Journals
2025 EN
Lehrer Steven · Rheinstein Peter H.
Abstract Background Type 2 diabetes (T2D), but not type 1, protected against amyotrophic lateral sclerosis (ALS). In T2D serum insulin is normal or elevated in the early stages. Type 1 diabetes, characterized by a total lack of insulin, is associated with an increased risk of ALS. The antidiabetic metformin also protects against ALS. Connexin 43 (Cx43), an astrocyte protein, operates as an open channel via which toxic substances from astrocytes reach motor neurons to cause ALS. Methods In the current study we analyzed FDA MedWatch data to determine whether insulin or metformin could reduce the risk of ALS. We performed in silico molecular docking studies and molecular dynamics simulation with Cx43 to determine if insulin or metformin dock within the Cx43 channel and can block it effectively, again reducing risk of ALS. Results In MedWatch, Insulin use is associated with a significantly reduced risk of ALS (Proportional Reporting Ratio 0.401). Metformin use is associated with a significantly reduced risk of ALS (PRR 0.567). The Human insulin heterodimer docked within center of the Cx43 channel, effectively blocking it. Molecular dynamics simulation showed that the block is highly stable and may be responsible for the protective effect of T2D on ALS. Metformin docks within the Cx43 channel, but the relatively small size of the metformin molecule may not allow it to obstruct the passage of toxic substances from astrocytes to motor neurons. Conclusion MedWatch data indicate that both insulin and metformin reduce risk of ALS. The results of our in silico docking study and molecular dynamics simulation corroborate our previous findings with Cx31. Insulin docks within the open hemichannel of hexameric Cx43, potentially blocking it. Molecular dynamics simulation showed that the block is stable and may be responsible for the protective effect of T2D and insulin on ALS.
Journals
2025 EN
Street Steven T. G. · Shteinberg Ekaterina · Hernandez Juan Diego Garcia
+4 more
Abstract Stealth precision polymer nanofibers show great promise as therapeutic delivery systems. However, existing systems are largely limited to poly(ethylene glycol) (PEG) and suffer from challenging functionalization, hampering their translation. This work develops a modular, easily functionalizable platform for biocompatible stealth nanofibers based on a combination of ring‐opening polymerisation (ROP), photoinduced electron/energy transfer reversible addition–fragmentation chain transfer (PET‐RAFT) polymerisation, and crystallization‐driven self‐assembly (CDSA). Low length‐dispersity poly(fluorenetrimethylenecarbonate)‐ b ‐poly(N‐(2‐hydroxypropyl) methacrylamide) (PFTMC‐ b ‐PHPMA) nanofibers may be produced in a single‐step via CDSA, with a length that is dependent on the PHPMA DP n . Separately, living CDSA leads to nanofibers with length control between 30 nm and ca. 700 nm. Incorporation of fluorescein into the PET‐RAFT polymerization results in fluorescent PFTMC‐ b ‐PHPMA block copolymers that can undergo CDSA, forming fluorescent nanoparticles for preliminary cell studies. PFTMC‐ b ‐PHPMA nanofibers exhibited minimal toxicity to cells as well as limited cellular association, in line with previous studies on neutral polymer nanofibers. In comparison, PFTMC‐ b ‐PHPMA nanospheres exhibited no cellular association. These results indicate that the unique shape and core‐crystallinity of PFTMC‐ b ‐PHPMA nanofibers ideally positions them for use as therapeutic delivery systems. Overall, the results described herein provide the basis for a modular, easily functionalizable platform for precision stealth polymer nanofibers for a variety of prospective biomedical applications.
Journals
2025 EN
Biswas Souvick · McAnally Mason · Chambreau Steven D.
+3 more
Abstract Hypergolic ionic liquids (HILs) represent a critical pool of reactive ionic liquids which ignite spontaneously in absence of oxygen when mixed with an oxidizer such as white fuming nitric acid (WFNA, HNO 3 ) or hydrogen peroxide (H 2 O 2 ). These HILs have emerged as greener alternatives to the toxic hydrazine family of fuels for operations in space under anaerobic conditions. Here, we report on the unusual atmospheric ignition chemistry of the 1‐ethyl‐3‐methylimidazolium cyanoborohydride ([EMIM][CBH])‐H 2 O 2 bipropellant while comparing with the parent hypergolic reaction by exploiting a chirped‐pulse triggered droplet merging technique in an ultrasonic levitation apparatus under controlled environment. Significant enhancements of the ignition performance and noticeable differences of product distribution in the simulated atmosphere containing molecular oxygen are revealed. The critical mechanistic role of the surrounding oxygen plausibly involves the reaction with a suitable intermediate (iminomethyl)boronic acid, [(HO) 2 BCH=NH] formed in the initial reactions of the IL and H 2 O 2 which eventually generates catalytic hydroperoxyl (⋅HO 2 ) and hydroxyl (⋅OH) radicals ‐ further promoting the ignition reaction. This systematic case study conceptually demonstrates that under atmospheric conditions, well‐defined HIL ‐ oxidizer combinations provide excellent ignition performance and effectively be used as universal fuel both in space and in the terrestrial atmosphere simplifying the multistage propulsion system.
