Targeting pericentric non-consecutive motifs for heterochromatin initiation.

Pericentric heterochromatin is a critical component of chromosomes marked by histone H3 K9 (H3K9) methylation1-3. However, what recruits H3K9-specific histone methyltransferases to pericentric regions in vertebrates remains unclear4, as does why pericentric regions in different species share the same H3K9 methylation mark despite lacking highly conserved DNA sequences2,5. Here we show that zinc-finger proteins ZNF512 and ZNF512B specifically localize at pericentric regions through direct DNA binding. Notably, both ZNF512 and ZNF512B are sufficient to initiate de novo heterochromatin formation at ectopically targeted repetitive regions and pericentric regions, as they directly recruit SUV39H1 and SUV39H2 (SUV39H) to catalyse H3K9 methylation. SUV39H2 makes a greater contribution to H3K9 trimethylation, whereas SUV39H1 seems to contribute more to silencing, probably owing to its preferential association with HP1 proteins. ZNF512 and ZNF512B from different species can specifically target pericentric regions of other vertebrates, because the atypical long linker residues between the zinc-fingers of ZNF512 and ZNF512B offer flexibility in recognition of non-consecutively organized three-nucleotide triplets targeted by each zinc-finger. This study addresses two long-standing questions: how constitutive heterochromatin is initiated and how seemingly variable pericentric sequences are targeted by the same set of conserved machinery in vertebrates.

Continuous carbon capture in an electrochemical solid-electrolyte reactor.

Electrochemical carbon-capture technologies, with renewable electricity as the energy input, are promising for carbon management but still suffer from low capture rates, oxygen sensitivity or system complexity1-6. Here we demonstrate a continuous electrochemical carbon-capture design by coupling oxygen/water (O2/H2O) redox couple with a modular solid-electrolyte reactor7. By performing oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) redox electrolysis, our device can efficiently absorb dilute carbon dioxide (CO2) molecules at the high-alkaline cathode-membrane interface to form carbonate ions, followed by a neutralization process through the proton flux from the anode to continuously output a high-purity (>99%) CO2 stream from the middle solid-electrolyte layer. No chemical inputs were needed nor side products generated during the whole carbon absorption/release process. High carbon-capture rates (440 mA cm-2, 0.137 mmolCO2 min-1 cm-2 or 86.7 kgCO2 day-1 m-2), high Faradaic efficiencies (>90% based on carbonate), high carbon-removal efficiency (>98%) in simulated flue gas and low energy consumption (starting from about 150 kJ per molCO2) were demonstrated in our carbon-capture solid-electrolyte reactor, suggesting promising practical applications.

Identification and Prioritization of Environmental Organic Pollutants: From an Analytical and Toxicological Perspective.

Exposure to environmental organic pollutants has triggered significant ecological impacts and adverse health outcomes, which have been received substantial and increasing attention. The contribution of unidentified chemical components is considered as the most significant knowledge gap in understanding the combined effects of pollutant mixtures. To address this issue, remarkable analytical breakthroughs have recently been made. In this review, the basic principles on recognition of environmental organic pollutants are overviewed. Complementary analytical methodologies (i.e., quantitative structure-activity relationship prediction, mass spectrometric nontarget screening, and effect-directed analysis) and experimental platforms are briefly described. The stages of technique development and/or essential parts of the analytical workflow for each of the methodologies are then reviewed. Finally, plausible technique paths and applications of the future nontarget screening methods, interdisciplinary techniques for achieving toxicant identification, and burgeoning strategies on risk assessment of chemical cocktails are discussed.

Community detection in the human connectome: Method types, differences and their impact on inference.

