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Computational modeling of eticyclidine drug adsorption and detection on c60 based nanostructures
Abstract The detection of Eticyclidine (PCE) as a psychotropic drug is difficult due to the limitations of conventional analytical techniques (such as the need for expensive instruments, expert labor, and time-consuming). In this computational study, structural, electronic, and optical properties were evaluated to assess the ability of pristine C 60 fullerene and its aluminum (AlC 59 ) and zinc (ZnC 59 ) doped forms as sensors/adsorbers for PCE using density functional theory (DFT), time-dependent DFT (TD-DFT), and quantum theory of atoms in molecules (QTAIM). The calculated structural/electronic properties of pristine C 60 (bond lengths, energy gaps, and UV spectra) were in excellent agreement with reported experimental data, supporting the validity of the computational approach. The weak/reversible binding interaction energy, recovery times, conductivity and reactivity of pure C 60 indicate its suitability for repeated use as an electrochemical sensor for PCE. However, AlC 59 has strong and irreversible binding, indicating that it can be used as an excellent adsorbent for PCE removal. ZnC 59 is moderately bound to PCE compared to C 60 and AlC 59 . TD-DFT calculations show a large red shift of the UV-Vis spectra when PCE is absorbed by AlC 59 and ZnC 59 , which provides evidence of strong optical responses, indicating their potential for use as colorimetric sensors. The results obtained from NCI/RDG, ELF, LOL and QTAIM analyses confirm that metal doping significantly enhances the strength of the interaction with PCE. We believe that the findings of this theoretical study can provide a reliable basis for the experimental development of C 60 -based materials for PCE sensing and adsorption.
Blue- versus green-absorbing anion channelrhodopsins, essential tools in optogenetics, differ fundamentally in gating mechanisms
The genomes of many protists encode at least one pair of spectrally distinct cation or anion channelrhodopsins. Two cation channelrhodopsins (CCRs) initiate different transduction cascades in Chlamydomonas . Two Guillardia anion channelrhodopsins (ACRs) are emerging molecular tools for optical inhibition of neuronal firing, but their functions in the source organism remain unclear. Furthermore, Gt ACR2 remains poorly investigated compared to Gt ACR1, although its faster channel kinetics makes it preferable for optogenetic control of neurons firing at high frequencies. Using patch-clamp recording in mammalian cells, photochemical characterization of purified proteins, and mutational analysis, we found a fundamental mechanistic difference between blue-absorbing Gt ACR2 and green-absorbing Gt ACR1, which may indicate different functions in the alga. Gt ACR2 exhibits only one channel gating mechanism, unlike Gt ACR1, in which we had detected two mechanisms. Gt ACR2’s faster channel closing strongly depends on the holding voltage, and its photocycle shows considerable intermediate reversibility. Photocurrents evoked by continuous light pulses reflecting secondary photochemistry reveal further differences between Gt ACR1 and Gt ACR2. Mutagenetic replacement of five divergent Gt ACR2 residues with those of Gt ACR1 reproduced the latter’s spectral sensitivity and slow biphasic channel closing. Only one Gt ACR2 mutation, R129C, which individually caused the most substantial red shift, restored the gating mechanism typical of Gt ACR1. Gt ACR2, but not Gt ACR1, exhibited a change in the F − /Cl − relative permeability during the single-turnover photocycle. Comparison to Chlamydomonas CCRs and ACRs from other protists suggests that these differences between blue- and green-absorbing ChRs are a general rule, which can guide further development of optogenetic tools.
Research on the residual mechanical properties of hybrid fiber ECCs after high-temperature exposure
Selective divergence between Grokipedia and Wikipedia articles
The launch of Grokipedia, an AI-generated encyclopedia developed by xAI, was presented as a response to perceived ideological and structural biases in Wikipedia, with the goal of producing more “truthful” entries using the Grok large language model. However, whether such an AI-driven alternative can systematically correct the biases and limitations of human-edited platforms remains unclear. Here we conduct a large-scale computational comparison of 17,790 matched article pairs drawn from the 20,000 most-edited English Wikipedia pages. We find that Grokipedia pages are longer, more syntactically complex, and contain fewer references per word. Similarity measures across the two platforms reveal a bimodal structure: many Grokipedia articles closely resemble their Wikipedia counterparts, while a considerable subset diverges. Political bias differences emerge primarily within the divergent subset, where Grokipedia shows a relative rightward shift in the ideological orientation of frequently cited news media sources, particularly in articles related to religion and history. These patterns indicate selective, topic-specific divergence rather than a uniform debiasing of Wikipedia content. More broadly, AI-generated encyclopedias may depart from established editorial norms by favoring narrative expansion over citation-based verification, raising questions about transparency, provenance, and the governance of knowledge in automated information systems.