Journals
2025 EN
Carì Gianluca · Saito Riku · Zorba Leandros P.
+4 more
Abstract The development of efficient and easily accessible Pd(II)‐NHC (NHC = N‐heterocyclic carbene) pre‐catalysts is presented. A series of well‐defined [Pd(NHC)(α/β‐η 3 ‐MeNAP)Br] (MeNAP = methylnaphthyl) pre‐catalysts has been synthesized by reacting [Pd(α/β‐η 3 ‐MeNAP)Br] 2 and various NHC·HCl precursors in the presence of K 2 CO 3 in acetone. The synthesized Pd(II)‐NHC derivatives displayed good to excellent catalytic activity, and rapid activation in classical Suzuki‐Miyaura, Buchwald–Hartwig, and Miyaura borylation reactions. Additionally, the synthesis of [Pd(IPr)(α‐η 3 ‐MeNAP)Br] (IPr = 1,3‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene) was successfully achieved employing aqueous ammonia as the base.
Journals
2025 EN
Vincent Collin J. · King David · Murkli Steven L.
+1 more
Abstract We report the synthesis and characterization of a new methylene‐bridged glycoluril dimer featuring anthracene walls ( H2 ). H2 displays good solubility in water (≥7 mM) but undergoes self‐association at concentrations above 2 mM. 1 H NMR experiments establish that H2 binds cationic dyes inside its cavity with a π‐stacked geometry that places the cationic residues at the ureidyl carbonyl portals of H2 . The binding constants of both naphthalene‐walled clip H1 and anthracene‐walled clip H2 toward a panel of dyes were measured by direct or competitive UV/Vis or fluorescence titrations in phosphate buffered saline (PBS). Binding constants cover the range from 10 3 – 10 8 M −1 . Dyes that feature cationic NMe 2 groups bind more strongly than analogous dyes with cationic NH 2 groups. We find that π‐extension of the aromatic walls from H1 to H2 generally results in an ≈ 10‐fold increase in binding affinity. Host•guest complexes of H1 and H2 with planar cationic dyes benefit from substantial cation‐π interactions.
Journals
2025 EN
GangaSah Yumeela · Cassegrain Simon · Zhou Wen
+4 more
Abstract A series of soluble ring‐unsubstituted early‐transition metallophthalocyanine (PcM) alkoxides with zirconium(IV) and niobium(V) metal centers was prepared via salt metathesis with PcM chlorides and a range of lithium or sodium alkoxides (NaOMe, NaOEt, LiO i Pr, and NaO t Bu); several examples were structurally characterized. Given their large ionic size, the metal centers protrude out of the Pc cavity, engendering cis ‐axial ligation of the alkoxides and thereby generating substantially improved solubility relative to the starting PcM chlorides. Seven‐coordinate PcM(OR) 3 ‐type coordination spheres were typically observed, with lithium‐ or sodium‐balanced “ ate ” species PcZr(O i Pr) 3 Li(THF) and PcZr(O t Bu) 3 Na(THF) isolated for PcZr(IV), compared to the neutral PcNb(O i Pr) 3 . With the highly steric R = t Bu the neutral six‐coordinate PcZr(O t Bu) 2 was also structurally characterized. The catalytic activity of the PcZr(IV) and PcNb(V) alkoxides was probed toward the ring‐opening polymerization (ROP) of rac ‐lactide, with PcZr(O i Pr) 3 Li(THF) being the most active, while the PcNb(V) systems were either inactive or yielded oligomers.
Journals
2025 EN
Moirangthem Ravina · Rokita Steven E.
Abstract The generality of delivering a bisquinone methide precursor to the major groove of DNA was tested with two naphthalimide conjugates differing in a single amide versus ester linkage. Both demonstrated an ability to cross‐link duplex DNA. Although a difference in their efficiency was not anticipated, the amide‐containing derivative consistently generated more cross‐linking than its ester‐containing analogue when tested with four different sequences of duplex DNA and one analogous RNA duplex. Both conjugates exhibited a specificity for a 5′‐…GTGTGT…‐3′ sequence in the absence of the preferred target of 5′‐GC and 5′‐CG. A corresponding conjugate containing acridine in place of naphthalimide did not express a sequence specificity and cross‐linked the test duplexes with an average efficiency similar to the median of that produced by the amide containing naphthalimide conjugate. With the plethora of naphthalimides available for cellular imaging and chemotherapy, quinone methide delivery may now be designed for many targets of choice. However, a variety of linkers should be surveyed to account for their surprising influence on cross‐linking.
