Journals
2025 EN
Gemperli Kat · Lu Xinguo · Chintalapati Keerthana
+16 more
Objective Mouse models of genetic dystonias have demonstrated abnormal striatal cholinergic interneuron excitability, but do not consistently demonstrate subjective dystonic features. To determine whether striatal cholinergic interneuron excitation can cause potentially dystonic motor behaviors, we first determined features correlated specifically with dystonia severity in people and then determined whether these features emerged in mice following striatal cholinergic interneuron excitation. Methods Eight movement disorders experts rated dystonia severity in 193 videos of people with cerebral palsy doing a seated task. Leg adduction variability metrics, which are known to correlate with leg dystonia severity during gait, were quantified in these videos of seated tasks. Metrics significantly associated with leg dystonia severity during seated tasks in people were then quantified in mice and compared between mice who underwent chemogenetic striatal cholinergic interneuron excitation (n = 17) and mice who did not (n = 17). Results Leg adduction variability correlated well with experts' leg dystonia severity scores in people. Leg adduction variability was also significantly increased in mice that underwent striatal cholinergic interneuron excitation compared to mice that did not ( p < 0.05). This difference was not present with acute excitation and emerged only after 14 days of ongoing excitation. Interpretation We demonstrate that leg adduction variability correlates with leg dystonia severity in people with cerebral palsy and that chronic, but not acute, striatal cholinergic interneuron excitation can cause leg adduction variability in mice. These results support targeting striatal cholinergic interneurons for dystonia drug development and demonstrate the potential value of using quantifiable leg adduction metrics to study dystonia pathophysiology. ANN NEUROL 2025;98:726–740
Journals
2025 EN
Barnum Lindsay · Samandari Mohamadmahdi · Suhail Yasir
+7 more
Upon injury, regenerating skin is metabolically active and requires oxygen for physiological processes related to wound healing. Such processes can be halted in hypoxic conditions common in chronic wounds. Microneedle arrays (MNAs) have been demonstrated to improve therapeutic delivery and wound healing. Recently, few studies have explored the use of oxygen‐releasing MNAs; however, they involve complex manufacturing and handling and fail to eliminate cytotoxic byproducts. To address these challenges, biodegradable and mechanically robust gelatin methacryloyl‐based MNAs are developed that can penetrate the tissue and release oxygen upon exposure to interstitial fluid and wound exudates. The oxygen release rate and biocompatibility of the developed MNAs with different compositions are evaluated and optimized. Interestingly, in vitro studies demonstrate that the optimized compositions can release oxygen at therapeutic levels and significantly increase viability of chronically hypoxic cells to match that of normoxic cells. In vivo studies further confirm that the optimized oxygen‐generating MNAs do not cause any harm or impair healing in a murine model of acute skin injury. Additionally, transcriptomic analysis reveals upregulation of key pathways related to fibroblast motility, lipid metabolism, and a marked reduction in inflammatory signaling, all of which contribute to improved wound healing. The developed strategy can introduce new opportunities in elimination of hypoxia and therefore treatment of chronic wounds.
Journals
2025 EN
Michael Praveesuda L. · Lam Yuen Ting · Mitchell Timothy C.
+8 more
This study presents a versatile perfusion bioreactor system designed to evaluate endothelialization on electrospun polycaprolactone (PCL)–gelatin vascular grafts under controlled flow conditions that mimic physiological and pathological shear stress. The bioreactor enables direct assessment of endothelial cell behavior on 3D graft structures, providing a more physiologically relevant platform compared to traditional static cultures. Electrospun PCL–gelatin grafts demonstrate uniform endothelial cell coverage when exposed to physiological shear stress (>10 dyn cm −2 ), with cells displaying alignment in the direction of flow. Under these conditions, endothelial cells upregulate endothelial nitric oxide synthase and platelet endothelial cell adhesion molecule‐1, markers associated with vascular homeostasis, anti‐inflammatory activity, and enhanced endothelial migration. In contrast, grafts subjected to pathological shear stress (<5 dyn cm −2 ) exhibit increased expression of intercellular adhesion molecule‐1, promoting monocyte adhesion and a proinflammatory response. These findings highlight the importance of physiological flow dynamics in regulating endothelial function and demonstrate the value of this bioreactor system as a platform prior to preclinical evaluation of vascular grafts. By providing a more accurate in vitro model, this system may accelerate the development of bioengineered vascular grafts with improved clinical outcomes.
