Regulating phenol tar in pyrolysis of lignocellulosic biomass: Product characteristics and conversion mechanisms.

The utilization of biomass pyrolysis is a crucial approach for sustainable development. This study used the typical biomass of pine (PI), rice husk (RH), and corn straw (ST) as feedstocks to evaluate the pyrolysis mechanisms, features and conversion mechanisms of the phenol tar product. The phenolic gaseous products were more trailing in ST, which mostly concentrated around 320-500 °C. Primary phenol tar is produced from lignin through the homolytic cleavage of ß-O and α-O, and C-C bond breakage, primarily occurring before 550 °C. As the degree of aromatization increases, the oxygenates progressively deoxygenate, and the primary tar demethoxylates to form secondary tar as the temperature increases. The pyrolysis of cellulose produces H radicals, which aid the transformation of lignin into phenol tar. This study can provide a theoretical basis for biomass pyrolysis to select the appropriate process parameters to improve the quality of bio-oil and regulate phenol tar products.

Non-Contact Measurement of Cardiopulmonary Activity Using Software Defined Radios.

Vital signs are important indicators to evaluate the health status of patients. Channel state information (CSI) can sense the displacement of the chest wall caused by cardiorespiratory activity in a non-contact manner. Due to the influence of clutter, DC components, and respiratory harmonics, it is difficult to detect reliable heartbeat signals. To address this problem, this paper proposes a robust and novel method for simultaneously extracting breath and heartbeat signals using software defined radios (SDR). Specifically, we model and analyze the signal and propose singular value decomposition (SVD)-based clutter suppression method to enhance the vital sign signals. The DC is estimated and compensated by the circle fitting method. Then, the heartbeat signal and respiratory signal are obtained by the modified variational modal decomposition (VMD). The experimental results demonstrate that the proposed method can accurately separate the respiratory signal and the heartbeat signal from the filtered signal. The Bland-Altman analysis shows that the proposed system is in good agreement with the medical sensors. In addition, the proposed system can accurately measure the heart rate variability (HRV) within 0.5m. In summary, our system can be used as a preferred contactless alternative to traditional contact medical sensors, which can provide advanced patient-centered healthcare solutions.

Effects of exogenous hydrogen sulfide and honokiol intervention on the proliferation, apoptosis, and calcium signaling pathway of rat enteric glial cells.

Hydrogen sulfide (H2S) is a gaseous signaling molecule that influences digestive and nervous system functions. Enteric glial cells (EGCs) are integral to the enteric nervous system and play a role in regulating gastrointestinal motility. This study explored the dual effects of exogenous H2S on EGCs and the influence of apoptosis-related pathways and ion channels in EGCs. We also administered honokiol for further interventional studies. The results revealed that low-concentration H2S increased the mitochondrial membrane potential (MMP) of EGCs, decreased the whole-cell membrane potential, downregulated BAX and caspase-3, upregulated Bcl2 expression, reduced apoptosis, and promoted cell proliferation. The Ca2+ concentration, Cx43 mRNA, and protein expression were also increased. A high concentration of H2S had the opposite effect. In addition, GFAP mRNA expression was upregulated in the test-low group, downregulated in the test-high group, and upregulated in the test-high + Hon group. Honokiol treatment increased MMP, reduced whole-cell membrane potential, inhibited BAX and caspase-3 expression, increased Bcl2 expression, decreased cell apoptosis, and increased cell proliferation. The Ca2+ concentration, Cx43 mRNA, and protein expression were also upregulated. In conclusion, our study showed that exogenous H2S can bidirectionally regulate EGC proliferation and apoptosis by affecting MMP and cell membrane potential via the Bcl2/BAX/caspase-3 pathway and modulate Cx43-mediated Ca2+ responses in EGCs to regulate colonic motility bidirectionally. Honokiol can ameliorate the damage to EGCs induced by high H2S concentrations through the Bcl2/BAX/caspase-3 pathway and improve colon motility by increasing Cx43 expression and Ca2+ concentration.

Interdependent stigma of seeking mental health services: Examining a new scale across eight countries/regions.

