Cross-coupling of organic fluorides with allenes: a silyl-radical-relay pathway for the construction of α-alkynyl-substituted all-carbon quaternary centres.

Controlling the transformation of versatile and reactive allenes is a considerable challenge. Herein, we report an efficient silylboronate-mediated cross-coupling reaction of organic fluorides with allenes to construct a series of sterically demanding α-ethynyl-containing all-carbon quaternary centers (ACQCs), using catalyst-free silyl-radical-relay reactions to selectively functionalize highly inert C-F bonds in organic fluorides. The key to the success of this transformation lies in the radical rearrangement of an in situ-generated allenyl radical to form a bulky tertiary propargyl radical; however, the transformation does not show efficiency when using the propargyl isomer directly. This unique reaction enables the cross-coupling of a tertiary carbon radical center with a C(sp2)-F bond or a benzylic C(sp3)-F bond. α-Ethynyl-containing ACQCs with (hetero)aromatic substituents and benzyl were efficiently synthesized in a single step using electronically and sterically diverse organic fluorides and allenes. The practical utility of this protocol is showcased by the late-stage functionalization of bioactive molecules and the modification of a liquid crystalline material.

Acupuncture in circadian rhythm sleep-wake disorders and its potential neurochemical mechanisms.

Circadian rhythm sleep-wake disorders (CRSWDs) are becoming increasingly common in modern societies due to lifestyle changes. The detrimental effects of CRSWDs on sleep and psychological health have attracted considerable attention recently. Alternative remedies for the treatment of CRSWDs have also gained attention in recent years owing to the limitations of medications. Several in vivo and clinical investigations have shown that acupuncture, one of the most important components of traditional Chinese medicine (TCM), has been shown to modulate sleep-related circadian rhythms. Owing to the lack of research on the mechanism and effectiveness of acupuncture in treating CRSWDs, clinical applications of acupuncture have not gained popularity. This paper reviews the acupuncture methods, acupoint selection, and biochemical indicators supplied by in vivo and clinical studies to explore the effectiveness of acupuncture, and summarizes the circadian rhythm mechanisms and the acupuncture characteristics on circadian rhythm. The neurochemical mechanisms linked to acupuncture in treating CRSWDs are also outlined from the perspective of the central and peripheral biological clocks. Lastly, the inadequacy of previous studies on CRSWDs and conflicting results regarding acupuncture are explored and future research directions are envisioned.

Chemometrics combined with comprehensive two-dimensional gas chromatography-mass spectrometry for the identification of Baijiu vintage.

The identification of baijiu vintage is crucial for quality assessment and economic value determination. However, its complex composition and multifaceted influences pose significant technical challenges, necessitating research into its aging mechanisms and the development of related identification methods. This study utilized Chemometrics in conjunction with GC × GC-TOFMS for Baijiu Vintage identification. Data compression achieved a reduction of over 1000-fold without compromising key information, enabling analysis on many samples and get their changing regular in a big matrix by MCR. Subsequently, MCR-ALS facilitated the extraction of physical and chemical meaningful information related to baijiu vintage. Key MCR principal components suitable for qualitative and quantitative assessments were selected using CARS-PLS. The regression model demonstrated errors of less than one year. Furthermore, a PLS-DA model provided 30 MCR principal components as potential markers. The research results provide technical support for baijiu vintage identification and lay the groundwork for studying the changing patterns of flavor compounds in baijiu.

Ultrasound Nanobubble Coupling Agent for Effective Noninvasive Deep-Layer Drug Delivery.

Conventional coupling agents (such as polyvinylpyrrolidone, methylcellulose, and polyurethane) are unable to efficiently transport drugs through the skin's dual barriers (the epidermal cuticle barrier and the basement membrane barrier between the epidermis and dermis) when exposed to ultrasound, hindering deep and noninvasive transdermal drug delivery. In this study, nanobubbles prepared by the double emulsification method and aminated hyaluronic acid are crosslinked with aldehyde-based hyaluronic acid by dynamic covalent bonding through the Schiff base reaction to produce an innovative ultrasound-nanobubble coupling agent. By amplifying the cavitation effect of ultrasound, drugs can be efficiently transferred through the double barrier of the skin and delivered to deep layers. In an in vitro model of isolated porcine skin, this agent achieves an effective penetration depth of 728 µm with the parameters of ultrasound set at 2 W, 650 kHz, and 50% duty cycle for 20 min. Consequently, drugs can be efficiently delivered to deeper layers noninvasively. In summary, this ultrasound nanobubble coupling agent efficiently achieves deep-layer drug delivery by amplifying the ultrasonic cavitation effect and penetrating the double barriers, heralding a new era for noninvasive drug delivery platforms and disease treatment.