Community structure is a fundamental topological characteristic of optimally organized brain networks. Currently, there is no clear standard or systematic approach for selecting the most appropriate community detection method. Furthermore, the impact of method choice on the accuracy and robustness of estimated communities (and network modularity), as well as method-dependent relationships between network communities and cognitive and other individual measures, are not well understood. This study analyzed large datasets of real brain networks (estimated from resting-state fMRI from n $$ n $$ = 5251 pre/early adolescents in the adolescent brain cognitive development [ABCD] study), and n $$ n $$ = 5338 synthetic networks with heterogeneous, data-inspired topologies, with the goal to investigate and compare three classes of community detection methods: (i) modularity maximization-based (Newman and Louvain), (ii) probabilistic (Bayesian inference within the framework of stochastic block modeling (SBM)), and (iii) geometric (based on graph Ricci flow). Extensive comparisons between methods and their individual accuracy (relative to the ground truth in synthetic networks), and reliability (when applied to multiple fMRI runs from the same brains) suggest that the underlying brain network topology plays a critical role in the accuracy, reliability and agreement of community detection methods. Consistent method (dis)similarities, and their correlations with topological properties, were estimated across fMRI runs. Based on synthetic graphs, most methods performed similarly and had comparable high accuracy only in some topological regimes, specifically those corresponding to developed connectomes with at least quasi-optimal community organization. In contrast, in densely and/or weakly connected networks with difficult to detect communities, the methods yielded highly dissimilar results, with Bayesian inference within SBM having significantly higher accuracy compared to all others. Associations between method-specific modularity and demographic, anthropometric, physiological and cognitive parameters showed mostly method invariance but some method dependence as well. Although method sensitivity to different levels of community structure may in part explain method-dependent associations between modularity estimates and parameters of interest, method dependence also highlights potential issues of reliability and reproducibility. These findings suggest that a probabilistic approach, such as Bayesian inference in the framework of SBM, may provide consistently reliable estimates of community structure across network topologies. In addition, to maximize robustness of biological inferences, identified network communities and their cognitive, behavioral and other correlates should be confirmed with multiple reliable detection methods.

Association between inflammatory bowel disease and cancer risk: evidence triangulation from genetic correlation, Mendelian randomization, and colocalization analyses across East Asian and European populations.

BACKGROUND: Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), has been associated with several cancer risks in observational studies, but the observed associations have been inconsistent and may face the bias of confounding and reverse causality. The potential causal relationships between IBD and the risk of cancers remain largely unclear. METHODS: We performed genome-wide linkage disequilibrium score regression (LDSC), standard two-sample Mendelian randomization (MR), and colocalization analyses using summary genome-wide association study (GWAS) data across East Asian and European populations to evaluate the causal relationships between IBD and cancers. Sensitivity analyses for the MR approach were additionally performed to explore the stability of the results. RESULTS: There were no significant genetic correlations between IBD, CD, or UC and cancers (all P values > 0.05) in East Asian or European populations. According to the main MR analysis, no significant causal relationship was observed between IBD and cancers in the East Asian population. There were significant associations between CD and ovarian cancer (odds ratio [OR] = 0.898, 95% CI = 0.844-0.955) and between UC and nonmelanoma skin cancer (OR = 1.002, 95% CI = 1.000-1.004, P = 0.019) in the European population. The multivariable MR analysis did not find any of the above significant associations. There was no shared causal variant to prove the associations of IBD, CD, or UC with cancers in East Asian or European populations using colocalization analysis. CONCLUSIONS: We did not provide robust genetic evidence of causal associations between IBD and cancer risk. Exposure to IBD might not independently contribute to the risk of cancers, and the increased risk of cancers observed in observational studies might be attributed to factors accompanying the diagnosis of IBD.

Non-iridium-based electrocatalyst for durable acidic oxygen evolution reaction in proton exchange membrane water electrolysis.

Iridium-based electrocatalysts remain the only practical anode catalysts for proton exchange membrane (PEM) water electrolysis, due to their excellent stability under acidic oxygen evolution reaction (OER), but are greatly limited by their high cost and low reserves. Here, we report a nickel-stabilized, ruthenium dioxide (Ni-RuO2) catalyst, a promising alternative to iridium, with high activity and durability in acidic OER for PEM water electrolysis. While pristine RuO2 showed poor acidic OER stability and degraded within a short period of continuous operation, the incorporation of Ni greatly stabilized the RuO2 lattice and extended its durability by more than one order of magnitude. When applied to the anode of a PEM water electrolyser, our Ni-RuO2 catalyst demonstrated >1,000 h stability under a water-splitting current of 200 mA cm-2, suggesting potential for practical applications. Density functional theory studies, coupled with operando differential electrochemical mass spectroscopy analysis, confirmed the adsorbate-evolving mechanism on Ni-RuO2, as well as the critical role of Ni dopants in stabilization of surface Ru and subsurface oxygen for improved OER durability.

Near thermal noise limit, 5W single frequency fiber laser base on the ring cavity configuration.

