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As complex materials are widely used in emerging technologies for environmental and energy applications, it is important to be able to quantify their stimuli-response behaviors. Light is a useful stimulus to modulate multifunctional electrochemical, magnetic, optical, and structural properties in metal–organic frameworks (MOFs); however, the underlying mechanisms and kinetics of light-induced structural changes are not well understood. Herein, a double [2 + 2] photocyclization in photoactive [Cd2(stil)2(Py2TTF)2] (stil2– = 4,4′-stilbenedicarboxylic acid, Py2TTF = 2,6-bis(4′-pyridyl)-tetrathiafulvalene) offers a powerful platform to quantitatively probe solid-state photocyclization kinetics. Variable-temperature Raman spectroscopy revealed a nonlinear temperature dependence of these parameters, which could be analyzed using the Johnson–Mehl–Avrami–Kolmogorov (JMAK) kinetic model to yield a maximum rate observed between 0 °C and 20 °C of approximately 0.172 s–1. These results offer the first example of the quantification of the photocyclization kinetics in a MOF. Density functional theory (DFT) calculations support a singlet reaction mechanism for the double [2 + 2] photocyclization, which is facilitated by the cofacial alignment of Py2TTF ligands. Establishing mechanistic and kinetic models that can be applied to multistimuli-responsive materials provides a powerful platform for their future design for applications in sensing, switching, and molecular separations.

1,1′-Bi-2-naphthol (BINOL)-derived chiral bifunctional sulfide and selenide catalysts that possess a hydroxy group are known to be effective catalysts for enantioselective bromolactonizations. When applied to asymmetric iodolactonizations of 4-pentenoic acids, these catalysts yield chiral γ-butyrolactone products that are important compounds in medicinal chemistry. Although chiral bifunctional selenides have shown good catalytic performances in enantioselective iodolactonizations, reactions with BINOL-derived chiral sulfide catalysts unexpectedly gave iodolactonization products in nearly racemic forms. The roles of chalcogenide moieties and hydroxy groups on bifunctional catalysts were investigated, and the importance of both a selenide moiety and a hydroxy group on chiral bifunctional selenide catalysts to achieve enantioselective iodolactonizations was clarified. An optimized chiral bifunctional selenide catalyst was applied to the asymmetric synthesis of chiral γ-butyrolactones and phthalides. Furthermore, the utility of chiral bifunctional selenides was also demonstrated in the catalytic enantioselective desymmetrizing iodolactonization of α,α-diallyl carboxylic acids., Chemical & pharmaceutical bulletin, 70(9), pp. 599-604; 2022

In this study, we used computational quantum chemistry to investigate the cation affinity for a range of nucleophiles to gauge the possibility of using organochalcogens as catalysts for cation transfer (reference data and geometries are provided in the repository https://github.com/armanderch/ca176 ). In general, the calculated gas-phase cation affinities decrease in the order Cl+ > Br+ > I+ > carbon-centered cation, the anionic nucleophiles have significantly larger cation affinities than the neutral ones, sulfides have larger cation affinities than selenides, and solvation lowers the cation affinities and especially for anionic nucleophiles. These observations are consistent with general chemical intuitions. The energies for the resulting condensed-phase cation transfer reactions show that transferring a carbon-centered cation from a neutral source (e.g., Me2CO3) to a chalcogen nucleophile (e.g., Me2S) is thermochemically viable. However, they are associated with large kinetic barriers. Overall, we find that SeMeC6H5 may be a suitable catalyst for transferring a carbon-centered cation from an active source such as MeCO3R or MeSO4R. In this study, we also find that double-hybrid DFT methods, e.g., DSD-PBEP86 to be reasonable for the study of these cation transfer processes.

