Ultrafiltration separation of Am(VI)-polyoxometalate from lanthanides.

Partitioning of americium from lanthanides (Ln) present in used nuclear fuel plays a key role in the sustainable development of nuclear energy1-3. This task is extremely challenging because thermodynamically stable Am(III) and Ln(III) ions have nearly identical ionic radii and coordination chemistry. Oxidization of Am(III) to Am(VI) produces AmO22+ ions distinct with Ln(III) ions, which has the potential to facilitate separations in principle. However, the rapid reduction of Am(VI) back to Am(III) by radiolysis products and organic reagents required for the traditional separation protocols including solvent and solid extractions hampers practical redox-based separations. Herein, we report a nanoscale polyoxometalate (POM) cluster with a vacancy site compatible with the selective coordination of hexavalent actinides (238U, 237Np, 242Pu and 243Am) over trivalent lanthanides in nitric acid media. To our knowledge, this cluster is the most stable Am(VI) species in aqueous media observed so far. Ultrafiltration-based separation of nanoscale Am(VI)-POM clusters from hydrated lanthanide ions by commercially available, fine-pored membranes enables the development of a once-through americium/lanthanide separation strategy that is highly efficient and rapid, does not involve any organic components and requires minimal energy input.

Genetic and immune determinants of E. coli liver abscess formation.

Systemic infections can yield distinct outcomes in different tissues. In mice, intravenous inoculation of Escherichia coli leads to bacterial replication within liver abscesses, while other organs such as the spleen clear the pathogen. Abscesses are macroscopic necrotic regions that comprise the vast majority of the bacterial burden in the animal, yet little is known about the processes underlying their formation. Here, we characterize E. coli liver abscesses and identify host determinants of abscess susceptibility. Spatial transcriptomics revealed that liver abscesses are associated with heterogenous immune cell clusters comprised of macrophages, neutrophils, dendritic cells, innate lymphoid cells, and T-cells that surround necrotic regions of the liver. Abscess susceptibility is heightened in the C57BL lineage, particularly in C57BL/6N females. Backcross analyses demonstrated that abscess susceptibility is a polygenic trait inherited in a sex-dependent manner without direct linkage to sex chromosomes. As early as 1 d post infection, the magnitude of E. coli replication in the liver distinguishes abscess-susceptible and abscess-resistant strains of mice, suggesting that the immune pathways that regulate abscess formation are induced within hours. We characterized the early hepatic response with single-cell RNA sequencing and found that mice with reduced activation of early inflammatory responses, such as those lacking the LPS receptor TLR4 (Toll-like receptor 4), are resistant to abscess formation. Experiments with barcoded E. coli revealed that TLR4 mediates a tradeoff between abscess formation and bacterial clearance. Together, our findings define hallmarks of E. coli liver abscess formation and suggest that hyperactivation of the hepatic innate immune response drives liver abscess susceptibility.

N4-acetylcytidine modifies primary microRNAs for processing in cancer cells.

N4 acetylcytidine (ac4C) modification mainly occurs on tRNA, rRNA, and mRNA, playing an important role in the expression of genetic information. However, it is still unclear whether microRNAs have undergone ac4C modification and their potential physiological and pathological functions. In this study, we identified that NAT10/THUMPD1 acetylates primary microRNAs (pri-miRNAs) with ac4C modification. Knockdown of NAT10 suppresses and augments the expression levels of mature miRNAs and pri-miRNAs, respectively. Molecular mechanism studies found that pri-miRNA ac4C promotes the processing of pri-miRNA into precursor miRNA (pre-miRNA) by enhancing the interaction of pri-miRNA and DGCR8, thereby increasing the biogenesis of mature miRNA. Knockdown of NAT10 attenuates the oncogenic characters of lung cancer cells by regulating miRNA production in cancers. Moreover, NAT10 is highly expressed in various clinical cancers and negatively correlated with poor prognosis. Thus, our results reveal that NAT10 plays a crucial role in cancer initiation and progression by modulating pri-miRNA ac4C to affect miRNA production, which would provide an attractive therapeutic strategy for cancers.

