DNA barcoding has greatly facilitated studies of taxonomy, biodiversity, biological conservation, and ecology. Here, we establish a reliable DNA barcoding library for Chinese snakes, unveiling hidden ...diversity with implications for taxonomy, and provide a standardized tool for conservation management. Our comprehensive study includes 1638 cytochrome c oxidase subunit I (COI) sequences from Chinese snakes that correspond to 17 families, 65 genera, 228 named species (80.6% of named species) and 36 candidate species. A barcode gap analysis reveals gaps, where all nearest neighbour distances exceed maximum intraspecific distances, in 217 named species and all candidate species. Three species‐delimitation methods (ABGD, sGMYC, and sPTP) recover 320 operational taxonomic units (OTUs), of which 192 OTUs correspond to named and candidate species. Twenty‐eight other named species share OTUs, such as Azemiops feae and A. kharini, Gloydius halys, G. shedaoensis, and G. intermedius, and Bungarus multicinctus and B. candidus, representing inconsistencies most probably caused by imperfect taxonomy, recent and rapid speciation, weak taxonomic signal, introgressive hybridization, and/or inadequate phylogenetic signal. In contrast, 43 species and candidate species assign to two or more OTUs due to having large intraspecific distances. If most OTUs detected in this study reflect valid species, including the 36 candidate species, then 30% more species would exist than are currently recognized. Several OTU divergences associate with known biogeographic barriers, such as the Taiwan Strait. In addition to facilitating future studies, this reliable and relatively comprehensive reference database will play an important role in the future monitoring, conservation, and management of Chinese snakes.
Substantial attention has been given to modern organocopper chemistry in recent years since copper salts are naturally abundant, cheap, and less toxic in comparison to precious metals. Copper salts ...also exhibit versatility in catalyzing and mediating carbon–carbon and carbon–heteroatom bond forming reactions. Despite the wide applications of copper salts in catalysis, reaction mechanisms have remained elusive. Using azacalix1arene3pyridine, an arene-embedded macrocycle, and its isolated and structurally well-defined ArCu(II) and ArCu(III) compounds as molecular tools, we now report an in-depth experimental and computational study on the mechanism of a Cu(II)-catalyzed oxidative cross-coupling reaction between arenes and boronic acids with air as the oxidant. Stoichiometric reaction of organocopper compounds with p-tolylboronic acid validated arylcopper(II) rather than arylcopper(III) as a reactive organometallic intermediate. XPS, EPR, 1H NMR, HRMS, and UV–vis spectroscopic evidence along with the isolation and quantification of all products and copper speciation, combined with computational analysis of the electronic structure and energetics of the transient intermediates, suggested a reaction sequence involving electrophilic metalation of arene by Cu(II), transmetalation of arylboronate to ArCu(II), the redox reaction between the resulting ArCu(II)Ar′ and ArCu(II) to form respectively ArCu(III)Ar′ and ArCu(I), and finally reductive elimination of ArCu(III)Ar′. Under aerobic catalytic conditions, all Cu(I) ions released from reductive elimination of ArCu(III)Ar′ and from protolysis of ArCu(I) were oxidized by oxygen to regenerate Cu(II) species that enters into the next catalytic cycle. The unraveled reactivity of arylcopper(II) compounds and the catalytic cycle would enrich our knowledge of modern organocopper chemistry and provide useful information in the design of copper-catalyzed reactions.
The study of new C–H silylation reagents and reactions remains an important topic. We reported that under Rh catalysis, silacyclobutanes (SCBs) for the first time were able to react with C(sp2)–H ...and C(sp3)–H bonds, however the underlying reasons for such a new reactivity were not understood. Through this combined computational and experimental study on C–H silylation with SCBs, we not only depict a reaction pathway that fully accounts for the reactivity and all the experimental findings but also streamline a more efficient catalyst that significantly improves the reaction rates and yields. Our key findings include: (1) the active catalytic species is a Rh–H as opposed to the previously proposed Rh–Cl; (2) the Rh–H is generated via a reductive elimination/β-hydride (β-H) elimination sequence, as opposed to previously proposed endocyclic β-H elimination; (3) the regio- and enantio-determining steps are identified; (4) and of the same importance, the discretely synthesized Rh–H is shown to be a more efficient catalyst. This work suggests that the Rh–H/diphosphine system should find further applications in C–H silylations involving SCBs.
•In this manuscript, the nanosecond plasma actuation is used to control the boundary layer flow of a typical CDA compressor airfoil.•The corresponding flow control mechanism has been uncovered using ...large eddy simulations.•It has been found that the nanosecond plasma actuation can influence the boundary layer flow through inducing two types of spanwise vortexes.•Especially, the plasma actuations located within the laminar boundary layer flow can act as a high-speed wall jet.•This finding further improves the ability of plasma actuation in controlling high-speed flows.