The stellar optoelectronic properties of metal halide perovskites provide enormous promise for next-generation optical devices with excellent conversion efficiencies and lower manufacturing costs. However, there is a long-standing ambiguity as to whether the perovskite surface/interface (e.g. structure, charge transfer or source of off-target recombination) or bulk properties are the more determining factor in device performance. We fabricated an array of CsPbI3 crystal and hybrid glass composites by sintering and globally visualised the property-performance landscape. Our findings reveal that the interface is the primary determinant of the crystal phases, optoelectronic quality, and stability of CsPbI3. In particular, the presence of a diffusion "alloying" layer is discovered to be critical for passivating surface traps, and beneficially altering the energy landscape of crystal phases. However, high-temperature sintering results in the promotion of a non-stoichiometric perovskite and excess traps at the interface, despite the short-range structure of halide is retained within the alloying layer. By shedding light on functional hetero-interfaces, our research offers the key factors for engineering high-performance perovskite devices.

Off-target interactions between antisense oligonucleotides (ASOs) with state-of-the-art modifications and biological components still pose clinical safety liabilities. To prevent both hybridization-dependent and -independent off-target interactions, a novel nanoarchitecture called BRace On a THERapeutic aSo (BROTHERS or BRO) consisting of typical gapmer ASO and partially complementary peptide nucleic acid (PNA) strand was devised. This non-canonical ASO/PNA hybrids have been shown to have non-specific protein-binding repellent characteristics. Feasible optimization of the structural and thermodynamic characteristics of this duplex system was also demonstrated to elicit in vivo operative toehold-mediated strand displacement (TMSD) reaction, which can reduce hybridization to RNA off-targets. The optimized BROs dramatically mitigated hepatotoxicity while maintaining the on-target knockdown activity of their parent ASOs in vivo. This new technique will not only bring a novel BRO class of drugs that would have a transformative impact on the extrahepatic delivery of ASOs, but also help uncover the toxicity mechanism of ASOs.

Diabetes is a risk factor for Alzheimer's disease (AD), which is also called type 3 diabetes with insulin reduction and insulin resistance in AD patient brains. However, the molecular mechanism coupling diabetes to AD onset remains incompletely understood. Here we show that inflammation, associated with obesity and diabetes elicited by high-fat diet (HFD), activates neuronal C/EBPβ/AEP signaling that drives AD pathologies and cognitive disorders. HFD stimulates diabetes and insulin resistance in neuronal Thy1-C/EBPβ transgenic (Tg) mice, accompanied with prominent mouse Aβ accumulation and hyperphosphorylated Tau aggregation in the brain, triggering cognitive deficits. These effects are profoundly diminished when AEP is deleted from C/EBPβ Tg mice. Chronic treatment with inflammatory lipopolysaccharide (LPS) facilitates AD pathologies and cognitive disorders in C/EBPβ Tg but not in wild-type mice, and these deleterious effects were substantially alleviated in C/EBPβ Tg/AEP -/- mice. Remarkably, the anti-inflammatory drug aspirin strongly attenuates HFD-induced diabetes and AD pathologies in neuronal C/EBPβ Tg mice. Therefore, our findings demonstrate that inflammation-activated neuronal C/EBPβ/AEP signaling couples diabetes to AD.

Cancer stem cells (CSC) are supported by the tumor microenvironment, and non-CSCs can regain CSC phenotypes in certain niches, leading to limited clinical benefits of CSC-targeted therapy. A better understanding of the mechanisms governing the orchestration of the CSC niche could help improve the therapeutic targeting of CSCs. Here, we report that Rab13, a small GTPase, is highly expressed in breast CSCs (BCSC). Rab13 depletion suppressed breast cancer cell stemness, tumorigenesis, and chemoresistance by reducing tumor-stroma cross-talk. Accordingly, Rab13 controlled the membrane translocation of C-X-C chemokine receptor type 1/2 (CXCR1/2), allowing tumor cells to interact with tumor-associated macrophages and cancer-associated fibroblasts to establish a supportive BCSC niche. Targeting the Rab13-mediated BCSC niche with bardoxolone-methyl (C-28 methyl ester of 2-cyano-3, 12-dioxoolen-1, 9-dien-28-oic acid; CDDO-Me) prevented BCSC stemness in vitro and in vivo. These findings highlight the novel regulatory mechanism of Rab13 in BCSC, with important implications for the development of therapeutic strategies for disrupting the BCSC niche.Significance:Targeting Rab13 perturbs formation of the breast cancer stem cell niche by inhibiting cross-talk between cancer cells and the tumor microenvironment, providing a therapeutic opportunity for niche-targeted breast cancer treatment.