Piecewise Developable Modeling Via Implicit Neural Deformation and Feature-Guided Cutting.

We propose a novel and automatic method to model shapes using a small set of discrete developable patches. Central to our approach is using implicit neural shape representation that makes our algorithm independent of tessellation and allows us to obtain the Gaussian curvature of each point analytically. With this powerful representation, we first deform the input shape to be an almost developable shape with clear and sparse salient feature curves. Then, we convert the deformed implicit field to a triangle mesh, which is further cut to disk topology along parts of the sparse feature curves. Finally, we achieve the resulting piecewise developable mesh by alternatingly optimizing discrete developability, enforcing manufacturability constraints, and merging patches. The feasibility and practicability of our method are demonstrated over various shapes. Compared to the state-of-the-art methods, our method achieves a better tradeoff between the number of developable patches and the approximation error.

[Research progress of signal pathways of microglia activation in sleep disorders].

Sleep is an extremely important physiological state to maintain human life. Sleep disorders can not only cause anxiety and depression, but also induce multi-system diseases that seriously affect brain function and physical health. The neuroinflammation is a key pathological process after sleep disorders, which can induce a series of nervous system diseases. In recent years, the role of microglia activation in neuroinflammation has been paid more and more attention and become a research hotspot in this field. The imbalance of the central microenvironment after sleep disorders leads to changes in the activation and polarization of microglia, which triggers neuroinflammatory response. The activation and polarization of microglia in the sleep disorders are regulated by multiple signaling pathways and complex molecular mechanisms. This paper summarizes five signaling pathways of microglia activation in central inflammation induced by sleep disorders, including P2X7 receptor (P2X7R), p38MAPK, Toll-like receptor 4 (TLR4)/NF-κB, JAK/STAT, and α7 nicotinic acetylcholine receptor (α7-nAChR) pathways, in order to provide reference for further research and clinical treatment targets selection of sleep disorders.

Practical Integer-Constrained Cone Construction for Conformal Parameterizations.

We propose a practical method to construct sparse integer-constrained cone singularities with low distortion constraints for conformal parameterizations. Our solution for this combinatorial problem is a two-stage procedure that first enhances sparsity for generating an initialization and then optimizes to reduce the number of cones and the parameterization distortion. Central to the first stage is a progressive process to determine the combinatorial variables, i.e., numbers, locations, and angles of cones. The second stage iteratively conducts adaptive cone relocations and merges close cones for optimization. We extensively test our method on a data set containing 3885 models, demonstrating practical robustness and performance. Our method achieves fewer cone singularities and lower parameterization distortion than state-of-the-art methods.

Synthesis of triarylmethanes by silyl radical-mediated cross-coupling of aryl fluorides and arylmethanes.

Although the cross-couplings of aryl halides with diarylmethanes are mostly achieved by transition-metal catalysis, aryl fluorides are rarely used as coupling partners owing to the high inertness of C-F bonds. Herein, we describe the efficient silylboronate-mediated cross-coupling reaction of aryl fluorides with arylalkanes under transition-metal-free, room-temperature conditions. The combination of silylboronate and KO t Bu is critical for driving a radical process via the cleavage of C-F and C-H bonds in two appropriate coupling precursors, resulting in a cross-coupling product. This practical cross-coupling protocol is applicable to a wide variety of aryl fluorides with a C(sp2)-F bond. This method can be extended to other coupling partners with a C(sp3)-H bond, including diarylmethanes, diarylethanes, and monoarylalkanes. Many di- and triarylalkanes with tertiary or quaternary carbon centers can be obtained easily in moderate to high yields. We believe that the developed silylboronate-mediated cross-coupling method is a valuable contribution to C-F and C-H activation chemistry.

Transition-metal-free silylboronate-mediated cross-couplings of organic fluorides with amines.

