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Ming J Cheng,1,* Nandita N Bal,1,* Priya Prabakaran,1 Rajiv Kumar,2,3 Thomas J Webster,1,4 Srinivas Sridhar,1,2 Eno E Ebong1,2,5 1Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 2Department of Physics, Northeastern University, Boston, MA, USA; 3Millipore Sigma, Milwaukee, WI, USA; 4Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia; 5Department of Neuroscience, Albert Einstein College of Medicine, New York, NY, USA *These authors contributed equally to this work Background: Clinical data show shed endothelial glycocalyx (GCX) components in blood samples of atherosclerotic patients, linking atherosclerotic development to endothelial GCX integrity. Healthy GCX has pores no >7 nm, and shed GCX has even larger pores. Therefore, we suggest targeting and treating atherosclerosis-prone blood vessels by using nanoscale vehicles to deliver drugs via the nanoscale GCX as it becomes dysfunctional. Materials and methods: To test our idea, we investigated permeability of nanoparticles in endothelium, as related to a GCX expression. The present work involves nanorods, which are expected to interact with larger portions of endothelial cell (EC) membranes, due to surface area of the nanorod long axis. Conventional nanorod diameters are orders of magnitude larger than the GCX pore size, so we adapted conventional synthesis methods to fabricate ultrasmall gold nanorods (GNRs). Our ultrasmall GNRs have an aspect ratio of 3.4, with a length of 27.9±3.1 nm and a diameter of 8.2±1.4 nm. In addition, we produced GNRs that are biocompatible and fluorescently visible, by coating the surface with functionalized polyethylene glycol and Alexa Fluor 647. To study GNR–GCX interactions, we used human ECs, for species relevance. Results: Under life-like flow conditions, the human ECs are densely covered with a 1.3 µm thick layer of GCX, which coincides with minimal GNR permeability. When the GCX is weakened from lack of flow (static culture) or the presence of GCX degradation enzyme in the flow stream, the GCX shows 40% and 60% decreased thickness, respectively. GCX weakness due to lack of flow only slightly increases cellular permeability to GNRs, while GCX weakness due to the presence of enzyme in the flow leads to substantial increase in GNR permeability. Conclusion: These results clarify that the GCX structure is an avenue through which drug-carrying nanoparticles can be delivered for targeting affected blood vessels to treat atherosclerosis. Keywords: human endothelial cells, gold nanoparticles, nanorods, glycocalyx, heparan sulfate

Danetta Hendricks Sloan,1 Karlynn BrintzenhofeSzoc,2 Tiffany Kichline,1 Karen Baker,1 Jean-Paul Pinzon,1 Christina Tafe,1 Lingsheng Li,1 M Jennifer Cheng,1 Ann Berger1 1Pain and Palliative Care, National Institutes of Health, Clinical Center, Bethesda, MD, 2School of Social Work, College of Allied Health Sciences, University of Cincinnati, Cincinnati, OH, USA Context: Patients with life-threatening or chronic illness report an experience of increased positive psychological, social, and/or spiritual change during diagnosis and/or treatment of their illness, even in the face of unfavorable prognosis. This transformation begins through the ability to make their life meaningful by forming meaningful connections that emerge through self-introspection and relationships with a divine entity, nature, and other people. The Healing Experience in All Life Stressors (HEALS) assessment provides a way to identify distress-causing changes that may interfere with the development of meaning and psycho–social–spiritual homeostasis.Objective: Preliminary examination of responses to items on the HEALS and examination of the factor structure.Method: The 48-item HEALS questionnaire was developed using a multistep process: literature review for concept development, item generation from qualitative data, and face and content validity by expert panel. In the current study, HEALS was completed by 100 patients diagnosed with life-limiting disease and seen by the palliative care team at a large research institution in the US. Exploratory factor analysis techniques were used to determine scale structure of the instrument.Results: Outcome testing of sample adequacy using Kaiser–Meyer–Olkin statistic was 0.75, which exceeds the recommended value of 0.60. The HEALS show very good internal consistency with a Cronbach’s a of 0.94. Overall results of the exploratory factor analysis established a four-factor questionnaire: 1) religion; 2) spirituality, demonstrated by a) interaction with a religious community and b) belief in higher power; 3) intrapersonal; and 4) interpersonal relationships expressed through psychological changes resulting in enhanced outlook and improvement in relationships with family and friends.Conclusion: This study involved the initial step to commence the process of scale validation, with promising outcomes identifying subscales as an effective way to assess the construct of healing. These findings support further examination using cognitive appraisal and confirmatory factor analysis. Keywords: palliative care, psycho-social spiritual assessment, validation, instrumentation

