METTL3 is essential for normal progesterone signaling during embryo implantation via m6A-mediated translation control of progesterone receptor.

Embryo implantation, a crucial step in human reproduction, is tightly controlled by estrogen and progesterone (P4) via estrogen receptor alpha and progesterone receptor (PGR), respectively. Here, we report that N6-methyladenosine (m6A), the most abundant mRNA modification in eukaryotes, plays an essential role in embryo implantation through the maintenance of P4 signaling. Conditional deletion of methyltransferase-like 3 (Mettl3), encoding the m6A writer METTL3, in the female reproductive tract using a Cre mouse line with Pgr promoter (Pgr-Cre) resulted in complete implantation failure due to pre-implantation embryo loss and defective uterine receptivity. Moreover, the uterus of Mettl3 null mice failed to respond to artificial decidualization. We further found that Mettl3 deletion was accompanied by a marked decrease in PGR protein expression. Mechanistically, we found that Pgr mRNA is a direct target for METTL3-mediated m6A modification. A luciferase assay revealed that the m6A modification in the 5' untranslated region (5'-UTR) of Pgr mRNA enhances PGR protein translation efficiency in a YTHDF1-dependent manner. Finally, we demonstrated that METTL3 is required for human endometrial stromal cell decidualization in vitro and that the METTL3-PGR axis is conserved between mice and humans. In summary, this study provides evidence that METTL3 is essential for normal P4 signaling during embryo implantation via m6A-mediated translation control of Pgr mRNA.

Multipartite entanglement generation with high-order non-Hermitian exceptional points from dressing-controlled atomic nonlinearity.

Multipartite entanglement has emerged as a valuable quantum resource for constructing large-scale quantum networks. However, the presence of non-Hermitian features induced by natural microscopic quantum systems significantly modifies the overall response of nonlinear parametric processes, thereby enabling direct manipulation of multipartite entanglement properties. In this study, we demonstrate the generation of multimode entanglement through atomic four-wave mixing (FWM) and analyze the properties of exceptional points (EP) under dressing control in non-Hermitian systems. By leveraging dressing-controlled atomic nonlinearity, we achieve versatile EPs and higher-order EPs by carefully tuning the atomic multi-parameter in the cascading FWM system. Additionally, we investigate the entanglement properties of various permutations of the output signal modes using the positive partial transpose (PPT) criterion. Notably, under non-Hermitian control, the application of single-, double-, and N-dressing splits leads to coherent multichannel control and further extends the scale of quantum entanglement. The outcomes of our research offer a novel approach to actively control non-Hermitian quantum phenomena without relying on artificial photonic structures. Furthermore, this paves the way for the realization of complex quantum information tasks by exploiting the non-Hermitian characteristics of the light-matter interaction.

Speed behaviour and mental workload of small-spacing expressway interchanges based on field driving test.

Many small-spacing interchanges (SSI) appear with the improvement of the expressway network. To investigate the speed and mental workload characteristics in the SSI and acquire the mechanism of the influence of speed on the drivers' workload, 37 participants were recruited to perform a field driving test. Each driver performed four driving conditions (i.e. ramp-mainline, mainline-ramp, mainline driving, and auxiliary lane driving). The speed and drivers' electrocardiogram (ECG) data were collected using SpeedBox speed acquisition equipment and PhysioLAB physiological instrument. The heart rate increase (HRI) index was used to analyse the drivers' mental workload regularity. The relationship model between speed and HRI was developed to examine the impact of speed on HRI. The results show that the speed variation in the SSI displayed two patterns: 'decrease - increase and continuous decrease.' The drivers' HRI variation presented four patterns: 'convex curve, continuously increasing, continuously decreasing and concave curve'. SSI's influenced area length is given based on the speed and HRI variation regularity. HRI is significantly higher when driving in the ramp-mainline condition in the SSI than when driving in other conditions, indicating that drivers are more nervous when merging with the mainline traffic. HRI increases significantly in the first 50% of the weaving area in four driving conditions, indicating that vehicle weaving greatly influences the drivers' mental workload. A positive correlation exists between vehicle speed and drivers' HRI without interference from other vehicles and road alignment.

The shorter spacing of the interchange will result in a more difficult driving task for the drivers. This study shows that drivers have the highest mental workload in ramp-mainline driving condition at small-spacing interchanges. The first half of the weaving area is the area where drivers' mental workload increases significantly, and is a high-risk section for small-spacing interchanges. This study can provide a reference for the revision of the allowable minimum interchange spacing in the corresponding specification, and the calibration of the simulation test parameters for similar scenarios.

Comparative transcriptome analysis of experimental cryptorchidism: of mice and cynomolgus monkeys.