C-N bond cross-couplings are fundamental in the field of organic chemistry. Herein, silylboronate-mediated selective defluorinative cross-coupling of organic fluorides with secondary amines via a transition-metal-free strategy is disclosed. The cooperation of silylboronate and potassium tert-butoxide enables the room-temperature cross-coupling of C-F and N-H bonds, effectively avoiding the high barriers associated with thermally induced SN2 or SN1 amination. The significant advantage of this transformation is the selective activation of the C-F bond of the organic fluoride by silylboronate without affecting potentially cleavable C-O, C-Cl, heteroaryl C-H, or C-N bonds and CF3 groups. Tertiary amines with aromatic, heteroaromatic, and/or aliphatic groups were efficiently synthesized in a single step using electronically and sterically varying organic fluorides and N-alkylanilines or secondary amines. The protocol is extended to the late-stage syntheses of drug candidates, including their deuterium-labeled analogs.

Seven new mitochondrial genomes of phytophagous scarab beetles (Coleoptera: Scarabaeidae) and phylogenetic implications.

Among Scarabaeidae, the phytophagous scarab lineage including Melolonthinae, Cetoniinae, Dynastinae, and Rutelinae is considered important due to its members roles as agricultural pests or pollinators. In this study, the near-complete mitochondrial genomes of seven species from six genera in the phytophagous scarab lineage were newly sequenced: Anomala russiventris (Fairmaire, 1893); Apogonia cf. basalis (Moser, 1915); Apogonia splendida (Boheman, 1858); Coenochilus striatus (Westwood, 1874); Trichogomphus mongol (Arrow, 1908); Sophrops subrugatus (Moser, 1921) and Tetraserica leishanica (Liu, Bai, Yang Ahrens, 2014). The complete mitochondrial genomes from the 6 species include 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), 2 ribosomal RNA genes (rRNAs), and 1 control region, which have a highly conserved gene arrangement, except for Tr. mongol with the rearrangement of 2 tRNA genes (tRNA-Ile and tRNA-Gln), which is a potential identified subfamily-level character of Dynastinae. In order to test whether the mitogenomic data are suited for high-level phylogenetic inferences, the substitution saturation and heterogeneity were analyzed. The results showed no sign that the phylogenetic inferences were biased by substitution saturation or the low heterogeneity of the sequence composition for most pairwise comparisons between the sequences for the entire dataset (13 PCGs) and the amino acids dataset (13 PCGs_AA). Based on the combined data of 13 PCGs and 13 PCGs_AA from the mitogenomes of 37 taxa, the phylogeny of the phytophagous lineage was explored using RAxML and Bayesian methods. The results confirmed that Cetoniinae, Rutelinae, and Dynastinae are monophyletic, and that the latter two are sister groups. Melolonthinae is a paraphyletic group, and its tribes, Diplotaxini, Euchirini, Melolonthini, Rhizotrogini, and Sericini, are a monophyletic group. The subfamily rank of Dynastinae and the tribe rank of Anomalini and Adoretini are supported.

The evolution of conglobation in Ceratocanthinae.

Conglobation is an adaptive behaviour occurring independently in various animal groups. Here, we study the evolution of conglobation in Ceratocanthinae, a beetle group with the ability to roll three body segments into a tight ball. It is here implied that this ability evolved only once in the Mesozoic. Evidence is offered suggesting that the high defensive strength of Ceratocanthinae is due not only to the spherical body shape but also to the thickness and stronger mechanical properties of the dorsal cuticle. We further validate five adaptive characters including the allometrically thickened body wall and find that the specific adaptation of different body segments are likely separate evolutionary events. Finally, we propose an "attackers stress" hypothesis to explain the origin of conglobation behaviours. This work contributes to understanding how and why conglobation behaviour may have evolved in this group.

Etherification of Fluoroarenes with Alkoxyboronic Acid Pinacol Esters via C-F Bond Cleavage.

Potassium-base-mediated defluoroetherification of aryl and heteroaryl fluorides with alkoxyboronic acid pinacol esters under transition-metal-free conditions is reported. This protocol efficiently and safely provides a wide variety of aryl ethers in high yields without using metal catalysts, specific ligands, and harsh conditions to selectively forge Csp2-O bonds via the Csp2-F cleavage. This method can be applied to the late-stage etherification of structurally complex Csp2-fluorides and bioactive alcohols, such as ß-estradiol, calciferol, and tocopherol.

Therapeutic carrier based on solanesol and hyaluronate for synergistic tumor treatment.