Wave packets, “negative times” and the elephant in the room
Multiscale fatigue crack initiation in hierarchical additively manufactured alloys
Bioinspired hierarchical microstructures offer a route toward engineered fatigue resistance in additively manufactured alloys. However, it remains unclear how discrete structural constituents independently govern damage accumulation, particularly during the critical fatigue initiation regime where short cracks strongly interact with local microstructure. Here, we investigate multiscale fatigue initiation in a dual-phase, nanolamellar AlCoCrFeNi 2.1 high-entropy alloy. By comparing microscale specimens that isolate the nanolamellar structure against macroscale specimens containing the full melt-pool architecture, we identify size-dependent fatigue initiation mechanisms. We find that failure is dictated by nanolamellar interfaces at the microscale, whereas mesoscale melt pool boundaries serve to initiate fatigue at the macroscale. This mechanistic shift is accompanied by a transition from macroscale quasi-brittle failure to microscale plasticity-driven crack extension. Our results provide a physical framework for understanding how structural hierarchy governs the transition from discrete microstructural deformation to continuum fatigue fracture behavior, informing the design of damage-tolerant, additively manufactured alloys.
Silicon-based agent alleviating intestinal ischemia/reperfusion injury in mice by inhibiting ferroptosis via activating AMPK-Sirt1 signaling pathway
Streamlined optical training of large-scale modern deep learning architectures with direct feedback alignment
Modern deep learning relies nearly exclusively on dedicated electronic hardware accelerators. Photonic approaches, with low consumption and high operation speed, are increasingly considered for inference but, to date, remain mostly limited to relatively basic tasks. Simultaneously, the problem of training deep and complex neural networks, overwhelmingly performed through backpropagation, remains a significant limitation to the size and, consequently, the performance of current architectures and a major compute and energy bottleneck. Here, we experimentally implement a versatile and scalable training algorithm, called direct feedback alignment, on a hybrid electronic-photonic platform. An optical processing unit performs large-scale random matrix multiplications, which is the central operation of this algorithm. We perform optical training of modern deep learning architectures, including Transformers, with more than 1B parameters, and obtain good performances on language, vision, and diffusion-based generative tasks. We study the scaling of the training time and demonstrate a potential advantage of our hybrid opto-electronic approach for ultra-deep and wide neural networks, thus opening a promising route to sustain the exponential growth of modern artificial intelligence beyond traditional von Neumann approaches.
Effect of dual task ladder training on physical function among badminton players
NAT10/ac <sup>4</sup> C drives intrahepatic cholangiocarcinoma by suppressing transposable elements via chromatin remodeling
Intrahepatic cholangiocarcinoma (ICC) poses a significant clinical challenge due to its insidious onset, aggressive biological behavior, and propensity for early metastasis, contributing to a dismal 5-y survival rate of less than 10%. Despite advances in understanding the dynamic changes in gene regulatory networks and chromatin landscapes during tumorigenesis, the functional interplay between RNA epitranscriptomic modifications and nuclear events in ICC remains poorly elucidated. Here, we identify N -acetyltransferase 10 (NAT10), the writer for N 4 -acetylcytidine (ac 4 C) mRNA modification, as a critical regulator of ICC malignancy. Integrated multiomics profiling reveals that NAT10-mediated ac 4 C modification enhances the mRNA stability of chromatin assembly factor 1 subunit A (CHAF1A), a key chromatin regulator. Mechanistically, the NAT10–ac 4 C–CHAF1A axis robustly and epigenetically suppresses the expression of the nuclear transposable element HERV9NC, leading to diminished double-stranded RNA accumulation. This epigenetic silencing not only fuels ICC proliferation and migration but also attenuates intrinsic innate immune responses, thereby fostering an immunosuppressive tumor microenvironment characterized by reduced cytotoxic T cell infiltration and impaired tumor surveillance. Pharmacological inhibition of NAT10 with small-molecule compounds demonstrated robust therapeutic efficacy in both patient-derived xenograft and orthotopic tumor transplantation models of ICC. Collectively, our study unveils NAT10 as a master integrator of RNA epitranscriptomic reprogramming and nuclear chromatin dynamics in ICC, providing interesting mechanistic insights into the molecular basis of ICC progression. We also establish NAT10-ac 4 C modification as a druggable vulnerability, offering a promising therapeutic strategy for this aggressive malignancy.