In most mammalian species, the testis descends from the abdomen into the scrotum during fetal or neonatal life. The failure of testicular descent, a pathological condition known as cryptorchidism, has long been the subject of scientific interest in a wide range of fields, including medicine, developmental biology, and evolutionary biology. In this study, we analyzed global gene expression changes associated with experimental cryptorchidism in mice by using RNA-seq. A total of 453 differentially expressed genes were identified, of which 236 genes were upregulated, and 217 genes were downregulated. Gene ontology, pathway, and gene network analysis highlighted the activation of inflammatory response in experimental cryptorchidism. By examining the promoter regions of differentially expressed genes, we identified 12 causal transcription factors. In addition, we also induced experimental cryptorchidism in two cynomolgus monkeys and performed RNA-seq. A cross-species comparison was performed at the gene expression level. Our study provides a valuable resource for further understanding the molecular mechanisms of cryptorchidism in mammals.

Multimode entanglement generation with dual-pumped four-wave-mixing of Rubidium Atoms.

Multimode entanglement is essential for the generation of quantum networks, which plays a central role in quantum information processing and quantum metrology. Here, we study the spatial multimode entanglement characteristics of the large scale quantum states via a dual-pumped four-wave-mixing (FWM) process of Rubidium atomics vapors. A linear mode transform approach is applied to solve the four- and six-mode Gaussian states and the analytical input-output relations are presented. Moreover, via reconstructing the full covariance matrix of the produced states, versatile entanglement with from two up to six modes is analyzed. The results show that most of the 1 versus n-mode and m versus n-mode states are entangled, and the amount of entanglement can be regulated due to the competitions of mode components caused by different interaction strengths of co-existing FWMs. Our study could be applied for any multimode Gaussian states with a quadratic Hamiltonian.

Controllable Si-C Bond Activation Enables Stereocontrol in the Palladium-Catalyzed [4+2] Annulation of Cyclopropenes with Benzosilacyclobutanes.

A novel and unusual palladium-catalyzed [4+2] annulation of cyclopropenes with benzosilacyclobutanes is reported. This reaction occurred through chemoselective Si-C(sp2 ) bond activation in synergy with ring expansion/insertion of cyclopropenes to form new C(sp2 )-C(sp3 ) and Si-C(sp3 ) bonds. An array of previously elusive bicyclic skeleton with high strain, silabicyclo[4.1.0]heptanes, were formed in good yields with excellent diastereoselectivity under mild conditions. An asymmetric version of the reaction with a chiral phosphoramidite ligand furnished a variety of chiral bicyclic silaheterocycle derivatives with good enantioselectivity (up to 95.5:4.5 er). Owing to the mild reaction conditions, the good stereoselectivity profile, and the ready availability of the functionalized precursors, this process constitutes a useful and straightforward strategy for the synthesis of densely functionalized silacycles.

Entanglement in a four-wave mixing process.

We investigate different kinds of entanglement in a four-wave mixing process with a degenerate pump. After analyses on means and quantum fluctuations of the three output beams (Stokes, anti-Stokes, and pump), we verify the existence of genuine tripartite entanglement, and quantify bipartite, two-mode, as well as tripartite entanglement with the covariance matrix. We find out that the input pump power and the nonlinear coupling strength are the physical origins to enhance entanglement at a given photon loss.

Transition-Metal-Free Oxidative C(sp2 )-H Hydroxylation of Terpyridines: A HOMO-Raising Strategy for the Construction of a New Super-Stable Terpyridine Chromophores.

Direct functionalization of terpyridines is an increasingly important topic in the field of dyes and catalysis as well as supramolecular chemistry, but its synthesis and transformation is usually challenging. Herein, a HOMO-raising strategy is reported for the construction of a super-stable novel terpyridine chromophores, in which the selective oxidation of terpyridines at its 3-position was determined successfully to the synthesis of phenol-functionalization of terpyridines (TPyOHs) bearing a hydrogen bonding group. The corresponding TPyOHs displayed strong aggregation-induced emission and exhibited highly selective and visual detection of ZnII cation with a record green terpyridine-based luminophore with nanomolar sensitivity (125 nm).

Cs2CO3-Initiated Trifluoro-Methylation of Chalcones and Ketones for Practical Synthesis of Trifluoromethylated Tertiary Silyl Ethers.

It was found that 1,2-trifluoromethylation reactions of ketones, enones, and aldehydes were easily accomplished using the Prakash reagent in the presence of catalytic amounts of cesium carbonate, which represents an experimentally convenient, atom-economic process for this anionic trifluoromethylation of non-enolisable aldehydes and ketones.

Generation of tripartite entanglement from cascaded four-wave mixing processes.

