Search

Amino acids have a crucial role in the field of asymmetric organocatalysis for the production of chiral compounds with high added value and specific biological activity. In particular, proline offers high activity and stereoselectivity for catalyzing aldol reactions in organic solvents. However, proline-based catalysts often lack water-solubility, accessibility, catalytic performance, or recovery in aqueous media. This work reports the design of proline-functionalized poly(methyl methacrylate) (PMMA) nanoparticles with a magnetic core that offer high availability of chiral units in water and high recyclability. A proline-based copolymerizable surfactant is designed and integrated onto the surface of PMMA nanoparticles through a miniemulsion polymerization process without using additional surfactants. The miniemulsion technique allows the incorporation of magnetite to the system to create a magnetically separable catalyst. The chiral nanocatalyst presents a high diastereoselective catalytic activity for the intermolecular aldol reaction between p-nitrobenzaldehyde and cyclohexanone in water., (© 2024 The Author(s). Macromolecular Rapid Communications published by Wiley‐VCH GmbH.)

Fluorine, the tiny robust atom, with its unique features has captured the attention of scientists in recent times, especially in drug discovery with its integration in small molecules, peptides, and proteins. However, studies to understand the 'fluorine effects' on the conformation of molecules that follow 'beyond the rule of 5' are in the infancy yet significant in molecular design and function. For the first time, using short hybrid peptide sequence as an appropriate model, we examined the substitution effect (size, stereoelectronic effect, and hydrogen bonding) using X-ray diffraction, 2D-NMR, and CD studies. The comparative study on their folding patterns with hydrogen-substituted analogs can provide valuable insights into fluorinated substrates' design., (© 2024 Wiley‐VCH GmbH.)

Histone deacetylases (HDACs) have been identified as promising targets for anticancer treatment. The study demonstrates virtual screening, molecular docking, and synthesis of 4-(2-aminoethyl) phenol derivatives as HDAC inhibitors. The virtual screening and molecular docking analysis led to the identification of 10 representative compounds, which were evaluated based on their drug-like properties. The results demonstrated that these compounds effectively interacted with the active site pocket of HDAC 3 through π-stacking, Zn 2+ coordination, hydrogen bonding, and hydrophobic interactions with catalytic residues. Furthermore, a series of 4-(2-aminoethyl) phenol derivatives were synthesized, and their HDAC inhibitory activity was evaluated. Compounds 18 and 20 showed significant HDAC inhibitory activity of 64.94 ± 1.17% and 52.45 ± 1.45%, respectively, compared to the solvent control. The promising results of this study encourage further research on 4-(2-aminoethyl) phenol derivatives and may provide significant insight into the design of novel small molecule HDAC inhibitors to fight against target-specific malignancies of chronic obstructive pulmonary disease and nonsmall cell lung cancer in the future., (© 2023 Wiley Periodicals LLC.)

Histone deacetylase (HDAC) enzymes 1–3 exist in several corepressor complexes and are viable drug targets. To date, proteolysis targeting chimeras (PROTACs) designed to target HDAC1–3 typically exhibit the selective degradation of HDAC3. Herein, we report cereblon-recruiting PROTACs that degrade HDAC1 with selectivity over HDAC3. [ABSTRACT FROM AUTHOR]

According to the FAO/WHO guidelines, selection of probiotics requires the assessment of survival under gastrointestinal stress and adhesion to human epithelial cells. These attributes were evaluated on Akkermansia muciniphila ATCC BAA-835 simulating the gastrointestinal transit (GIT) immediately followed by adhesion to human intestinal cell lines (CaCo2, HT-29, and HT-29-MTX) as an alternative approach to in vitro methods performed with fresh cells in each trial. The survival rate after GIT, as determined by plate counts and fluorescent probes, was significantly higher for A. muciniphila (about 8 Log CFU/mL) than for the probiotic Lacticaseibacillus rhamnosus GG ATCC 53103 (about 3 Log CFU/mL). The use of Live/Dead assay highlighted that A. muciniphila forms cell aggregates in the gastric phase as protective mechanism, explaining its high viability in the intestine. The rate of adhesion to human cell lines was always lower for strains tested after simulated GIT than for strains that did not undergo simulated GIT. Akkermansia muciniphila exhibited significantly higher adhesion than Lbs. rhamnosus GG, particularly to the mucus-secreting HT-29-MTX cells across a range of concentrations (2–8 Log CFU/mL). Finally, the bioinformatic analysis of A. muciniphila proteome confirmed the Amuc_1434 as a potential factor in binding to the human MUC2 protein. [ABSTRACT FROM AUTHOR]

