TGR5-mediated lateral hypothalamus-dCA3-dorsolateral septum circuit regulates depressive-like behavior in male mice.

Although bile acids play a notable role in depression, the pathological significance of the bile acid TGR5 membrane-type receptor in this disorder remains elusive. Using depression models of chronic social defeat stress and chronic restraint stress in male mice, we found that TGR5 in the lateral hypothalamic area (LHA) predominantly decreased in GABAergic neurons, the excitability of which increased in depressive-like mice. Upregulation of TGR5 or inhibition of GABAergic excitability in LHA markedly alleviated depressive-like behavior, whereas down-regulation of TGR5 or enhancement of GABAergic excitability facilitated stress-induced depressive-like behavior. TGR5 also bidirectionally regulated excitability of LHA GABAergic neurons via extracellular regulated protein kinases-dependent Kv4.2 channels. Notably, LHA GABAergic neurons specifically innervated dorsal CA3 (dCA3) CaMKIIα neurons for mediation of depressive-like behavior. LHA GABAergic TGR5 exerted antidepressant-like effects by disinhibiting dCA3 CaMKIIα neurons projecting to the dorsolateral septum (DLS). These findings advance our understanding of TGR5 and the LHAGABA→dCA3CaMKIIα→DLSGABA circuit for the development of potential therapeutic strategies in depression.

Mesenchymal stem cells-derived extracellular vesicle-incorporated H19 attenuates cardiac remodeling in rats with heart failure.

Cardiac remodeling is manifested by hypertrophy and apoptosis of cardiomyocytes, resulting in the progression of cardiovascular diseases. Long noncoding RNAs (lncRNAs) serve as modifiers of cardiac remodeling. In this study, we aimed to explore the molecular mechanism of H19 shuttled by mesenchymal stem cells (MSC)-derived extracellular vesicles (EV) in cardiac remodeling upon heart failure (HF). Using the GEO database, H19, microRNA (miR)-29b-3p, and CDC42 were screened out as differentially expressed biomolecules in HF. H19 and CDC42 were elevated, and miR-29b-3p was decreased after MSC-EV treatment in rats subjected to ligation of the coronary artery. MSC-EV alleviated myocardial injury in rats with HF. H19 downregulation exacerbated myocardial injury, while miR-29b-3p inhibitor alleviated myocardial injury. By contrast, CDC42 downregulation aggravated the myocardial injury again. PI3K/AKT pathway was activated by MSC-EV. These findings provide insights into how H19 shuttled by EV mitigates cardiac remodeling through a competitive endogenous RNA network regarding miR-29b-3p and CDC42.

1D Chiral Enantiomer Lead-Free Perovskites Induced Chiralopical Activity and Photoelectric Response.

Chirality is a fascinating geometrical concept with widespread applications in biology, chemistry, and materials. Incorporating chirality into hybrid perovskite materials can induce novel physical properties (chiral optical activity, nonlinear optics, etc.). Hybrid lead-free or lead-substituted perovskite materials, as representatives of perovskites, have been widely used in fields such as photovoltaics, sensors, catalysis, and detectors. However, the successful introduction of chirality into hybrid lead-free perovskites, which can enable their potential applications in areas such as circularly polarized light photodetectors, memories, and spin transistors, remains a challenging research topic. Here, we synthesized two new chiral lead-free perovskites, [(R)-2-methylpiperazine][BiI5] and [(S)-2-methylpiperazine][BiI5]. The material possesses a perovskite structure with a one-dimensional (1D) arrangement, denoted as ABX5. This structure is composed of chiral cations, specifically methylpiperazine, and endless chains of [BiI3] along the a-axis. These chains are assembled from distorted coplanar [BiI5]2- octahedra. The testing results revealed that (R)-1 and (S)-1 have narrow band gaps (Eg-R = 2.016 eV, Eg-S = 1.964 eV), high photoelectric response, and long carrier lifetime [R = 4.94 µs (τ), S = 7.85 µs (τ)]. It is worth noting that 1D chiral lead-free perovskites (R)-1 and (S)-1, which are synthesized in this study with narrow band gaps, high photoelectric response, and long carrier lifetime, have the potential to serve as alternative materials for the perovskite layer in future iterations of lead-free perovskite solar cells. Moreover, this research will inspire the preparation of multifunctional, lead-free perovskites.

The small peptide VISP1 acts as a selective autophagy receptor regulating plant-virus interactions.