We investigate the possibility of an experimentally feasible cascaded four-wave mixing (FWM) system [Phys. Rev. Lett. 113, 023602 (2014)] to generate tripartite entanglement. We verify that genuine tripartite entanglement is present in this system by calculating the covariances of three output beams and then considering the violations of the inequalities of the three-mode entanglement criteria, such as two-condition criterion, single-condition criterion, optimal single-condition criterion and the positivity under partial transposition (PPT) criterion. We also consider the possibilities of the bipartite entanglement of any pair of the three output beams using the Duan-Giedke-Cirac-Zoller criterion and PPT criterion. We find that the tripartite entanglement and the bipartite entanglement for the two pairs are present in the whole gain region. The entanglement characteristics under different entanglement criteria are also considered. Our results pave the way for the realization and application of multipartite entanglement based on the cascaded FWM processes.

Asymmetric Michael Addition of Aldimino Esters with Chalcones Catalyzed by Silver/Xing-Phos: Mechanism-Oriented Divergent Synthesis of Chiral Pyrrolines.

The mechanism-oriented reaction design for the divergent synthesis of chiral molecules from simple starting materials is highly desirable. In this work, aromatic amide-derived nonbiarylatropisomer/silver (silver/Xing-Phos) complex was used to catalyze the Michael addition of glycine aldimino esters to chalcones and successfully applied to the subsequent cyclocondensation to afford substituted cis-Δ(1)-pyrroline derivatives with up to 98 % ee. Besides the inherent performance of the chiral Ag/Xing-Phos catalyst system, it was found that the workup of such reactions played an important role for the stereoselective construction of stereodivergent Δ(1)-pyrrolines, in which an epimerization of the cis-Δ(1)-pyrrolines to the trans-isomers during was revealed.

Catalytic asymmetric bromochlorination of aromatic allylic alcohols promoted by multifunctional Schiff base ligands.

It was found that the tridentate O,N,O-type Schiff base ligand bearing suitable substituents was a highly effective promoter in the catalytic asymmetric bromochlorination reaction, in which the corresponding aromatic bromochloroalcohols with vicinal halogen-bearing stereocenters were formed with perfect regioselectivity, with moderate to excellent enantioselectivities (up to 93% ee), and with good yields and chemoselectivities.

[Inhibitory Effect of Feiji Recipe on IDO Induced Immune Escape on the Murine Model of Lewis Lung Carcinoma].

OBJECTIVE: To study the effect of Feiji Recipe (FR) intervening indoleamine 2,3-dioxygenase (IDO) induced immune escape on the murine model of Lewis lung carcinoma. Methods Totally 48 C57BL/6 mice inoculated with Lewis lung cancer cells transfected with human (enhanced green fluorescent protein,EGFP)-IDO gene were divided into four groups according to radom digit table, i.e., the model group (administered with normal saline by gastrogavage) , the Chinese medicine group (treated with FR Decoction at the daily dose of 100 mg/g by gastrogavage), the 1-methyl-D-trytaphan (1-MT) group (administered with 1-MT mixed liquor at the daily dose of 100 mg/kg by gastrogavage), and the Paclitaxel group (treated with Paclitaxel at the daily dose of 15 mg/kg by peritoneal injection), 12 in each group. The intervention was started from the 2nd day of modeling. The survival time was observed in 24 of them. Ratios of CD4+ CD25+ FoxP3+ regulatory T cells (Treg) in the spleen were detected in the rest 24 mice by flow cytometry respectively. RESULTS: Compared with the model group, the survival time was significantly prolonged in the Chinese medicine group and the 1-MT group (P < 0.01); ratios of Treg cells remarkably decreased in the Chinese medicine group, the 1-MT group, and the Paclitaxel group (P < 0. 01). Compared with the Paclitaxel group, the survival time was significantly prolonged in the Chinese medicine group and the 1-MT group (P < 0.01); ratios of Treg cells decreased significantly in the 1-MT group (P < 0.05). CONCLUSION: FR could inhibit the proliferation of lung cancer cells and immune eseape, improve the immune function, and prolong the survival of tumor-bearing mice.

Enantioselective copper-catalyzed azide-alkyne click cycloaddition to desymmetrization of maleimide-based bis(alkynes).

A copper catalyst system derived from TaoPhos and CuF2 was used successfully for catalytic asymmetric Huisgen [3+2] cycloaddition of azides and alkynes to give optically pure products containing succinimide- and triazole-substituted quaternary carbon stereogenic centers. The desired products were obtained in good yields (60-80 %) and 85:15 to >99:1 enantiomeric ratio (e.r.) in this click cycloaddition reaction.

Synthesis of bi- and bis-1,2,3-triazoles by copper-catalyzed Huisgen cycloaddition: A family of valuable products by click chemistry.