The China Space Station Telescope (CSST, also known as Xuntian) is a serviceable two-meter-aperture wide-field telescope operating in the same orbit as the China Space Station. The CSST plans to survey a sky area of 17,500 deg2 of the medium-to-high Galactic latitude to a depth of 25–26 AB mag in at least 6 photometric bands over 255–1,000 nm. Within such a large sky area, slitless spectra will also be taken over the same wavelength range as the imaging survey. Even though the CSST survey is not dedicated to time-domain studies, it would still detect a large number of transients, such as supernovae (SNe). In this paper, we simulate photometric SN observations based on a strawman survey plan using the Sncosmo package. During its 10-year survey, the CSST is expected to observe about 5 million SNe of various types. With quality cuts, we obtain a “gold” sample that comprises roughly 7,400 SNe Ia, 2,200 SNe Ibc, and 6,500 SNe II candidates with correctly classified percentages reaching 91%, 63%, and 93% (formally defined as classification precision), respectively. The same survey can also trigger alerts for the detection of about 15,500 SNe Ia (precision 61%) and 2,100 SNe II (precision 49%) candidates at least two days before the light maxima. Moreover, the near-ultraviolet observations of the CSST will be able to catch hundreds of shock-cooling events serendipitously every year. These results demonstrate that the CSST can make a potentially significant contribution to SN studies. [ABSTRACT FROM AUTHOR]

We explore the possibility that domain wall networks generate the stochastic gravitational wave background (SGWB) observed as a strong common power-law process in the Data Release-2 of Parkes Pulsar Timing Array. We find that a broad range of parameters, specifically wall tension around σDW ∼ (29–414 TeV)3 and wall-decay temperature within Td ∼ 20–257 MeV, can explain this phenomenon at a 68% credible level. Meanwhile, the same parameters could ease the Hubble tension if particles from these domain wall networks decay into dark radiation. We establish a direct analytical relationship, ΩGW(fp, T0)h2 ∼ Ωradh2(ΩvΔNeff)2, to illustrate this coincidence, underlining its importance in the underlying physics and potential applicability to a wider range of models and data. Conversely, if the common power-law process is not attributed to domain wall networks, our findings impose tight limits on the wall tension and decay temperature. [ABSTRACT FROM AUTHOR]

The symbiotic relationship between the gut microbiome and the human body is a concept that has grown in popularity in recent years. Bacteriophages (phages) are components of the gut microbiota and their imbalance plays a role in the pathogenesis of numerous intestinal disorders. Meanwhile, as a new antimicrobial agent, phage therapy (PT) offers unique advantages when compared with antibiotics and brings a new dawn for treatment of multidrugresistant bacteria in intestinal and extraintestinal disorders. In this review, we provide a brief introduction to the characterization of phages, particularly focusing on newly discovered phages. Additionally, we outline the involvement of gut phages in disease pathogenesis and discuss the status and challenges of utilizing phages as therapeutic targets for treatment of enteric infection. [ABSTRACT FROM AUTHOR]

In mice with acute gouty arthritis, this study intends to examine the mechanism of action of Akkermansia muciniphila AKK PROBIO. We developed a mouse model of acute gouty arthritis using sodium urate. The efficiency and mechanism of AKK PROBIO in preventing acute gouty arthritis in mice were then determined by examining the degree of foot swelling, pain threshold, blood biochemical indicators, histological alterations, and messenger RNA (mRNA) expression changes. The results of the animal experiment showed that AKK PROBIO can lessen mouse foot edema severity and increase pain threshold. AKK PROBIO can enhance the enzyme activity of superoxide dismutase (SOD) and the level of glutathione (GSH) in the ankle joint tissues of mice with acute arthritis while decreasing the enzyme activity of myeloperoxidase (MPO) and the level of malondialdehyde (MDA). Interleukin 6 (IL‐6), interleukin 10 (IL‐10), interleukin 1 beta (IL‐1β), and tumor necrosis factor‐alpha (TNF‐α) levels are all reduced by AKK PROBIO in the blood of mice with acute arthritis. Results from histopathology showed that AKK PROBIO reduced tissue damage in the mouse ankle and foot joints. In the tissues of the ankle joints of mice with acute arthritis, the results of the quantitative polymerase chain reaction (qPCR) and Western blot experiments suggested that AKK PROBIO may inhibit the mRNA and protein expression of extracellular signal‐regulated kinase 1/2 (ERK1/2), cyclooxygenase‐2 (COX‐2), and prostaglandin E2 (PGE2) in the tissues. AKK PROBIO can also regulate gut microbiota, inhibit harmful bacteria, and enhance valeric acid in the intestine, isobutyric acid, and isovaleric acid. Therefore, it is evident that AKK PROBIO prevents acute gouty arthritis better than glucosamine sulfate. It is a strain that has probiotic potential. [ABSTRACT FROM AUTHOR]

Developing straightforward but flexible approaches to PROTAC synthesis that can incorporate the structural elements of emerging designs can improve the quality and efficiency of PROTAC development. Solid-phase approaches could offer many advantages over conventional PROTAC synthesis if diverse chemistries and topographies can be incorporated. We have exploited the backbone-amide-linked (BAL) resin to employ an array of solid-phase organic reactions, providing access to VHL- and IAP-targeting degraders using the BRD4-targeting JQ1 conjugates as examples., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