Ming J Cheng,1 Rajiv Kumar,2 Srinivas Sridhar,1–3 Thomas J Webster,1,4 Eno E Ebong1 1Department of Chemical Engineering, 2Department of Physics, Northeastern University, 3Department of Radiation Oncology, Harvard Medical School, Boston, MA, USA; 4Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia Abstract: Cardiovascular diseases are facilitated by endothelial cell (EC) dysfunction and coincide with EC glycocalyx coat shedding. These diseases may be prevented by delivering medications to affected vascular regions using circulating nanoparticle (NP) drug carriers. The objective of the present study was to observe how the delivery of 10 nm polyethylene glycol-coated gold NPs (PEG-AuNP) to ECs is impacted by glycocalyx structure on the EC surface. Rat fat pad endothelial cells were chosen for their robust glycocalyx, verified by fluorescent immunolabeling of adsorbed albumin and integrated heparan sulfate (HS) chains. Confocal fluorescent imaging revealed a ~3 µm thick glycocalyx layer, covering 75% of the ECs and containing abundant HS. This healthy glycocalyx hindered the uptake of PEG-AuNP as expected because glycocalyx pores are typically 7 nm wide. Additional glycocalyx models tested included: a collapsed glycocalyx obtained by culturing cells in reduced protein media, a degraded glycocalyx obtained by applying heparinase III enzyme to specifically cleave HS, and a recovered glycocalyx obtained by supplementing exogenous HS into the media after enzyme degradation. The collapsed glycocalyx was ~2 µm thick with unchanged EC coverage and sustained HS content. The degraded glycocalyx showed similar changes in EC thickness and coverage but its HS thickness was reduced to 0.7 µm and spanned only 10% of the original EC surface. Both dysfunctional models retained six- to sevenfold more PEG-AuNP compared to the healthy glycocalyx. The collapsed glycocalyx permitted NPs to cross the glycocalyx into intracellular spaces, whereas the degraded glycocalyx trapped the PEG-AuNP within the glycocalyx. The repaired glycocalyx model partially restored HS thickness to 1.2 µm and 44% coverage of the ECs, but it was able to reverse the NP uptake back to baseline levels. In summary, this study showed that the glycocalyx structure is critical for NP uptake by ECs and may serve as a passive pathway for delivering NPs to dysfunctional ECs. Keywords: glycocalyx, heparan sulfate, endothelial cells, NP, gold

Electrocatalytic reduction of CO2 to energy-rich hydrocarbons such as alkanes, alkenes, and alcohols is a very challenging task. So far, only copper has proven to be capable of such a conversion. We report density functional theory (DFT) calculations combined with the Poisson-Boltzmann implicit solvation model to show that single-atom alloys (SAAs) are promising electrocatalysts for CO2 reduction to C1 hydrocarbons in aqueous solution. The majority component of the SAAs studied is either gold or silver, in combination with isolated single atoms, M (M = Cu, Ni, Pd, Pt, Co, Rh, and Ir), replacing surface atoms. We envision that the SAA behaves as a one-pot tandem catalyst: first gold (or silver) reduces CO2 to CO, and the newly formed CO is then captured by M and is further reduced to C1 hydrocarbons such as methane or methanol. We studied 28 SAAs, and found about half of them selectively favor the CO2 reduction reaction over the competing hydrogen evolution reaction. Most of those promising SAAs contain M = Co, Rh, or Ir. The reaction mechanism of two SAAs, Rh@Au(100) and Rh@Ag(100), is explored in detail. Both of them reduce CO2 to methane but via different pathways. For Rh@Au(100), reduction occurs through the pathway ∗CO → ∗CHO → ∗CHOH → ∗CH + H2O(l) → ∗CH2 + H2O(l) → ∗CH3 + H2O(l) → ∗ + H2O(l) + CH4(g); whereas, for Rh@Ag(100), the pathway is ∗CO → ∗CHO → ∗CH2O→ ∗OCH3 → ∗O + CH4(g) → ∗OH + CH4(g) → ∗ + H2O(l) + CH4(g). The minimum applied voltages to drive the two electrocatalytic systems are -1.01 and -1.12 VRHE for Rh@Au(100) and Rh@Ag(100), respectively, at which the Faradaic efficiencies for CO2 reduction to CO are 60% for gold and 90% for silver. This suggests that SAA can efficiently reduce CO2 to methane with as small as 40% loss to the hydrogen evolution reaction for Rh@Au(100) and as small as 10% for Rh@Ag(100). We hope these computational results can stimulate experimental efforts to explore the use of SAA to catalyze CO2 electrochemical reduction to hydrocarbons. (Figure Presented).

We propose a mechanism of water splitting on cobalt oxide surface with atomistic thermodynamic and kinetic details. The density-functional theory studies suggest that the oxidation process could proceed with several nonelectrochemical (spontaneous) intermediate steps, following the initial electrochemical hydroxyl-to-oxo conversion. More specifically, the single oxo sites CoIV=O can hop (via surface proton/electron hopping) to form oxo pair CoIV(=O)-O-CoIV=O, which will undergo nucleophilic attack by a water molecule and form the hydroperoxide CoIII-OOH. Encounter with another oxo would generate a superoxo CoIII-OO, followed by the O2 release. Finally the addition and deprotonation of a fresh water molecule will restart the catalytic cycle by forming the hydroxyl CoIII-OH at this active site. Our theoretical investigations indicate that all nonelectrochemical reactions are kinetically fast and thermodynamically downhill. This hypothesis is supported by recent in situ spectroscopic observations of surface superoxo that is stabilized by hydrogen bonding to adjacent hydroxyl group as an intermediate on fast-kinetics Co catalytic site.

Addition of Fe to Ni- and Co-based (oxy)hydroxides has been shown to enhance the activity of these materials for electrochemical oxygen evolution. Here we show that Fe cations bound to the surface of oxidized Au exhibit enhanced oxygen evolution reaction (OER) activity. We find that the OER activity increases with increasing surface concentration of Fe. Density functional theory analysis of the OER energetics reveals that oxygen evolution over Fe cations bound to a hydroxyl-terminated oxidized Au (Fe-Au2O3) occurs at an overpotential ∼0.3V lower than over hydroxylated Au2O3 (0.82V). This finding agrees well with experimental observations and is a consequence of the more optimal binding energetics of OER reaction intermediates at Fe cations bound to the surface of Au2O3. These findings suggest that the enhanced OER activity reported recently upon low-potential cycling of Au may be due to surface Fe impurities rather than to "superactive" AuIII surfaquo species.