Inhibition of NKCC1 Ameliorates Anxiety and Autistic Behaviors Induced by Maternal Immune Activation in Mice.

Autism spectrum disorder (ASD) is thought to result from susceptibility genotypes and environmental risk factors. The offspring of women who experience pregnancy infection have an increased risk for autism. Maternal immune activation (MIA) in pregnant animals produces offspring with autistic behaviors, making MIA a useful model for autism. However, how MIA causes autistic behaviors in offspring is not fully understood. Here, we show that NKCC1 is critical for mediating autistic behaviors in MIA offspring. We confirmed that MIA induced by poly(I:C) infection during pregnancy leads to autistic behaviors in offspring. We further demonstrated that MIA offspring showed significant microglia activation, excessive dendritic spines, and narrow postsynaptic density (PSD) in their prefrontal cortex (PFC). Then, we discovered that these abnormalities may be caused by overexpression of NKCC1 in MIA offspring's PFCs. Finally, we ameliorated the autistic behaviors using PFC microinjection of NKCC1 inhibitor bumetanide (BTN) in MIA offspring. Our findings may shed new light on the pathological mechanisms for autism caused by pregnancy infection.

Growth performance, lipid metabolism, and systemic immunity of weaned piglets were altered by buckwheat protein through the modulation of gut microbiota.

Tartary buckwheat protein (BWP) is well known for the wide-spectrum antibacterial activity and the lipid metabolism- regulating property; therefore, BWP can be applied as feed additives to improve the animal's nutritional supply. With the aim to investigate the bioactive actions of the BWP, growth performance, lipid metabolism and systemic immunity of the weaned piglets were measured, and the alterations of pig gut microbiota were also analyzed. According to the results, the growth performances of the weaned piglets which were calculated as the average daily gain (ADG) and the average daily feed intake (ADFI) were significantly increased when compared to the control group. Simultaneously, the serum levels of the total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) were decreased, while the levels of high-density lipoprotein cholesterol (HDL-C) were increased in the BWP group. Moreover, the relative abundances of Lactobacillus, Prevotella_9, Subdoligranulum, Blautia, and other potential probiotics in the gut microbiota of weaned piglets were obviously increased in the BWP group. However, the relative abundances of Escherichia-Shigella, Campylobacter, Rikenellaceae_RC9_gut_group and other opportunistic pathogens were obviously decreased in the BWP group. In all, BWP was proved to be able to significantly improve the growth performance, lipid metabolism, and systemic immunity of the weaned piglets, and the specific mechanism might relate to the alterations of the gut microbiota. Therefore, BWP could be explored as a prospective antibiotic alternative for pig feed additives.

SYNTAXIN OF PLANTS81 regulates root meristem activity and stem cell niche maintenance via ROS signaling.

Root growth and development depend on continuous cell division and differentiation in root tips. In these processes, reactive oxygen species (ROS) play a critical role as signaling molecules. However, few ROS signaling regulators have been identified. In this study, we found knockdown of a syntaxin gene, SYNTAXIN OF PLANTS81 in Arabidopsis thaliana (AtSYP81) resulted in a severe reduction in root meristem activity and disruption of root stem cell niche (SCN) identity. Subsequently, we found AtSYP81 was highly expressed in roots and localized on the endoplasmic reticulum (ER). Interestingly, the reduced expression of AtSYP81 conferred a decreased number of peroxisomes in root meristem cells, raising a possibility that AtSYP81 regulates root development through peroxisome-mediated ROS production. Further transcriptome analysis revealed that class III peroxidases, which are responsible for intracellular ROS homeostasis, showed significantly changed expression in the atsyp81 mutants and AtSYP81 overexpression lines, adding evidence of the regulatory role of AtSYP81 in ROS signaling. Accordingly, rescuing the decreased ROS level via applying ROS donors effectively restored the defects in root meristem activity and SCN identity in the atsyp81 mutants. APETALA2 (AP2) transcription factors PLETHORA1 and 2 (PLT1 and PLT2) were then established as the downstream effectors in this pathway, while potential crosstalk between ROS signaling and auxin signaling was also indicated. Taken together, our findings suggest that AtSYP81 regulates root meristem activity and maintains root SCN identity by controlling peroxisome- and peroxidase-mediated ROS homeostasis, thus both broadening and deepening our understanding of the biological roles of SNARE proteins and ROS signaling.