DnaA binding to oriCII regulates transcription from Pseudomonas aeruginosa gidAB-parAB locus linked to the chromosome segregation and streptomycin resistance
Abstract In many bacteria, the DnaA protein, responsible for chromosome replication initiation, also acts as a transcription factor regulating its own gene expression and the expression of other loci. Here, we show that in the opportunistic human pathogen Pseudomonas aeruginosa , DnaA directly regulates the gidAB-parAB operon. DnaA binds to the DnaA boxes preceding the promoter located upstream of the gidA gene within oriCII and deletions in this region impair gidAB-parAB expression and reduce intracellular ParB levels. Additional regulatory elements, including three internal promoters, further contribute to the multilayered regulatory scheme of the gidAB-parAB operon. Since the products of gidA and gidB (glucose-inhibited cell division proteins) are important for cell growth, division, and survival, and those of parA and parB are central to chromosome segregation, regulation of this operon by DnaA suggests a functional link between replication initiation and the regulation of essential cell-cycle-related processes. These findings indicate a regulatory role for the oriCII region and a new function for DnaA in coordinating the gene expression required for proper replication, chromosome segregation, and bacterial growth in P. aeruginosa . Our data are also clinically significant, demonstrating that P. aeruginosa gidB gene disruption results in higher levels of streptomycin resistance.
Microstructural evolution and nanograin coherence in VO2 thin films grown by pulsed laser deposition
Abstract Vanadium dioxide (VO 2 ) thin films exhibit a reversible semiconductor–metal transition near room temperature, and their performance is strongly governed by microstructural and interfacial factors. In this study, VO 2 thin films were deposited on Z-cut quartz substrates by pulsed laser deposition under varying oxygen partial pressures and substrate temperatures. Plan-view transmission electron microscopy (TEM) techniques such as selected-area electron diffraction (SAD) and nanobeam diffraction (NBD) as well as confocal Raman spectroscopy were employed to examine the microstructure and crystallographic features of the films. The VO 2 films display a dense, polygonal morphology, composed of faceted grains with characteristic sizes of 50–200 nm. These polygonal grains are formed during deposition in the high-temperature metallic R phase and transform upon cooling into semi-coherent VO 2 M1 nanograins with minimal lattice mismatch. The observed morphology is attributed to surface and interface energy anisotropy acting across the amorphous SiO 2 interlayer, which promotes random in-plain orientation. Confocal Raman mapping further supports phase uniformity and orientation variation across the grains. Overall, this work provides new insight into the mechanisms governing polygonal grain formation and coherence within VO 2 thin films on quartz, highlighting how interface-energy-driven growth can stabilize ordered microstructures even in the absence of epitaxial constraint.
Regulated development of cannibalistic supergiant cells in the ciliate <i>Euplotes gigatrox</i>
Virtually all paradigms in developmental biology apply to differentiating cells and tissues within multicellular animals and plants. However, unicellular eukaryotes, which must simultaneously perform all activities necessary for a cell as well as an organism, also form complex and specialized structures, using exclusively subcellular processes. Here, we describe a ciliate ( Euplotes gigatrox sp. nov.) undergoing drastic morphological transformations within a genetically uniform population, the most spectacular being the appearance of “supergiants” that increase in size, change shape, and modify their locomotion and feeding behavior to cannibalize clonal relatives. We explore supergiant formation from the perspective of life cycle, ecological strategy, and gene expression, demonstrating that supergiants are a distinct, regulated, transcriptionally unique stage. Differentiation appears to depend on internal and external conditions, suggesting that regulatory loops have evolved to ensure coupling between environmental and physiological conditions. This system provides a blueprint for approaching both cell differentiation and functional ecology in unicellular organisms, which might open new avenues for the generalization and contextualization of known morphogenetic mechanisms, as well as the discovery of new ones.