Supplementary Data from Rab13 Sustains Breast Cancer Stem Cells by Supporting Tumor–Stroma Cross-talk

We present an approximate approach for the calculation of ionization potential (IP) and electron affinity (EA) by exploiting the complementary energy non-linearity errors for a species M and its one-electron-ionized counterpart (M

This paper systematically examines the performance of contemporary wavefunction and density functional theory methods to identify robust and cost-efficient methods for predicting gas-phase anion binding energies. This includes the local coupled cluster LNO-CCSD(T) and DLPNO-CCSD(T), as well as double-hybrid DSD-PBEP86-D3(BJ) and various hybrid functionals M06-2X, B3LYP-D3(BJ), ωB97M-V, and ωB97X-V. The focus is on dual-hydrogen-bonding anion receptors that are commonly found in supramolecular chemistry and organocatalysis, namely, (thio)ureas, deltamides, (thio)squaramides, and croconamides as well as the yet-to-be-explored rhodizonamides. Of the methods examined, M06-2X emerged as the overall best performing method as the other functionals including DSD-PBEP86-D3(BJ) and the local coupled cluster DLPNO-CCSD(T) method displayed systematic errors that increase with the degree of carbonylation of the receptors. Hybrid ONIOM models that employed semiempirical methods (PM7, GFN1-xTB, and GFN2-xTB) and "threefold"-corrected small-basis set potentials (HF-3c, B97-3c, and PBEh-3c) were explored, and the best models resulted in 50- to 500-fold reduction in CPU time compared to W1-local. These calculations provide important insight into the structure-binding relationships where there is a direct correlation between Brønsted acidity and anion binding affinity, though the strength of the correlation also depends on other factors such as hydrogen-bonding geometry and the geometrical distortion that the receptor needs to undergo to bind the anion.

Nanoconfinement offers opportunities to tune physical properties of molecular entities by altering their assembled structures. This also applies to acene-based molecules with potentially rich π–π interactions. Unlike most of the previous cases with acene-based guests directly incorporated into hosts, we take a further step by oligomerizing a fluorescent anthryl monomer, 9-vinylanthracene, inside nanochannels of a metal–organic framework, which is a pillared three-dimensional kagome net of [Zn2(bdc)2(dabco)] (bdc2– = 1,4-benzenedicarboxylate; dabco = 1,4-diazabicyclo[2.2.2]octane). The fluorescence emission of the guest can be significantly enhanced after oligomerization, which is likely due to the suppressed nonemissive interaction between the oligomerized molecules in the nanospace and the MOF wall. The case we have demonstrated for fluorescence enhancement via confined oligomerization provides inspiration for the design of luminescent composites and is encouraging for further exploration of molecules in a nanoconfined space.

IntroductionControversies surround the issue if chronic consumption of a high-sugar diet is detrimental to health or not. This study investigates whether lifelong consumption of a higher sucrose diet will induce overeating, and obesity, and cause metabolic dysfunctions such as hyperglycemia and dyslipidaemia in C57BL/6N mice, compared to a lower sucrose diet.MethodsMale C57BL/6N mice at 3 weeks of age were randomized into consuming a diet with 25 or 10% kcal from sucrose for the rest of their lives. Body weight, food and water intake, fasting blood glucose, insulin, and lipid levels were measured at regular intervals. At the end of the study, organs and tissues were collected and gene expression was measured.ResultsThere was no discernible difference in the impact on food intake, body composition, glucose and lipid homeostasis, liver triglyceride content, life expectancy, as well as gene expression related to intermediary metabolism between mice fed a diet with 10 vs. 25% kcal as sucrose over their lifespan. We also showed that switching from a 25% kcal diet to a 10% kcal diet at different life stages, or vice versa, did not appear to affect these outcomes of interest.DiscussionThe results from our study suggest that lifelong consumption of a higher sugar diet generally did not induce overeating and obesity, disrupt carbohydrate metabolism and lipid homeostasis, and reduce life expectancy compared with a lower sugar diet. Our unorthodox findings disagreed with the popular belief that higher sugar consumption is detrimental to health, which should be confirmed in future studies.