Density functional theory (DFT) calculations are performed to investigate the energetics of the CO2 electrochemical reduction on metal (M) porphyrin-like motifs incorporated into graphene layers. The objective is to develop strategies that enhance CO2 reduction while suppressing the competitive hydrogen evolution reaction (HER). We find that there exists a scaling relation between the binding energy of the catalyst to hydrogen and that to COOH, a key intermediate in the reduction of CO2 to CO; however, the M-H bond is stronger than the M-COOH bond, driving the reaction toward the HER rather than the reduction of CO2 to CO. This scaling relation holds even with axial ligation to the metal cation coordinated to the porphyrin ring. When 4f lanthanide or 5f actinide elements are used as the reactive center, the scaling relation still holds but the M-COOH bond is stronger than the M-H bond, and the reaction favors the reduction of CO2 to CO. By contrast, there is no scaling relation between the binding energy of the catalyst to H and that to OCHO, the key intermediate in CO2 reduction to formic acid. Interestingly, we find that coordination of a ligand to an unoccupied axial site can make the M-OCHO bond stronger than the M-H bond, resulting in preferential formic acid formation. This means that the axial ligand effectively enhances CO2 reduction to formic acid and suppresses the HER. Our DFT calculations have also identified several promising electrocatalysts for CO2 reduction to HCOOH with almost zero overpotentials.

Density functional theory calculations are used to study the energetics of the electrochemical oxygen evolution reaction (OER) of water and the reverse oxygen reduction reaction (ORR) on metal-porphyrin-like centers incorporated into graphene layers or single-walled carbon nanotubes (SWCNTs). The objective is to explore the reductions in computational thermodynamic overpotential that can be achieved relative to catalysis on metal oxide surfaces (OER) or platinum (ORR) by varying the metal center and axial ligand. This permits a degree of simultaneous control over the free energy gap between the lowest energy OH and highest energy OOH intermediates, and the position of the oxo (O) intermediate in this gap. Optimal choice of metal toward the right of the first transition series largely controls the gap. Given a suitable metal such as Fe, the overpotential for OER can be tuned over a range greater than 0.35 V by choice of the axial ligand. For OER occurring within the SWCNTs, a minimum predicted overpotential of 0.35 V is found, very close to the gap-imposed limit of 0.30 V for this system. Similarly, the overpotential of ORR can be tuned over a range more than 0.30 V by selection of the axial ligand. While the calculations necessarily have limited accuracy, the principles should provide a transferable path toward overpotential optimization for the OER and ORR.

This work reports Ag(I)-catalyzed oxidative cyclizations of 1,4-diynamide-3-ols with 8-methylquinoline oxide to form 2-substituted furan-4-carboxamides. The reaction chemoselectivity is distinct from that reported in previous work by Hashmi. We performed density functional theory calculations to elucidate our proposed mechanism after evaluation of the energy profiles of two possible pathways. In this Ag(I) catalysis, the calculations suggest that the amide and alkyne groups of the 3,3-dicarbonyl-2-alkyne intermediates tend to chelate with the Ag(I) catalyst, further inducing a formyl attack at the Ag(I)-π-alkyne moiety to deliver the observed products.

Phosphinopyridyl ligands are used to synthesize a class of Ni(II) bis(chelate) complexes, which have been comprehensively characterized in both solid and solution phases. The structures display a square-planar configuration within the primary coordination sphere, with axially positioned labile binding sites. Their electrochemical data reveal two redox couples during the reduction process, suggesting the possibility of accessing two-electron reduction states. Significantly, these complexes serve as robust catalysts for homogeneous photocatalytic H 2 evolution. In a system utilizing an organic photosensitizer and a sacrificial electron donor, an optimal turnover number of 27,100 is achieved in an alcohol-containing aqueous solution. A series of photophysical and electrochemical measurements were conducted to elucidate the reaction mechanism of photocatalytic hydrogen generation. Density function theory calculations propose a catalytic pathway involving two successive one-electron reduction steps, followed by two proton discharges. The sustained photocatalytic activity of these complexes stems from their distinct ligand system, which includes phosphine and pyridine donors that aid in stabilizing the low oxidation states of the Ni center., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

A C 1 -symmetric hexapole helicene (HH) and a C 3 -symmetric dodecapole helicene (DH) were prepared, and their three-dimensional structures were verified by X-ray crystallography and density functional theory calculations. The molecular geometries and local helical configurations of their most stable diastereomers were correctly predicted by arranging suitable conformations of the peripheral aryl rings. Importantly, the outermost three [5]helicenes with a consistent configuration in DH were observed to increase the thermostability, enantiomerization barrier (Δ H ⧧ = 40.5 kcal/mol), specific rotation ([α] 24 D = -4228°) and absorption dissymmetry factor ( g abs = 1.35 × 10 -3 at 453 nm).