The administration of nanodrugs can lead to metabolism related systemic toxicity due to the use of inert carriers in large quantities. Carrier materials that offer therapeutic effects are therefore a promising means of addressing this limitation. Herein, a hyaluronate-based nanocarrier was prepared from hyaluronic acid (HA) and solanesol. Solanesyl thiosalicylate (STS) derived from solanesol has certain antitumor effects and was used to modify HA. The conjugate (HA-STS) self-assembled into nanoparticles acting as a drug carrier. The synthesis of the conjugates was confirmed by 1H NMR spectroscopy. Doxorubicin (DOX) was loaded into the HA-STS nanoparticles with a relatively high content of 6.0%. pH-sensitive drug release behavior was achieved by introducing a hydroazone bond between STS and HA. A cytotoxicity assay indicated that the blank nanoparticles had an antitumor effect, which was enhanced by loading with an additional drug. Moreover, in vivo antitumor experiments indicated that the HA-STS-DOX showed superior tumor inhibition compared with free DOX, as well as lower cardiotoxicity and hepatotoxicity, demonstrating the advantages of the bioactive drug vehicles in cancer therapy.

Silylboronate-Mediated Defluorosilylation of Aryl Fluorides with or without Ni-Catalyst.

The defluorosilylation of aryl fluorides to access aryl silanes was achieved under transition-metal-free conditions via an inert C-F bond activation. The defluorosilylation, mediated by silylboronates and KOtBu, proceeded smoothly at room temperature to afford various aryl silanes in good yields. Although a comparative experiment indicated that Ni catalyst facilitated this transformation more efficiently, the transition-metal-free protocol is advantageous from a green chemistry perspective.

Bergenin alleviates H2 O2 -induced oxidative stress and apoptosis in nucleus pulposus cells: Involvement of the PPAR-γ/NF-κB pathway.

Bergenin is a C-glucoside of 4-O-methyl gallic acid with a variety of biological activities, such as antioxidant and anti-inflammatory. Herein, we investigated the involvement of bergenin in the protective effect against H2 O2 -induced oxidative stress and apoptosis in human nucleus pulposus cells (HNPCs) and the underlying mechanisms. HNPCs were cotreated with various concentrations of bergenin and 200 µM H2 O2 for 24 h. Cell viability was detected by Cell Counting Kit-8 and lactate dehydrogenase release assays. Reactive oxygen species (ROS) was evaluated utilizing 2',7'-dichlorofluorescein-diacetate. Superoxide dismutase (SOD) and catalase (CAT) activities and glutathione (GSH) levels were measured to assess oxidative stress. Apoptosis was evaluated using terminal deoxynucleotidyl transferase dUTP nick end labeling and caspase-3/7 activity assays. Expression of protein was determined by western blotting. Results indicated that treatment with bergenin significantly alleviated H2 O2 -induced viability reduction and ROS overproduction in HNPCs in a dose-dependent manner. Bergenin alleviated H2 O2 -induced oxidative stress in HNPCs by increased activity of superoxide dismutase and level of glutathione peroxidase. H2 O2 -induced apoptosis and activity of caspase-3/7 were also suppressed by bergenin treatment in HNPCs. Western blotting showed that H2 O2 -induced decrease in expression of peroxisome proliferator-activated receptor γ (PPAR-γ) and increase in nuclear factor κB (NF-κB) were inhibited by bergenin. However, the inhibitory effect of bergenin on H2 O2 -induced viability reduction, oxidative stress and apoptosis were noticeably abrogated in PPAR-γ knockdown HNPCs. In conclusion, our results indicated that bergenin alleviates H2 O2 -induced oxidative stress and apoptosis in HNPCs by activating PPAR-γ and suppressing NF-κB pathway.

Catalyst-free carbosilylation of alkenes using silyl boronates and organic fluorides via selective C-F bond activation.

A regioselective carbosilylation of alkenes has emerged as a powerful strategy to access molecules with functionalized silylated alkanes, by incorporating silyl and carbon groups across an alkene double bond. However, to the best of our knowledge, organic fluorides have never been used in this protocol. Here we disclose the catalyst-free carbosilylation of alkenes using silyl boronates and organic fluorides mediated by tBuOK. The main feature of this transformation is the selective activation of the C-F bond of an organic fluoride by the silyl boronate without undergoing potential side-reactions involving C-O, C-Cl, heteroaryl-CH, and even CF3 groups. Various silylated alkanes with tertiary or quaternary carbon centers that have aromatic, hetero-aromatic, and/or aliphatic groups at the ß-position are synthesized in a single step from substituted or non-substituted aryl alkenes. An intramolecular variant of this carbosilylation is also achieved via the reaction of a fluoroarene with a ω-alkenyl side chain and a silyl boronate.