A recent study has examined the accuracy of NIST heats of formation for a set of C, H, and O-containing species with a proposed low-cost quantum chemistry approach. In the present study, we have used high-level methods such as W1X-2 to obtain these data more rigorously, which we have then used to assess the NIST and the previously computed values. We find that many of these NIST data that are as suggested to be unreliable by the previous study are indeed inconsistent with our high-level reference values. However, we also find substantial deviations for the previously computed values from our benchmark. Thus, we have assessed the performance of alternative low-cost methods. In our assessment, we have additionally examined C, H, N, and O-containing species for which heats of formation are available from the NIST database. We find the ωB97M-V/ma-def2-TZVP, DSD-PBEP86/ma-def2-TZVP, and CCSD(T)-F12b/aug'-cc-pVDZ methods to be adequate for obtaining heats of formation with the atomization approach, once their atomic energies are optimized with our benchmark. Notably, the low-cost ωB97M-V method yields values that agree to be within 10 kJ mol

Hypertension and type 2 diabetes mellitus (T2DM) are important, intertwined public health issues. People with both conditions face significantly elevated risks of cardiovascular (CV) and renal complications. To optimize patient care, a multidisciplinary expert panel met to review recent evidence on optimal blood pressure (BP) targets, implications of albuminuria, and treatment regimens for hypertensive patients with T2DM, with the aim of providing recommendations for physicians in Hong Kong. The panel reviewed the relevant literature, obtained by searching PubMed for the publication period from January 2015 to June 2021, to address five discussion areas: (i) BP targets based on CV/renal benefits; (ii) management of isolated systolic or diastolic hypertension; (iii) roles of angiotensin II receptor blockers; (iv) implications of albuminuria for CV/renal events and treatment choices; and (v) roles and tools of screening for microalbuminuria. The panel held three virtual meetings using a modified Delphi method to address the discussion areas. After each meeting, consensus statements were derived and anonymously voted on by every panelist. A total of 17 consensus statements were formulated based on recent evidence and expert insights regarding cardioprotection and renoprotection for hypertensive patients with T2DM.

In the present study, we have investigated the applicability of long-range-corrected (LC) functionals to a Kohn-Sham (KS) Koopmans'-type theorem. Specifically, we have examined the performance of optimally tuned LCgau-core functionals (in combination with BOP and PW86-PW91 exchange-correlation functionals) by calculating the ionization potential (IP) within the context of Koopmans' prediction. In the LC scheme, the electron repulsion operator, 1/

Activation of Mas-related G protein-coupled receptor X2 (MRGPRX2) is a crucial non-IgE pathway for mast cell activation associated with allergic reactions and inflammation. Only a few peptides and small compounds targeting MRGPRX2 have been reported, with limited information on their pharmacological activity.We sought to develop novel small molecule MRGPRX2 antagonists to treat MRGPRX2 mediated allergies and inflammation.A computational approach was used to design novel small molecules as MRGPRX2 antagonists. The shortlisted molecules were synthesized and characterized by LCMS and NMR. Inhibitory activity on MRGPRX2 signalling was assessed in vitro using functional bioassays (β-hexosaminidase, calcium flux, and chemokine synthesis) and receptor activation assays (β-arrestin recruitment and Western blot) in human LAD-2 mast cells and HTLA cells. In vivo effects of the novel MRGPRX2 antagonists were assessed using a mouse model of acute allergy and systemic anaphylaxis.The novel small molecules demonstrated higher binding affinity with MRGPRX2 in the docking study. The half-maximal inhibitory concentration is in the low micromolar range (5-21μM). The small molecules inhibited not only the early phase of mast cell activation but also the late phase, associated with chemokine and prostaglandin release. Further, the Western blotting analysis showed the inhibition of downstream PLC-γ, ERK1/2 and Akt signalling pathway. Moreover, in the mouse models of allergies, the small molecule administration effectively blocks acute, systemic allergic reactions and inflammation and prevents systemic anaphylaxis.The small molecules might hold a significant therapeutic promise to treat MRGPRX2 mediated allergies and inflammation.