In this study, we present an ultralow noise single-frequency fiber laser operating at 1550 nm, utilizing a traveling-wave ring cavity configuration. The frequency noise of the laser approaches the thermal noise limit, achieving a white noise level of 0.025 Hz2/Hz, resulting in an instantaneous linewidth of 0.08 Hz. After amplification, the output power reaches 4.94 W while maintaining the same low white noise level as the laser oscillator. The integration linewidths of the laser oscillator and amplifier are 221 Hz and 665 Hz, respectively, with both exhibiting relative intensity noises that approach the quantum shot noise limit. To the best of our knowledge, this work shows the lowest frequency noise combined with relatively high power for this type of ring cavity fiber laser.

Associations of metabolic changes and polygenic risk scores with cardiovascular outcomes and all-cause mortality across BMI categories: a prospective cohort study.

BACKGROUND: Associations between metabolic status and metabolic changes with the risk of cardiovascular outcomes have been reported. However, the role of genetic susceptibility underlying these associations remains unexplored. We aimed to examine how metabolic status, metabolic transitions, and genetic susceptibility collectively impact cardiovascular outcomes and all-cause mortality across diverse body mass index (BMI) categories. METHODS: In our analysis of the UK Biobank, we included a total of 481,576 participants (mean age: 56.55; male: 45.9%) at baseline. Metabolically healthy (MH) status was defined by the presence of < 3 abnormal components (waist circumstance, blood pressure, blood glucose, triglycerides, and high-density lipoprotein cholesterol). Normal weight, overweight, and obesity were defined as 18.5 ≤ BMI < 25 kg/m2, 25 ≤ BMI < 30 kg/m2, and BMI ≥ 30 kg/m2, respectively. Genetic predisposition was estimated using the polygenic risk score (PRS). Cox regressions were performed to evaluate the associations of metabolic status, metabolic transitions, and PRS with cardiovascular outcomes and all-cause mortality across BMI categories. RESULTS: During a median follow-up of 14.38 years, 31,883 (7.3%) all-cause deaths, 8133 (1.8%) cardiovascular disease (CVD) deaths, and 67,260 (14.8%) CVD cases were documented. Among those with a high PRS, individuals classified as metabolically healthy overweight had the lowest risk of all-cause mortality (hazard ratios [HR] 0.70; 95% confidence interval [CI] 0.65, 0.76) and CVD mortality (HR 0.57; 95% CI 0.50, 0.64) compared to those who were metabolically unhealthy obesity, with the beneficial associations appearing to be greater in the moderate and low PRS groups. Individuals who were metabolically healthy normal weight had the lowest risk of CVD morbidity (HR 0.54; 95% CI 0.51, 0.57). Furthermore, the inverse associations of metabolic status and PRS with cardiovascular outcomes and all-cause mortality across BMI categories were more pronounced among individuals younger than 65 years (Pinteraction < 0.05). Additionally, the combined protective effects of metabolic transitions and PRS on these outcomes among BMI categories were observed. CONCLUSIONS: MH status and a low PRS are associated with a lower risk of adverse cardiovascular outcomes and all-cause mortality across all BMI categories. This protective effect is particularly pronounced in individuals younger than 65 years. Further research is required to confirm these findings in diverse populations and to investigate the underlying mechanisms involved.

Observation of 2†µm multiple annular structured vortex pulsed beams by cavity-mode tailoring.

In the past few years, annular structured beams have been extensively studied due to their unique "doughnut" structure and characteristics such as phase and polarization vortices. Especially in the 2 µm wavelength range, they have shown promising applications in fields such as novel laser communication, optical processing, and quantum information processing. In this Letter, we observed basis vector patterns with orthogonality and completeness by finely cavity-mode tailoring with end-mirror space position in a Tm:CaYAlO4 laser. Multiple annular structured beams including azimuthally, linearly, and radially polarized beams (APB, LPB, and RPB) operated at a Q-switched mode-locking (QML) state with a typical output power of ∼18 mW around 1962 nm. Further numerical simulation proved that the multiple annular structured beams are the coherent superposition of different Hermitian Gaussian modes. Using a self-made M-Z interferometer, we have demonstrated that the obtained multiple annular beams have a vortex phase with orbital angular momentum (OAM) of l = ±1. To the best of our knowledge, this is the first observation of vector and scalar annular vortex beams in the 2 µm solid-state laser.