Selective macroautophagy/autophagy is tightly regulated by cargo receptors that recruit specific substrates to the ATG8-family proteins for autophagic degradation. Therefore, identification of selective receptors and their new cargoes will improve our understanding of selective autophagy functions in plant development and stress responses. We have recently demonstrated that the small peptide VISP1 acts as a selective autophagy receptor to mediate degradation of suppressors of RNA silencing (VSRs) of several RNA and DNA viruses. Moreover, VISP1 induces symptom recovery through fine-tuning the balance of plant immunity and virus pathogenicity. Our findings provide new insights into the double-edged sword roles of selective autophagy in plant-virus interactions.

The Plasma Concentration of Ticagrelor and Aspirin as a Predictor of Bleeding Complications in Chinese Acute Coronary Syndrome Patients With Dual Antiplatelet Therapy: A Prospective Observational Study.

PURPOSE: This study evaluated the association among the plasma concentration of ticagrelor, ARC124910XX, aspirin, and salicylic acid with the risk of recent bleeding in patients with the acute coronary syndrome. To this end, we developed an accurate model to predict bleeding. METHODS: A total of 84 patients included in this study cohort between May 2021 and November 2021. The risk factors were identified by univariate and multivariate analyses, and statistically significant risk factors identified in the multivariate analysis were included in the nomogram. We used the calibration curve and the receiver operating characteristic curve to verify the accuracy of the prediction model. RESULTS: Multivariable logistic analysis showed that ticagrelor concentration (odds ratio [OR]: 2.47, 95% confidence interval [CI], 1.51-4.75, P = 0.002), ST-segment elevation acute myocardial infarction (OR: 32.2, 95% CI, 2.37-780, P = 0.016), and lipid-lowering drugs (OR: 11.52, 95% CI, 1.91-110, P = 0.015) were positively correlated with bleeding. However, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (OR: 0.04, 95% CI, 0.004-0.213, P < 0.001) was negatively correlated with bleeding. The receiver operating characteristic curve analysis showed that ticagrelor concentration and these factors together predict the occurrence of bleeding (area under receiver operating characteristic curve = 0.945, 95% CI, 0.896-0.994) and that ticagrelor concentration >694.90 ng/mL is the threshold of bleeding concentration (area under receiver operating characteristic curve = 0.696, 95% CI, 0.558-0.834). CONCLUSION: In patients with acute coronary syndrome treated with dual antiplatelet therapy, ticagrelor concentration >694.90 ng/mL was an independent risk factor for bleeding (OR: 2.47, 95% CI, 1.51-4.75, P = 0.002), but ARC124910XX and salicylic acid concentration did not affect bleeding risk ( P > 0.05).

A selective autophagy receptor VISP1 induces symptom recovery by targeting viral silencing suppressors.

Selective autophagy is a double-edged sword in antiviral immunity and regulated by various autophagy receptors. However, it remains unclear how to balance the opposite roles by one autophagy receptor. We previously identified a virus-induced small peptide called VISP1 as a selective autophagy receptor that facilitates virus infections by targeting components of antiviral RNA silencing. However, we show here that VISP1 can also inhibit virus infections by mediating autophagic degradation of viral suppressors of RNA silencing (VSRs). VISP1 targets the cucumber mosaic virus (CMV) 2b protein for degradation and attenuates its suppression activity on RNA silencing. Knockout and overexpression of VISP1 exhibit compromised and enhanced resistance against late infection of CMV, respectively. Consequently, VISP1 induces symptom recovery from CMV infection by triggering 2b turnover. VISP1 also targets the C2/AC2 VSRs of two geminiviruses and enhances antiviral immunity. Together, VISP1 induces symptom recovery from severe infections of plant viruses through controlling VSR accumulation.

Effects of ZSM-5 zeolite on pyrolysis of polystyrene: from stabilizing to catalyzing.

Nonisothermal pyrolysis measurements of polystyrene (PS)/ZSM-5 zeolite hybrids are conducted in N2 and thermogravimetric results have been kinetically analyzed with different isoconversional methods. Experimental results show that the addition of 5 and 10 wt.% ZSM-5 zeolite has increased the initial pyrolysis temperature of PS while the addition of 20 and 30 wt.% ZSM-5 zeolite can significantly decrease the initial pyrolysis temperature of PS. Elevated activation energy is resulted by adding low zeolite amount whereas reduced activation energy is obtained by adding high ZSM-5 amounts. The effect of zeolite ZSM-5 on PS pyrolysis can thus be observed to transfer from stabilizing to catalyzing. Furthermore, the pyrolysis mechanism functions of PS/zeolite hybrids are determined by integrating the master plots method with a new compensation effect method, and the most appropriate reaction models are found to be F0.92, F0.85, F0.56 and A1.32 for describing the pyrolysis of the PS/ZSM-5 hybrids with a zeolite loading of 5, 10, 20 and 30 wt.%, respectively. With the kinetic parameters thus available, the temperature-dependent mass conversion curves have been recast, leading to satisfactory simulations for PS/ZSM-5 hybrids.