In the present study, we have examined density functional theory methods for the calculation of the interaction energy between a small molecule and its environment. For simple systems such as a neutral solute in a neutral solvent, good accuracy can be attained using low-cost "3c" methods, in particular r

In the present study, we have examined the electronic structures related to the fluorescence properties of small Ag42+ complexes encapsulated in zeolites. We find that interaction between Ag42+ and coordinated water molecules, which was previously proposed to be the origin of fluorescence, may not be a sufficient condition by itself. Refinement of the previously used all-silicon-cage model to include framework Al atoms leads to an asymmetric environment, and this alters the electronic structure in favor of fluorescence. We have further examined the substitution of the H2O ligands by NH3, H2S, PH3, CO and CS. Among these systems, Ag42+ binds most strongly to NH3 but the energetics for the H2S and PH3 complexes is also reasonable. The energy of the fluorescent light is related to the energy of the lowest-energy triplet state, and these energies for the H2O, NH3, H2S and PH3 systems span the range of ∼2–3 eV, i.e., roughly the visible range. Thus, the use of different ligands appears to be an attractive means for tailoring the luminescence properties., Physical Chemistry Chemical Physics, 23(3), pp.1984-1993; 2021

Innovative and robust photosensitisation materials play a cardinal role in advancing the combined effort towards efficient solar energy harvesting. Here, we demonstrate the photocathode functionality of a Metal–Organic Framework (MOF) featuring cofacial pairs of photo- and electro-active 1,4,5,8-naphthalenediimide (NDI) ligands, which was successfully applied to markedly reduce the overpotential required for CO2 reduction to CO by a well-known rhenium molecular electrocatalyst. Reduction of [Cd(DPNDI)(TDC)]n (DPNDI = N,N′-di(4-pyridyl)-1,4,5,8-naphthalenediimide, H2TDC = thiophene-2,5-dicarboxylic acid) to its mixed-valence state induces through-space Intervalence Charge Transfer (IVCT) within cofacial DPNDI units. Irradiation of the mixed-valence MOF in the visible region generates a DPNDI photoexcited radical monoanion state, which is stabilised as a persistent species by the inherent IVCT interactions and has been rationalised using Density Functional Theory (DFT). This photoexcited radical monoanion state was able to undergo charge transfer (CT) reduction of the rhenium molecular electrocatalyst to effect CO generation at a lower overpotential than that required by the discrete electrocatalyst itself. The exploitation of cofacial MOFs opens new directions for the design philosophy behind light harvesting materials., The photocathode functionality of a Metal–Organic Framework (MOF) featuring cofacial photo- and electro-active ligands provides a new approach to CO2 reduction via charge transfer with a rhenium electrocatalyst.

Redox-active ionic liquids (RAILs) are gaining attention as a material that can create a wide range of functions. We herein propose a charge-transfer (CT) RAIL by mixing two RAILs, specifically a carbazole-based ionic liquid ([CzC4ImC1][TFSI]) as a donor and a viologen-based ionic liquid ([C4VC7][TFSI]2) as an acceptor. We investigated the effect of CT interaction on the physicochemical properties of the CT ionic liquid (CT-IL) using the results of temperature-dependent measurements of UV-vis absorption, viscosity, and ionic conductivity as well as cyclic voltammograms. We employed the Walden analysis and the Grunberg–Nissan model to elucidate the effect of the CT interaction on the viscosity and ionic conductivity. The CT interaction reduces the viscosity by reducing the electrostatic attraction between the dicationic viologen and TFSI anion. It also reduces the ionic conductivity by the CT association of the dicationic viologen and carbazole. The electrochemically reversible responses of the viologens in [C4VC7][TFSI]2 and CT-IL are consistent with the Nernstian and the interacting two-redox site models. Notably, the transport and electrochemical properties are modulated by CT interaction, leading to unique features that are not present in individual component ILs. The inclusion of CT interaction in RAILs thus provides a powerful means to expand the scope of functionalized ionic liquids., A redox-active ionic liquid (RAIL) consisting of a carbazole and viologen shows charge transfer (CT) interaction. The physicochemical properties are modulated by the CT interaction by comparison with the individual RAILs.