Intra- and Peritumoral Based Radiomics for Assessment of Lymphovascular Invasion in Invasive Breast Cancer.

BACKGROUND: Radiomics has been applied for assessing lymphovascular invasion (LVI) in patients with breast cancer. However, associations between features from peritumoral regions and the LVI status were not investigated. PURPOSE: To investigate the value of intra- and peritumoral radiomics for assessing LVI, and to develop a nomogram to assist in making treatment decisions. STUDY TYPE: Retrospective. POPULATION: Three hundred and sixteen patients were enrolled from two centers and divided into training (N = 165), internal validation (N = 83), and external validation (N = 68) cohorts. FIELD STRENGTH/SEQUENCE: 1.5 T and 3.0 T/dynamic contrast-enhanced (DCE) and diffusion-weighted imaging (DWI). ASSESSMENT: Radiomics features were extracted and selected based on intra- and peritumoral breast regions in two magnetic resonance imaging (MRI) sequences to create the multiparametric MRI combined radiomics signature (RS-DCE plus DWI). The clinical model was built with MRI-axillary lymph nodes (MRI ALN), MRI-reported peritumoral edema (MPE), and apparent diffusion coefficient (ADC). The nomogram was constructed with RS-DCE plus DWI, MRI ALN, MPE, and ADC. STATISTICAL TESTS: Intra- and interclass correlation coefficient analysis, Mann-Whitney U test, and least absolute shrinkage and selection operator regression were used for feature selection. Receiver operating characteristic and decision curve analyses were applied to compare performance of the RS-DCE plus DWI, clinical model, and nomogram. RESULTS: A total of 10 features were found to be associated with LVI, 3 from intra- and 7 from peritumoral areas. The nomogram showed good performance in the training (AUCs, nomogram vs. clinical model vs. RS-DCE plus DWI, 0.884 vs. 0.695 vs. 0.870), internal validation (AUCs, nomogram vs. clinical model vs. RS-DCE plus DWI, 0.813 vs. 0.695 vs. 0.794), and external validation (AUCs, nomogram vs. clinical model vs. RS-DCE plus DWI, 0.862 vs. 0.601 vs. 0.849) cohorts. DATA CONCLUSION: The constructed preoperative nomogram might effectively assess LVI. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Grape seed proanthocyanidin improves intestinal inflammation in canine through regulating gut microbiota and bile acid compositions.

Although certain progress has been made in treating canine inflammatory bowel disease (IBD), a large proportion of dogs have a poor prognosis and may develop resistance and side effects. Therefore, it is of great significance to prevent or alleviate canine IBD through nutritional intervention. Plant polyphenol can interact with intestinal bacteria and has important prospects in the intestinal health improvement. This study evaluated the effect of grape seed proanthocyanidin (GSP), a plant-derived natural polyphenol, on Labrador Retrievers with mild IBD. In Experiment 1 of this study, GSP alleviated persistent intestinal inflammation in canines by improving inflammatory indexes and reducing intestinal permeability. Moreover, GSP treatment increased the abundance of bacteria with potential anti-inflammatory properties and engaging bile acid metabolism, including Ruminococcaceae, Faecalibacterium, Ruminococcus_torques_group, and Lachnospiraceae_NK4A136_group. Notably, targeted metabolomic analysis identified elevated productions of fecal chenodeoxycholic acid and its microbial transformation product lithocholic acid, which might contribute to relieving canine intestinal inflammation. Further, in Experiment 2, fecal microbiota transplantation was used to determine whether gut microbiota is a potential mechanism for GSP efficacy. Dogs with mild IBD received the fecal microbiota from the group administered GSP and mirrored the improvement effects of GSP, which results verified that gut microbial alteration could be an underlying mechanism for GSP efficiency on canine IBD. Our findings highlight that the mechanism of the GSP function on canine IBD is mediated by altering gut microbial composition and improving bile acid metabolism. This study proposes a natural polyphenol-based dietary strategy for improving canine intestinal health.