Interaction between systemic arterial reservoir behavior and cerebrovascular vasoreactivity during acute controlled hypocapnia
Educational policies can strengthen climate coalitions
Building public support for ambitious climate policies is a central challenge for governments seeking to decarbonize their economies. Many climate change mitigation policies impose visible material costs on citizens, and governments have limited fiscal capacity to deploy compensatory measures. Education is often used as a tool to build public awareness about climate change, but its effect on support for climate policies is not well understood. We evaluate the effects of a climate education policy through the study of a real-world large-scale educational intervention: a 3-h interactive workshop which has so far been implemented in over 500 French universities. We employed a randomized control trial reaching 1,845 students across 167 workshops. Students who took the workshop expressed 7 percentage points higher support for costly climate policies, including a beef tax, short-haul flight ban, and meat-free university canteen, compared with the control group. The workshop increased beliefs in the effectiveness of these policies and elicited more positive emotions about climate action. Evidence from a subsample of follow-up survey respondents suggests these effects may persist for at least 6 wk. We find no evidence that the workshop increases willingness to donate to a climate NGO. Overall, the results suggest that well-designed climate education can play a role in broadening public coalitions for ambitious climate policies by strengthening perceived policy effectiveness and support for costly policies.
Changing landscape of 16 S-RMTase-mediated aminoglycoside resistance in clinical Klebsiella pneumoniae isolates from Chile between 1997 and 2023
Cysteine thiol-to-sulfonate oxidation induces unfolding for the functional switching of the extracellular HMGB1 protein
Oxidation of cysteine thiols to sulfonate groups (–SO 3 – ) by reactive oxygen species can regulate protein function. Near the end of inflammation, this modification in the extracellular HMGB1 protein abolishes its proinflammatory activity. Using NMR spectroscopy, we investigated how thiol-to-sulfonate oxidation switches HMGB1’s function. Our data show that the oxidation of cysteine 106 (C106) induces unfolding of the HMGB1 B-box domain. In contrast, other chemical modifications, such as S-glutathionylation, at the same cysteine did not have this effect, highlighting the unique impact of thiol-to-sulfonate oxidation. Employing 13 C direct-detected NMR, we characterized the oxidized B-box domain. NMR data confirmed global unfolding but revealed residual α-helical propensity near the second and third helices. NMR paramagnetic relaxation enhancement data revealed electrostatic impacts of the C106 thiol-to-sulfonate oxidation. To test whether unfolding is driven by negative charge in a hydrophobic environment, we analyzed the C106D variant, as aspartate electrostatically mimics cysteine sulfonate. However, the C106D variant remained folded, even though NMR confirmed a negative charge at D106. Further NMR experiments showed that the –SO 3 − group at residue 106 drastically slows down the protein folding kinetics, compared with the –COO − group at the same position, suggesting that –SO 3 − introduces a large desolvation penalty for protein folding. This study illuminates protein unfolding via thiol-to-sulfonate oxidation of a cysteine residue in a hydrophobic environment as a mechanism for protein functional switching. Since HMGB1 is a therapeutic target for inflammatory diseases, understanding this inactivation mechanism offers insight for designing covalent inhibitors.
Enhanced fuel economy and emission reduction in parallel HEV powertrains through swarm and deterministic algorithms
Deciphering and targeting the pathogenic circuit of nonlytic hepatitis E virus infection using macrophage-augmented organoids
The pathophysiology caused by nonlytic viral infections is complex, often driven by macrophage-mediated immune responses that lead to hyperinflammation and collateral tissue damage. To conceptualize this complexity, we propose a pathogenic circuit comprising three interconnected nodes: nonlytic infection, inflammation, and immune-mediated cell death. To investigate this circuit, we combined hepatitis E virus (HEV), a prototypical nonlytic RNA virus, and macrophage-augmented organoids (MaugOs) as an innovative model. Here, we report successful recapitulation of the pathogenic circuit induced by HEV infection in MaugOs. Nonlytic HEV infection triggered robust inflammatory responses and subsequent cell death involving pyroptosis, apoptosis, and necroptosis pathways. By pharmacologically targeting individual circuit nodes as well as individual cell death pathways, we have dissected their interactions and identified potential therapeutic targets. Finally, we developed multitarget strategies by simultaneously targeting two or three nodes through rational drug combinations to effectively disrupt the pathogenic loop. Collectively, these findings elucidate the architecture of the pathogenic circuit underlying nonlytic HEV infection in MaugOs and inform the development of innovative multitarget therapies for improved disease treatment.