A C-H functionalizing annulation reaction of boron-doped polycyclic aromatic hydrocarbons (PAHs) with alkynes is described. This metal-free π-extension provides a new synthetic route to fusion atom B-doped polycyclic aromatic hydrocarbons (PAHs) that is demonstrated with the synthesis of a family of new, functionalized, structurally constrained 6a,15a-diborabenzo[ tuv ]naphtho[2,1- b ]picenes. These annulation products exhibit deep LUMO energy levels, strong visible-range absorptions, and sterically accessible π-systems that can adopt herringbone or π-stacked solid-state structures based on choice of substituents. From regioselectivity and DFT calculations, we propose an annulation mechanism involving intramolecular electrophilic aromatic substitution of a zwitterionic intermediate., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

exo-6b 2 -Methyl-substituted pentabenzocorannulene (exo-PBC-Me) was synthesized by the palladium-catalyzed cyclization of 1,2,3-triaryl-1H-cyclopenta[l]phenanthrene. Its bowl-shaped geometry with an sp 3 carbon atom in the backbone and a methyl group located at the convex (exo) face was verified by X-ray crystallography. According to DFT calculations, the observed conformer is energetically more favorable than the endo one by 39.9 kcal/mol. Compared to the nitrogen-doped analogs with intact π-conjugated backbones (see the main text), exo-PBC-Me displayed a deeper bowl depth (avg. 1.93 Å), redshifted and broader absorption (250-620 nm) and emission (from 585 to more than 850 nm) bands and a smaller optical HOMO-LUMO gap (2.01 eV). exo-PBC-Me formed polar crystals where all bowl-in-bowl stacking with close π ⋅ ⋅ ⋅ π contacts is arranged unidirectionally, providing the potential for applications as organic semiconductors and pyroelectric materials. This unusual structural feature, molecular packing, and properties are most likely associated with the assistance of the methyl group and the sp 3 carbon atom in the backbone., (© 2024 Wiley-VCH GmbH.)

Kopsileuconines A-D (1-4), four monoterpenoid bisindole alkaloids with unprecedented skeletons, along with their biosynthetically related precursors (5-8) were isolated from the roots of Kopsia hainanensis. Compound 1 possessed an undescribed C-6-C-5' dimerization pattern of aspidofractinine-type alkaloids. Compounds 2-4 were rhazinilam-kopsine (2) and rhazinilam-aspidofractinine type (3 and 4) bisindole alkaloids with undescribed skeletons, respectively. Their structures with absolute configurations were fully accomplished by extensive spectroscopic analysis, quantum-chemical calculations, and X-ray crystallography. A plausible biosynthetic pathway for 1-4 was proposed. Compound 2 exhibited a significant inhibitory effect against human lung cancer cell lines PC9 (EGFR mutant), with an IC 50 value of 15.07 ± 1.19 μM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Stereochemical-controlled hydrogen bond donors play essential roles in the pharmaceutical industry. Consequently, organic molecules that bear difluoromethyl (CF2H) groups at chiral centers are emerging as pivotal components in pharmaceuticals due to their distinct hydrogenbonding property. However, a general approach for introducing CF2H groups in an enantioselective manner remained elusive. Here, we show that enantioconvergent difluoromethylation of racemic alkyl electrophiles, through alkyl radical intermediates, represents a new strategy for constructing CF2H-containing stereocenters. This strategy is enabled by using copper catalysts bound with a chiral diamine ligand bearing electron-deficient phenyl groups, and a nucleophilic difluoromethyl-zinc reagent. This method allows for the high-yield conversion of a diverse range of alkyl halides into their alkyl-CF2H analogs with excellent enantioselectivity (up to 99% e.e.). Mechanistic studies, supported by DFT calculations, revealed a route involving asymmetric difluoromethylation of alkyl radicals and crucial non-covalent interactions in the enantio-determining steps.

X-ray photoelectron spectroscopy, reflection-absorption infrared spectroscopy, and temperature-programmed reaction/desorption have been employed to investigate the reaction of CH3-CHCl-C(=O)Cl on Cu (100), with the aid of density functional theory (DFT) calculations. Experimentally, CH3-CH=C=O (methylketene) is found to be the product from the dechlorination of CH3-CHCl-C(=O)Cl on Cu(100) at 120 K. The CH3-CH=C=O generated on the surface would dimerize to form 2,4-dimethylcyclobutane-1,3-dione below 180 K. In agreement with the experimental findings, our DFT molecular dynamics simulations demonstrate that the dechlorination of CH3-CHCl-C(=O)Cl, resulting in CH3-CH=C=O and two Cl atoms, occurs readily, completing within 0.6 ps at 300 K. The simulations also indicate that the cleavage of the CH-Cl bond precedes that of the C(=O)-Cl bond. The static DFT calculations suggest that the dimerization of CH3-CH=C=O primarily occurs through the coupling of two C=C bonds, which has a lower barrier of 38.08 kJ mol-1 compared to the 69.05 kJ mol-1 barrier for C=C + C=O coupling., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Background: There is a call to action for health care systems to assess and address burnout among physician trainees. To address this need for programmatic change, we developed a novel initiative to (1) proactively assess trainee burnout and identify drivers and (2) provide resources and recommendations for preventing and reducing burnout., Approach: This pilot burnout tracking initiative began in 2020. A two-question burnout survey was disseminated to physician trainees at a hospital devoted exclusively to clinical research. The survey assessed burnout level and drivers of burnout. An algorithm was created to recommend action steps based on trainee responses. Participating training programmes completed a 23-question survey annually to provide information about their trainees and feedback., Evaluation: Seven of 10 (70%) programmes completed the annual survey in the first year, and 12 of the 15 (80%) programmes completed it the second year. Reported average burnout levels and drivers of burnout varied across programmes; all drivers of burnout were cited as key drivers by at least one programme. Most programmes had conversations with their trainees and found these conversations helpful. All responding programmes who administered the trainee survey felt the initiative improved their ability to track and reduce burnout., Implications: An initiative to systematically track burnout levels and offer targeted interventions was feasible and useful. This project can be a model for institution-wide efforts to address trainee burnout and extend to other clinical health care settings and academic medicine faculty., (Published 2023. This article is a U.S. Government work and is in the public domain in the USA.)