Although the presence of mental health stigma associated with seeking help has been demonstrated in many parts of the world, this work has largely been from an independent perspective (i.e., "I will be perceived as crazy") rather than from an interdependent perspective (i.e., "My family will be viewed negatively"). Interdependent stigma of seeking help (i.e., the extent to which people believe their family would be devalued and shamed if they seek psychological help) may be an important type of stigma that has not been assessed. Based on self-construal theory, the present study sought to develop and evaluate the psychometric properties of an Interdependent Stigma of Seeking Help (ISSH) scale in eight different countries and regions (i.e., Australia, Brazil, Germany, Hong Kong, Taiwan, Türkiye, the UAE, the United States). Findings suggest that the psychometric properties of the eight-item ISSH are adequate for research purposes (a unidimensional scale with full invariance and internal consistency estimates from .84 to .94). The ISSH was moderately related to other measures of stigma and psychological distress. Some differences in the relationship with specific outcomes by country and region were found, and there were notable country differences in the latent mean levels of ISSH, with Hong Kong and Taiwan having the highest means, and Australia, the United States, and Brazil having the lowest levels. Results suggest that the ISSH could be used to help clarify the complex relationships between stigma and other variables of interest and might be useful in developing culturally relevant interventions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Evaluation of the anti-aging potential of acetyl tripeptide-30 citrulline in cosmetics.

Acetyl tripeptide-30 citrulline, a commercialized bio-active peptide, is widely used in anti-wrinkle formulations. Volunteer-based tests have demonstrated that topical application of products containing acetyl tripeptide-30 citrulline significantly reduces the visibility of stretch marks. However, there is still a lack of research dedicated to systematically and holistically evaluating its cosmetic properties and elucidating its mechanisms of action. In this study, we assessed the cosmetic potential of acetyl tripeptide-30 citrulline using human immortalized keratinocytes (HaCaT) and mouse embryonic fibroblasts (3T3). Our findings reveal that acetyl tripeptide-30 citrulline exhibits anti-inflammatory and antioxidant activities in skin cells, particularly effective against the inflammatory markers cyclooxygenase-2 (COX2), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6), and the extent of inhibition of reactive oxygen species (ROS) production ranged from 95 % to 340 %. Moreover, acetyl tripeptide-30 citrulline specifically up-regulates Collagen IV and down-regulates matrix metalloproteinase-9 (MMP9), enhances the expression of skin barrier proteins transglutaminase 1 (TGM1) and filaggrin (FLG), thereby demonstrating its reparative capabilities. Additionally, acetyl tripeptide-30 citrulline increases the expression of the water channel protein aquaporin 3 (AQP3), thus improving skin hydration function. These results substantiate the previously proclaimed cosmetic attributes of acetyl tripeptide-30 citrulline and support its efficacy as an anti-aging agent in dermatological applications.

STING-mediated IL-6 Inhibits OATP1B1 Expression via the TCF4 Signaling Pathway in Cholestasis.

Background and Aims: Organic anion-transporting polypeptides (OATPs) play a crucial role in the transport of bile acids and bilirubin. In our previous study, interleukin 6 (IL-6) reduced OATP1B3 levels in cholestatic disease. However, it remains unclear whether IL-6 inhibits OATP1B1 expression in cholestatic diseases. This study aimed to investigate whether IL-6 can inhibit OATP1B1 expression and explore the underlying mechanisms. Methods: The effect of stimulator of interferon genes (STING) signaling on inflammatory factors was investigated in a cholestatic mouse model using RT-qPCR and enzyme-linked immunosorbent assay. To assess the impact of inflammatory factors on OATP1B1 expression in hepatocellular carcinoma, we analyzed OATP1B1 expression by RT-qPCR and Western Blot after treating PLC/PRF/5 cells with TNF-α, IL-1ß, and IL-6. To elucidate the mechanism by which IL-6 inhibits OATP1B1 expression, we examined the expression of the OATP1B1 regulator TCF4 in PLC/PRF/5 and HepG2 cells using RT-qPCR and Western Blot. The interaction mechanism between ß-catenin/TCF4 and OATP1B1 was investigated by knocking down ß-catenin/TCF4 through siRNA transfection. Results: The STING inhibitor decreased inflammatory factor levels in the cholestatic mouse model, with IL-6 exhibiting the most potent inhibitory effect on OATP1B1. IL-6 downregulated ß-catenin/TCF4, leading to decreased OATP1B1 expression. Knocking-down ß-catenin/TCF4 counteracted the ß-catenin/TCF4-mediated repression of OATP1B1. Conclusions: STING-mediated IL-6 up-regulation may inhibit OATP1B1, leading to reduced transport of bile acids and bilirubin by OATP1B1. This may contribute to altered pharmacokinetics in patients with diseases associated with increased IL-6 production.