3D Printed Zn-doped Mesoporous Silica-incorporated Poly-L-lactic Acid Scaffolds for Bone Repair.

Poly-L-lactic acid (PLLA) lacks osteogenic activity, which limits its application in bone repair. Zinc (Zn) is widely applied to strengthen the biological properties of polymers due to its excellent osteogenic activity. In the present study, Zn-doped mesoporous silica (Zn-MS) particles were synthesized by one-pot hydrothermal method. Then, the particles were induced into PLLA scaffolds prepared by selective laser sintering technique, aiming to improve their osteogenic activity. Our results showed that the synthesized particles possessed rosette-like morphology and uniform mesoporous structure, and the composite scaffold displayed the sustained release of Zn ion in a low concentration range, which was attributed to the shield effect of the PLLA matrix and the strong bonding interaction of Si-O-Zn. The scaffold could evidently promote osteogenesis differentiation of mouse bone marrow mesenchymal stem cells by upregulating their osteogenesis-related gene expression. Besides, Zn-MS particles could significantly increase the compressive strength of the PLLA scaffold because of their rosette-like morphology and mesoporous structure, which can form micromechanical interlocking with the PLLA matrix. The Zn-MS particles possess great potential to improve various polymer scaffold properties due to their advantageous morphology and physicochemical properties.

Acyl Fluorides from Carboxylic Acids, Aldehydes, or Alcohols under Oxidative Fluorination.

We describe a novel reagent system to obtain acyl fluorides directly from three different functional group precursors: carboxylic acids, aldehydes, or alcohols. The transformation is achieved via a combination of trichloroisocyanuric acid and cesium fluoride, which facilitates the synthesis of various acyl fluorides in high yield (up to 99%). It can be applied to the late-stage functionalization of natural products and drug molecules that contain a carboxylic acid, an aldehyde, or an alcohol group.

Synaptic Protein Phosphorylation Networks Are Associated With Electroacupuncture-Induced Circadian Control in the Suprachiasmatic Nucleus.

Phosphorylation is one of the most important posttranslational modifications and regulates the physiological process. While recent studies highlight a major role of phosphorylation in the regulation of sleep-wake cycles to a lesser extent, the phosphoproteome in the suprachiasmatic nucleus (SCN) is not well-understood. Herein, we reported that the EA treatment elicits partial reparation of circadian rhythmicity when mice were exposure to constant darkness for long time. We investigated the effects of EA on circadian rhythms in constant darkness between EA stimulation and free-running control. Next, mass spectrometry-based phosphoproteome was utilized to explore the molecular characteristics of EA-induced phosphorylation modification in the SCN. A total of 6,192 distinct phosphosites on 2,488 proteins were quantified. Functional annotation analysis and protein-protein interaction networks demonstrated the most significant enriched phosphor-proteins and phosphosites involved in postsynapse and glutamatergic synapse. The current data indicated that most of the altered molecules are structural proteins. The target proteins, NMDAR and CAMK2, were selected for verification, consistent with the results of LC-MS/MS. These findings revealed a complete profile of phosphorylation modification in response to EA.

Design of Multifunctional Mesosphere-Ionosphere Sounding System and Preliminary Results.

This paper describes a novel sounding system for which the functions of the medium frequency (MF) radar and the ionosonde are integrated on the same hardware platform and antenna structure, namely the middle atmosphere-ionosphere (MAI) system. Unlike the common MF radar, MAI system adopts the pseudo-random (PRN) phase-coded modulation technology, which breaks the limitation of the traditional monopulse mode. Through the pulse compression, only a small peak power is needed to achieve the signal-to-noise ratio (SNR) requirement. The excellent anti-jamming performance is also very suitable for the ionospheric sounding. One transmitting and six receiving modes are adopted for the MF sounding. While neglecting the structure of the T/R switches, the coupling interference between the transmitter and the receiver may also be avoided. Moreover, by employing a miniaturized antenna array composed of progressive-wave antennas for the MF receiving and ionospheric sounding, the MAI system takes account of the requirements of the inversion algorithms of MF radar and the large bandwidth need for the ionospheric sounding concurrently. Such an antenna structure can also greatly simplify the system structure and minimize the difficulty of deployment. The experiments verified the availability of the system scheme and its engineering application significance. Through further analysis of the sounding data, the wind field of the mesosphere, the electron density of D layer and electron density profile from layers E to F were obtained at the identical location. The capability of MAI system can play an important role in studying the interaction and coupling mechanism between the mesosphere and ionosphere.