Browse Articles

Longitudinal trajectories and predictors of glycated hemoglobin among type 2 diabetes patients concomitant with hypertension: spline based linear mixed-effects model

Catalytic ROS‐Amplifying Self‐Immolative Linkers Enable Carrier‐Free Prodrugs for Refractory Tumors

ABSTRACT Redox‐buffering systems in tumors heighten chemoresistance, yet most ROS‐responsive linkers used in prodrug design consume oxidants, exhibit limited sensitivity to endogenous ROS, and often require external triggers or complex formulations, constraining clinical translation. Here we report a phenylselanyl cyclohexenone self‐immolative linker that couples ROS‐triggered cleavage with organoselenium‐mediated redox amplification within a single small‐molecule architecture. Oxidation of the selanyl group generates a selenoxide that undergoes aromatization‐assisted β‐elimination followed by 1,6‐self‐elimination, releasing the payload together with a redox‐active selenium species. The released selenium species is proposed to engage in a GSH‐dependent redox cycle that increases intracellular oxidative burden, thereby reinforcing ROS‐triggered activation and weakening antioxidant buffering. This modular motif enables the construction of carrier‐free prodrugs spanning chemotherapeutics and small‐molecule inhibitors. These prodrugs remain stable in neutral media yet are efficiently activated by endogenous ROS, achieving improved biodistribution, reduced systemic toxicity, and enhanced antitumor activity across breast cancer, pancreatic ductal adenocarcinoma, and patient‐derived leukemia models. By coupling selective activation with catalytic redox amplification, this ROS‐amplifying self‐immolative linker provides a modular strategy for overcoming redox‐associated drug resistance and for advancing the translational potential of small‐molecule prodrugs.

Canonical autophagy remains inactive in induced pluripotent stem cells and neuronal progenitor cells following DNA damage induced by BPDE or etoposide

Abstract (Macro-)Autophagy is a key cellular stress response mediating the recycling of long-lived or damaged proteins and organelles. In stem cells, autophagy is essential for the decision between quiescence, self-renewal and differentiation. We observed that induced pluripotent stem cells (iPSCs) and thereof derived neural progenitor cells (NPCs) have a functional autophagy machinery, as shown by starvation-induced autophagic flux and ULK1 activation. Using the human iPSC lines iPS11 and iPS12 and thereof derived NPCs (niPS11 and niPS12), we investigated whether genotoxic stress induced by low doses (IC 20 ) of benzo[a]pyrene diolepoxide (BPDE) or etoposide can similarly activate autophagy, as previously reported for cancer cell lines. While both BPDE and etoposide induced the DNA damage markers phospho-p53 Ser15 and γH2AX and slightly altered the expression of DNA repair proteins such as XPC, they did not trigger autophagic flux in either iPSCs or NPCs. After genotoxin treatment, ULK1 activation was only observed in NPCs, but this was not sufficient to trigger a significant downstream autophagic response. Mass spectrometry revealed minimal proteomic changes in iPSCs and moderate changes in NPCs, mainly involving mitotic regulators. In summary, no significant activation of canonical autophagy was detectable in iPSCs and NPCs within the tested time frame and under low-dose genotoxic conditions, although both cell types retain a functional autophagic machinery.

Efficacy of field-based surveys for detecting and assessing demographics of giant snakes (Malayopython reticulatus) in Malaysia

Abstract Evaluating sustainable levels of offtake is central to regulating the commercial harvest of wildlife species, but methods developed for temperate-zone mammal and bird species may be inapplicable to tropical rainforest reptiles. For example, population viability models require information on abundance and on rates of growth, maturation, survival, and reproduction. For some intensively harvested reptiles - especially well-camouflaged ambush predators in densely vegetated habitats - such data are difficult to obtain. The feasibility of gathering this information is central to current debates about how best to evaluate the sustainability of commercial harvesting of reticulated pythons ( Malayopython reticulatus) in Asia. Over a five-year period, we conducted 527 riverside surveys (with mark-recapture) for this species in a protected area in Sabah, Malaysia. Detectability of pythons was dependent on moon phase but always low (mean = 20%); and the total number of pythons captured ( N  = 159 total, N  = 83 during standardized surveys) and recaptured ( N  = 25) despite that intensive long-term effort was insufficient to enable robust mathematical modelling. Our results suggest that attempts to base sustainable-harvesting targets for M. reticulatus on mathematical models are futile, and that repeated surveys of the attributes of harvested specimens provide a more reliable basis from which to evaluate sustainability.