Nrf2/ASPM axis regulated vasculogenic mimicry formation in hepatocellular carcinoma under hypoxia.

BACKGROUND: Hypoxic microenvironment is a common feature of most solid tumors including hepatocellular carcinoma (HCC). Vasculogenic mimicry (VM) formation by tumor cells could provide blood supply to tumor cells under hypoxia. NFE2 like basic leucine zipper (bZIP) transcription factor 2 (Nrf2), a regulator of cellular homeostasis, may promote tumor progression in the hypoxic conditions. However, the role and regulatory mechanisms of Nrf2 in HCC are not fully elucidated. METHODS: Nrf2 and assembly factor for spindle microtubules (ASPM) expression modulations were conducted by lentiviral transfections. Western blot, immunofluorescence, ChIP-qPCR, dual-luciferase reporter gene assay, flow cytometry, RNA sequencing, multiple bioinformatics databases analysis, cell function assays in vitro, mouse model in vivo and human HCC tissues were employed to assess the effect of Nrf2/ASPM axis on HCC progression under hypoxia. RESULTS: Nrf2 and ASPM expression facilitated epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs) feature, and VM formation of HCC cells under hypoxia. Furthermore, Nrf2-regulated ASPM expression, via binding directly to the promoter region of ASPM and transcriptionally promoting ASPM expression. ASPM re-expression in Nrf2 knockdown cells or ASPM knockdown in Nrf2 overexpression cells reversed the cellular function caused by Nrf2. Meantime, retinol metabolism pathway was disrupted following abnormal ASPM expression. Nrf2/ASPM axis in murine models accelerated tumor growth and VM, corroborating in vitro findings. All-trans retinoic acid treatment reversed stemness and VM of HCC cells in vitro and in vivo. Clinically, Nrf2 and ASPM expressions were related to poor prognosis of HCC patients. CONCLUSIONS: Nrf2 drives EMT, CSCs characteristics and VM in HCC under hypoxia through the modulation of ASPM. Retinol metabolism pathway was dysregulated in HCC cells with ASPM overexpression. Nrf2/ASPM axis and related pathway provided potential therapeutic target for HCC.

Topical retinoids: Novel derivatives, nano lipid-based carriers, and combinations to improve chemical instability and skin irritation.

BACKGROUND: Retinoids, defined as synthetic or natural derivatives of vitamin A, have been extensively studied as anti-aging molecules that are widely applied in cosmetics. However, due to their physicochemical property, retinoids are highly unstable and extremely sensitive to light, oxygen, and temperature. Moreover, topical application of retinoids often leads to cutaneous irritation. These instabilities and irritant properties of retinoids limit their application in cosmetic and pharmaceutical products. AIM: Our study aimed to provide a systematic review to summarize the mechanisms underlying the instability and irritant properties of retinoids, as well as recent developments in addressing these challenges. METHODS: A comprehensive PubMed search was conducted using the following keywords: retinoids, chemical instability, skin irritation, retinoid derivatives, nano lipid-based carriers, liposomes, penetration-enhancer vesicles, ethosomes, niosomes, nanoemulsions, solid lipid nanoparticles, vitamins, soothing and hydrating agents, antioxidants and metal chelator and retinol combinations. Relevant researches published between 1968 and 2023 and studies related to these reports were reviewed. RESULTS: The development of new retinoid derivatives, the utilization of new delivery systems like nano lipid-based carriers and the combination with other compounds like vitamins, soothing agents, antioxidants and metal chelator have been explored to improve the stability, bioavailability, and toxicity of the retinoid family. CONCLUSIONS: Through advancements in formulation techniques, structure modification of retinoid derivatives and development of novel nano lipid-based carriers, the chemical instability and skin irritation of retinoids has been mitigated, ensuring their efficacy and potency over extended periods.

