Structure-Based Design of "Head-to-Tail" Macrocyclic PROTACs.

Macrocyclization is a compelling strategy for conventional drug design for improving biological activity, target specificity, and metabolic stability, but it was rarely applied to the design of PROTACs possibly due to the mechanism and structural complexity. Herein, we report the rational design of the first series of "Head-to-Tail" macrocyclic PROTACs. The resulting molecule exhibited pronounced Brd4 protein degradation with low nM DC values while almost totally dismissing the "hook effect", which is a general character and common concern of a PROTAC, in multiple cancer cell lines.

Comparison of activated sludge and virus interactions in aerobic and anaerobic membrane bioreactors.

Membrane bioreactors (MBRs) are effective sewage treatment technologies, yet the differences in virus removal efficiency between aerobic (AeMBR) and anaerobic membrane bioreactors (AnMBR), remain inadequately understood. This study compared the virus removal efficiency of AeMBR and AnMBR, focusing on the interactions between aerobic (AeS) and anaerobic (AnS) activated sludge and viruses in the sewage treatment process. Results showed average log removal values (LRVs) for MS2 of 2.

Associations of baseline and longitudinal changes in basic activity of daily living with risk of cardiovascular disease among older adults in China.

Background And Aims: The purpose of this study was to examine the associations of basic activities of daily living (BADL) and its longitudinal changes with cardiovascular disease (CVD) risk among older population.

Methods And Results: We conducted a prospective analysis of the Chinese Longitudinal Healthy Longevity Survey between 2008 and 2018 in 7051 participants aged 65 years or over. Cox proportional hazards models were performed to evaluate the associations of baseline and longitudinal changes in BADL with the incidence of CVD.

Adhesive polyelectrolyte coating on PLGA particles prolongs drug retention to vessel lesion.

Restenosis, the re-narrowing of blood vessels after drug-coated balloons (DCBs), remains a major clinical issue. While rapamycin is the current clinical option for preventing restenosis due to its effectiveness and low toxicity, its delivery is limited by poor tissue absorption and rapid clearance, leading to suboptimal drug retention. Here, we developed the adhesive-polyelectrolyte-coated poly(lactic-co-glycolic acid) (PLGA) particles using in-situ UV-triggered polymerization, encapsulating rapamycin.

Oxidized yeast glucan alleviates lead-induced toxicity in mice by improving intestinal health to inhibit Pb absorption and reducing kidney oxidative stress.

This study investigated the protective effects and Pb-excretion mechanisms of yeast glucans (YG) with varying oxidation degrees in Pb-exposed mice. Results demonstrated that all three glucans effectively reduced blood lead levels, alleviated inflammation, and mitigated liver damage in Pb-exposed mice, with highly oxidized yeast glucan (OYG2) exhibiting the greatest efficacy. Furthermore, the glucans attenuated Pb-induced oxidative stress and pathological changes in the kidney by elevating glutathione and superoxide dismutase levels, thereby restoring renal excretory function (blood urea nitrogen and creatinine).

The effect of digital infrastructure development on household energy consumption expenditure--taking broadband China strategy as an example.

The provision of digital infrastructure and affordable energy for households is an important direction for improving the living conditions of the population. The link between digital infrastructure development and affordable energy should be examined if multiple sustainable development goals are to be achieved simultaneously for the residential sector. This study employs a staggered difference-in-differences model to investigate the effect of digital infrastructure development on household energy consumption expenditure (HECE) by using the Broadband China Strategy as an example.

Sex-specific associations between maternal exposure to metal mixtures and fetal growth trajectories: A prospective birth cohort study.

Background: The associations of prenatal metals exposure with birth outcomes have been widely assessed. However, evidence on the associations between metal mixtures and fetal intrauterine growth trajectories is scarce.

Objectives: This study aimed to explore the associations of metal mixtures with fetal intrauterine growth trajectories overall and by sex.

Impact of physicochemical and microbial drivers on the formation of disinfection by-products in drinking water distribution systems: A multivariate Bayesian network modeling approach.