We have examined the conformational space of model systems for the hydrogen-bonded and covalent linkages between the sugar and lignin components of lignocellulose. Specifically, glucose and paracoumaryl alcohol moieties are used in our models. Multistage screening protocols are used to identify and validate a set of lowest-energy isomers. We found a cost-effective screening process involving an initial screening with DFTB3/3ob using a 20 kJ mol

Significance Aggression is dependent on the sex of the conspecific in almost all animal species. But the neuronal basis of how sex-specific chemosensory signals regulate aggression is poorly understood. Using the fruit fly model of Drosophila melanogaster , we demonstrate that activation of a group of GABAergic central brain neurons, known to respond to sex-specific pheromonal stimuli, enhances aggression in dyadic male encounters. Inactivation of this neuronal group decreases aggression and increases the reciprocal social behavior of courtship. Our results can help trace the neural circuit from pheromone processing in the sensory neurons to behavior integration in the central brain and ultimately help understand how neurons encode the behavior of aggression.

We present an approximate approach for the simulation of UV/vis spectra using conventional [non-time-dependent (non-TD)] DFT computations. It uses Kohn-Sham orbitals and orbital energies to estimate both the excitation energies and the associated oscillator strengths. For a wide range of systems from small molecules to large molecular dyes used in electrochromic and solar-cell applications, reasonable UV/vis spectra are generated, each with just two conventional DFT computations. The accuracy is generally comparable to what one would expect from TD-DFT calculations. In comparison to TD-DFT, the protocol of the present study provides an intuitive and notably more rapid means for simulating electronic absorption properties. It enables efficient screening of materials for a wide range of relevant applications., The Journal of Physical Chemistry Letters, 11(18), pp.7882-7885; 2020

We have used quantum chemistry computations, in conjunction with isodesmic-type reactions, to obtain accurate heats of formation (HoFs) for the small fullerenes C20 (2358.2 ± 8.0 kJ mol-1), C24 (2566.2 ± 7.6), and the lowest-energy isomers of C32 (2461.1 ± 15.4), C42 (2629.0 ± 20.5), and C54 (2686.2 ± 25.3). As part of this endeavor, we have also obtained accurate HoFs for several medium-sized molecules, namely 216.6 ± 1.4 for fulvene, 375.5 ± 1.5 for pentalene, 670.8 ± 2.9 for acepentalene, and 262.7 ± 2.5 for acenaphthylene. We combine the energies of the small fullerenes and previously obtained energies for larger fullerenes (from C60 to C6000) into a full picture of fullerene thermochemical stability. In general, the per-carbon energies can be reasonably approximated by the "R+D"model that we have previously developed [ Chan et al. J. Chem. Theory Comput. 2019, 15, 1255-1264 ], which takes into account Resonance and structural Deformation factors. In a case study on C54, we find that most of the high-deformation-energy atoms correspond to the sites of the C-Cl bond in the experimentally captured C54Cl8.In another case study, we find that C60 has the lowest value for the maximum local-deformation energy when compared with similar-sized fullerenes, which is consistent with its "special stability". These results are indicative of structural deformation playing an important role in the reactivity of fullerenes., The journal of physical chemistry. A, 124(33), pp.6688-6698; 2020

Aggression is known to be regulated by pheromonal information in many species. But how central brain neurons processing this information modulate aggression is poorly understood. Using the fruit fly model of

Cancer stem cells (CSC) are supported by the tumor microenvironment, and non-CSCs can regain CSC phenotypes in certain niches, leading to limited clinical benefits of CSC-targeted therapy. A better understanding of the mechanisms governing the orchestration of the CSC niche could help improve the therapeutic targeting of CSCs. Here, we report that Rab13, a small GTPase, is highly expressed in breast CSCs (BCSC). Rab13 depletion suppressed breast cancer cell stemness, tumorigenesis, and chemoresistance by reducing tumor-stroma cross-talk. Accordingly, Rab13 controlled the membrane translocation of C-X-C chemokine receptor type 1/2 (CXCR1/2), allowing tumor cells to interact with tumor-associated macrophages and cancer-associated fibroblasts to establish a supportive BCSC niche. Targeting the Rab13-mediated BCSC niche with bardoxolone-methyl (C-28 methyl ester of 2-cyano-3, 12-dioxoolen-1, 9-dien-28-oic acid; CDDO-Me) prevented BCSC stemness in vitro and in vivo. These findings highlight the novel regulatory mechanism of Rab13 in BCSC, with important implications for the development of therapeutic strategies for disrupting the BCSC niche. Significance: Targeting Rab13 perturbs formation of the breast cancer stem cell niche by inhibiting cross-talk between cancer cells and the tumor microenvironment, providing a therapeutic opportunity for niche-targeted breast cancer treatment.