Journals
2025 EN
Guo Chaofei · Liu Tiancun · Wang Zhenzhen
+5 more
Abstract Although the catalytic activity is heavily reliant on the electronic structure of the catalyst, understanding the impact of electron spin regulation on electrocatalytic performance is still rarely investigated. This work presents a novel approach involving the single‐atom coordination of cobalt (Co) within metalloporphyrin‐based three‐dimensional covalent organic frameworks (3D‐COFs) to facilitate the catalytic conversion for sodium‐iodine batteries. The spin state of Co is modulated by altering the oxidation state of the porphyrin‐centered Co, achieving optimal catalysis for iodine reduction. Experimental results demonstrate that Co II and Co III are incorporated into the 3D‐COFs, exhibiting spin ground states of S=1/2 and S=0, respectively. The low spin state of Co III is favorable to hybridize with the sp 3d orbitals of I 3 − , thus facilitating the conversion of I 3 − to I − . Density‐functional theory (DFT) calculations further reveal that the presence of Co III enhances iodide adsorption and accelerates the formation of NaI in 3D‐COFs‐Co III , thereby promoting its rapid kinetic behaviors. Notably, the I 2 @3D‐COFs‐Co III cathode achieves a high reversible capacity of 227.7 mAh g −1 after 200 cycles at 0.5 C and demonstrates exceptional cyclic stability, exceeding 2000 cycles at 10 C with a minor capacity fading rate of less than one 0.01 % per cycle.
Journals
2025 EN
Kmiec Steven · Ruoff Erick · Manthiram Arumugam
Abstract Sodium‐based batteries are gaining momentum due to the abundance and lower cost of sodium compared to lithium. Solid‐state sodium batteries can also provide further safety advantages. However, sodium‐based solid‐state electrolytes (SSEs) that meet all the rigorous requirements, such as high ionic conductivity, oxidative stability with the cathode, and ease of processability, are lacking. We present here a new class of sodium‐based oxyhalide electrolytes NaNbCl 6‐2x O x with a facile mechanochemical synthesis. The oxyhalide NaNbCl 4 O exhibits close to two orders of magnitude higher ambient‐temperature sodium‐ion conductivity (1.03×10 −4 S cm −1 ) compared to the halide counterpart NaNbCl 6 (3×10 −6 S cm −1 ). Structural motifs unique to the oxygen content in NaNbCl 6‐2x O x are identified with 23 Na and 93 Nb magic angle spinning nuclear magnetic resonance (MAS NMR) spectroscopy and x‐ray diffraction (XRD). Solid‐state sodium batteries assembled with NaNbCl 4 O electrolyte and the cobalt‐ and nickel‐free layered Na 0.70 Fe 0.3 Mn 0.65 Al 0.05 O 2 cathode exhibit a maximum discharge capacity of 155 mAh g −1 with good cycle life at ambient temperature.
Journals
2025 EN
Roshanzadeh Amir · Medeiros Hyllana C. D. · Herrera Christopher K.
+8 more
Abstract Photodynamic therapy (PDT) has emerged as a promising targeted treatment for cancer. However, current PDT is limited by low tissue penetration, insufficient phototoxicity (toxicity with light irradiation), and undesirable cytotoxicity (toxicity without light irradiation). Here, we report the discovery of cyanine‐carborane salts as potent photosensitizers (PSs) that harness the near‐infrared (NIR) absorbing [cyanine + ] with the inertness of [carborane − ]. The implementation of [cyanine + ] [carborane − ] salts dramatically enhance cancer targeting of the PSs and decrease cytotoxicity. We characterize the cellular uptake of the cyanine‐carborane PSs, organelle localization, generation of reactive oxygen species (ROS) with the ability to cogenerate multiple ROS species, suppression of pro‐metastatic pathways, and activation of apoptotic pathways. We further demonstrate the ability of optimized PSs to eliminate tumors in vivo using an orthotopic mouse model of breast cancer. These newly developed [cyanine + ] [carborane − ] salt PSs introduce a potent therapeutic approach against aggressive breast cancer while decreasing side effects.