The Cu(I)-catalyzed azide-alkyne cycloaddition reaction, also known as click chemistry, has become a useful tool for the facile formation of 1,2,3-triazoles. Specifically, the utility of this reaction has been demonstrated by the synthesis of structurally diverse bi- and bis-1,2,3-triazoles. The present review focuses on the synthesis of such bi- and bistriazoles and the importance of using copper-promoted click chemistry (CuAAC) for such transformations. In addition, the application of bitriazoles and the related CuAAAC reaction in different fields, including medicinal chemistry, coordination chemistry, biochemistry, and supramolecular chemistry, have been highlighted.

Four pins assisted reduction of complex segmental femoral fractures: a technique for closed reduction.

Complex segmental femoral fractures are usually not amenable to closed reduction. The purpose of this study was to evaluate a series of patients who had undergone four pins assisted reduction and intramedullary nail fixation to determine the therapeutic effect of this closed reduction technique. Between December 2010 and January 2013, 15 consecutive patients with segmental femoral fractures were treated with four pins assisted reduction at our hospital. The patient was placed in a supine position on a radiolucent fracture table and a gentle traction was attempted on the limb. Usually, the proximal fracture segment exhibited the typical deformity of flexion, external rotation, and abduction, the middle segment exhibited adduction and distal fracture segment exhibited flexion. Four Schanz pins were placed percutaneously to fix one cortex and did not penetrate into the medullary cavity, and the "T" sharp handles were fixed on the Schanz pins. The fragments were then reduced by reversing the deforming forces for segmental fractures by two assistants. And then, the reduction could be easily achieved and intramedullary nail fixation was performed. Radiographs were evaluated for the quality of the reduction and fracture union. Closed reduction was achieved in all patients using the four pins technology. All 15 fractures united uneventfully. No patient had a rotational malunion or limb length discrepancy at the time of the last follow-up. Thirteen of the fifteen (86.7%) patients had anatomic reduction and two of them (13.3%) had minor varus alignment of 3° and 5°. Knee stiffness was observed in 2 patients and no implant failure was observed. Surgical treatment of complex segmental femoral fractures with four pins assisted reduction and intramedullary nail fixation techniques can result in excellent reductions and a high union rate.

Complexes of Soluble Dietary Fiber and Polyphenols from Lotus Root Regulate High-Fat Diet-Induced Hyperlipidemia in Mice.

In this paper, complexes of soluble dietary fiber (SDF) and polyphenols (PPs) isolated from lotus roots were prepared (SDF-PPs), as well as physical mixtures (SDF&PPs), which were given to high-fat-diet (HFD)-fed mice. The results demonstrated that SDF-PPs improve lipid levels and reverse liver injury in hyperlipidemic mice. Western blotting and real-time quantitative Polymerase Chain Reaction (RT-qPCR) results showed that SDF-PPs regulated liver lipids by increasing the phosphorylation of Adenine monophosphate activated protein kinase (AMPK), up-regulating the expression of Carnitine palmitoyltransferase1 (CPT1), and down-regulating the expression of Fatty acid synthase (FAS) and 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA), as well as the transcription factor sterol-regulatory element binding protein (SPEBP-1) and its downstream liposynthesis genes. Additionally, the intervention of SDF-PPs could modulate the composition of intestinal gut microbes, inducing an increase in Lachnospiraceae and a decrease in Desulfovibrionaceae and Prevotellaceae in high-fat-diet-fed mice. Thus, the research provides a theoretical basis for the application of lotus root active ingredients in functional foods and ingredients.

Development of a novel multifunctional n,p ligand for highly enantioselective palladium-catalyzed asymmetric allylic etherification of alcohols and silanols.

CycloN2P2-Phos! The use of the multidentate phosphine, CycloN2P2-Phos, which contains four heteroatoms (two nitrogen and two phosphorus atoms), in the palladium-catalyzed asymmetric allylic etherification (AAE) of alcohols and silanols leads to excellent levels of enantioselectivity (up to 99 % ee).

Corrigendum: Crosstalk between cGAS-STING pathway and autophagy in cancer immunity.

[This corrects the article DOI: 10.3389/fimmu.2023.1139595.].

Crosstalk between cGAS-STING pathway and autophagy in cancer immunity.

The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is critical in cancer immunity. Autophagy is a highly conserved process that is responsible for the degradation of cytoplasmic material and is involved in both innate and adaptive immunity. Recently, cGAS-STING and autophagy have been shown to be interconnected, which may influence the progression of cancer. Although cGAS-STING and autophagy have been shown to be interrelated in innate immunity, little has been reported about cancer immunity. As cancer immunity is key to treating tumors, it is essential to summarize the relationship and interactions between the two. Based on this, we systematically sorted out the recent findings of cGAS-STING and autophagy in cancer immunity and explored the interactions between cGAS-STING and autophagy, although these interactions have not been extensively studied. Lastly, we provide an outlook on how cGAS-STING and autophagy can be combined, with the hope that our research can help people better understand their potential roles in cancer immunity and bring light to the treatment of cancer.