Blocking the IFN-gamma signal in the choroid plexus confers resistance to experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory infiltration and demyelination in the central nervous system (CNS). IFN-gamma (IFN-γ), a critically important immunomodulator, has been widely studied in MS pathology. The confusing and complex effects of IFN-γ in MS patients and rodent models, however, cause us to look more closely at its exact role in MS. In this study, we identified the role of the IFN-γ signaling in the choroid plexus (CP) in the experimental autoimmune encephalomyelitis (EAE) model. We found that the IFN-γ signal was rapidly amplified when CNS immune cell infiltration occurred in the CP during the progressive stage. Furthermore, using two CP-specific knockdown strategies, we demonstrated that blocking the IFN-γ signal via knockdown of IFN-γR1 in the CP could protect mice against EAE pathology, as evidenced by improvements in clinical scores and infiltration. Notably, knocking down IFN-γR1 in the CP reduced the local expression of adhesion molecules and chemokines. This finding suggests that IFN-γ signaling in the CP may participate in the pathological process of EAE by preventing pathological T helper (Th) 17+ cells from infiltrating into the CNS. Finally, we showed that the unbalanced state of IFN-γ signaling between peripheral lymphocytes and the choroid plexus may determine whether IFN-γ has a protective or aggravating effect on EAE pathology. Above all, we discovered that IFN-γR1-mediated IFN-γ signaling in the CP was a vital pathway in the pathological process of EAE.

Occurrence and Ecological Risk of Alkylamine Triazines in Chinese Estuarine Sediments: An Emerging Class of Persistent, Mobile, and Toxic Substances.

Identifying persistent, mobile, and toxic (PMT) substances from synthetic chemicals is critical for chemical management and ecological risk assessment. Inspired by the triazine analogues (e.g., atrazine and melamine) in the original European Union's list of PMT substances, the occurrence and compositions of alkylamine triazines (AATs) in the estuarine sediments of main rivers along the eastern coast of China were comprehensively explored by an integrated strategy of target, suspect, and nontarget screening analysis. A total of 44 AATs were identified, of which 23 were confirmed by comparison with authentic standards. Among the remaining tentatively identified analogues, 18 were emerging pollutants not previously reported in the environment. Tri- and di-AATs were the dominant analogues, and varied geographic distributions of AATs were apparent in the investigated regions. Toxic unit calculations indicated that there were acute and chronic risks to algae from AATs on a large geographical scale, with the antifouling biocide cybutryne as a key driver. The assessment of physicochemical properties further revealed that more than half of the AATs could be categorized as potential PMT and very persistent and very mobile substances at the screening level. These results highlight that AATs are a class of PMT substances posing high ecological impacts on the aquatic environment and therefore require more attention.

Direct and continuous generation of pure acetic acid solutions via electrocatalytic carbon monoxide reduction.

Electrochemical CO2 or CO reduction to high-value C2+ liquid fuels is desirable, but its practical application is challenged by impurities from cogenerated liquid products and solutes in liquid electrolytes, which necessitates cost- and energy-intensive downstream separation processes. By coupling rational designs in a Cu catalyst and porous solid electrolyte (PSE) reactor, here we demonstrate a direct and continuous generation of pure acetic acid solutions via electrochemical CO reduction. With optimized edge-to-surface ratio, the Cu nanocube catalyst presents an unprecedented acetate performance in neutral pH with other liquid products greatly suppressed, delivering a maximal acetate Faradaic efficiency of 43%, partial current of 200 mA⋅cm-2, ultrahigh relative purity of up to 98 wt%, and excellent stability of over 150 h continuous operation. Density functional theory simulations reveal the role of stepped sites along the cube edge in promoting the acetate pathway. Additionally, a PSE layer, other than a conventional liquid electrolyte, was designed to separate cathode and anode for efficient ion conductions, while not introducing any impurity ions into generated liquid fuels. Pure acetic acid solutions, with concentrations up to 2 wt% (0.33 M), can be continuously produced by employing the acetate-selective Cu catalyst in our PSE reactor.

Controllable nonautonomous localized waves and dynamics for a quasi-1D Gross-Pitaevskii equation in Bose-Einstein condensations with attractive interaction.