Peripheral sensory neurons are the gateway to the environment across species. In Drosophila, olfactory and gustatory senses are required to initiate courtship, as well as for the escalation of courtship patterns that lead to copulation. To be successful, copulation must last long enough to ensure the transfer of sperm and seminal fluid that ultimately leads to fertilization. The peripheral sensory information required to regulate copulation duration is unclear. Here, we employed genetic manipulations that allow driving gene expression in the male genitalia as a tool to uncover the role of these genitalia specific neurons in copulation. The fly genitalia contain sex-specific bristle hairs innervated by mechanosensory neurons. To date, the role of the sensory information collected by these peripheral neurons in male copulatory behavior is unknown. We confirmed that these MSNs are cholinergic and co-express both fru and dsx. We found that the sensory information received by the peripheral sensory neurons from the front legs (GRNs) and mechanosensory neurons (MSNs) at the male genitalia contribute to the regulation of copulation duration. Moreover, our results show that their function is required for copulation persistence, which ensures copulation is undisrupted in the presence of environmental stress before sperm transfer is complete.

Peripheral sensory neurons are the gateway to the environment across species. In Drosophila, olfactory and gustatory senses are required to initiate courtship, as well as for the escalation of courtship patterns that lead to copulation. To be successful, copulation must last long enough to ensure the transfer of sperm and seminal fluid that ultimately leads to fertilization. The fly genitalia contain sex-specific bristle hairs innervated by mechanosensory neurons. To date, the role of the sensory information collected by these peripheral neurons in male copulatory behavior is unknown. Here, we employed genetic manipulations that allow driving gene expression in the male genitalia as a tool to uncover the role of these genitalia specific neurons in copulation. We found that the sensory information received by the mechanosensory neurons (MSNs) at the male genitalia plays a key role in copulation duration. We confirmed that these MSNs are cholinergic and co-express both fru and dsx. Moreover, our results show that the function of these fru/dsx cholinergic MSNs is required for copulation persistence, which ensures copulation is undisrupted in the presence of environmental stress before sperm transfer is complete.

Lead halide perovskite (LHP) semiconductors show exceptional optoelectronic properties. Barriers for their applications, however, lie in their polymorphism, instability to polar solvents, phase segregation, and susceptibility to the leaching of lead ions. We report a family of scalable composites fabricated through liquid-phase sintering of LHPs and metal-organic framework glasses. The glass acts as a matrix for LHPs, effectively stabilizing nonequilibrium perovskite phases through interfacial interactions. These interactions also passivate LHP surface defects and impart bright, narrow-band photoluminescence with a wide gamut for creating white light-emitting diodes (LEDs). The processable composites show high stability against immersion in water and organic solvents as well as exposure to heat, light, air, and ambient humidity. These properties, together with their lead self-sequestration capability, can enable breakthrough applications for LHPs.

