Molecular Sciences Institute

Given the profound industrial relevance of metal surfaceetching,we performed a detailed density functional theory investigation ofthe nature of intermolecular interactions between the O2 (and Cl2) etchant(s) and the ruthenium (Ru) (and tantalum(Ta)) surface(s). We assessed the formation energies of the MOx and MClx familiesof molecular entities (where M denotes Ta or Ru and x spans from 1to 6), in the gas phase, along with the landscapes of adsorption anddesorption energies for Ox/MOx and Clx/MClx on the metal surfaces, to offer valuable insightsinto the energy profiles required for the fundamental understandingof O2- and Cl2-plasma environments. Our findingsunveil that molecular RuO4 may stand out as a prime byproductfor etching the Ru surface when exposed to the O2-plasma,while etching Ru by the Cl2 plasma is much more energeticallychallenging. Conversely, TaCl3, TaCl4, and TaCl5 may emerge as the predominant etching byproducts for theTa surface in the Cl2 plasma environment. The climbingimage nudged elastic band calculations carried out for analyzing detailedetching reaction paths reveal that the desorption of RuO4 from the Ru surface is a rate-limiting phenomenon, characterizedby the formation of a metastable intermediate state [RuRuO4], effectively reducing the energy needed for etching.

Higher abundance of oral human papilloma virus (HPV), Porphyromonas gingivalis (Pg) and Fusobacterium nucleatum (Fn) correlate with worse survival of head and neck squamous cell carcinoma (HNSCC). One-third of males globally are HPV-positive, one-fifth have high-risk HPV-16 and is transmitted through oral sex. In our ex vivo clinical study of HNSCC patients, HPV ELISA detected viruses in 100% of saliva and 75% of oral-rinse samples (n = 44). Cell culture studies showed 1000-fold higher Pg/Fn in their saliva and 100-fold higher in oral-rinse samples than non-cancer control participants. Bean-lectin (FRIL) gum (trapped) aggregated 93% of HPV in saliva and 80% in oral-rinse samples in ELISA. Single dose of bean gum + protegrin-1 (antimicrobial peptide) reduced Pg/Fn > 99% in saliva and oral-rinse samples (n = 42). Although protegrin was effective against anaerobic Pg/Fn, it did not kill capsule forming bacteria including Streptococci, providing selectivity and protection of oral commensal bacteria. These findings from ex vivo clinical studies support potential value of advancing these biologics to clinical trials as adjuncts to current therapeutic strategies or as prophylaxis to control pathogenic microbes associated with HNSCC.

Von Neumann architectures face inherent limitations, prompting the rise of neuromorphic computing as a promising alternative. Artificial synapses play a crucial role in replicating the dynamic plasticity of biological synapses, enabling efficient information processing and adaptive learning. We developed a composite nanofilm device composed of denatured bovine serum albumin (dBSA) and molybdenum disulfide (MoS2) using a liquid–liquid interfacial assembly technique. The dBSA-MoS2 current response to humidity is 13.12 times higher than that of pure MoS2. At a relative humidity of 80%, the dBSA-MoS2 device exhibits more pronounced negative differential resistance and hysteresis phenomena than pure MoS2, and the resistance switching ratio of the dBSA-MoS2 device is 3.20- and 2.64-fold higher than those of MoS2 at 0.72 and 1.52 V, respectively. The incorporation of dBSA creates additional pathways for proton transport, which not only improves the electrical properties of dBSA-MoS2 but also enables it to emulate biological synaptic functions. Consequently, the dBSA-MoS2 device was used to simulate the biological synaptic behaviors: long-term potentiation and long-term depression. When integrated into a three-layer artificial neural network for handwritten number recognition, the dBSA-MoS2 device achieved an impressive accuracy of 92.30%. These findings underscore the potential of dBSA-MoS2 composites as next-generation artificial synapses, offering significant promise for neuromorphic computing and future bioelectronic applications.