The development of new antibiotics continues to pose challenges, particularly considering the growing threat of multidrug-resistant Staphylococcus aureus. Structurally diverse natural products provide a promising source of antibiotics. Herein, we outline a concise approach for the collective asymmetric total synthesis of polycyclic xanthene myrtucommulone D and five related congeners. The strategy involves rapid assembly of the challenging benzopyrano[2,3-a]xanthene core, highly diastereoselective establishment of three contiguous stereocenters through a retro-hemiketalization/double Michael cascade reaction, and a Mitsunobu-mediated chiral resolution approach with high optical purity and broad substrate scope. Quantum mechanical calculations provide insight into stereoselective construction mechanism of the three contiguous stereocenters. Additionally, this work leads to the discovery of an antibacterial agent against both drug-sensitive and drug-resistant S. aureus. This compound operates through a unique mechanism that promotes bacterial autolysis by activating the two-component sensory histidine kinase WalK. Our research holds potential for future antibacterial drug development., (© 2024. The Author(s).)

Alkanes, ideal raw materials for industrial chemical production, typically exhibit limited reactivity due to their robust and weakly polarized C-H bonds. The challenge lies in selectively activating these C-H bonds under mild conditions. To address this challenge, various C-H activation mechanisms have been developed. Yet, classifying these mechanisms depends on the overall stoichiometry, which can be ambiguous and sometimes problematic. In this study, we utilized density functional theory calculations combined with intrinsic bond orbital (IBO) analysis to examine electron flow in the four primary alkane C-H activation mechanisms: oxidative addition, σ-bond metathesis, 1,2-addition, and electrophilic activation. Methane was selected as the representative alkane molecule to undergo C-H heterolytic cleavage in these reactions. Across all mechanisms studied, we find that the CH 3 moiety in methane consistently uses an electron pair from the cleaved C-H bond to form a σ-bond with the metal. Yet, the electron pair that accepts the proton differs with each mechanism: in oxidative addition, it is derived from the d -orbitals; in σ-bond metathesis, it resulted from the metal-ligand σ-bonds; in 1,2-addition, it arose from the π-orbital of the metal-ligand multiple bonds; and in electrophilic activation, it came from the lone pairs on ligands. This detailed analysis not only provides a clear visual understanding of these reactions but also showcases the ability of the IBO method to differentiate between mechanisms. The electron flow discerned from IBO analysis is further corroborated by results from absolutely localized molecular orbital energy decomposition analysis, which also helps to quantify the two predominant interactions in each process. Our findings offer profound insights into the electron dynamics at play in alkane C-H activation, enhancing our understanding of these critical reactions.

Stepwise oxidative addition of copper(I) complexes to form copper(III) species via single electron transfer (SET) events has been widely proposed in copper catalysis. However, direct observation and detailed investigation of these fundamental steps remain elusive owing largely to the typically slow oxidative addition rate of copper(I) complexes and the instability of the copper(III) species. We report herein a novel aryl-radical-enabled stepwise oxidative addition pathway that allows for the formation of well-defined alkyl-Cu III species from Cu I complexes. The process is enabled by the SET from a Cu I species to an aryl diazonium salt to form a Cu II species and an aryl radical. Subsequent iodine abstraction from an alkyl iodide by the aryl radical affords an alkyl radical, which then reacts with the Cu II species to form the alkyl-Cu III complex. The structure of resultant [(bpy)Cu III (CF 3 ) 2 (alkyl)] complexes has been characterized by NMR spectroscopy and X-ray crystallography. Competition experiments have revealed that the rate at which different alkyl iodides undergo oxidative addition is consistent with the rate of iodine abstraction by carbon-centered radicals. The Cu II intermediate formed during the SET process has been identified as a four-coordinate complex, [Cu II (CH 3 CN) 2 (CF 3 ) 2 ], through electronic paramagnetic resonance (EPR) studies. The catalytic relevance of the high-valent organo-Cu III has been demonstrated by the C-C bond-forming reductive elimination reactivity. Finally, localized orbital bonding analysis of these formal Cu III complexes indicates inverted ligand fields in σ(Cu-CH 2 ) bonds. These results demonstrate the stepwise oxidative addition in copper catalysis and provide a general strategy to investigate the elusive formal Cu III complexes.

Background: Visual art can enhance wellbeing and quality-of-life; however, the experience of visual art for people with mild-to-moderate vision loss has not been examined., Methods: Eight participants (6 females, 2 males; Mean age = 81 years, SD = 7.9, range 70-91 years; 4 with mild vision loss and 4 with moderate vision loss based on binocular visual acuity) completed a mixed-methods study comprising: a semi-structured interview on visual art experience; an eye examination; and questionnaires about visual functioning and quality-of-life., Results: Various themes were identified: visual perception of art (e.g. altered colours, visual distortions, etc.), viewing conditions, elements of art, personal preference, deriving meaning, appreciation of art, impact of impaired visual perception, and social aspects of art., Conclusions: The overall experience of art is influenced by how an individual sees, perceives, and makes meaning from art. Even mild vision loss can impair this experience and impact emotional and social wellbeing.