The Frontiers in Medicinal Chemistry (FiMC) is the largest international Medicinal Chemistry conference in the German speaking area and took place from April 3 rd to 5 th 2023 in Vienna (Austria). Fortunately, after being cancelled in 2020 and two years (2021-2022) of entirely virtual meetings, due to the COVID-19 pandemic, the FiMC could be held in a face-to-face format again. Organized by the Division of Medicinal Chemistry of the German Chemical Society (GDCh), the Division of Pharmaceutical and Medicinal Chemistry of the German Pharmaceutical Society (DPhG), together with the Division of Medicinal Chemistry of the Austrian Chemical Society (GÖCH), the Austrian Pharmaceutical Society (ÖPhG), and a local organization committee from the University of Vienna headed by Thierry Langer, the meeting brought together 260 participants from 21 countries. The program included 38 lectures by leading scientists from industry and academia as well as early career investigators. Moreover, 102 posters were presented in two highly interactive poster sessions., (© 2023 The Authors. ChemMedChem published by Wiley-VCH GmbH.)

The colloidal-chemical properties of oxyethylated polypropylene glycols (pluronics), soluble and slightly soluble in water and containing a hydrophobic polypropylene glycol block with the same length but with different degrees of oxyethylation, were analyzed. It was determined that both pluronics are characterized by high surfactant properties, making it possible to use them as surfactants in heterophase polymerization processes. The observed differences in the kinetic specific features of the polymerization of styrene and methyl methacrylate (average particle diameter and polymerization rate, the character of the monomer conversion—time curves) allowed us to infer that the formation of the polymer-monomer particles occurs by different mechanisms. The obtained results showed that these surfactants are promising for the synthesis of polymer suspensions with a narrow particle size distribution and an average diameter in the range from 0.09 to 1.7 µm. [ABSTRACT FROM AUTHOR]

Large-scale structure (LSS) surveys will increasingly provide stringent constraints on our cosmological models. Recently, the density-marked correlation function (MCF) has been introduced, offering an easily computable density-correlation statistic. Simulations have demonstrated that MCFs offer additional, independent constraints on cosmological models beyond the standard two-point correlation (2PCF). In this study, we apply MCFs for the first time to SDSS CMASS data, aiming to investigate the statistical information regarding clustering and anisotropy properties in the Universe and assess the performance of various weighting schemes in MCFs, and finally obtain constraints on Ωm. Upon analyzing the CMASS data, we observe that, by combining different weights (α = [−0.2, 0, 0.2, 0.6]), the MCFs provide a tight and independent constraint on the cosmological parameter Ωm, yielding Ωm = 0.293 ± 0.006 at the 1σ level, which represents a significant reduction in the statistical error by a factor of 3.4 compared to that from 2PCF. Our constraint is consistent with recent findings from the small-scale clustering of BOSS galaxies (Zhai et al. Astronphys. J. 948, 99 (2023)) within the 1σ level. However, we also find that our estimate is lower than the Planck measurements by about 2.6σ, indicating the potential presence of new physics beyond the standard cosmological model if all the systematics are fully corrected. The method outlined in this study can be extended to other surveys and datasets, allowing for the constraint of other cosmological parameters. Additionally, it serves as a valuable tool for forthcoming emulator analysis on the Chinese Space Station Telescope (CSST). [ABSTRACT FROM AUTHOR]

We investigate the tolerance for systematic errors in lensing analysis applied to a patchwork map of Cosmic Microwave Background polarization. We focus on the properties of the individual polarization maps that comprise the patchwork and discuss the associated calibration residuals that are coherent on those subpatches. We numerically simulate the polarization field modulated as a whole patchwork and apply a suite of lensing analyses to reveal the response of the reconstructed gravitational lensing potential and delensing efficiency. At systematic error levels expected in the near future, we find that it is possible to reconstruct the lensing potential accurately on scales larger than the subpatch size and that there is no severe degradation of the lensing B -mode removal efficiency in the subsequent delensing analysis. [ABSTRACT FROM AUTHOR]

The fabrication of charcoal briquettes was considered using two distinct bases: palmyra palm and oil palm shells. The critical role of binders - namely tapioca starch, molasses, and termite mound clay (TMC) - were emphasized in influencing the properties of the briquettes. ANOVA results revealed that both the type of binder and charcoal significantly impacted various characteristics, such as proximate components like volatile matter content, and physical properties including combustion time. Briquettes made from palmyra palm shells notably demonstrated superior performance in terms of combustion time and onset time of saturation (OTS). Among the binders, tapioca starch was distinguished for contributing to the lowest ash content and the highest fixed carbon in the briquettes. Conversely, briquettes bound with TMC, despite having the lowest volatile matter percentage, also exhibited the highest ash content and fragility, in addition to the shortest combustion time. These findings highlight the importance of selecting appropriate binders to enhance the efficiency and sustainability of charcoal briquettes, aligning with the increasing demand for environmentally conscious energy solutions in the face of escalating global energy needs. [ABSTRACT FROM AUTHOR]