Wide-field color imaging through multimode fiber with single wavelength illumination: plug-and-play approach.

Multimode fiber (MMF) is extensively studied for its ability to transmit light modes in parallel, potentially minimizing optical fiber size in imaging. However, current research predominantly focuses on grayscale imaging, with limited attention to color studies. Existing colorization methods often involve costly white light lasers or multiple light sources, increasing optical system expenses and space. To achieve wide-field color images with typical monochromatic illumination MMF imaging system, we proposed a data-driven "colorization" approach and a neural network called SpeckleColorNet, merging U-Net and conditional GAN (cGAN) architectures, trained by a combined loss function. This approach, demonstrated on a 2-meter MMF system with single-wavelength illumination and the Peripheral Blood Cell (PBC) dataset, outperforms grayscale imaging and alternative colorization methods in readability, definition, detail, and accuracy. Our method aims to integrate MMF into clinical medicine and industrial monitoring, offering cost-effective high-fidelity color imaging. It serves as a plug-and-play replacement for conventional grayscale algorithms in MMF systems, eliminating the need for additional hardware.

Laser-induced plasma micromachining on surfaces parallel to the incident laser in different solutions.

Laser-induced plasma micromachining (LIPMM) is an advanced technology that utilizes the plasma generated from laser breakdown to remove material, thereby facilitating the fabrication of microstructures. This paper explores the use of LIPMM on 304 stainless steel surfaces parallel to the laser beam in different solutions, focusing on the impact of the liquid environment on the machining process. It presents a theoretical analysis of the material removal mechanisms unique to this orientation and experimentally investigates how water, a salt solution, and ethanol affect plasma shockwave characteristics. Notably, the plasma shockwave in the salt solution demonstrates the most significant peak pressure and energy, enhancing the micromachining efficiency. These findings suggest that varying the liquid environment can significantly influence LIPMM's effectiveness, offering potential improvements in precision and control. This study broadens the understanding of LIPMM applications, especially in orientations not commonly explored, and opens new possibilities for advanced micromachining techniques in various industrial applications.

Thorium Cluster Synthesized by a Solvent-Free Flux Approach: The Richest Coordination Diversity and Application Exploration.

The renaissance of research interests in actinide oxo clusters in the past decade arises from both the concerns of radioactive contamination and their potential utility as nanoscale materials. Compared to the uranium cluster, the thorium (Th) cluster shows less coordination variation. Herein, we presented a unique Th cluster (ThC-1) that exhibits the most diverse coordination chemistry found within a single Th cluster via a solvent-free flux synthesis approach. The melt triazole not only offers a unique solvation environment that may be responsible for the coordination diversity in ThC-1 but also represents the first nitrogen-donor capping ligand in Th clusters. The potential utility of ThC-1 as a heterogeneous catalyst was also explored for a classical CO2 cycloaddition reaction. This work offers a novel approach in synthesizing Th clusters, broadening the realm of the structural diversity of Th.

Value of blood oxygenation level-dependent magnetic resonance imaging in early evaluation of the response and prognosis of esophageal squamous cell carcinoma treated with definitive chemoradiotherapy: a preliminary study.