Journals
2025 EN
Achouba Yanis · Peres Basile · Ascoët Steven
+16 more
Abstract Natural peptides from animal venoms effectively modulate ion channel activity. While photoswitches regulate small compound pharmacology, their application to natural peptides rich in disulfide bridges and active on ion channels is novel due to larger pharmacophores. A pilot study integrating azobenzene photoswitches into charybdotoxin (ChTx), known for blocking potassium channels is initiated. Two click‐chemistry‐compatible azobenzene are synthesized differing in length and amide orientation (Az 1 & Az 2 ). Az 1 is grafted onto ChTx at various amino acid positions using L‐azidohomoalanine mutation. ChTx monomers outperformed dimers, particularly with azobenzene at position 14, by exhibiting optimal photoswitching activity. In the cis configuration, Az 1 altered ChTx's pharmacophore, reducing potassium channel blockage, while conversely, Az 2 increased ChTx potency. This study pioneers photoswitch application to complex peptides, leveraging structure‐activity relationships. Successful integration depends on precise azobenzene positioning and chemical grafting guided by SAR insights. This advancement underscores the adaptability of photoswitch technology to intricate peptide structures, offering new avenues for pharmacological modulation.
Journals
2025 EN
Guan Xiushuai · Wang Xiaokun · Zhang Xiaochao
+3 more
Abstract The thermodynamic stability and intrinsic kinetic inertia of CO 2 present a critical challenge for its effective activation in the synthesis of high‐value dimethyl carbonate (DMC). In this work, we report the fabrication of novel O‐Ce‐O vacancy clusters (V O‐Ce‐O ) incorporated into CeO 2 nano‐sheets with a near single‐unit‐cell thickness to construct atomically adjacent multiple active sites on their surfaces. These active sites significantly enhance the activation of both CO 2 and CH 3 OH. Impressively, the as‐prepared CeO 2 with V O‐Ce‐O catalyst exhibits an excellent DMC yield of 31.2 mmol g −1 , surpassing previously reported Ce‐based catalysts under equivalent reaction conditions. Experimental results and theoretical calculations reveal that oxygen vacancy increases the reducibility of lattice oxygen, facilitating CO 2 activation, while cerium vacancies weaken the *CH 3 O adsorption, promoting the coupling reaction between *CH 3 O and *CO 2 to form the intermediate (*CH 3 OC(O) 2 ). Notably, the formation of vacancy clusters reduces the energy barrier for the rate‐controlled step (*CH 3 OC(O) 2 dissociation to *CH 3 OCO), thereby boosting the DMC yield. Our new findings provide valuable insights into surface engineering and active site modulation of cerium‐based catalysts, offering a viable pathway for green resource utilization of CO 2 .
Journals
2025 EN
Sun Yue · Abella Laura · Emge Thomas J.
+8 more
Abstract Endohedral metallofullerenes are chemically more inert compared to empty fullerenes, primarily due to their intramolecular electron transfer. In this work, we report an inverse electron demand Diels–Alder (IEDDA) reaction on M 3 N@C 80 (M=Lu, Sc), where they show significantly higher reactivity than empty fullerenes. The molecular structures of the [4+2] cycloadducts were unambiguously characterized. Moreover, the cycloadducts can fully revert to pristine M 3 N@C 80 via retro‐cycloaddition upon thermal treatment. With the unusual reactivity and reversibility, the IEDDA reaction enables an effective separation approach for metallofullerenes from their soot extracts, opening path to efficient and economical scale‐up synthesis of metallofullerenes in laboratory and industrial settings.
Journals
2025 EN
Chen Zixuan · Ming Hongwei · Li Zhi
+9 more
Abstract Here, we investigate PbSnS 2 , a wide band gap (1.13 eV) compound, as a promising thermoelectric material for power generation. Single crystal X‐ray diffraction analysis reveals its 2D‐layered structure, akin to the GeSe structure type, with Pb and Sn atoms sharing the same crystallographic site. The polycrystalline PbSnS 2 exhibits an intrinsically ultralow lattice thermal conductivity ( κ lat ) of 0.37 W m −1 K −1 at 573 K. However, the low carrier concentration ( n ) leads to suboptimal electrical conductivity ( σ ), capping the ZT value at 0.1. Accordingly, the halogen elements (Cl, Br, and I) are employed as the n‐type dopants to improve the n . The DFT results indicate a significant weakening of Pb/Sn─S bonds upon halogen‐doping, contributing to the observed reduction in κ lat . Our analysis indicates the activation of multiconduction band transport driven by halogen substitution. The PbSnS 1.96 Br 0.04 has a high power factor of five times that of intrinsic PbSnS 2 . Halogen‐doping weakens the Pb/Sn─S bonds and enhances the phonon scattering, leading to an ultralow κ lat of 0.29 W m −1 K −1 at 873 K for PbSnS 1.96 Br 0.04 . Consequently, PbSnS 1.96 Br 0.04 achieved a maximum ZT value of 0.82 at 873 K.