The paper analyzes a spectral approach to reconstructing a scalar field on the sphere, given only information about a masked version of the field, together with precise information about the (smooth) mask. The theory is developed for a general mask and later specialized to the case of an axially symmetric mask. Numerical experiments are given for the case of an axial mask motivated by the cosmic microwave background, assuming that the underlying field is a realization of a Gaussian random field with an artificial angular power spectrum of moderate degree (l≤100). The recovery is highly satisfactory in the absence of noise and even in the presence of moderate noise. [ABSTRACT FROM AUTHOR]

The ikaite columns in the Ikka Fjord, SW Greenland, represent a permanently cold and alkaline environment known to contain a rich bacterial diversity. 16S and 18S rRNA gene amplicon and metagenomic sequencing was used to investigate the microbial diversity in the columns and for the first time, the eukaryotic and archaeal diversity in ikaite columns were analyzed. The results showed a rich prokaryotic diversity that varied across columns as well as within each column. Seven different archaeal phyla were documented in multiple locations inside the columns. The columns also contained a rich eukaryotic diversity with 27 phyla representing microalgae, protists, fungi, and small animals. Based on metagenomic sequencing, 25 high-quality MAGs were assembled and analyzed for the presence of genes involved in cycling of nitrogen, sulfur, and phosphorous as well as genes encoding carbohydrate-active enzymes (CAZymes), showing a potentially very bioactive microbial community. [ABSTRACT FROM AUTHOR]

Reusable catalysts are attractive alternatives to the metal-free catalysts accelerating the Groebke–Blackburn–Bienayme reaction for the efficient synthesis of imidazo[1,2-α]pyridines. Herein, we report the synthesis of a reusable defective borocarbonitride catalyst with Lewis acidic boron and Lewis basic nitrogen, which switches the nature of the catalyst from Lewis acid to a frustrated Lewis pair (FLP). Furthermore, FLPs catalyzed the Groebke–Blackburn–Bienayme-type one-pot multi-component (2-aminopyridine, aldehyde and trimethylsilyl cyanide) reaction to afford 3-aminoimidazo[1,2-α] pyridines. Moreover, FLPs were employed for the synthesis of fused heterocyclic compounds for the first time. The noteworthy features of this protocol are its short reaction time, wide functional group tolerance, good yields and catalyst recovery. [ABSTRACT FROM AUTHOR]

Introduction: Pain is a clinically relevant health care issue with limited therapeutic options, creating the need for new and improved analgesic strategies. The amygdala is a limbic brain region critically involved in the regulation of emotional-affective components of pain and in pain modulation. The central nucleus of amygdala (CeA) serves major output functions and receives nociceptive information via the external lateral parabrachial nucleus (PB). While amygdala neuroplasticity has been linked causally to pain behaviors, non-neuronal pain mechanisms in this region remain to be explored. As an essential part of the neuroimmune system, astrocytes that represent about 40--50% of glia cells within the central nervous system, are required for physiological neuronal functions, but their role in the amygdala remains to be determined for pain conditions. In this study, we measured time-specific astrocyte activation in the CeA in a neuropathic pain model (spinal nerve ligation, SNL) and assessed the effects of astrocyte inhibition on amygdala neuroplasticity and pain-like behaviors in the pain condition. Methods and Results: Glial fibrillary acidic protein (GFAP, astrocytic marker) immunoreactivity and mRNA expression were increased at the chronic (4 weeks post-SNL), but not acute (1 week post-SNL), stage of neuropathic pain. In order to determine the contribution of astrocytes to amygdala pain-mechanisms, we used fluorocitric acid (FCA), a selective inhibitor of astrocyte metabolism. Whole-cell patch-clamp recordings were performed from neurons in the laterocapsular division of the CeA (CeLC) obtained from chronic neuropathic rats. Preincubation of brain slices with FCA (100 µM, 1 h), increased excitability through altered hyperpolarization-activated current (Ih) functions, without significantly affecting synaptic responses at the PB-CeLC synapse. Intra-CeA injection of FCA (100 µM) had facilitatory effects on mechanical withdrawal thresholds (von Frey and paw pressure tests) and emotional-affective behaviors (evoked vocalizations), but not on facial grimace score and anxiety-like behaviors (open field test), in chronic neuropathic rats. Selective inhibition of astrocytes by FCA was confirmed with immunohistochemical analyses showing decreased astrocytic GFAP, but not NeuN, signal in the CeA. Discussion: Overall, these results suggest a complex modulation of amygdala pain functions by astrocytes and provide evidence for beneficial functions of astrocytes in CeA in chronic neuropathic pain. [ABSTRACT FROM AUTHOR]

Class I histone deacetylases (HDACs) are considered promising targets in current cancer research. To obtain subtype-selective and potent HDAC inhibitors, we used the aminobenzamide scaffold as the zinc-binding group and prepared new derivatives with a pyrazole ring as the linking group. The synthesized compounds were analyzed in vitro using an enzymatic assay against HDAC1, -2, and -3. Compounds 12b, 15b, and 15i were found to be potent HDAC1 inhibitors, also in comparison to the reference compounds entinostat and tacedinaline, with IC 50 values of 0.93, 0.22, and 0.68 μM, respectively. The best compounds were measured for their cellular effect and target engagement in acute myeloid leukemia (AML) cells. In addition, we studied the interaction of the compounds with HDAC subtypes using docking and molecular dynamic simulations. In summary, we have developed a new chemotype of HDAC1 inhibitors that can be used for further structure-based optimization., (© 2024 The Author(s). Archiv der Pharmazie published by Wiley‐VCH GmbH on behalf of Deutsche Pharmazeutische Gesellschaft.)