This paper investigates dynamical behaviors and controllability of some nonautonomous localized waves based on the Gross-Pitaevskii equation with attractive interatomic interactions. Our approach is a relation constructed between the Gross-Pitaevskii equation and the standard nonlinear Schrödinger equation through a new self-similarity transformation which is to convert the exact solutions of the latter to the former's. Subsequently, one can obtain the nonautonomous breather solutions and higher-order rogue wave solutions of the Gross-Pitaevskii equation. It has been shown that the nonautonomous localized waves can be controlled by the parameters within the self-similarity transformation, rather than relying solely on the nonlinear intensity, spectral parameters, and external potential. The control mechanism can induce an unusual number of loosely bound higher-order rogue waves. The asymptotic analysis of unusual loosely bound rogue waves shows that their essence is energy transfer among rogue waves. Numerical simulations test the dynamical stability of obtained localized wave solutions, which indicate that modifying the parameters in the self-similarity transformation can improve the stability of unstable localized waves and prolong their lifespan. We numerically confirm that the rogue wave controlled by the self-similarity transformation can be reproduced from a chaotic initial background field, hence anticipating the feasibility of its experimental observation, and propose an experimental method for observing these phenomena in Bose-Einstein condensates. The method presented in this paper can help to induce and observe new stable localized waves in some physical systems.

Improved RRT* Algorithm for Disinfecting Robot Path Planning.

In this paper, an improved APF-GFARRT* (artificial potential field-guided fuzzy adaptive rapidly exploring random trees) algorithm based on APF (artificial potential field) guided sampling and fuzzy adaptive expansion is proposed to solve the problems of weak orientation and low search success rate when randomly expanding nodes using the RRT (rapidly exploring random trees) algorithm for disinfecting robots in the dense environment of disinfection operation. Considering the inherent randomness of tree growth in the RRT* algorithm, a combination of APF with RRT* is introduced to enhance the purposefulness of the sampling process. In addition, in the context of RRT* facing dense and restricted environments such as narrow passages, adaptive step-size adjustment is implemented using fuzzy control. It accelerates the algorithm's convergence and improves search efficiency in a specific area. The proposed algorithm is validated and analyzed in a specialized environment designed in MATLAB, and comparisons are made with existing path planning algorithms, including RRT, RRT*, and APF-RRT*. Experimental results show the excellent exploration speed of the improved algorithm, reducing the average initial path search time by about 46.52% compared to the other three algorithms. In addition, the improved algorithm exhibits faster convergence, significantly reducing the average iteration count and the average final path cost by about 10.01%. The algorithm's enhanced adaptability in unique environments is particularly noteworthy, increasing the chances of successfully finding paths and generating more rational and smoother paths than other algorithms. Experimental results validate the proposed algorithm as a practical and feasible solution for similar problems.

Bidirectional Two-Sample Mendelian Randomization Study of Immunoglobulin G N-Glycosylation and Senescence-Associated Secretory Phenotype.

Observational studies revealed changes in Immunoglobulin G (IgG) N-glycosylation during the aging process. However, it lacks causal insights and remains unclear in which direction causal relationships exist. The two-sample bidirectional Mendelian randomization (MR) design was adopted to explore causal associations between IgG N-glycans and the senescence-associated secretory phenotype (SASP). Inverse variance weighted (IVW) and Wald ratio methods were used as the main analyses, supplemented by sensitivity analyses. Forward MR analyses revealed causal associations between the glycan peak (GP) and SASP, including GP6 (odds ratio [OR] = 0.428, 95% confidence interval [CI] = 0.189-0.969) and GP17 (OR = 0.709, 95%CI = 0.504-0.995) with growth/differentiation factor 15 (GDF15), GP19 with an advanced glycosylation end-product-specific receptor (RAGE) (OR = 2.142, 95% CI = 1.384-3.316), and GP15 with matrix metalloproteinase 2 (MMP2) (OR = 1.136, 95% CI =1.008-1.282). The reverse MR indicated that genetic liability to RAGE was associated with increased levels of GP17 (OR = 1.125, 95% CI = 1.003-1.261) and GP24 (OR = 1.222, 95% CI = 1.046-1.428), while pulmonary and activation-regulated chemokines (PARC) exhibited causal associations with GP10 (OR = 1.269, 95% CI = 1.048-1.537) and GP15 (OR = 1.297, 95% CI = 1.072-1.570). The findings provided suggested evidence on the bidirectional causality between IgG N-glycans and SASP, which might reveal potential regulatory mechanisms.

The Causality between Human Immunoglobulin G (IgG) N-Glycosylation and Aging: A Mendelian Randomization Study.