Investigating the cognitive and affective dynamics of social media addiction: Insights from peer contexts.

Informed by the interaction of person-affect-cognition-execution (I-PACE) theory, the present studies examined the association between peer rejection, peer popularity, and social media addiction (SMA) at both between-person and within-person levels. Two distinct processes, the fear-driven/compensation-seeking process and the reward-driven process were explored. In Study 1, using a cross-sectional sample of high school students (N = 318), both processes were supported via different cognitive mediators. Support for the fear-driven/compensation-seeking process was demonstrated by finding that avoidance expectancy was a significant cognitive mediator between peer-nominated rejection and SMA. In turn, the reward-driven process was supported by the significant mediation of reward expectancy between peer-nominated popularity and SMA. In Study 2, using ecological momentary assessment with college students (N = 54), we found the fear-driven/compensation-seeking process partially supported through both between-person and within-person mediations. Specifically, negative affect and social media craving were two affective mediators that linked peer rejection and addictive social media use behaviors. On the other hand, the reward-driven process was predominantly supported by within-person mediations, in which positive affect and social media craving were found to be mediators of the relationship between peer popularity and addictive social media use behaviors. The results underscore that adolescents experiencing rejection tend to use social media to avoid negative feelings and compensate for interpersonal deficits, while adolescents experiencing popularity tend to use social media to maintain positive feelings and gain social rewards. Implications for the assessment, case formulation, and treatment of SMA in counseling practice are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Development of graphitic carbon nitride quantum dots-based oxygen self-sufficient platforms for enhanced corneal crosslinking.

Keratoconus, a disorder characterized by corneal thinning and weakening, results in vision loss. Corneal crosslinking (CXL) can halt the progression of keratoconus. The development of accelerated corneal crosslinking (A-CXL) protocols to shorten the treatment time has been hampered by the rapid depletion of stromal oxygen when higher UVA intensities are used, resulting in a reduced cross-linking effect. It is therefore imperative to develop better methods to increase the oxygen concentration within the corneal stroma during the A-CXL process. Photocatalytic oxygen-generating nanomaterials are promising candidates to solve the hypoxia problem during A-CXL. Biocompatible graphitic carbon nitride (g-C3N4) quantum dots (QDs)-based oxygen self-sufficient platforms including g-C3N4 QDs and riboflavin/g-C3N4 QDs composites (RF@g-C3N4 QDs) have been developed in this study. Both display excellent photocatalytic oxygen generation ability, high reactive oxygen species (ROS) yield, and excellent biosafety. More importantly, the A-CXL effect of the g-C3N4 QDs or RF@g-C3N4 QDs composite on male New Zealand white rabbits is better than that of the riboflavin 5'-phosphate sodium (RF) A-CXL protocol under the same conditions, indicating excellent strengthening of the cornea after A-CXL treatments. These lead us to suggest the potential application of g-C3N4 QDs in A-CXL for corneal ectasias and other corneal diseases.

Effects of edge disorder on the stability of quantum oscillations in two-dimensional coupled systems.

This paper utilizes the theory of quantum diffusion to analyze the electron probability and spreading width of a wavepacket on each layer in a two-dimensional (2D) coupled system with edge disorder, aiming to clarify the effects of edge disorder on the stability of the electron periodic oscillations in 2D coupled systems. Using coupled 2D square lattices with edge disorder as an example, we show that, the electron probability and wavepacket spreading width exhibit periodic oscillations and damped oscillations, respectively, before and after the wavepacket reaches the boundary. Furthermore, these electron oscillations exhibit strong resistance against disorder perturbation with a longer decay time in the regime of large disorder, due to the combined influences of ordered and disordered site energies in the central and edge regions. Finally, we numerically verified the universality of the results through bilayer graphene, demonstrating that this anomalous quantum oscillatory behavior is independent of lattice geometry. Our findings are helpful in designing relevant quantum devices and understanding the influence of edge disorder on the stability of electron periodic oscillations in 2D coupled systems.

Fe Crystalline Phases in Fe/C Composites Modulated the Selective Adsorption of Pb(II) from Industrial Wastewater with Cd(II): An Electronic-Scale Perspective.