Many studies discuss the impact of music programs on prison inmates. However, few studies have investigated the impact of music programs on formerly incarcerated individuals (FIIs), and none of them have focused on the programs' characteristics. This phenomenological study explores the characteristics of a music-based rehabilitation program for FIIs. Five FIIs and three staff members who participated in a group music program were interviewed. The following four themes emerged: Continuity —the importance of the FIIs' previous positive acquaintance with the program while still being in prison. Egalitarian approach —the importance of the staff treating the FIIs with understanding, tolerance, non-judgmentalism, and the use of an eye-level approach. Cultural sensitivity —the staff members' sensitivity to the FIIs' different backgrounds to form a connection. Playfulness —the program's ability to break free from a "fight-or-flight" mode and experience a counter mode of playfulness. The findings are discussed through the perspective of positive criminology. [ABSTRACT FROM AUTHOR]

A conserved intracellular allosteric binding site (IABS) was recently identified at several G protein-coupled receptors (GPCRs). This target site allows the binding of allosteric modulators and enables a new mode of GPCR inhibition. Herein, we report the development of a NanoBRET-based assay platform based on the fluorescent ligand LT221 (5), to detect intracellular binding to CCR6 and CXCR1, two chemokine receptors that have been pursued as promising drug targets in inflammation and immuno-oncology. Our assay platform enables cell-free as well as cellular NanoBRET-based binding studies in a nonisotopic and straightforward manner. By combining this screening platform with a previously reported CXCR2 assay, we investigated CXCR1/CXCR2/CCR6 selectivity profiles for both known and novel squaramide analogues derived from navarixin, a known intracellular CXCR1/CXCR2 antagonist and phase II clinical candidate for the treatment of pulmonary diseases. By means of these studies we identified compound 10, a previously reported tert-butyl analogue of navarixin, as a low nanomolar intracellular CCR6 antagonist. Further, our assay platform clearly indicated intracellular binding of the CCR6 antagonist PF-07054894, currently evaluated in phase I clinical trials for the treatment of ulcerative colitis, thereby providing profound evidence for the existence and the pharmacological relevance of a druggable IABS at CCR6., (© 2024 The Authors. ChemMedChem published by Wiley-VCH GmbH.)

This work introduces polarimetric Fourier phase retrieval (PPR), a physically inspired model to leverage polarization of light information in Fourier phase retrieval problems. We provide a complete characterization of its uniqueness properties by unraveling equivalencies with two related problems, namely, bivariate phase retrieval and a polynomial autocorrelation factorization problem. In particular, we show that the problem admits a unique solution, which can be formulated as a greatest common divisor (GCD) of measurement polynomials. As a result, we propose algebraic solutions for PPR based on approximate GCD computations using the null-space properties of Sylvester matrices. Alternatively, existing iterative algorithms for phase retrieval, semidefinite positive relaxation and Wirtinger flow, are carefully adapted to solve the PPR problem. Finally, a set of numerical experiments permits a detailed assessment of the numerical behavior and relative performances of each proposed reconstruction strategy. They further demonstrate the fruitful combination of algebraic and iterative approaches toward a scalable, computationally efficient, and robust to noise reconstruction strategy for PPR. [ABSTRACT FROM AUTHOR]

We present a tentative constraint on cosmological parameters Ωm and σ8 from a joint analysis of galaxy clustering and galaxy-galaxy lensing from DESI Legacy Imaging Surveys Data Release 9 (DR9), covering approximately 10000 square degrees and spanning the redshift range of 0.1 to 0.9. To study the dependence of cosmological parameters on lens redshift, we divide lens galaxies into seven approximately volume-limited samples, each with an equal width in photometric redshift. To retrieve the intrinsic projected correlation function wp(rp) from the lens samples, we employ a novel method to account for redshift uncertainties. Additionally, we measured the galaxy-galaxy lensing signal ΔΣ(rp) for each lens sample, using source galaxies selected from the shear catalog by applying our Fourier_Quad pipeline to DR9 images. We model these observables within the flat ACDM framework, employing the minimal bias model. To ensure the reliability of the minimal bias model, we apply conservative scale cuts: rp > 8 and 12 h−1Mpc, for wp(rp) and ΔΣ(rp), respectively. Our findings suggest a mild tendency that S 8 ≡ σ 8 Ω m / 0.3 increases with lens redshift, although this trend is only marginally significant. When we combine low redshift samples, the value of S8 is determined to be 0.84 ± 0.02, consistent with the Planck results but significantly higher than the 3× 2pt analysis by 2–5σ. Despite the fact that further refinements in measurements and modeling could improve the accuracy of our results, the consistency with standard values demonstrates the potential of our method for more precise and accurate cosmology in the future. [ABSTRACT FROM AUTHOR]