Deficiency of astrocyte CysLT1R ameliorates depression-like behaviors in mice by modulating glutamate synaptic transmission.

Our previous study suggests that hippocampal cysteinyl leukotriene receptor 1 (CysLT1R) could be involved in depression. Herein we hypothesize that CysLT1R may regulate depression by affecting synaptic glutamate cycling based on existence of CysLT1R in the astrocytes that participate in occurrence of depression. We found that CysLT1R expression was significantly increased in the astrocyte of chronic unpredictable mild stress (CUMS)-induced depression-like mice, CysLT1R astrocyte-specific conditional knockout (AcKO) significantly improved depression-like behaviors, as indicated by decreased immobility time in the forced swimming test and tail suspension test and increased sucrose preference in the sucrose preference test, and knockdown of CysLT1R in the astrocyte of dentate gyrus (DG), the region with the most significant increase of CysLT1R in the astrocyte of depression-like mice, produced similar effects. Correspondingly, overexpression of CysLT1R in the astrocyte of DG induced depression-like behaviors in mice. The further study showed that CysLT1R AcKO ameliorated synaptic plasticity impairment, as reflected by increased synapse, LTP and PSD95, and promoted glutamate transporter 1 (GLT-1) expression by inhibiting NF-κB p65 nuclear translocation mediated by ß-arestin2 and clatrhin, subsequently decreased glutamate in synaptic cleft and GluN2B on postsynaptic membrane in depression-like mice. The present study also showed that GLT-1 agonist or NF-κB inhibitor ameliorated depressive-like behaviors induced by overexpression of the astrocyte CysLT1R of DG. Our study demonstrated that astrocyte CysLT1R regulated depression by modulating glutamate synaptic transmission, suggesting that CysLT1R could be a potential target for developing novel drugs of anti-depression.

Interpretation of ischiofemoral impingement via a clinical test using hip triaxial dynamic magnetic resonance imaging.

BACKGROUND: The present study aimed to use magnetic resonance (MR) to explore the dynamic changes of the ischiofemoral space (IFS) under the triaxial motion of the hip joint and verify the clinical test mechanism for ischiofemoral impingement (IFI). METHODS: A prospective design was used to screen 37 patients with clinically confirmed IFI, which included a total of 67 lateral hips, and 39 healthy controls with a total of 69 lateral hips. A dynamic MR examination was performed in positions designed by a simulated IFI test (adduction, adduction with 30° external rotation, 30° internal rotation, supine with 30° flexion, and prone with 30° backward extension). The IFS (mm) and quadratus femoris space (QFS, mm) were measured in different positions. All the data were evaluated independently by three musculoskeletal radiologists. The differences between the two groups were compared using the two-tailed t-test. RESULTS: The IFS and QFS in the case group were smaller than those in the control group. The IFS and QFS were significantly reduced in the prone with backward extension and adduction with external rotation positions of the hip. The correlation coefficients of the IFI test and long-stride walking (LSW) test were -0.621 and -0.715 for IFS and -0.653 and -0.696 for QFS, respectively. CONCLUSIONS: In this study, the mechanism of the IFI-specific clinical examination (IFI and LSW tests) was verified by triaxial dynamic MR imaging of the hip joint, which provided a dynamic imaging basis for the clinical application of the IFI-specific impingement test. The IFI impingement test can be used as a specific clinical test for IFI screening.

Hippocampal CysLT1R overexpression or activation accelerates memory deficits, synaptic dysfunction, and amyloidogenesis in young APP/PS1 transgenic mice.