Fe oxide or Fe0-based materials display weak removal capacity for Pb(II), especially in the presence of Cd(II), and the electronic-scale mechanisms are not reported. In this study, Fe3C(220) modified black carbon (BC) [Fe3C(220)@BC] with high adsorption and selectivity for Pb(II) from industrial wastewater with Cd(II) was developed. The quantitative experiment suggested that Fe species accounted for 80.5-100 and 18.4-33.8% of Pb(II) and Cd(II) removal, respectively. Based on X-ray absorption near-edge structure analysis, 57.3% of adsorbed Pb2+ was reduced to Pb0; however, 61.6% of Cd2+ existed on Fe3C@BC. Density functional theory simulation unraveled that Cd(II) adsorption was attributed to the cation-π interaction with BC, whereas that of Pb(II) was ascribed to the stronger interactions with different Fe phases following the order: Fe3C(220) > Fe0(110) > Fe3O4(311). Crystal orbital bond index and Hamilton population analyses were innovatively applied in the adsorption system and displayed a unique discovery: the stronger Pb(II) adsorption on Fe phases was mediated by a combination of covalent and ionic bonding, whereas ionic bonding was mainly accounted for Cd(II) adsorption. These findings open a new chapter in understanding the functions of different Fe phases in mediating the fate and transport of heavy metals in both natural and engineered systems.

Alloying and confinement effects on hierarchically nanoporous CuAu for efficient electrocatalytic semi-hydrogenation of terminal alkynes.

Electrocatalytic alkynes semi-hydrogenation to produce alkenes with high yield and Faradaic efficiency remains technically challenging because of kinetically favorable hydrogen evolution reaction and over-hydrogenation. Here, we propose a hierarchically nanoporous Cu50Au50 alloy to improve electrocatalytic performance toward semi-hydrogenation of alkynes. Using Operando X-ray absorption spectroscopy and density functional theory calculations, we find that Au modulate the electronic structure of Cu, which could intrinsically inhibit the combination of H* to form H2 and weaken alkene adsorption, thus promoting alkyne semi-hydrogenation and hampering alkene over-hydrogenation. Finite element method simulations and experimental results unveil that hierarchically nanoporous catalysts induce a local microenvironment with abundant K+ cations by enhancing the electric field within the nanopore, accelerating water electrolysis to form more H*, thereby promoting the conversion of alkynes. As a result, the nanoporous Cu50Au50 electrocatalyst achieves highly efficient electrocatalytic semi-hydrogenation of alkynes with 94% conversion, 100% selectivity, and a 92% Faradaic efficiency over wide potential window. This work provides a general guidance of the rational design for high-performance electrocatalytic transfer semi-hydrogenation catalysts.

Application of physiologically based pharmacokinetic modeling of novel drugs approved by the U.S. food and drug administration.

Physiologically based pharmacokinetic (PBPK) models which can leverage preclinical data to predict the pharmacokinetic properties of drugs rapidly became an essential tool to improve the efficiency and quality of novel drug development. In this review, by searching the Application Review Files in Drugs@FDA, we analyzed the current application of PBPK models in novel drugs approved by the U.S. Food and Drug Administration (FDA) in the past five years. According to the results, 243 novel drugs were approved by the FDA from 2019 to 2023. During this period, 74 Application Review Files of novel drugs approved by the FDA that used PBPK models. PBPK models were used in various areas, including drug-drug interactions (DDI), organ impairment (OI) patients, pediatrics, drug-gene interaction (DGI), disease impact, and food effects. DDI was the most widely used area of PBPK models for novel drugs, accounting for 74.2 % of the total. Software platforms with graphical user interfaces (GUI) have reduced the difficulty of PBPK modeling, and Simcyp was the most popular software platform among applicants, with a usage rate of 80.5 %. Despite its challenges, PBPK has demonstrated its potential in novel drug development, and a growing number of successful cases provide experience learned for researchers in the industry.

Hepatic GDP-fucose transporter SLC35C1 attenuates cholestatic liver injury and inflammation by inducing CEACAM1 N153 fucosylation.

