methylation and RNA N6-methyladenosine. The combined effects of l-2HG result in a metabolic liability that renders tumors cells reliant on exogenous serine to support proliferation, redox homeostasis, and tumor growth. In concert with these data, high-l-2HG kidney cancers demonstrate reduced expression of multiple serine biosynthetic enzymes. Collectively, our data indicate that high-l-2HG renal tumors could be specifically targeted by strategies that limit serine availability to tumors.

Comparative Pharmacokinetics and Safety Assessment of 1st- and 2nd-Generation Zinpentraxin Alfa Drug Products in Healthy Volunteers: A Randomized Crossover Study.

Zinpentraxin alfa is a recombinant form of the human pentraxin-2 that was studied in idiopathic pulmonary fibrosis (IPF). To improve the purity and yield of the drug material, a 2nd-generation drug product was developed. To characterize and compare the pharmacokinetic (PK) properties of the 1st- and 2nd-generation zinpentraxin alfa, PK studies were conducted in healthy volunteers (HVs). In a phase 1 randomized, double-blind, 2-sequence crossover, sequential 2-stage study (ISRCTN59409907), single intravenous (IV) doses of 1st- and 2nd-generation zinpentraxin alfa at 10 mg/kg were studied with a blinded interim analysis (IA) at the end of stage 1. Bioequivalence (BE) was achieved for the maximum observed plasma concentration (Cmax), but the overall exposure was higher for the 2nd- compared to the 1st-generation zinpentraxin alfa. The study was stopped after stage 1 as the gating criteria were met based on the result of the blinded IA. Safety profiles were similar for the 1st- and 2nd-generation drug products, and antidrug antibody (ADA) was not observed in this study.

MES-CTNet: A Novel Capsule Transformer Network Base on a Multi-Domain Feature Map for Electroencephalogram-Based Emotion Recognition.

Emotion recognition using the electroencephalogram (EEG) has garnered significant attention within the realm of human-computer interaction due to the wealth of genuine emotional data stored in EEG signals. However, traditional emotion recognition methods are deficient in mining the connection between multi-domain features and fitting their advantages. In this paper, we propose a novel capsule Transformer network based on a multi-domain feature for EEG-based emotion recognition, referred to as MES-CTNet. The model's core consists of a multichannel capsule neural network(CapsNet) embedded with ECA (Efficient Channel Attention) and SE (Squeeze and Excitation) blocks and a Transformer-based temporal coding layer. Firstly, a multi-domain feature map is constructed by combining the space-frequency-time characteristics of the multi-domain features as inputs to the model. Then, the local emotion features are extracted from the multi-domain feature maps by the improved CapsNet. Finally, the Transformer-based temporal coding layer is utilized to globally perceive the emotion feature information of the continuous time slices to obtain a final emotion state. The paper fully experimented on two standard datasets with different emotion labels, the DEAP and SEED datasets. On the DEAP dataset, MES-CTNet achieved an average accuracy of 98.31% in the valence dimension and 98.28% in the arousal dimension; it achieved 94.91% for the cross-session task on the SEED dataset, demonstrating superior performance compared to traditional EEG emotion recognition methods. The MES-CTNet method, utilizing a multi-domain feature map as proposed herein, offers a broader observation perspective for EEG-based emotion recognition. It significantly enhances the classification recognition rate, thereby holding considerable theoretical and practical value in the EEG emotion recognition domain.

Temporal stability of tongue microbiota in older patients - A pilot study.

Background/purpose: Healthy states of human microbiota depend on a stable community of symbiotic microbes irrespective of external challenges from the environment. Thus, long-term stability of the oral microbiota is of importance, particularly for older patient populations. Materials and methods: We used next-generation sequencing (NGS) to examine the tongue microbiota of 18 individuals receiving long-term care over a 10-month period. Results: Beta diversity analysis demonstrated temporal stability of the tongue microbiota, as microbial compositions from all time points were indistinguishable from each other (P = 0.0887). However, significant individual variation in microbial composition (P = 0.0001) was observed, underscoring the presence of a unique microbial profile for each patient. Conclusion: The temporal dynamics of tongue microbiota exhibit long-term stability, providing diagnostic implications for oral diseases within older patient populations.

A Strain-Promoted Divergent Chemical Steroidation Unveils Potent Anti-Inflammatory Pseudo-Steroidal Glycosides.

The development of novel agents with immunoregulatory effects is a keen way to combat the growing threat of inflammatory storms to global health. To synthesize pseudo-steroidal glycosides tethered by ether bonds with promising immunomodulatory potential, we develop herein a highly effective deoxygenative functionalization of a novel steroidal donor (steroidation) facilitated by strain-release, leveraging cost-effective and readily available Sc(OTf)3 catalysis. This transformation produces a transient steroid-3-yl carbocation which readily reacts with O-, C-, N-, S-, and P-nucleophiles to generate structurally diverse steroid derivatives. DFT calculations were performed to shed light on the mechanistic details of the regioselectivity, underlying an acceptor-dependent steroidation mode. This approach can be readily extended to the etherification of sugar alcohols to enable the achievement of a diversity-oriented, pipeline-like synthesis of pseudo-steroidal glycosides in good to excellent yields with complete stereo- and regiospecific control for anti-inflammatory agent discovery. Immunological studies have demonstrated that a meticulously designed cholesteryl disaccharide can significantly suppress interleukin-6 secretion in macrophages, exhibiting up to 99% inhibition rates compared to the negative control. These findings affirm the potential of pseudo-steroidal glycosides as a prospective category of lead agents for the development of novel anti-inflammatory drugs.

The impact of micropolymorphism in Anpl-UAA on structural stability and peptide presentation.

Micropolymorphism significantly shapes the peptide-binding characteristics of major histocompatibility complex class I (MHC-I) molecules, affecting the host's resistance to pathogens, which is particularly pronounced in avian species displaying the "minimal essential MHC" expression pattern. In this study, we compared two duck MHC-I alleles, Anpl-UAA*77 and Anpl-UAA*78, that exhibit markedly different peptide binding properties despite their high sequence homology. Through mutagenesis experiments and crystallographic analysis of complexes with the influenza virus-derived peptide AEAIIVAMV (AEV9), we identified a critical role for the residue at position 62 in regulating hydrogen-bonding interactions between the peptide backbone and the peptide-binding groove. This modulation affects the characteristics of the B pocket and the stability of the loop region between the 310 helix and the α1 helix, leading to significant changes in the structure and stability of the peptide-MHC-I complex (pMHC-I). Moreover, the proportion of different residues at position 62 among Anpl-UAAs may reflect the correlation between pAnpl-UAA stability and duck body temperature. This research not only advances our understanding of the Anpl-UAA structure but also deepens our insight into the impact of MHC-I micropolymorphism on peptide binding.

Access to Reverse Glycosyl Azides and Rare Sugar-Based Glycosyl Azides via Radical Decarboxylative Azidation: Divergent Synthesis of 4'-C-Azidonucleosides as Potential Antiviral Agents.

The radical decarboxylative azidation of structurally diverse uronic acids has been established as an efficient approach to reverse glycosyl azides and rare sugar-derived glycosyl azides under the action of Ag2CO3, 3-pyridinesulfonyl azide, and K2S2O8. The power of this method has been highlighted by the divergent synthesis of 4'-C-azidonucleosides using Vorbrüggen glycosylation of nucleobases with 4-C-azidofuranosyl acetates. The antiviral assessment of the resulting nucleosides revealed one compound as a potential inhibitor of covalently closed circular DNA.