The formation of disinfection byproducts (DBPs) in drinking water distribution systems (DWDS) is significantly affected by numerous factors, including physicochemical water properties, microbial community composition and structure, and the characteristics of organic DBP precursors. However, the codependence of various factors remains unclear, particularly the contribution of microbial-derived organics to DBP formation, which has been inadequately explored. Herein, we present a Bayesian network modeling framework incorporating a Bayesian-based microbial source tracking method and excitation-emission fluorescence spectroscopy-parallel factor analysis to capture the critical drivers influencing DBP formation and explore their interactions.

Lactoferrin targeting INTL1 receptor inhibits hepatocellular carcinoma progression via apoptosis and cell cycle signaling pathways.

Hepatocellular carcinoma (HCC) constitutes 90% of liver cancer cases and ranks as the third leading cause of cancer-related mortality, necessitating urgent development of alternative therapies. Lactoferrin (LF), a natural iron-binding glycoprotein with reported anticancer effects, is investigated for its potential in liver cancer treatment, an area with limited existing studies. This study focuses on evaluating LF's anti-liver cancer effects on HCC cells and assessing the preventive efficacy of oral LF administration in a murine model.

Altered neurovascular coupling and structure-function coupling in Moyamoya disease affect postoperative collateral formation.

Chronic ischemia in moyamoya disease (MMD) impaired white matter microstructure and neural functional network. However, the coupling between cerebral blood flow (CBF) and functional connectivity and the association between structural and functional network are largely unknown. 38 MMD patients and 20 sex/age-matched healthy controls (HC) were included for T1-weighted imaging, arterial spin labeling imaging, resting-state functional MRI and diffusion tensor imaging.

Strategic analysis of avian conservation within key areas and key species - A case study of Baiyangdian, China.

Global climate change and extensive human activities are causing rapid transformations in natural ecosystems, leading to the rapid loss of suitable habitats for wildlife, which urgently requires measures to protect global biodiversity. In the past decade, China has invested heavily in ecological restoration, but current projects often do not prioritize biodiversity conservation. Therefore, developing systematic conservation strategies and using quantitative methods to identify conservation key areas and key species within a regional scale is of great importance for current ecological restoration.

The impact of digital infrastructure on air quality: Mediating role of public environmental attention and industrial development.

The digital economy has significantly enhanced economic quality, and studying its implications on the environment can provide empirical support for policies that foster environment-economy coordination. This paper examines the impact of digital infrastructure on air quality, focusing on the mechanisms of public environmental attention and industrial development. It further analyzes heterogeneity in urban locations, degree of urbanization, and environmental regulation intensity.

A complementary and integrated strategy for multicomponent characterization and attribution of Danning tablet based on convergence and liquid chromatography combined with mass spectrometry.

Danning tablet (DNT) is a traditional Chinese medicine (TCM) that contains seven herbal ingredients. It has been clinically used to treat liver and gallbladder diseases in humans. However, the complex composition of TCM prescriptions makes it challenging to fully analyze different polar range compounds.

Co-metabolism of Norfloxacin by Chlorella pyrenoidosa: Carbon source effects, biotransformation mechanisms, and key driving genes.

Co-metabolism with appropriate carbon sources has been demonstrated to effectively enhance the removal of ubiquitous recalcitrant micropollutant by microalgae. However, the specific impacts of carbon sources on the co-metabolism of antibiotics by microalgae remain insufficiently explored. In this study, transcriptomics, gene network analysis, extracellular polymeric substances (EPS), and enzymatic activity involved in co-metabolic pathways of norfloxacin (NFX), were systematically evaluated to investigate the underlying biological mechanisms involved in NFX co-metabolism by Chlorella pyrenoidosa.

Shared genetic architecture and bidirectional clinical risks within the psycho-metabolic nexus.

Background: Increasing evidence suggests a complex interplay between psychiatric disorders and metabolic dysregulations. However, most research has been limited to specific disorder pairs, leaving a significant gap in our understanding of the broader psycho-metabolic nexus.

Methods: This study leveraged large-scale cohort data and genome-wide association study (GWAS) summary statistics, covering 8 common psychiatric disorders and 43 metabolic traits.

Tunable aptamer-MXene sensing interface for label-free and real-time detection of toxic pollutants in water samples.