BACKGROUND AND AIMS: Inflammatory response is crucial for bile acid (BA)-induced cholestatic liver injury, but molecular mechanisms remain to be elucidated. Solute Carrier Family 35 Member C1 (SLC35C1) can transport Guanosine diphosphate-fucose into the Golgi to facilitate protein glycosylation. Its mutation leads to the deficiency of leukocyte adhesion and enhances inflammation in humans. However, little is known about its role in liver diseases. APPROACH AND RESULTS: Hepatic SLC35C1 mRNA transcripts and protein expression were significantly increased in patients with obstructive cholestasis and mouse models of cholestasis. Immunofluorescence revealed that the upregulated SLC35C1 expression mainly occurred in hepatocytes. Liver-specific ablation of Slc35c1 ( Slc35c1 cKO ) significantly aggravated liver injury in mouse models of cholestasis induced by bile duct ligation and 1% cholic acid-feeding, evidenced by increased liver necrosis, inflammation, fibrosis, and bile ductular proliferation. The Slc35c1 cKO increased hepatic chemokine Ccl2 and Cxcl2 expression and T cell, neutrophil, and F4/80 macrophage infiltration but did not affect the levels of serum and liver BA in mouse models of cholestasis. Liquid chromatography with tandem mass spectrometry analysis revealed that hepatic Slc35c1 deficiency substantially reduced the fucosylation of cell-cell adhesion protein CEACAM1 at N153. Mechanistically, cholestatic levels of conjugated BAs stimulated SLC35C1 expression by activating the STAT3 signaling to facilitate CEACAM1 fucosylation at N153, and deficiency in the fucosylation of CEACAM1 at N135 enhanced the BA-stimulated CCL2 and CXCL2 mRNA expression in primary mouse hepatocytes and Primary Liver Carcinoma/Poliomyelitis Research Foundation/5- ASBT cells. CONCLUSIONS: Elevated hepatic SLC35C1 expression attenuates cholestatic liver injury by enhancing CEACAM1 fucosylation to suppress CCL2 and CXCL2 expression and liver inflammation.

Deep Learning-Based Automated Cell Detection-Facilitated Meat Quality Evaluation.

Meat consumption is increasing globally. The safety and quality of meat are considered important issues for human health. During evaluations of meat quality and freshness, microbiological parameters are often analyzed. Counts of indicator cells can provide important references for meat quality. In order to eliminate the error of manual operation and improve detection efficiency, this paper proposed a Convolutional Neural Network (CNN) with a backbone called Detect-Cells-Rapidly-Net (DCRNet), which can identify and count stained cells automatically. The DCRNet replaces the single channel of residual blocks with the aggregated residual blocks to learn more features with fewer parameters. The DCRNet combines the deformable convolution network to fit flexible shapes of stained animal cells. The proposed CNN with DCRNet is self-adaptive to different resolutions of images. The experimental results indicate that the proposed CNN with DCRNet achieves an Average Precision of 81.2% and is better than traditional neural networks for this task. The difference between the results of the proposed method and manual counting is less than 0.5% of the total number of cells. The results indicate that DCRNet is a promising solution for cell detection and can be equipped in future meat quality monitoring systems.

Review and Comparative Analysis of Methods and Advancements in Predicting Protein Complex Structure.

Protein complexes perform diverse biological functions, and obtaining their three-dimensional structure is critical to understanding and grasping their functions. In many cases, it's not just two proteins interacting to form a dimer; instead, multiple proteins interact to form a multimer. Experimentally resolving protein complex structures can be quite challenging. Recently, there have been efforts and methods that build upon prior predictions of dimer structures to attempt to predict multimer structures. However, in comparison to monomeric protein structure prediction, the accuracy of protein complex structure prediction remains relatively low. This paper provides an overview of recent advancements in efficient computational models for predicting protein complex structures. We introduce protein-protein docking methods in detail and summarize their main ideas, applicable modes, and related information. To enhance prediction accuracy, other critical protein-related information is also integrated, such as predicting interchain residue contact, utilizing experimental data like cryo-EM experiments, and considering protein interactions and non-interactions. In addition, we comprehensively review computational approaches for end-to-end prediction of protein complex structures based on artificial intelligence (AI) technology and describe commonly used datasets and representative evaluation metrics in protein complexes. Finally, we analyze the formidable challenges faced in current protein complex structure prediction tasks, including the structure prediction of heteromeric complex, disordered regions in complex, antibody-antigen complex, and RNA-related complex, as well as the evaluation metrics for complex assessment. We hope that this work will provide comprehensive knowledge of complex structure predictions to contribute to future advanced predictions.