Journals
2025 EN
Street Steven T. G. · Shteinberg Ekaterina · Hernandez Juan Diego Garcia
+4 more
“Uh? Just a box!” Stealth polymer nanofibers show great promise for therapeutic delivery; however, they remain hard to functionalise. In their Research Article (DOI: 10.1002/chem.202500108), S. T. G. Street, S. M. Willerth and co‐workers explain how they harnessed light‐catalysed PET‐RAFT polymerization and crystallization‐driven self‐assembly to synthesize precision stealth nanofibers that are easy to modify, exhibit little toxicity, and display minimal interaction with U‐87 MG cells.
Journals
2025 EN
Davis John W. · Mai Steven L. · Harmouch Wissam
+5 more
ABSTRACT Introduction Atrial fibrillation‐related stroke is a leading cause of morbidity and mortality. The comparative effectiveness and safety of left atrial appendage closure (LAAC) devices, compared with one another and with anticoagulation, is unclear. Methods We conducted a systematic review and network meta‐analysis (NMA) of all clinical trials comparing the Watchman and Amplatzer Amulet LAAC devices with each other or with warfarin or direct oral anticoagulants (DOACs). The primary comparison was between LAAC devices with secondary comparisons to anticoagulation. The primary effectiveness outcomes were any stroke and all‐cause death. Safety outcomes included any thromboembolism, device embolization, and pericardial effusion. Results There were 476 articles identified from the search and 6 eligible RCTs were included ( n = 3666). There was no difference in the risk of stroke with Amulet versus Watchman (RR = 1.48, 95% CI: 0.64–3.46, I 2 = 41.3%), nor in the risk of death (RR = 1.00, 95% CI: 0.59–1.70, I 2 = 45.0%). Risk of thromboembolism was not significantly different with Amulet versus Watchman (RR = 0.73, 95% CI: 0.18–2.97, I 2 = 0%), nor was risk of device embolization (RR = 2.29, 95% CI: 0.71, 7.43, I 2 = 0%). Both devices exhibited increased risk of pericardial effusion compared with warfarin, with Amulet at highest relative risk (RR = 27.08, 95% CI: 3.53–207.98, I 2 = 0%) followed by Watchman (RR = 12.79, 95% CI: 1.73–94.85, I 2 = 0%). Amulet also carried higher relative risk of pericardial effusion than Watchman (RR = 2.12, 95% CI: 1.45–3.09). Conclusion In this NMA, the Amulet and Watchman LAAC devices were associated with similar risks for stroke, mortality, thromboembolism, and device embolization. Pericardial effusion risk was higher with Amulet than Watchman.
Journals
2025 EN
Jamali Armin · Yousefi Hossein · Mashkour Mahdi
+3 more
ABSTRACT This study investigated the use of fog‐spraying deposition of wood cellulose nanofiber (WCNFs) suspensions on tissue paper (TP) to create air filter media. High‐purity WCNFs, confirmed using ATR‐FTIR spectroscopy, were found to be composed of cellulose I β structures via x‐ray diffraction with a crystallinity of 67%. The measured zeta potential of the aqueous suspension of WCNFs was −13 ± 1 mV, indicating the absence of acid hydration during their isolation. This study used nine grammage levels of sprayed WCNFs (ranging from 0.3 to 10 g/m 2 ) and investigated the influence of tert‐butanol (TB) on the performance of the medium. After coating, the specimens were freeze‐dried and imaged using FE‐SEM to confirm the proper distribution of WCNFs on the TP substrate. The key findings revealed that increasing the grammage level from 0.3 to 2 g/m 2 led to increased particulate matter (PM) adsorption and a significant pressure drop. However, increasing the grammage level from 2 to 10 g/m 2 decreased the adsorption efficiency, particularly for PM size of 0.3 µm (PM 0.3 ). The study concluded that the specimens prepared with a deposition of 2 g/m 2 grammage level of WCNFs containing TB were the optimal treatment, demonstrating an adsorption efficiency of 94.1% for PM 0.3 and a pressure drop of 123 Pa, compared to the corresponding values for bare TP, which were only 9.1% and 18 Pa, respectively.