BACKGROUND: To find a useful hypoxia non-invasive biomarker for evaluating early treatment response and prognosis to definitive chemoradiotherapy (dCRT) in patients with esophageal squamous cell carcinoma (ESCC), using blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI). METHODS: The R2* values were obtained pre- and 2-3 weeks post-dCRT in 28 patients with ESCC using BOLD MRI. Independent samples t-test (normality) or Mann-Whitney U test (non-normality) was used to compare the differences of R2*-related parameters between the complete response (CR) and the non-CR groups. Diagnostic performance of parameters in predicting response was tested with receiver operating characteristic (ROC) curve analysis. The 3-year overall survival (OS) was evaluated using Kaplan Meier curve, log rank test, and Cox proportional hazards regression analysis. RESULTS: The post-R2*, ∆R2*, and ∆%R2* in the CR group were significantly higher than those in the non-CR group (P = 0.002, 0.003, and 0.006, respectively). The R2*-related parameters showed good prediction of tumor response, with AUC ranging from 0.813 to 0.829. The 3-year OS rate in patients with ∆R2* >-7.54 s- 1 or CR were significantly longer than those with ∆R2* ≤ -7.54 s- 1 (72.37% vs. 0.00%; Hazard ratio, HR = 0.196; 95% confidence interval, 95% CI = 0.047-0.807; P = 0.024) or non-CR (76.47% vs. 29.27%; HR = 0.238, 95% CI = 0.059-0.963; P = 0.044). CONCLUSIONS: The preliminary results demonstrated that the R2* value might be a useful hypoxia non-invasive biomarker for assessing response and prognosis of ESCC treated with dCRT. BOLD MRI might be used as a potential tool for evaluating tumor oxygenation metabolism, which is routinely applied in clinical practice and beneficial to clinical decision-making. A large sample size was needed for further follow-up studies to confirm the findings.

Effectiveness and safety of awake prone positioning in COVID-19-related acute hypoxaemic respiratory failure: an overview of systematic reviews.

OBJECTIVE: To evaluate and summarize systematic reviews of the effects and safety of awake prone positioning for COVID-19-related acute hypoxaemic respiratory failure. METHODS: A comprehensive search was conducted on PubMed, Embase, the Cochrane Library, Web of Science, CNKI, CSPD, CCD and CBM from their inception to March 28, 2023. Systematic reviews (SRs) of awake prone positioning (APP) for COVID-19-related acute hypoxaemic respiratory failure in adults were included. Two reviewers screened the eligible articles, and four reviewers in pairs extracted data and assessed the methodological quality/certainty of the evidence of all included SRs by AMSTAR 2 and GRADE tools. The overlap of primary studies was measured by calculating corrected covered areas. Data from the included reviews were synthesized with a narrative description. RESULTS: A total of 11 SRs were included. The methodological quality of SRs included 1 "High", 4 "Moderate", 2 "Low" and 4 "Critically low" by AMSTAR 2. With the GRADE system, no high-quality evidence was found, and only 14 outcomes provided moderate-quality evidence. Data synthesis of the included SR outcomes showed that APP reduced the risk of requiring intubation (11 SRs) and improving oxygenation (3 SRs), whereas reduced significant mortality was not found in RCT-based SRs. No significant difference was observed in the incidence of adverse events between groups (8 SRs). The corrected covered area index was 27%, which shows very high overlap among studies. CONCLUSION: The available SRs suggest that APP has benefits in terms of reducing intubation rates and improving oxygenation for COVID-19-related acute hypoxemic respiratory failure, without an increased risk of adverse events. The conclusion should be treated with caution because of the generally low quality of methodology and evidence. TRIAL REGISTRATION: The protocol for this review was registered with PROSPERO: CRD42023400986. Registered 15 April 2023.

Baicalin ameliorates the gut barrier function and intestinal microbiota of broiler chickens.

The deoxynivalenol (DON)-contaminated feeds can impair chicken gut barrier function, disturb the balance of the intestinal microbiota, decrease chicken growth performance and cause major economic loss. With the aim of investigating the ameliorating effects of baicalin on broiler intestinal barrier damage and gut microbiota dysbiosis induced by DON, a total of 150 Arbor Acres broilers are used in the present study. The morphological damage to the duodenum, jejunum, and ileum caused by DON is reversed by treatment with different doses of baicalin, and the expression of tight junction proteins (ZO-1, claudin-1, and occludin) is also significantly increased in the baicalin-treated groups. Moreover, the disturbance of the intestinal microbiota caused by DON-contaminated feed is altered by baicalin treatment. In particular, compared with those in the DON group, the relative abundances of Lactobacillus, Lachnoclostridium, Ruminiclostridium and other beneficial microbes in the baicalin-treated groups are significantly greater. However, the percentage of unclassified_f__Lachnospiraceae in the baicalin-treated groups is significantly decreased in the DON group. Overall, the current results demonstrate that different doses of baicalin can improve broiler intestinal barrier function and the ameliorating effects on broiler intestinal barrier damage may be related to modulations of the intestinal microbiota.