The flow control effects of nanosecond plasma actuation on the boundary layer flow of a typical compressor controlled diffusion airfoil are investigated using large eddy simulation method. Three types of plasma actuation are designed to control the boundary layer flow, and two mechanisms of compressor airfoil boundary layer flow control using nanosecond plasma actuation have been found. The plasma actuations located within the laminar boundary layer flow can induce a small vortex structure through influencing on the density and pressure of the flow field. As the small vortex structure moves downstream along the blade surface with the main flow, it can suppress the turbulent flow mixing and reduce the total pressure loss. The flow control effect of the small vortex structure is summarized as wall jet effect. Differently, the plasma actuation located within the turbulent boundary layer flow can act on the shear layer flow and induce a large vortex structure. While moving downstream, this large vortex structure can suppress the turbulent flow mixing too.
Synaptic abnormality is an important pathologic feature of autism spectrum disorders (ASDs) and responsible for various behavioral defects in these neurodevelopmental disorders. Microglia are the ...major immune cells in the brain and also play an important role in synapse refinement. Although dysregulated synaptic pruning by microglia during the brain development has been associated with ASDs, the underlying mechanism has yet to be fully elucidated. Herein, we observed that expression of Transmembrane protein 59 (TMEM59), a protein recently shown to regulate microglial function, was decreased in autistic patients. Furthermore, we found that both male and female mice with either complete or microglia-specific loss of
developed ASD-like behaviors. Microglial TMEM59-deficient mice also exhibited enhanced excitatory synaptic transmission, increased dendritic spine density, and elevated levels of excitatory synaptic proteins in synaptosomes. TMEM59-deficient microglia had impaired capacity for synapse engulfment both
and
Moreover, we demonstrated that TMEM59 interacted with the C1q receptor CD93 and TMEM59 deficiency promoted CD93 protein degradation in microglia. Downregulation of CD93 in microglia also impaired synapse engulfment. These findings identify a crucial role of TMEM59 in modulating microglial function on synapse refinement during brain development and suggest that TMEM59 deficiency may contribute to ASDs through disrupting phagocytosis of excitatory synapse and thus distorting the excitatory-inhibitory (E/I) neuronal activity balance.
Microglia play an important role in synapse refinement. Dysregulated synaptic pruning by microglia during brain development has been associated with autism spectrum disorders (ASDs). However, the underlying mechanism has yet to be fully elucidated. Herein, we observe that the expression of Transmembrane protein 59 (TMEM59), an autophagy-related protein, is decreased in autistic patients. Moreover, we find ASD-like behaviors in mice with complete loss and with microglia-specific loss of
Mechanistic studies reveal that TMEM59 deficiency in microglia impairs their synapse engulfment ability likely through destabilizing the C1q receptor CD93, thereby leading to enhanced excitatory neurotransmission and increased dendritic spine density. Our findings demonstrate a crucial role of microglial TMEM59 in early neuronal development and provide new insight into the etiology of ASDs.
Chimeric antigen receptor (CAR)‐T cell immunotherapy is approved in the treatment of hematological malignancies, but remains far from satisfactory in solid tumor treatment due to inadequate ...intra‐tumor CAR‐T cell infiltration. Herein, an injectable supramolecular hydrogel system, based on self‐assembly between cationic polymer mPEG‐PCL‐PEI (PPP) conjugated with T cell targeting anti‐CD3e f(ab')2 fragment and α‐cyclodextrin (α‐CD), is designed to load plasmid CAR (pCAR) with a T cell specific CD2 promoter, which successfully achieves in situ fabrication and effective accumulation of CAR‐T cells at the tumor site in humanized mice models. More importantly, due to this tumor microenvironment reprogramming, secretion of cellular inflammatory cytokines (interleukin‐2 (IL‐2), tumor necrosis factor‐α (TNF‐α), and interferon‐γ (IFN‐γ)) or tumor killer protein granzyme B is significantly promoted, which reverses the immunosuppressive microenvironment and significantly enhances the intra‐tumor CAR‐T cells and cytotoxic T cells infiltration. To the best of the current knowledge, this is a pioneer report of using injectable supramolecular hydrogel for in situ reprogramming CAR‐T cells, which might be beneficial for solid tumor CAR‐T immunotherapy.
An injectable CAR plasmid (pCAR)‐loaded supramolecular hydrogel system for long‐term and sustained reprogramming of CAR‐T cells in situ for solid tumor immunotherapy is introduced. After injection locally adjacent to a solid tumor, the supramolecular hydrogel platform produces in situ CAR‐T cells by sustaining release of T cell‐targeting nanocomplexes‐carrying pCAR and significantly diminishes the immunosuppressive microenvironment or facilitates the clearance of solid tumors.
Mutations in colony-stimulating factor 1 receptor (CSF1R) are known to cause adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), which has been recently demonstrated as a ...primary microgliopathy characterized by cognitive impairment. Although the molecular mechanism underlying CSF1R-mediated microgliopathy remains unclear, therapeutic strategies have generally targeted modulation of microglial function. In particular, the microglial inhibitor, minocycline, has been shown to attenuate learning and memory deficits in several neurodegenerative diseases. The objectives of this study were to investigate the pathogenic mechanisms underlying ALSP and to explore the therapeutic effects of minocycline in an in vivo model of ALSP. We hypothesized that inhibiting microglial activation via minocycline could reverse the behavior and pathological defects in ALSP model mice.