Mitochondrial remodeling is dysregulated in metabolic diseases but the underlying mechanism is not fully understood. We report here that BDNF (brain derived neurotrophic factor) provokes mitochondrial fission and clearance in skeletal muscle via the PRKAA/AMPK-PINK1-PRKN/Parkin and PRKAA-DNM1L/DRP1-MFF pathways. Depleting Bdnf expression in myotubes reduced fatty acid-induced mitofission and mitophagy, which was associated with mitochondrial elongation and impaired lipid handling. Muscle-specific bdnf knockout (MBKO) mice displayed defective mitofission and mitophagy, and accumulation of dysfunctional mitochondria in the muscle when they were fed with a high-fat diet (HFD). These animals also have exacerbated body weight gain, increased intramyocellular lipid deposition, reduced energy expenditure, poor metabolic flexibility, and more insulin resistance. In contrast, consuming a BDNF mimetic (7,8-dihydroxyflavone) increased mitochondrial content, and enhanced mitofission and mitophagy in the skeletal muscles. Hence, BDNF is an essential myokine to maintain mitochondrial quality and function, and its repression in obesity might contribute to impaired metabolism. Abbreviations: 7,8-DHF: 7,8-dihydroxyflavone; ACACA/ACC: acetyl Coenzyme A carboxylase alpha; ACAD: acyl-Coenzyme A dehydrogenase family; ACADVL: acyl-Coenzyme A dehydrogenase, very long chain; ACOT: acyl-CoA thioesterase; CAMKK2: calcium/calmodulin-dependent protein kinase kinase 2, beta; BDNF: brain derived neurotrophic factor; BNIP3: BCL2/adenovirus E1B interacting protein 3; BNIP3L/NIX: BCL2/adenovirus E1B interacting protein 3-like; CCL2/MCP-1: chemokine (C-C motif) ligand 2; CCL5: chemokine (C-C motif) ligand 5; CNS: central nervous system; CPT1B: carnitine palmitoyltransferase 1b, muscle; Cpt2: carnitine palmitoyltransferase 2; CREB: cAMP responsive element binding protein; DNM1L/DRP1: dynamin 1-like; E2: estrogen; EHHADH: enoyl-CoenzymeA hydratase/3-hydroxyacyl CoenzymeA dehydrogenase; ESR1/ER-alpha: estrogen receptor 1 (alpha); FA: fatty acid; FAO: fatty acid oxidation; FCCP: carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone; FFA: free fatty acids; FGF21: fibroblast growth factor 21; FUNDC1: FUN14 domain containing 1; HADHA: hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha; HFD: high-fat diet; iWAT: inguinal white adipose tissues; MAP1LC3A/LC3A: microtubule-associated protein 1 light chain 3 alpha; MBKO; muscle-specific bdnf knockout; IL6/IL-6: interleukin 6; MCEE: methylmalonyl CoA epimerase; MFF: mitochondrial fission factor; NTRK2/TRKB: neurotrophic tyrosine kinase, receptor, type 2; OPTN: optineurin; PA: palmitic acid; PARL: presenilin associated, rhomboid-like; PDH: pyruvate dehydrogenase; PINK1: PTEN induced putative kinase 1; PPARGC1A/PGC-1α: peroxisome proliferative activated receptor, gamma, coactivator 1 alpha; PRKAA/AMPK: protein kinase, AMP-activated, alpha 2 catalytic subunit; ROS: reactive oxygen species; TBK1: TANK-binding kinase 1; TG: triacylglycerides; TNF/TNFα: tumor necrosis factor; TOMM20: translocase of outer mitochondrial membrane 20; ULK1: unc-51 like kinase 1

Composite ab initio methods based on local coupled-cluster approaches calculate the CCSD(T)/CBS energy at a significantly reduced computational cost than the corresponding canonical methods. While showing promising performance for general thermochemistry, local composite ab initio methods have not been tested for fullerenes. Here we examine the performance of several local G4(MP2)-based methods for calculating the relative stability of a diverse set of C40 fullerenes. We use canonical G4(MP2) isomerization energies as reference data. Fullerenes provide a challenging problem for DLPNO-G4(MP2)-based methods. The DLPNObased methods result in overall root-mean-square deviations (RMSDs) of 28.6 (NormalPNO with CCSD(T0)), 23.0 (NormalPNO with CCSD(T1)), and 16.1 (TightPNO with CCSD(T0)) kJ mol–1. The local natural orbital LNO-G4(MP2) method provides the best overall performance with an RMSD of 4.9 kJ mol–1. The DLPNO-G4(MP2) and LNO-G4(MP2) methods systematically overestimate the canonical G4(MP2) isomerization energies. Therefore, they provide valuable upper limits of the fullerene isomerization energies., Computational and Theoretical Chemistry, 1217, art. no. 113874; 2022