Boosting Alkaline Oxygen Evolution Kinetics by Tailoring the Noncovalent Interaction on CoOOH

ABSTRACT Understanding the effect of noncovalent interactions of intermediates at the polarized catalyst‐electrolyte interface is key to improving the kinetics of electrocatalytic reactions. Herein, we employ cobalt oxyhydroxide (CoOOH) as a model catalyst, select carboxylate‐based additives to strategically modulate the interfacial electronic double layer (EDL), and investigate the effect of carboxylate anions on the oxygen evolution reaction (OER) kinetics under alkaline media. We demonstrate that the hydrogen bonds formed between oxygen atoms within ‐COO − fragments of carboxylate anions and interfacial H 2 O molecules can disrupt the arrangement of the hydration shell around K + , leading to fast migration of OH − to the CoOOH surface. Experimental results, including rotating ring‐disk electrode (RRDE) measurements, in situ X‐ray absorption spectroscopy (XAS), in situ attenuated total reflectance surface‐enhanced infrared absorption spectroscopy (ATR‐SEIRAS), and ab initio molecular dynamics (AIMD) theory simulations, reveal that the negative electrostatic potential on the oxygen atom in the ‐COO − fragments can partially neutralize the localized electric field generated by hydrated K + ions in the electrolyte, which sufficiently destabilizes the adsorbed oxygenated intermediates and accelerates the deprotonation process, thereby leading to promoted charge accumulation and accelerated alkaline OER kinetics.

Performance and emission multi-objective optimization of γ-Al2O3 nanoparticle-enhanced E10 bioethanol–gasoline combustion in spark-ignition engines

Site‐Selective B─H Activation via HAT Toward Xanthyl‐ <i>closo</i> ‐Carboranes as Bench‐Stable Precursors of Organosulfur Boron Clusters

ABSTRACT In this work, a light mediated direct regioselective B─H functionalization to afford unexplored xanthyl‐ closo ‐carboranes is described by a nitrogen‐centered radical (NCR)‐mediated hydrogen atom transfer (HAT) process. To directly activate a B─H bond in an icosahedral carborane, which contains 10 B─H with very similar electronic properties, represents a challenging goal. The reaction is applied to several mono and disubstituted o ‐ and m ‐carboranes affording, in discrete to good yields, boryl xanthates which act as novel bench‐stable and versatile platforms for the functionalization of the carborane cage with sulfur‐containing functionalities: alkyl‐ and aryl sulfides, thiols, thioesters and sulfonyl chlorides are readily obtained. The reaction has also been scaled up and an analogue of the pesticide Chlorbenside has been synthesized. EPR studies, additionally to deuteration experiments, confirm the formation of an NCR as the promoter of a HAT process to the most electron‐rich boron vertex with the lowest B─H bond dissociation energy (BDE), to produce a B(9)‐centered radical. A deep computational study contributes to the mechanism proposal.

Prevalence and a LASSO-derived prediction model for screening-positive mild cognitive impairment among older adults in Wuhan

Abstract This study aimed to investigate the prevalence of screening-positive mild cognitive impairment (s-MCI) and to develop a parsimonious prediction model using machine learning methods to identify high-risk older adults in Wuhan, China. A total of 2,190 community-dwelling adults aged ≥ 60 years were recruited through multistage cluster sampling from 30 residential committees in 13 districts. MCI screening was conducted with the Community Screening Instrument for Dementia (CSI-D). The Least Absolute Shrinkage and Selection Operator (LASSO) was employed to select predictive variables, and multiple machine learning classifiers were compared. Model performance was assessed using the area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA). SHapley Additive exPlanations (SHAP) was used to interpret the best-performing model. The screening-positive rate of MCI was 35.3%. The final prediction model retained four predictors: age, occupation, sleep disorders, and literacy level. XGBoost showed slightly better discrimination than logistic regression in the validation set (AUC: 0.693 vs. 0.671). Based on SHAP values, sleep disorders, advanced age, lower education level, and farmer occupation were the most important contributors to the prediction. The burden of screening-positive MCI is considerable among older adults in Wuhan. The LASSO-derived prediction model, comprising easily obtainable variables, can serve as a practical risk-stratification tool to support targeted early screening, without implying a unique etiological role for the selected predictors.