In vivo detection of the epimer metabolites of sweroside via ultra-performance liquid chromatography time-of-flight mass spectrometry combined with DNPH derivatization.

The metabolites of sweroside were first investigated in vivo with ultra-performance liquid chromatography time-of-flight mass spectrometry (UPLC-TOF-MS) in combination with 2,4-dinitrophenylhydrazine derivatization. In addition, the mass detection sensitivity of the major metabolites, epinaucledal and naucledal, via UPLC-TOF-MS was significantly enhanced, and the epimer metabolites were distinctly discovered from plasma following gavage of sweroside in rats. The plasma concentration of epinaucledal and naucledal was quantified via UPLC-TOF-MS in negative mode using erythrocentaurin as the internal standard. The maximum mean plasma concentrations of naucledal and epinaucledal were 75.36 ± 20.10 and 43.52 ± 15.60 ng/ml within 2 h, respectively, following gavage of sweroside at 20 mg/kg. Moreover, the area under the concentration-time curve of naucledal was three times that of epinaucledal. The metabolic process of conversion of sweroside to epinaucledal and naucledal was deduced, and the pharmacological effects of epinaucledal and naucledal will clarify the clinical efficacy of sweroside.

Preliminary study of HPV integration status on the occurrence and development of vaginal intraepithelial neoplasia.

AIM: The aim of this study was to investigate how the integration status of HPV in the vaginal epithelium affects the development of vaginal intraepithelial neoplasia (VaIN). METHODS: Twenty-four vaginal tissues were collected before applying high-throughput viral integration detection (HIVID), medical records of them were documented, including age, thin-prep cytologic test (TCT) and HPV test results, colposcopic biopsy pathology, and other clinical data, such as history of total hysterectomy for cervical lesions, whether they were infected with HPV16/18 with a follow-up span of 2 years. We summarized the distribution of HPV integration on the host chromosome and HPV type, as well as the hotspot integration gene and its role in the development of VaIN. RESULTS: In this study, 24 cases suffered from VaIN were involved. HPV integration was detected in 11 cases; furthermore, we discovered HPV 16 and 73, chromosome 1 and 2 possessed most HPV integration sites while EMBP1, CLO5A1, EHF, ELF5 as dominate hot spots. Taken clinical outcome into account, we found a significant difference between HPV integration occurrence and VaIN (p = 0.011). CONCLUSION: (1) This study found a statistical difference between HPV integration and the occurrence of VaIN; (2) HPV integration may provide a new clinical predictor for VaIN and facilitate risk assessment and stratified management of high-risk patients.

Does Tranexamic Acid Reduce Elbow Swelling and Improve Early Function Following Arthroscopic Arthrolysis? A Double-Blind Randomized Controlled Trial.