Four ethanol fractionated crude extracts (EFCEs [A-D]) purified from the leaves of Cinnamomum macrostemon Hayata were screened for antioxidative effects and mitochondrial function in HaCaT cells. The higher cell viability indicated that EFCE C was mildly toxic. Under the treatment of 50 ng/mL EFCE C, the hydrogen peroxide (H2O2)-induced cytosolic and mitochondrial reactive oxygen species levels were reduced as well as the H2O2-impaired cell viability, mitochondrial membrane potential (MMP), ATP production, and mitochondrial mass. The conversion of globular mitochondria to tubular mitochondria is coincident with EFCE C-restored mitochondrial function. The mitophagy activator rapamycin showed similar effects to EFCE C in recovering the H2O2-impaired cell viability, MMP, ATP production, mitochondrial mass, and also mitophagic proteins such as PINK1, Parkin, LC3 II, and biogenesis protein PGC-1α. We thereby propose the application of EFCE C in the prevention of oxidative stress in skin cells., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Cervi Cornu is the ossified antler, or the base antler that falls off in the spring of the following year after the pilose antler is sawn off from Cervus elaphus or C. nippon, as a precious traditional Chinese medicine, has been recognized for its medicinal value and widely used in clinical practice. However, the origins of Cervi Cornu are miscellaneous, and Cervi Cornu is even mixed with adulterants in the market. Currently, there is a shortage of ways to identify Cervi Cornu and no standard to control the quality of Cervi Cornu. So it is valuable to develop a way to effectively identify Cervi Cornu from the adulterants. In this study, the differences in the mitochondrial barcode cytochrome b(Cytb) gene sequences of C. elaphus, C. nippon and their related species were compared and the specific single nucleotide polymorphism(SNP) sites on the Cytb sequences of Cervi Cornu were screened out. According to the screened SNPs, Cervi Cornu-specific primers dishmy-F and dishmy-R were designed. The PCR system was established and optimized, and the tolerance and feasibility of Taq polymerases and PCR systems affecting the repeatability of the PCR method were investigated. The amplification products of C. elaphus and C. nippon were digested using the restriction enzyme MseⅠ. The results showed that after electrophoresis of the product from PCR with the annealing temperature of 56 ℃ and 35 cycles, a single specific band at about 100 bp was observed for C. elaphus samples, and the product of C. elaphus samples was 60 bp shorter than that of C. nippon samples. There was no band for adulterants from other similar species such as Alces alces, Rangifer tarandus, Odocoileus virginianus, O. hemionus, Cap-reolus pygargus, Przewalskium albirostis and negative controls. The polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) method established in this study can quickly and accurately identify Cervi Cornu originated from C. elaphus in crude drugs, standard decoctions, and formula granules, and distinguish the origins of Cervi Cornu products, i.e., C. nippon and similar species. This study can be a reference for other studies on the quality standard of other formula granules of traditional Chinese medicines.

A new series of biaryls, bi-linear-terphenylenes (BLTPs), were prepared using the tert-butyllithium-mediated cyclization as the key synthetic step. The three-dimensional structures of the studied compounds were verified using X-ray crystallography and DFT calculations. Tetraaryl(ethynyl)-substituted BLTPs are highly crowded molecules, and the internal rotation around the central C-C bond is restricted due to a high barrier (>50 kcal/mol). These structures contain several aryl/terphenylenyl/aryl sandwiches, where the through-space π-π (TSPP) interactions are strongly reflected in the shielding of 1 H NMR chemical shifts, reduction of oxidation potentials, increasing aromaticity of the central six-membered ring and decreasing antiaromaticity of the four-membered rings in a terphenylenyl moiety based on NICS(0) and iso-chemical shielding surfaces. Despite the restricted C-C bond associated intramolecular TSPP interactions for BLTPs in the ground state, to our surprise, the electronic coupling between two linear terphenylenes (LTPs) in BLTPs in the excited state is weak, so that the excited-state behavior is dominated by the corresponding monomeric LTPs. In other words, all BLTPs undergo ultrafast relaxation dynamics via strong exciton-vibration coupling, acting as a blue-light absorber with essentially no emission., (© 2023 Wiley-VCH GmbH.)

The oxidative dehydrogenation of propane, primarily sourced from shale gas, holds promise in meeting the surging global demand for propylene. However, this process necessitates high operating temperatures, which amplifies safety concerns in its application due to the use of mixed propane and oxygen. Moreover, these elevated temperatures may heighten the risk of overoxidation, leading to carbon dioxide formation. Here we introduce a microchannel reaction system designed for the oxidative dehydrogenation of propane within an aqueous environment, enabling highly selective and active propylene production at room temperature and ambient pressure with mitigated safety risks. A propylene selectivity of over 92% and production rate of 19.57 mmol m Cu -2 h -1 are simultaneously achieved. This exceptional performance stems from the in situ creation of a highly active, oxygen-containing Cu catalytic surface for propane activation, and the enhanced propane transfer via an enlarged gas-liquid interfacial area and a reduced diffusion path by establishing a gas-liquid Taylor flow using a custom-made T-junction microdevice. This microchannel reaction system offers an appealing approach to accelerate gas-liquid-solid reactions limited by the solubility of gaseous reactant., (© 2024. The Author(s).)