We present a forecast of the cosmological parameter estimation using fast radio bursts (FRBs) from the upcoming Square Kilometre Array (SKA), focusing on the issues of dark energy, the Hubble constant, and baryon density. We simulate 105 and 106 localized FRBs from a 10-year SKA observation, and find that: (1) using 106 FRB data alone can tightly constrain dark-energy equation of state parameters better than CMB+BAO+SNe, providing an independent cosmological probe to explore dark energy; (2) combining the FRB data with gravitational-wave standard siren data from 10-year observation with the Einstein Telescope, the Hubble constant can be constrained to a sub-percent level, serving as a powerful low-redshift probe; (3) using 106 FRB data can constrain the baryon density Ωbh to a precision of ∼0.1%. Our results indicate that SKA-era FRBs will provide precise cosmological measurements to shed light on both dark energy and the missing baryon problem, and help resolve the Hubble tension. [ABSTRACT FROM AUTHOR]

The principles underlying the variational approach prove to be invaluable tools in articulating physical phenomena, particularly when dealing with conserved quantities. The derivation of gravitational field equations from the Euler–Lagrange equation, a result of the first-order derivative of Lagrange field density, is a well-established concept. However, within the context of this paper, the field equations stem from the second-order differentiable field Lagrangian in the Euler–Lagrange equation. The Euler–Lagrange equation of the first-order differentiable field Lagrangian yields the gravitational field equations incorporating matter fields and the cosmological constant. On the other hand, the Euler–Lagrange equation of the second-order differentiable field Lagrangian gives rise to the equation governing the cosmological constant. The procedure of determining the cosmological constant through the Euler–Lagrange equation adheres to fundamental mathematical theory encompassing higher-order Euler–Lagrange equations. This theory implies that utilizing higher-order Euler–Lagrange equations may result in instability due to negative energy. The cosmological constant is postulated to be intertwined with negative vacuum energy density. The value assigned to the gravitational constant, as ascertained through the employment of the general relativistic equation, is not only significantly small and nonzero but also demonstrates remarkable compatibility with the value inferred from observational deductions. [ABSTRACT FROM AUTHOR]

N‐Substitution of a thermally unstable diboratriazole 1 with a trimethylsilyl group affords a remarkably stable diboratriazole derivative 2. Ring contraction of 2 with an N‐heterocyclic carbene accompanied by the release of N2 as well as 1,4‐hydrogen shift affords a carbene‐stabilized azadiboriridine 3. Abstraction of the H−B3mem hydride in 3 with methyl trifluoromethanesulfonate leads to the isolation of a hitherto unknown azadiboriridinylium 4, the first BN analogue of cyclopropenylium cation. X‐ray diffraction analysis and computational studies confirmed the delocalization of π electrons over the B2N three‐membered ring, indicating the 2π aromatic feature. Compound 4 undergoes ring expansion reactions with azobenzene and pyridazine to furnish triazadiborolidinylium species 5 and 6, the latter of which possesses a cationic B2N3 ring with a pronounced 6π aromatic property. Moreover, the reaction of 4 with a diazo compound produces a cationic B2N3C pentafulvene derivative 7. [ABSTRACT FROM AUTHOR]

The Chinese Space Station Telescope (CSST) is a cutting-edge two-meter astronomical space telescope currently under construction. Its primary Survey Camera (SC) is designed to conduct large-area imaging sky surveys using a sophisticated seven-band photometric system. The resulting data will provide unprecedented data for studying the structure and stellar populations of the Milky Way. To support the CSST development and scientific projects related to its survey data, we generate the first comprehensive Milky Way stellar mock catalogue for the CSST SC photometric system using the TRILEGAL stellar population synthesis tool. The catalogue includes approximately 12.6 billion stars, covering a wide range of stellar parameters, photometry, astrometry, and kinematics, with magnitude reaching down to g=27.5 mag in the AB magnitude system. The catalogue represents our benchmark understanding of the stellar populations in the Milky Way, enabling a direct comparison with the future CSST survey data. Particularly, it sheds light on faint stars hidden from current sky surveys. Our crowding limit analysis based on this catalogue provides compelling evidence for the extension of the CSST Optical Survey (OS) to cover low Galactic latitude regions. The strategic extension of the CSST-OS coverage, combined with this comprehensive mock catalogue, will enable transformative science with the CSST. [ABSTRACT FROM AUTHOR]

Developing straightforward but flexible approaches to PROTAC synthesis that can incorporate the structural elements of emerging designs can improve the quality and efficiency of PROTAC development. Solid‐phase approaches could offer many advantages over conventional PROTAC synthesis if diverse chemistries and topographies can be incorporated. We have exploited the backbone‐amide‐linked (BAL) resin to employ an array of solid‐phase organic reactions, providing access to VHL‐ and IAP‐targeting degraders using the BRD4‐targeting JQ1 conjugates as examples. [ABSTRACT FROM AUTHOR]