BACKGROUND: Immunoglobulin G (IgG) N-glycosylation is considered a potential biomarker for aging and various pathological conditions. However, whether these changes in IgG N-glycosylation are a consequence or a contributor to the aging process remains unclear. This study aims to investigate the causality between IgG N-glycosylation and aging using Mendelian randomization (MR) analysis. METHODS: We utilized genetic variants associated with IgG N-glycosylation traits, the frailty index (FI), and leukocyte telomere length (LTL) from a previous genome-wide association study (GWAS) on individuals of European ancestry. Two-sample and multivariable MR analyses were conducted, employing the inverse-variance weighted (IVW) method. Sensitivity analyses were performed to assess potential confounding factors. RESULTS: Using the IVW method, we found suggestive evidence of a causal association between GP14 and FI (ß 0.026, 95% CI 0.003 to 0.050, p = 0.027) and LTL (ß -0.020, 95% CI -0.037 to -0.002, p = 0.029) in the two-sample MR analysis. In the multivariable MR analysis, suggestive evidence was found for GP23 and FI (ß -0.119, 95% CI -0.219 to -0.019, p = 0.019) and GP2 and LTL (ß 0.140, 95% CI 0.020 to 0.260, p = 0.023). CONCLUSIONS: In conclusion, our results supported a potentially causal effect of lower GP23 levels on an advanced aging state. Additional verification is required to further substantiate the causal relationship between glycosylation and aging.

Construct Phenylethanoid Glycosides Harnessing Biosynthetic Networks, Protein Engineering and One-Pot Multienzyme Cascades.

Phenylethanoid glycosides (PhGs) exhibit a multitude of structural variations linked to diverse pharmacological activities. Assembling various PhGs via multienzyme cascades represents a concise strategy over traditional synthetic methods. However, the challenge lies in identifying a comprehensive set of catalytic enzymes. This study explores biosynthetic PhG reconstruction from natural precursors, aiming to replicate and amplify their structural diversity. We discovered 12 catalytic enzymes, including four novel 6'-OH glycosyltransferases and three new polyphenol oxidases, revealing the intricate network in PhG biosynthesis. Subsequently, the crystal structure of CmGT3 (2.62 Å) was obtained, guiding the identification of conserved residue 144# as a critical determinant for sugar donor specificity. Engineering this residue in PhG glycosyltransferases (FsGT61, CmGT3, and FsGT6) altered their sugar donor recognition. Finally, a one-pot multienzyme cascade was established, where the combined action of glycosyltransferases and acyltransferases boosted conversion rates by up to 12.6-fold. This cascade facilitated the reconstruction of 26 PhGs with conversion rates ranging from 5-100 %, and 20 additional PhGs detectable by mass spectrometry. PhGs with extra glycosyl and hydroxyl modules demonstrated notable liver cell protection. This work not only provides catalytic tools for PhG biosynthesis, but also serves as a proof-of-concept for cell-free enzymatic construction of diverse natural products.

Cobalt-Doped Bismuth Nanosheet Catalyst for Enhanced Electrochemical CO2 Reduction to Electrolyte-Free Formic acid.

Electrochemical carbon dioxide (CO2) reduction reaction (CO2RR) to valuable liquid fuels, such as formic acid/formate (HCOOH/HCOO-) is a promising strategy for carbon neutrality. Enhancing CO-2RR activity while retaining high selectivity is critical for commercialization. To address this, we developed metal-doped bismuth (Bi) nanosheets via a facile hydrolysis method. These doped nanosheets efficiently generated high-purity HCOOH using a porous solid electrolyte (PSE) layer. Among the evaluated metal-doped Bi catalysts, Co-doped Bi demonstrated improved CO2RR performance compared to pristine Bi, achieving ~90% HCOO- selectivity and boosted activity with a low overpotential of ~1.0 V at a current density of 200 mA cm-2. In a solid electrolyte reactor, Co-doped Bi maintained HCOOH Faradaic efficiency of ~72% after a 100-hour operation under a current density of 100 mA cm-2, generating 0.1 M HCOOH at 3.2 V. Density functional theory (DFT) results revealed that Co-doped Bi required a lower applied potential for HCOOH generation from CO2, due to stronger binding energy to the key intermediates OCHO* compared to pure Bi. This study shows that metal doping in Bi nanosheets modifies the chemical composition, element distribution, and morphology, improving CO2RR catalytic activity performance by tuning surface adsorption affinity and reactivity.