Stable and low-cost field-effect transistor (FET)-based biosensors are vital for the on-site detection of toxic pollutants in environmental monitoring applications. In this study, a tunable aptamer-MXene sensing interface was constructed to develop renewable FET biosensors. This was achieved through the reversible disulfide bond (-S-S-) reaction between the SH-TiCT film and thiolated aptamer.

Highly Strained Polymeric Monolayer Stacked for Wafer-Scale and Transferable Nanodielectrics.

As the keystones of molecular electronics, high-quality nanodielectric layers are challenging to assemble due to the strictest criteria for their reliability and uniformity over a large area. Here, we report a strained poly(4-vinylphenol) monolayer, ready to be stacked to form defect-free wafer-scale nanodielectrics. The thickness of the nanodielectrics can be precisely adjusted in integral multiples of the 1.

One-Pot Synthesis of Oxygen Vacancy-Rich Amorphous/Crystalline Heterophase CaWO Nanoparticles for Enhanced Radiodynamic-Immunotherapy.

Radiodynamic therapy that employs X-rays to trigger localized reactive oxygen species (ROS) generation can tackle the tissue penetration issue of phototherapy. Although calcium tungstate (CaWO) shows great potential as a radiodynamic agent benefiting from its strong X-ray absorption and the ability to generate electron-hole (e-h) pairs, slow charge carrier transfer and fast e-h recombination greatly limit its ROS-generating performance. Herein, via a one-pot wet-chemical method, oxygen vacancy-rich amorphous/crystalline heterophase CaWO nanoparticles (Ov-a/c-CaWO NPs) with enhanced radiodynamic effect are synthesized for radiodynamic-immunotherapy of cancer.

Metabolic Engineering of Corynebacterium glutamicum for High-Level Production of 1,5-Pentanediol, a C5 Diol Platform Chemical.

The biobased production of chemicals is essential for advancing a sustainable chemical industry. 1,5-Pentanediol (1,5-PDO), a five-carbon diol with considerable industrial relevance, has shown limited microbial production efficiency until now. This study presents the development and optimization of a microbial system to produce 1,5-PDO from glucose in Corynebacterium glutamicum via the l-lysine-derived pathway.

Multilingual SEIR public opinion propagation model with social enhancement mechanism and cross transmission mechanisms.

The propagation of public opinion in multilingual environments presents unique challenges due to the diversity of languages, cultures, and values. This study develops an SEIR-based model tailored for multilingual contexts, incorporating mechanisms such as social enhancement, forgetting, and cross-transmission. The model's purpose is to improve transparency, inclusivity, and effectiveness in public opinion management, particularly in diverse linguistic settings.

Proposal for a quantum mechanical test of gravity at millimeter scale.

The experimental verification of the Newton law of gravity at small scales has been a longstanding challenge. Recently, torsion balance experiments have successfully measured gravitational force at the millimeter scale. However, testing gravity force on quantum mechanical wave function at small scales remains difficult.

Iodine-131 radioembolization boosts the immune activation enhanced by icaritin/resiquimod in hepatocellular carcinoma.

Transarterial radioembolization (TARE) is a recommended locoregional strategy for intermediate hepatocellular carcinoma (HCC), whereas, the effect is insufficient to reverse the immunosuppression tumor microenvironment, and the overall benefits for patients remain to be improved. In this study, a multifunctional microsphere (MS) I-ICT/R848-MS is developed to propose an approach combined with TARE, icaritin (ICT) and immune modulator resiquimod (R848). ICT and iodine-131 (I) radiation can induce immunogenic cell death, which, in combination with R848, will boost dendritic cell (DC) maturation.

Multiscale analysis of CO adsorption mechanisms on porous carbon: An investigation into the impact of intrinsic defects and pore size.

Porous carbon adsorption represents a critical component of CCUS technologies, with microporous structures playing an essential role in CO capture. The preparation of porous carbon introduces intrinsic defects, making it essential to consider both pore size and these defects for a comprehensive understanding of the CO adsorption mechanism. This study investigates the mechanisms of CO adsorption influenced by intrinsic defects and pore size using multiscale methods, incorporating experimental validation, Grand Canonical Monte Carlo simulations, and Density Functional Theory simulations.