Photocatalytic H2 generation through water splitting faces inherent challenges, including the necessity for gas product separation and thermodynamic limitations of the oxygen evolution reaction. Herein, we propose a novel strategy to circumvent these obstacles by integrating the hydrogen evolution half-reaction with value-added furfurylamine oxidative transformation in a unified photocatalytic system. A polyoxometalate-supported single-atom photocatalyst demonstrates exceptional performance in synchronously driving both redox processes under photoexcitation. Systematic investigations reveal that photogenerated electrons efficiently reduce protons to generate H2 (evolution rate: 494 umol·g–1·h–1), while the corresponding holes mediate selective oxidation of furfurylamine to N-furfurylidenefurfurylamine with 99% selectivity. Through advanced structural characterization (X-ray single crystal diffractometer) and density functional theory, we establish that the atomically dispersed metal centers coordinated with lacunary polyoxometalate frameworks create open active sites that significantly enhance interfacial charge transfer kinetics (improved by 3.7 times compared to nanoparticle counterparts). This synergistic configuration not only suppresses electron–hole recombination but also provides optimal adsorption configurations for organic substrates. To our knowledge, this work represents the first demonstration of constructing a closed redox cycle through coupled hydrogen production and biomass valorization using polyoxometalate-anchored single-atom photocatalysts.

We designed a molecular switch based on a cavitand and pyrene. The controllable switching properties of the cavitand paired with flexible chains are some of the best combinations for achieving robustness in complex environments. A rigid chain cavitand was also synthesized as a control, and its single crystals with high molecular weights were obtained.

Natural killer (NK) cell homeostasis and effector functions require context-dependent signaling via numerous receptors, including the interleukin-15 receptor (IL-15R). Post-translational modifications can regulate receptor signaling, impacting receptor turnover and trafficking. Core fucosylation is one such modification known to impact receptor expression and is uniquely mediated by fucosyltransferase 8 (FUT8). We identified FUT8 as an essential gene required for IL-15R responsiveness in a human NK cell genome-wide CRISPR screen. To further validate core fucosylation in IL-15R signaling and NK cell biology, mice lacking Fut8 in NK cells (Fut8fl/flNcr1cre/+) were generated. The loss of core fucose in murine NK cells resulted in severe NK cell lymphopenia, with a reduction in IL-15Rβ (IL-2RB/CD122) expression, impairing in vivo homeostatic proliferation. The loss of FUT8 also decreased NK cell cytotoxicity, tumor immunity, and early viral immunity. Taking these results together, we have identified FUT8 as a key modulator of NK cell biology by regulating their development, IL-15R expression, and signaling.

Optogenetic gene therapy is a promising mutation-independent treatment that aims to restore visual perception in patients blinded by retinal diseases that cause photoreceptor degeneration. Still, low sensitivity or slow kinetics of currently utilized optogenetic proteins limit the efficacy of such approaches. Here, we evaluated the therapeutic potential of three channelrhodopsin variants: ChRmine, from the algae Rhodomonas lens, ChRmine-T119A, a faster-closing ChRmine variant, and ChroME2s, a second-generation Chronos-based opsin.We expressed these opsins in retinal ganglion cells of rd1 mice, a model of severe retinal degeneration. Single cell electrophysiology demonstrates opsin’s large sensitivity to a range of light intensities as well as opsin-expressing retinal ganglion cells generated action potentials in response to light stimulation. Behavioral tests showed ChRmine-T119A’s efficacy at 360 lux compared to unmodified ChRmine and ChroME2s. ChRmine and ChroME2s did restore light perception at higher light intensities. Additionally, our dose–response study with ChRmine-T119A revealed that lower viral titers were more effective at restoring light sensitivity. Our study demonstrates that these ChRmine- and ChroME-based opsins can enhance vision in late-stage blinding diseases.

Since it was firstdescribed in the 1950s, there has been no explanationof the extraordinarily high selectivity for the formation of the thermodynamicallyless stable cis-2-alkenoic acids from the treatmentof α,α′-dibromoketones with aqueous base. Veryearly on, it was suggested that such specificity must arise via “concertedprocesses” but without elaboration. Provided here is a detailedmechanistic description of the reaction based on computational insight,identifying a stereospecific first step for the ring closure to a3-ring cyclopropanone, which follows Woodward–Hoffmann rulesfor a two-electron allylic cation, accompanied by departure of a bromineatom in an SN2-like process. The stereochemistry establishedin this step persists in the second step, which involves ring openingof the 3-ring to give a cis-2-alkenoic acid. Othermechanistic pathways have higher energies. With this new understanding,further synthetic applications of the Rappe Rearrangement are suggested.