Despite the recent advancements of Cu catalysis for the cross-coupling of alkyl electrophiles and the frequently proposed involvement of alkyl-Cu(III) complexes in such reactions, little is known about the reactivity of these high-valent complexes. Specifically, although the reversible interconversion between an alkyl-Cu III complex and an alkyl radical/Cu II pair has been frequently proposed in Cu catalysis, direct observation of such steps in well-defined Cu III complexes remains elusive. In this study, we report the synthesis and investigation of alkyl-Cu III complexes, which exclusively undergo a Cu-C homolysis pathway to generate alkyl radicals and Cu II species. Kinetic studies suggest a bond dissociation energy of 28.6 kcal/mol for the Cu III -C bonds. Moreover, these four-coordinate complexes could be converted to a solvated alkyl-Cu III -(CF 3 ) 2 , which undergoes highly efficient C-CF 3 bond-forming reductive elimination even at low temperatures (-4 °C). These results provide strong support for the reversible recombination of alkyl radicals with Cu II to form alkyl-Cu III species, an elusive step that has been proposed in Cu-catalyzed mechanisms. Furthermore, our work has demonstrated that the reactivity of Cu III complexes could be significantly influenced by subtle changes in the coordination environment. Lastly, the observation of the highly reactive neutral alkyl-Cu III -(CF 3 ) 2 species (or with weakly bound solvent molecules) suggests they might be the true intermediates in many Cu-catalyzed trifluoromethylation reactions.

An acyl radical reaction of bicyclo[2.2.2]octenone to yield either rearranged or cyclized isotwistane products is described. The influence of ring strain on the reaction was demonstrated by alternating the sizes of the fused ring in the starting material. DFT calculations showed that the reaction is under thermodynamic control and proceeds via a 5- exo - trig cyclization intermediate, which undergoes either hydrogen-atom transfer (HAT) to give a cyclized product or rearrangement via a twistane intermediate to give a rearranged product.

The rotation of a C = C bond in an alkene can be efficiently accelerated by creating the high-strain ground state and stabilizing the transition state of the process. Herein, the synthesis, structures, and properties of several highly twisted alkenes are comprehensively explored. A facile and practical synthetic approach to target molecules is developed. The twist angles and lengths of the central C = C bonds in these molecules are 36-58° and 1.40-1.43 Å, respectively, and confirmed by X-ray crystallography and DFT calculations. A quasi-planar molecular half with the π-extended substituents delivers a shallow rotational barrier (down to 2.35 kcal/mol), indicating that the rotation of the C = C bond is as facile as that of the aryl-aryl bond in 2-flourobiphenyl. Other versatile and unique properties of the studied compounds include a broad photoabsorption range (from 250 up to 1100 nm), a reduced HOMO-LUMO gap (1.26-1.68 eV), and a small singlet-triplet energy gap (3.65-5.68 kcal/mol)., (© 2023. Springer Nature Limited.)

A series of hexapole helicenes (HHs) and nonuple helicenes (NHs) were prepared from 1,3,5-tris[2-(arylethynyl)phenyl]benzene through two steps, namely, iodocyclization and subsequent palladium-catalyzed annulation with ortho -bromoaryl carboxylic acids. The crucial advantages of this synthetic method are the facile introduction of substituents, high regioselectivity, and efficient backbone extension. Three-dimensional structures of three C 1 -symmetric HHs and one C 3 -symmetric NH were elucidated using X-ray crystallography. Unlike most conventional multiple helicenes, the HHs and NHs investigated herein possess a unique structural feature where some double helical moieties share a terminal naphthalene unit. Chiral resolution of a HH and an NH was successfully achieved, and the enantiomerization barrier (Δ H ‡ ) of the HH was experimentally determined to be 31.2 kcal/mol. A straightforward method for predicting the most stable diastereomer was developed based on density functional theory calculations and structural considerations. It was found that the relative potential energies (Δ H r s) of all diastereomers for two HHs and one NH can be obtained using minimal computational effort to analyze the types, helical configurations, numbers, and Δ H ( MP - MM ) s [= H ( M , P / P , M ) - H ( M , M / P , P )] of the double helicenyl fragments.

Key Message: Two candidate genes (ZmbZIP113 and ZmTSAH1) controlling low-temperature germination ability were identified by QTL-seq and integrative transcriptomic analyses. The functional verification results showed that two candidate genes positively regulated the low-temperature germination ability of IB030. Low-temperature conditions cause slow maize (Zea mays L.) seed metabolism, resulting in slow seedling emergence and irregular seedling emergence, which can cause serious yield loss. Thus, improving a maize cultivar's low-temperature germination ability (LTGA) is vital for increasing yield production. Wild relatives of maize, such as Z. perennis and Tripsacum dactyloides, are strongly tolerant of cold stress and can thus be used to improve the LTGA of maize. In a previous study, the genetic bridge MTP was constructed (from maize, T. dactyloides, and Z. perennis) and used to obtain a highly LTGA maize introgression line (IB030) by backcross breeding. In this study, IB030 (Strong-LTGA) and Mo17 (Weak-LTGA) were selected as parents to construct an F 2 offspring. Additionally, two major QTLs (qCS1-1 and qCS10-1) were mapped. Then, RNA-seq was performed using seeds of IB030 and the recurrent parent B73 treated at 10 °C for 27 days and 25 °C for 7 days, respectively, and two candidate genes (ZmbZIP113 and ZmTSAH1) controlling LTGA were located using QTL-seq and integrative transcriptomic analyses. The functional verification results showed that the two candidate genes positively regulated LTGA of IB030. Notably, homologous cloning showed that the source of variation in both candidate genes was the stable inheritance of introgressed alleles from Z. perennis. This study was thus able to analyze the LTGA mechanism of IB030 and identify resistance genes for genetic improvement in maize, and it proved that using MTP genetic bridge confers desirable traits or phenotypes of Z. perennis and tripsacum essential to maize breeding systems., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A simple visible-light-induced CuCl-catalyzed synthesis was developed for highly functionalized carbon-centered compounds (α-alk/aryloxy-α-diaryl/alkylaryl-acetaldehydes/ketones) at room temperature using benzoquinone, alkyl/aryl alcohol, and alkyl/aryl terminal/internal alkynes. Late-stage functionalized compounds show good antifungal activities, especially against Candida krusei fungal strain, in in vitro experiments (the Broth microdilution method). Moreover, toxicity tests (zebrafish egg model experiments) indicated that these compounds had negligible cytotoxicity. The green chemistry metrics (E-factor value is 7.3) and eco-scale (eco-scale value is 58.8) evaluations show that the method is simple, mild, highly efficient, eco-friendly, and environmentally feasible., (© 2023 Wiley-VCH GmbH.)