BACKGROUND: Tranexamic acid (TXA) reduces bleeding and hematoma rates in open elbow arthrolysis. However, its effects on arthroscopic elbow arthrolysis remain unclear. This study aims to evaluate the effect of TXA on elbow arthroscopic procedures and compare bleeding volume, hemarthrosis, visual analog scale (VAS) for pain, range of motion (ROM), and Mayo Elbow Performance Score (MEPS) in the early postoperative period between patients who received intra-articular TXA and those who did not. METHODS: A prospective, double-blind, randomized controlled trial enrolling 80 patients with stiff elbows who underwent arthroscopic arthrolysis was performed from January 2021 to December 2022. Intra-articularly, 1 g of TXA in 100 ml of saline or placebo (control group) was administered after the arthroscopic operation according to randomization. Parameters were recorded and compared between the groups, including bleeding volume of drainage, hemoglobin (Hgb) level, ratio of arm and forearm circumference of the surgical side to the contralateral side, grading of hematoma, VAS, ROM and MEPS within one week postoperatively. And during one year follow-up, ROM and MEPS were recorded. RESULTS: All patients enrolled in this study demonstrated significant improvements in ROM (flexion-extension) and MEPS one week postoperatively, with no significant differences observed between the two groups. Compared to the control group, the TXA group exhibited significant differences in the bleeding volume of drainage (61.45±47.7 ml vs. 89.8±47.0 ml, p=0.030) and a higher Hgb level 24 hours postoperatively (13.5±1.5 g/dL vs. 12.6±1.8 g/dL p=0.049). While the ratio of arm and forearm circumferences significantly increased 24 hours postoperatively compared to preoperative values in TXA group (1.05±0.06 vs. 1.02±0.04 and 1.02±0.06 vs. 0.98±0.04, with p=0.019 and p=0.005, respectively), this difference vanished one week postoperatively for the ratio of arm circumference. However, it persisted for the ratio of forearm circumference (1.02±0.07 vs. 0.98±0.04, p=0.003). Furthermore, there was no significant difference in MEPS, VAS or ROM between the two groups one week postoperatively. CONCLUSION: Patients with stiff elbows who underwent arthroscopic arthrolysis achieved satisfactory clinical outcomes very early postoperatively. Compared to the control group, patients who underwent arthroscopic elbow arthrolysis with intra-articular administration of TXA exhibited significantly less bleeding volume of drainage and slightly higher Hgb levels postoperatively. One week postoperatively, slightly more swelling in the upper arm region was noted in the control group compared to the TXA group. These findings suggest that the intra-articular injection of TXA after arthroscopic release for elbow stiffness may statistically reduce complications related to postoperative bleeding. However, it's clinical relevance needs further investigation.

Time-Frequency Aliased Signal Identification Based on Multimodal Feature Fusion.

The identification of multi-source signals with time-frequency aliasing is a complex problem in wideband signal reception. The traditional method of first separation and identification especially fails due to the significant separation error under underdetermined conditions when the degree of time-frequency aliasing is high. The single-mode recognition method does not need to be separated first. However, the single-mode features contain less signal information, making it challenging to identify time-frequency aliasing signals accurately. To solve the above problems, this article proposes a time-frequency aliasing signal recognition method based on multi-mode fusion (TRMM). This method uses the U-Net network to extract pixel-by-pixel features of the time-frequency and wave-frequency images and then performs weighted fusion. The multimodal feature scores are used as the classification basis to realize the recognition of the time-frequency aliasing signals. When the SNR is 0 dB, the recognition rate of the four-signal aliasing model can reach more than 97.3%.

Enhancement of Broadband Reverse Saturable Absorption of Red/Black Phosphorus Heterojunction.

Although laser technology brings convenience to production and daily life, it also causes high-energy damage. Therefore, there is an urgent need to develop optical limiting materials for laser protection. In this study, a novel nonlinear optical material, red/black phosphorus lateral heterojunction, is successfully prepared through solvothermal and ultrasonic treatment. Using the Z-scan method, the nonlinear optical properties of the red/black phosphorus heterojunction are determined at wavelengths of 532 and 1064 nm. These results indicate that the red/black phosphorus heterojunction exhibits reverse saturable absorption properties in 1.2.3-glycerol. Interestingly, the red/black phosphorus heterojunction shows an enhanced performance over red phosphorus by introducing the black phosphorus phase. Moreover, the red/black phosphorus heterojunction is doped into organically modified silicate gel glass with excellent broadband optical limiting performance. This study highlights the promising prospect of the red/black phosphorus heterojunction in the nonlinear optical and optical limiting fields.

Lipid concomitant γ-oryzanol decreased oil absorbency of French fries by changing the microstructure of French fries and physical properties of frying oil.