YEATS domain-containing protein GAS41 regulates nuclear shape by working in concert with BRD2 and the mediator complex in colorectal cancer.

The maintenance of nuclear shape is essential for cellular homeostasis and disruptions in this process have been linked to various pathological conditions, including cancer, laminopathies, and aging. Despite the significance of nuclear shape, the precise molecular mechanisms controlling it are not fully understood. In this study, we have identified the YEATS domain-containing protein 4 (GAS41) as a previously unidentified factor involved in regulating nuclear morphology. Genetic ablation of GAS41 in colorectal cancer cells resulted in significant abnormalities in nuclear shape and inhibited cancer cell proliferation both in vitro and in vivo. Restoration experiments revealed that wild-type GAS41, but not a YEATS domain mutant devoid of histone H3 lysine 27 acetylation or crotonylation (H3K27ac/cr) binding, rescued the aberrant nuclear phenotypes in GAS41-deficient cells, highlighting the importance of GAS41's binding to H3K27ac/cr in nuclear shape regulation. Further experiments showed that GAS41 interacts with H3K27ac/cr to regulate the expression of key nuclear shape regulators, including LMNB1, LMNB2, SYNE4, and LEMD2. Mechanistically, GAS41 recruited BRD2 and the Mediator complex to gene loci of these regulators, promoting their transcriptional activation. Disruption of GAS41-H3K27ac/cr binding caused BRD2, MED14 and MED23 to dissociate from gene loci, leading to nuclear shape abnormalities. Overall, our findings demonstrate that GAS41 collaborates with BRD2 and the Mediator complex to control the expression of crucial nuclear shape regulators.

Single-electron transfer between sulfonium and tryptophan enables site-selective photo crosslinking of methyllysine reader proteins.

The identification of readers, an important class of proteins that recognize modified residues at specific sites, is essential to uncover the biological roles of post-translational modifications. Photoreactive crosslinkers are powerful tools for investigating readers. However, existing methods usually employ synthetically challenging photoreactive warheads, and their high-energy intermediates generated upon irradiation, such as nitrene and carbene, may cause substantial non-specific crosslinking. Here we report dimethylsulfonium as a methyllysine mimic that binds to specific readers and subsequently crosslinks to a conserved tryptophan inside the binding pocket through single-electron transfer under ultraviolet irradiation. The crosslinking relies on a protein-templated σ-π electron donor-acceptor interaction between sulfonium and indole, ensuring excellent site selectivity for tryptophan in the active site and orthogonality to other methyllysine readers. This method could escalate the discovery of methyllysine readers from complex cell samples. Furthermore, this photo crosslinking strategy could be extended to develop other types of microenvironment-dependent conjugations to site-specific tryptophan.

Innovative Nanotechnology in Drug Delivery Systems for Advanced Treatment of Posterior Segment Ocular Diseases.

Funduscopic diseases, including diabetic retinopathy (DR) and age-related macular degeneration (AMD), significantly impact global visual health, leading to impaired vision and irreversible blindness. Delivering drugs to the posterior segment of the eye remains a challenge due to the presence of multiple physiological and anatomical barriers. Conventional drug delivery methods often prove ineffective and may cause side effects. Nanomaterials, characterized by their small size, large surface area, tunable properties, and biocompatibility, enhance the permeability, stability, and targeting of drugs. Ocular nanomaterials encompass a wide range, including lipid nanomaterials, polymer nanomaterials, metal nanomaterials, carbon nanomaterials, quantum dot nanomaterials, and so on. These innovative materials, often combined with hydrogels and exosomes, are engineered to address multiple mechanisms, including macrophage polarization, reactive oxygen species (ROS) scavenging, and anti-vascular endothelial growth factor (VEGF). Compared to conventional modalities, nanomedicines achieve regulated and sustained delivery, reduced administration frequency, prolonged drug action, and minimized side effects. This study delves into the obstacles encountered in drug delivery to the posterior segment and highlights the progress facilitated by nanomedicine. Prospectively, these findings pave the way for next-generation ocular drug delivery systems and deeper clinical research, aiming to refine treatments, alleviate the burden on patients, and ultimately improve visual health globally.