The mold Monascus , also called red yeast rice, anka, or koji, has been used as the natural food coloring agent and food additives for more than 1000 years in Asian countries. It has also been used in Chinese herbology and traditional Chinese medicine due to its easing digestion and antiseptic effects. However, under different culture conditions, the ingredients in Monascus -fermented products may be changed. Therefore, an in-depth understanding of the ingredients, as well as the bioactivities of Monascus -derived natural products, is important. Here, through the thorough investigation into the chemical constituents of M. purpureus wmd2424, five previously undescribed compounds, monascuspurins A-E ( 1 - 5 ), were isolated from the EtOAc extract of mangrove-derived fungus Monascus purpureus wmd2424 cultured in RGY medium. All the constituents were confirmed via HRESIMS and 1D- and 2D-NMR spectroscopy. Their antifungal activity was also evaluated. Our results showed that four constituents (compounds 3 - 5 ) possessed mild antifungal activity against Aspergillus niger , Penicillium italicum , Candida albicans , and Saccharomyces cerevisiae . It is worth mentioning that the chemical composition of the type strain Monascus purpureus wmd2424 has never been studied.

With the relay process of Ag(I)/Au(I) catalysts, a one-pot synthesis of skeletally rearranged (1-hydroxymethylidene)indene derivatives from 2-alkynylbenzaldehydes and α-diazo esters is described. This cascade sequence involves Au(I)-catalyzed 5- endo-dig attack of highly enolizable aldehydes at the tethered alkynes, leading to carbocyclizations with a formal 1,3-hydroxymethylidene transfer. On the basis of density functional theory calculations, the mechanism likely involves formation of cyclopropylgold carbenes, followed by an appealing 1,2-cyclopropane migration.

Rationale: Anti-glomerular basement membrane (anti-GBM) disease has been reported to coexist with other immune-mediated glomerular disorders, including antineutrophil cytoplasmic autoantibody positive glomerulonephritis and membranous glomerulopathy. It is well known that anti-GBM disease often manifests as type I crescentic glomerulonephritis on renal biopsy. However, concurrent cases of both type I crescentic glomerulonephritis and IgA nephropathy are rare., Patient Concerns: We report the case of a 40-years-old woman with microscopic hematuria, mild proteinuria and an immunocompromised status. Laboratory data revealed serum creatinine showed progressive progress, suddenly rising from the normal range to 316.2μmol/L within 4 months. The CD4 lymphocyte count was 0.274 × 109/L (reference value 0.35-1.82 × 109/L). The anti-GBM antibody titer was 192.4 IU/mL (reference range: <20 RU/mL)., Diagnoses: Renal biopsy was performed after admission. The pathological diagnosis was type I crescentic glomerulonephritis, IgA nephropathy, and clinical anti-GBM disease., Interventions: The patient was seriously ill on admission and progressed rapidly. Combined with poor immune function, we immediately initiated high-frequency plasma exchange (PE). In addition, to avoid rebound of antibody levels, PE was performed for 5 times. Follow-up treatment was combined with standard-dose corticosteroids and cyclophosphamide., Outcomes: The patient was followed up for 1 year. On the last visit, her serum creatinine decreased to 103.5μmol/L, anti-GBM antibody remained negative, and proteinuria and hematuria disappeared., Lessons: This case illustrates that when crescentic nephritis or anti-GBM disease is combined with other immune diseases, especially when the immune function is extremely low, if the application of high-dose steroid shocks may induce fatal infections, to some extent high frequency PE has certain advantages., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

This work reports cascade cyclization between 1-allenyl-2-alkynylbenzenes and nitrosoarenes. When these two components reacted alone under N 2 , N,O-functionalized indane-fused isoxazolidines 3 were obtained selectively. DFT calculations verify that this reaction sequence involves unprecedented nitrone/alkyne cycloadditions, followed by diradical rearrangement.

In our continued search for bioactive metabolites from cultures of rare Actinobacteria resources from all over Taiwan and various natural ecological environments, an active antimicrobial strain of Acrocarpospora punica 04107M was collected in Taitung County in Taiwan and prepared from soil. The bioassay-guided fractionation of the BuOH extract of a culture broth from A. punica 04107M led to the isolation of five previously undescribed compounds: Acrocarposporins A−E (Compounds 1−5). All the constituents were confirmed by HRESIMS and 1D- and 2D-NMR spectroscopy. Their antifungal activity was also evaluated. Our results showed that four constituents (Compounds 1, 2, 4, and 5) possessed mild antifungal activity against Aspergillus niger, Penicillium italicum, Candida albicans, and Saccharomyces cerevisiae. It is worth mentioning that the chemical composition of Acrocarpospora punica 04107M has never been studied. This is the first report on diterpenoid metabolites from the genus Acrocarpospora.