BACKGROUND: The aim of this research was to evaluate the possibility of lipid concomitant γ-oryzanol reducing oil absorbency of fried foods and the underlying mechanism. Therefore, the influence of γ-oryzanol on moisture and oil content, and distribution and micromorphology of French fries and the viscosity, fatty acid composition and total polar compounds content of rice bran oil (RBO) after frying were studied. RESULTS: Our results showed that the incorporation of low concentration of γ-oryzanol [low addition group (LAG)] (5.754 g/kg) decreased the oil absorbency and porous structure of French fries during frying. Additionally, LAG incorporation inhibited the degradation of linoleic acid, decreased the growth rate of saturated fatty acids, total polar compounds and viscosity of frying oil. CONCLUSIONS: Consequently, it was recommended to incorporate a small amount of γ-oryzanol in frying oil because it could inhibit oil absorption behavior of French fries. © 2023 Society of Chemical Industry.

Regio- and Diaseteroselective Synthesis of Polysubstituted Piperidines Enabled by Boronyl Radical-Catalyzed (4+2) Cycloaddition.

Piperidines are widely present in small molecule drugs and natural products. Despite many methods have been developed for their synthesis, new approaches to polysubstituted piperidines are highly desirable. This work presents a radical (4+2) cycloaddition reaction for synthesis of piperidines featuring dense substituents at 3,4,5-positions that are not readily accessible by known methods. Using commercially available diboron(4) compounds and 4-phenylpyridine as the catalyst precursors, the boronyl radical-catalyzed cycloaddition between 3-aroyl azetidines and various alkenes, including previously unreactive 1,2-di-, tri-, and tetrasubstituted alkenes, has delivered the polysubstituted piperidines in generally high yield and diastereoselectivity. The reaction also features high modularity, atom economy, broad substrate scope, metal-free conditions, simple catalysts and operation. The utilization of the products has been demonstrated by selective transformations. A plausible mechanism, with the ring-opening of azetidine as the rate-limiting step, has been proposed based on the experimental and computational results.

Identification of a Glutamatergic Claustrum-Anterior Cingulate Cortex Circuit for Visceral Pain Processing.

Chronic visceral pain is a major challenge for both patients and health providers. Although the central sensitization of the brain is thought to play an important role in the development of visceral pain, the detailed neural circuits remain largely unknown. Using a well-established chronic visceral hypersensitivity model induced by neonatal maternal deprivation (NMD) in male mice, we identified a distinct pathway whereby the claustrum (CL) glutamatergic neuron projecting to the anterior cingulate cortex (ACC) is critical for visceral pain but not for CFA-evoked inflammatory pain. By a combination of in vivo circuit-dissecting extracellular electrophysiological approaches and visceral pain related electromyographic (EMG) recordings, we demonstrated that optogenetic inhibition of CL glutamatergic activity suppressed the ACC neural activity and visceral hypersensitivity of NMD mice whereas selective activation of CL glutamatergic activity enhanced the ACC neural activity and evoked visceral pain of control mice. Further, optogenetic studies demonstrate a causal link between such neuronal activity and visceral pain behaviors. Chemogenetic activation or inhibition of ACC neural activities reversed the effects of optogenetic manipulation of CL neural activities on visceral pain responses. Importantly, molecular detection showed that NMD significantly enhances the expression of NMDA receptors and activated CaMKIIα in the ACC postsynaptic density (PSD) region. Together, our data establish a functional role for CL→ACC glutamatergic neurons in gating visceral pain, thus providing a potential treatment strategy for visceral pain.SIGNIFICANCE STATEMENT Studies have shown that sensitization of anterior cingulate cortex (ACC) plays an important role in chronic pain. However, it is as yet unknown whether there is a specific brain region and a distinct neural circuit that helps the ACC to distinguish visceral and somatic pain. The present study demonstrates that claustrum (CL) glutamatergic neurons maybe responding to colorectal distention (CRD) rather than somatic stimulation and that a CL glutamatergic projection to ACC glutamatergic neuron regulates visceral pain in mice. Furthermore, excessive NMDA receptors and overactive CaMKIIα in the ACC postsynaptic density (PSD) region were observed in mice with chronic visceral pain. Together, these findings reveal a novel neural circuity underlying the central sensitization of chronic visceral pain.