The effect of Covid-19 vaccines on semen parameters of patients undergoing infertility investigations: a self-controlled before-and-after study

Environmental context related to hydrogen sulphide and regional variation in utilisation of ROCK inhibitors in Japan: a nationwide ecological analysis

Abstract Regional variation in healthcare utilisation is widely documented, yet the contribution of natural environmental context to prescribing patterns remains poorly understood. Geological environments shape long-term background exposure to naturally occurring substances, but population-level evidence linking geological context to ophthalmic prescribing is limited. Experimental studies have suggested that hydrogen sulphide (H 2 S) may interact with the RhoA/Rho kinase (ROCK) signalling pathway, which is the pharmacological target of ROCK inhibitor medications used for glaucoma. We conducted a nationwide ecological cross-sectional study using prefecture-level data from all 47 prefectures of Japan. Annual per-capita prescription volumes of ripasudil ophthalmic solution were obtained from the National Database of Health Insurance Claims, and geological context was quantified using the volcanic rock area ratio (VRAR) as a geological background indicator reflecting long-term environmental context, including potential exposure to H 2 S, rather than a direct measure of exposure. Associations were analysed using locally estimated scatterplot smoothing (LOESS), multiple linear regression, and random forest modelling with adjustment for demographic and healthcare-related covariates. Ophthalmic prescribing patterns showed marked regional variation across Japan, and analyses identified a consistent non-linear association between geological context and per-capita ROCK inhibitor prescriptions, with prescription levels peaking in prefectures with intermediate VRARs. Multivariable linear regression showed limited explanatory power, whereas random forest models suggested that geological context was among the most influential predictors among the examined variables. These findings suggest that regional geological context may represent a previously underexplored structural factor associated with variation in ophthalmic prescribing patterns, highlighting a potential intersection between environmental context and population-level pharmacological utilisation.

Molecularly Engineered Robust Polyelectrolyte for Continuous CO ₂ Electroreduction to Pure Formic Acid

ABSTRACT Electrocatalytic CO 2 conversion to liquid fuels requires coordinated advances in catalysis and product isolation, whereas current research emphasizes the former over separation challenges essential for industrial viability. Traditional liquid electrolytes incur efficiency losses from carbonate formation, while solid‐state systems face mechanical and ionic‐transport limitations. Here, we report a mechanically resilient trimethylammonium polyelectrolyte for CO 2 ‐to‐liquid product conversion without electrolyte consumption. The molecularly aligned trimethylammonium polycations create continuous hydroxide‐conducting channels, achieving record conductivity (53 mS cm −1 , 20°C) that outperforms state‐of‐the‐art solid electrolytes. The mechanically robust polyelectrolyte maintains structural integrity and high ionic conductivity during rapid‐water‐flux operation, supporting continuous flow production of pure formic acid at a partial current density of 288 mA cm −2 in liter scale. The molecularly engineered polyelectrolytes address the catalysis and product‐separation dichotomy by enabling continuous CO 2 ‐to‐liquid‐fuel conversion and autonomous product isolation under industrial operating conditions, delivering a scalable pathway for pure liquid‐fuel‐production electrolyzers.

Pathological evidence of neurotropism and oculotropism in wild black-headed gulls naturally infected with H5N1 high pathogenicity avian influenza

Evidence for resource transfer via common endophyte networks

Abstract Fungal symbionts play essential roles in ecosystems influencing plant development and biodiversity. Mycorrhizal fungi can form common mycorrhizal networks (CMNs) where a fungus connects the roots of at least two plants via continuous extraradical mycelium and transfers resources such as nitrogen and carbon. In addition to mycorrhizal fungi, there is another group of fungal mutualists known as endophytes. They also support plant development and may form common endophyte networks (CENs). Whether endophytes can transfer soil resources like nitrogen, carbon, and water through such networks remains an open question. To test this, we established a CEN experiment in split petri dishes involving Arabidopsis thaliana hosts and three phylogenetically diverse endophytes ( Trichoderma viride , Mucor hiemalis , and Fusarium temperatum ) to test whether resources like isotopically labelled amino acid 15 nitrogen (N), amino acid 13 carbon (C), 15 N-ammonium, or deuterated water can be transferred by donor to receiver plants connected via CENs. We show that the tested endophytes can form CENs and transfer growth limiting resources from donor plant soil to receiver plant tissues. F. temperatum boosted plant growth by 38% relative to the uninoculated control, and it enriched plant 15 N content derived from amino acids by 55%. Surprisingly, we also observed amino acid-derived 13 C transport from donor plant soil to receiver plant tissues by T. viride (+ 2.83% &gt; control). We also demonstrate that soil resource transfer, evaluated as isotope enrichment, by all three endophytes shifted in the presence of two versus a single host plant even when root systems were physically separated to avoid competition, underscoring that endophytic functioning, not just that of plants, also shifts when CENs are formed. Our results demonstrate that non-mycorrhizal fungi, like endophytes, can form networks similar to the idea of CMNs and transfer plant growth relevant resources. Endophytes display a broad array of symbiotic functions with their hosts, and formation of CENs may be a newly discovered component of their symbiotic tool kit.