In this paper, we investigate in detail the structures of the variational characterization AN,t of the spherical t-design, its gradient \nabla AN,t, and its Hessian \scrH (AN,t) in terms of fast spherical harmonic transforms. Moreover, we propose solving the minimization problem of AN,t using the trust-region method to provide spherical t-designs with large values of t. Based on the obtained spherical tdesigns, we develop (semidiscrete) spherical tight framelets as well as their truncated systems and their fast spherical framelet transforms for the practical spherical signal/image processing. Thanks to the large spherical t-designs and localization property of our spherical framelets, we are able to provide signal/image denoising using local thresholding techniques based on a fine-tuned spherical cap restriction. Many numerical experiments are conducted to demonstrate the efficiency and effectiveness of our spherical framelets and spherical designs, including Wendland function approximation, ETOPO data processing, and spherical image denoising. [ABSTRACT FROM AUTHOR]

Sirtuin 2 (SIRT2) belongs to the family of silent information regulators (sirtuins), which comprises nicotinamide adenine dinucleotide (NAD + )-dependent protein lysine deacetylases. With a distribution across numerous tissues and organs of the human body, SIRT2 is involved in a wide range of physiological and pathological processes, such as regulating the cell cycle, energy metabolism, DNA repair, and tumorigenesis. Aberrant expression of SIRT2 has been closely associated with particular etiologies of human diseases, positioning SIRT2 as a promising therapeutic target. Herein, we detail the design overview and findings of novel symmetrical 2,7-disubstituted 9H-fluoren-9-one derivatives targeting SIRT2. SG3 displayed the most potent SIRT2-selective inhibitory profile, with an IC 50 value of 1.95  μ M $\mu {\rm{M}}$ , and reduced the cell viability of human breast cancer MCF-7 cells accompanied by hyperacetylation of α-tubulin. Finally, molecular docking, molecular dynamics simulations, and binding free energy calculations using molecular mechanics/generalized born surface area method were performed to verify the binding ability of SG3 to SIRT2. Taken together, these results could enhance our understanding of the structural elements necessary for inhibiting SIRT2 and shed light on the mechanism of inhibition., (© 2024 The Author(s). Archiv der Pharmazie published by Wiley‐VCH GmbH on behalf of Deutsche Pharmazeutische Gesellschaft.)

Cancer is one of the primary causes of mortality worldwide. Despite nowadays are numerous therapeutic treatments to fight tumor progression, it is still challenging to completely overcome it. It is known that Histone Deacetylases (HDACs), epigenetic enzymes that remove acetyl groups from lysines on histone's tails, are overexpressed in various types of cancer, and their inhibition represents a valid therapeutic strategy. To date, some HDAC inhibitors have achieved FDA approval. Nevertheless, several other potential drug candidates have been developed. This review aims primarily to be comprehensive of the studies done so far regarding HDAC inhibitors bearing heterocyclic rings since their therapeutic potential is well known and has gained increasing interest in recent years. Hence, inserting heterocyclic moieties in the HDAC-inhibiting scaffold can be a valuable strategy to provide potent and/or selective compounds. Here, in addition to summarizing the properties of novel heterocyclic HDAC inhibiting compounds, we also provide ideas for developing new, more potent, and selective compounds for treating cancer., (© 2024 The Authors. ChemMedChem published by Wiley-VCH GmbH.)

The Ni-catalyzed enantioselective addition reaction of aryl halides to aldehydes was studied with cyanobis(oxazoline) as chiral ligands and Mn as reductant. Aryl and heteroaryl bromides reacted with phenyl aldehyde at room temperature to produce dibenzyl alcohols in 16-99 % yields with 53-92 % ees. Moreover, the coupling of phenyl chloride with a variety of aryl, heteroaryl and alkyl aldehydes was demonstrated in the presence of cyanobis(oxazoline)/Ni(II) at 60 °C in generally high yields with moderate enantioselectivities., (© 2024 Wiley-VCH GmbH.)

24 C3'-focused hybrids of aryl/penta-1,4-dien-3-one/amine (APDA) were designed and synthesized. Of these hybrids, 2 n demonstrated improved antiproliferative effects on HER2-positive breast cancer cells (SKBr3 and BT474) and triple-negative breast cancer (TNBC) cells (MDA-MB-231 and MDA-MB-468) with IC 50 values ranging from 7.45 to 10.75 μM, but less toxicity to normal breast cells MCF-10A than the first generation of hybrid 1. Additionally, 2 n retained its ability to inhibit HSP90C-terminus, leading to the degradation of HSP90 client proteins HER2, EGFR, pAKT, AKT, and CDK4, without inducing a heat-shock response. Notably, 2 n also demonstrated improved thermostability compared to 1 and maintained in vitro metabolic stability in simulated intestinal fluid. These findings will provide a scientific basis for developing HSP90C-terminal inhibitors in the future., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