We generated a Csf1r haploinsufficiency mouse model of ALSP using CRISPR/Cas9 genome editing and conducted electrophysiological recordings of long-term potentiation (LTP) and behavioral tests to validate the recapitulation of clinical ALSP characteristics in 8- to 11-month-old mice. RNA-sequencing was used to explore enriched gene expression in the molecular pathogenesis of ALSP. Microglial activation was assessed by immunofluorescent detection of Iba1 and CD68 in brain sections of male ALSP mice and pro-inflammatory activation and phagocytosis were assessed in Csf1r
microglia. Therapeutic effects were assessed by behavioral tests, histological analysis, and morphological examination after four weeks of intraperitoneal injection with minocycline or vehicle control in Csf1r
mice and wild-type control littermates.
We found that synaptic function was reduced in LTP recordings of neurons in the hippocampal CA1 region, while behavioral tests showed impaired spatial and cognitive memory specifically in male Csf1r
mice. Increased activation, pro-inflammatory cytokine production, and enhanced phagocytic capacity were also observed in Csf1r
microglia. Treatment with minocycline could suppress the activation of Csf1r
microglia both in vitro and in vivo. Notably, the behavioral and pathological deficits in Csf1r
mice were partially rescued by minocycline administration, potentially due to inhibition of microglial inflammation and phagocytosis in Csf1r
mice.
Our study shows that CSF1R deficiency results in aberrant microglial activation, characterized by a pro-inflammatory phenotype and enhanced phagocytosis of myelin. Our results also indicate that microglial inhibition by minocycline can ameliorate behavioral impairment and ALSP pathogenesis in CSF1R-deficient male mice, suggesting a potential therapeutic target for CSF1R-related leukoencephalopathy. Collectively, these data support that minocycline confers protective effects against CSF1R-related microgliopathy in male ALSP model mice.
A general and mild hydrosilylation of thioalkynes is described. With the cationic catalyst Cp*Ru(MeCN)3+ and the bulky silane (TMSO)3SiH, a range of thioalkynes underwent smooth hydrosilylation at ...room temperature with excellent α regioselectivity and syn stereoselectivity. DFT calculations provided important insight into the mechanism, particularly the unusual syn selectivity with the Cp*Ru(MeCN)3+ catalyst. The sulfenyl group in the substrates was found to provide important chelation stabilization to direct the reaction through a new mechanistic pathway.
A rich source of vinyl silanes: A general, mild, and highly stereoselective hydrosilylation of electron‐rich alkynes gave a range of stereodefined multisubstituted vinyl silanes with high efficiency (see scheme; R1, R2=alkyl, aryl; TMS=trimethylsilyl). Unprecedented syn selectivity was observed with the cationic catalyst Cp*Ru(MeCN)3+. DFT calculations provided important insight into the mechanism.
Post‐stroke depression, a common complication after stroke, severely affects the recovery and quality of life of patients with stroke. Owing to its complex mechanisms, post‐stroke depression ...treatment remains highly challenging. Hippocampal synaptic plasticity is one of the key factors leading to post‐stroke depression; however, the precise molecular mechanisms remain unclear. Numerous studies have found that neurotrophic factors, protein kinases and neurotransmitters influence depressive behaviour by modulating hippocampal synaptic plasticity. This review further elaborates on the role of hippocampal synaptic plasticity in post‐stroke depression by summarizing recent research and analysing possible molecular mechanisms. Evidence for the correlation between hippocampal mechanisms and post‐stroke depression helps to better understand the pathological process of post‐stroke depression and improve its treatment.
The construction of an efficient oxygen reduction reaction and oxygen evolution reaction (ORR/OER) bifunctional electrocatalyst is of great significance but still remains a giant challenge for ...high-performance metal–air batteries. In this study, uniform FeS/Fe3C nanoparticles embedded in a porous N,S-dual doped carbon honeycomb-like composite (abbr. FeS/Fe3C@NS-C-900) have been conveniently fabricated by pyrolysis of a single-crystal Fe-MOF, which has a low potential gap ΔE of ca. 0.72 V, a competitive power density of 90.9 mW/cm2, a specific capacity as high as 750 mAh/g Zn , and excellent cycling stabilities over 865 h (1730 cycles) at 2 mA/cm2 when applied as a cathode material for rechargeable zinc–air batteries. In addition, the two series-linked Zn–air batteries successfully powered a 2.4 V LED light as a real power source. The efficient ORR/OER bifunctional electrocatalytic activity and long-term durability of the obtained composite might be attributed to the characteristic honeycomb-like porous structure with sufficient accessible active sites, the synergistic effect of FeS and Fe3C, and the N,S codoped porous carbon, which provides a promising application potential for portable electronic Zn–air battery related devices.