Environmental detection of amoxicillin using a molecularly imprinted graphene oxide-polyethylenimine electrochemical sensor

Evaluating orthokeratology lens fitting and the visual quality of artificial intelligence-fitted personalized lenses in myopic children with corneal asymmetry

Firmicutes/Bacteroidetes ratio of the gut microbiota and its association with abdominal obesity and insulin resistance (METS-IR) in Korean adults

Bandwidth-efficient and reliable communication in smart grid systems for modern energy networks using Trellis and Turbo Trellis Coded Modulation

Abstract Smart Grids rely on robust communication infrastructures to monitor, control, and stabilize information in real time across geographically distributed energy resources. Trellis Coded Modulation (TCM) is a well-established technique for improving spectral efficiency and reliability, particularly in bandwidth-constrained and noisy channels. By combining convolutional coding with multilevel modulation, TCM achieves significant coding gains without increasing bandwidth, making it well suited for Smart Grid communication links. Turbo Trellis Coded Modulation (TTCM) extends TCM by incorporating parallel concatenated trellis encoders with iterative decoding, further enhancing performance and robustness under a wide range of channel distortions, including additive noise and fading. In this paper, we present the underlying mathematical framework for TCM and TTCM, simulation results under AWGN and Rayleigh fading channels, and comparisons to uncoded transmission. We also discuss future prospects of TCM, including integration with AI-driven adaptive coding and 5G-enabled Smart Grid infrastructures, highlighting the critical role of high-reliability communication systems in next-generation energy networks. Consequently, TTCM offers a hybrid solution that combines strong error correction with efficient bandwidth utilization, ensuring dependable communication for reliability-critical Smart Grid applications.

Overexpression of miR-219 as a potential therapeutic strategy of glioblastoma cells in vitro

Monitoring Redox Pathways and Performance Limitations in Lithium‐Sulfur Batteries Using In Situ ^7/6 Li and ³³ S NMR Spectroscopies

ABSTRACT Lithium‐sulfur (Li‐S) batteries offer high capacity and reduced costs in comparison to the traditional lithium‐ion systems. However, the complex series of redox mechanisms that occur in this battery chemistry and accompanying structural transformations are often associated with different routes for cell failure. Therefore, a fundamental understanding of the underlying mechanisms is essential to accelerate the development of these batteries. The combination of operando 6/7 Li and 33 S NMR spectroscopy is reported for the first time, providing real‐time structural information on the reaction pathways of the sulfur redox processes. The evolution of the polysulfides (poly‐S) in the electrolyte and dendrite formation on the anode was monitored with 7 Li and 6 Li NMR spectroscopy. Via 33 S NMR experiments, the exact onset of Li 2 S formation was determined. By following the evolution of poly‐S species and Li 2 S, we could track the entire redox pathway and identify performance‐limiting mechanisms. The accumulation of soluble poly‐S, resulting from an incomplete poly‐S to S 8 reduction reaction during charge, was identified as one process leading to capacity fade, while degradation via a poly‐S shuttle mechanism was negligible, at least during the first few cycles.

Hydrogen-exchange behavior of the L20A mutant of the protein A B domain in guanidinium chloride: evidence for persistent native-like contacts

Abstract Residual structure in unfolded proteins plays a crucial role in directing folding pathways. Here, we examined the unfolded state of the B domain of staphylococcal protein A carrying the L20A mutation, which disrupts native hydrophobic contacts between Leu20 and helix H3 (residues 41–56). The L20A mutant markedly reduced the thermodynamic stability of the native state. Using dimethylsulfoxide (DMSO)-quenched hydrogen/deuterium (H/D)-exchange NMR spectroscopy, we measured H/D-exchange kinetics for backbone amide protons in 6 M guanidinium chloride. At defined exchange times, the reaction mixture was rapidly transferred to a DMSO solution using a spin desalting column, thereby quenching exchange and allowing accurate NMR measurements. Even under the strongly denaturing condition of 6 M guanidinium chloride, the L20A mutant exhibited substantially lower protection against H/D exchange than the wild-type protein, particularly for residues in helix H3. These results indicate that native-like tertiary contacts between Leu20 and helix H3 persist in the unfolded ensemble and contribute to stabilizing residual structure. Our findings demonstrate that DMSO-quenched H/D-exchange NMR combined with targeted mutation provides a powerful approach for dissecting residual interactions and elucidating how early native-like contacts shape folding pathways.