With the growing demand for energy supply and the natural decline of oil reservoirs, the development of new enhanced oil recovery (EOR) techniques become more and more critical. Polymer flooding EOR is one of the most successful chemical EOR methods but suffers many drawbacks at high temperatures and high salinity (HT‐HS) conditions. Superparamagnetic nanoparticles (NPs) have been recently investigated for subsurface applications, including in EOR, due to their unique physicochemical properties. Their applicability under harsh reservoir conditions, however, is yet to be examined. In this work, a novel approach is developed to synthesize superparamagnetic Fe3O4 (NPs) with unique surface functionalization (SMag‐NPs) and to form stable polyacrylamide (PAM) dispersions (SMag‐NPs‐PAM). Both stability and core flooding experiment results demonstrate the promising future of the new dispersion. The SMag‐NPs‐PAM dispersion is not only stable at HT‐HS conditions, but also show excellent EOR capability at HT‐HS by recovering, 61.72% of the initial oil quantity, which is significantly higher than those from conventinal NPs‐PAM disperison and pure PAM fluid. These findings show the promising application potential of SMag‐NPs‐PAM for improving oil recovery in challenging HT‐HS reservoir conditions. [ABSTRACT FROM AUTHOR]

In the present study, a combined kinetic and heat transfer model was developed to study the kinetics and predict thermal runaway of vinyl chloride (VC) suspension polymerization. Reactor temperature, monomer conversion, mole of initiator, radical concentrations in the two phases (i.e., VC‐rich phase and PVC‐rich phase), and average molecular properties were mapped during non‐isothermal processes. Meanwhile, the risk of thermal runaway was evaluated using S–Z (divergence) and H–J criteria. Simulation results show that a lower jacket temperature Tj and a larger heat transfer coefficient U are able to postpone or even avoid the risk of thermal runaway. Both of the criteria serve well for the prediction of thermal runaway during non‐isothermal processes. To prevent the occurrence of thermal runaway to the greatest extent, model‐based design of strategies for an isothermal polymerization process was done. Specifically, either jacket temperature Tj or heat transfer coefficient U can be fine‐tuned to maintain a 50°C isothermal process. [ABSTRACT FROM AUTHOR]

Background: Preeclampsia (PE) is a common pregnancy-related disorder characterized by disrupted maternal-fetal immune tolerance, involving diffuse inflammatory responses and vascular endothelial damage. Alterations in the gut microbiota (GM) during pregnancy can affect intestinal barrier function and immune balance. Aims and purpose: This comprehensive review aims to investigate the potential role of short-chain fatty acids (SCFAs), essential metabolites produced by the GM, in the development of PE. The purpose is to examine their impact on colonic peripheral regulatory T (Treg) cells, the pathogenic potential of antigen-specific helper T (Th) cells, and the inflammatory pathways associated with immune homeostasis. Key insights: An increasing body of evidence suggests that dysbiosis in the GM can lead to alterations in SCFA levels, which may significantly contribute to the development of PE. SCFAs enhance the number and function of colonic Treg cells, mitigate the pathogenic potential of GM-specific Th cells, and inhibit inflammatory progression, thereby maintaining immune homeostasis. These insights highlight the potential significance of GM dysregulation and SCFAs produced by GM in the pathogenesis of PE. While the exact causes of PE remain elusive, and definitive clinical treatments are lacking, the GM and SCFAs present promising avenues for future clinical applications related to PE, offering a novel approach for prophylaxis and therapy. [ABSTRACT FROM AUTHOR]

Unnatural helical peptidic foldamers have attracted considerable attention owing to their unique folding behaviours, diverse artificial protein binding mechanisms, and promising applications in chemical, biological, medical, and material fields. Unlike the conventional α-helix consisting of molecular entities of native α-amino acids, unnatural helical peptidic foldamers are generally comprised of well-defined backbone conformers with unique and unnatural structural parameters. Their folded structures usually arise from unnatural amino acids such as N-substituted glycine, N-substituted-β-alanine, β-amino acid, urea, thiourea, α-aminoxy acid, α-aminoisobutyric acid, aza-amino acid, aromatic amide, γ-amino acid, as well as sulfono-γ-AA amino acid. They can exhibit intriguing and predictable three-dimensional helical structures, generally featuring superior resistance to proteolytic degradation, enhanced bioavailability, and improved chemodiversity, and are promising in mimicking helical segments of various proteins. Although it is impossible to include every piece of research work, we attempt to highlight the research progress in the past 10 years in exploring unnatural peptidic foldamers as protein helical segment mimics, by giving some representative examples and discussing the current challenges and future perspectives. We expect that this review will help elucidate the principles of structural design and applications of existing unnatural helical peptidic foldamers in protein segment mimicry, thereby attracting more researchers to explore and generate novel unnatural peptidic foldamers with unique structural and functional properties, leading to more unprecedented and practical applications. [ABSTRACT FROM AUTHOR]