BACKGROUND: Our previous studies demonstrated that cysteinyl leukotrienes receptor 1 (CysLT1R) knockout, pharmacological blockade, or hippocampus knockdown produced beneficial effects against Alzheimer's disease (AD); however, whether CysLT1R upregulation has deleterious effects on AD remains elusive. METHODS: In this study, we investigated the changes in behaviors, hippocampal amyloidogenesis, and synapse plasticity after CysLT1R overexpression by microinfusion of the lentiviral vector, containing its coding sequence of mouse (LV-CysLT1R), into the bilateral dentate gyri (DG) of the hippocampus or CysLT1R activation by repeated systemic administration of its agonist YM-17690 (0.1 mg/kg, once a day, i.p., for 28 d). RESULTS: The behavior data showed that overexpression of CysLT1R in hippocampal DG or administration of YM-17690 deteriorated behavioral performance in Morris water maze (MWM), Y-maze tests, and novel object recognition (NOR) in young APP/PS1 mice. The further studies showed that these treatments significantly destroyed synaptic function, as evidenced by impaired hippocampal long-term potentiation (LTP), decreased spine density, low number of synapses, and decreased postsynaptic protein (PSD95), and promoted the generation of amyloid ß (Aß) through increased expression of BACE1 and PS1 in the hippocampus of young APP/PS1 mice. CONCLUSIONS: Together, our results indicate that CysLT1R upregulation accelerates memory impairment in young APP/PS1 mice, which is associated with promoting synaptic dysfunction and amyloidogenesis in the hippocampus.

Enantioselective Reductive Homocoupling of Allylic Acetates Enabled by Dual Photoredox/Palladium Catalysis: Access to C2-Symmetrical 1,5-Dienes.

Transition-metal-catalyzed reductive coupling reactions have emerged as powerful protocols to construct C-C bonds. However, the development of enantioselective C(sp3)-C(sp3) reductive coupling remains challenging. Herein, we report a highly regio-, diastereo-, and enantioselective reductive homocoupling of allylic acetates through cooperative palladium and photoredox catalysis using diisopropylethylamine or Hantzsch ester as a homogeneous organic reductant. This straightforward protocol enables the stereoselective construction of C(sp3)-C(sp3) bonds under mild reaction conditions. A series of C2-symmetrical chiral 1,5-dienes were easily prepared with excellent enantioselectivities (up to >99% ee), diastereoselectivities (up to >95:5 dr), and regioselectivities (up to >95:5 rr). The resultant chiral 1,5-dienes can be directly used as chiral ligands in asymmetric synthesis, and they can be also transformed into other valuable chiral ligands.

A small peptide inhibits siRNA amplification in plants by mediating autophagic degradation of SGS3/RDR6 bodies.

Selective autophagy mediates specific degradation of unwanted cytoplasmic components to maintain cellular homeostasis. The suppressor of gene silencing 3 (SGS3) and RNA-dependent RNA polymerase 6 (RDR6)-formed bodies (SGS3/RDR6 bodies) are essential for siRNA amplification in planta. However, whether autophagy receptors regulate selective turnover of SGS3/RDR6 bodies is unknown. By analyzing the transcriptomic response to virus infection in Arabidopsis, we identified a virus-induced small peptide 1 (VISP1) composed of 71 amino acids, which harbor a ubiquitin-interacting motif that mediates interaction with autophagy-related protein 8. Overexpression of VISP1 induced selective autophagy and compromised antiviral immunity by inhibiting SGS3/RDR6-dependent viral siRNA amplification, whereas visp1 mutants exhibited opposite effects. Biochemistry assays demonstrate that VISP1 interacted with SGS3 and mediated autophagic degradation of SGS3/RDR6 bodies. Further analyses revealed that overexpression of VISP1, mimicking the sgs3 mutant, impaired biogenesis of endogenous trans-acting siRNAs and up-regulated their targets. Collectively, we propose that VISP1 is a small peptide receptor functioning in the crosstalk between selective autophagy and RNA silencing.

Comparison of three treatment methods for simple bone cyst in children.

BACKGROUND: The unicameral bone cyst (UBC) is a kind of benign tumor whose clinical treatments and efficacy are controversial. The purpose of this study was to evaluate the efficacy of the elastic stable intramedullary nail (ESIN), the injection of autologous bone marrow (ABM), and the combination of ESIN and ABM in the treatment of bone cyst in children. METHODS: Eighty-three cases with simple bone cyst were analyzed retrospectively. Twenty-eight cases were treated with ABM. Twenty-eight cases were treated with ESIN. Twenty-seven cases were treated with ABM and ESIN. All cases were diagnosed through X-ray, CT, or MRI scans. For the suspicious ones, the pathological biopsy was performed for an accurate diagnosis. X-ray examinations were carried out for the postoperative follow-up. Capanna criteria for bone cyst was used for postoperative evaluation of three methods. RESULTS: All cases accomplished the follow-up. The effective rate of the ABM + ESIN group was significantly higher than that of the ABM group (P < 0.05), and the cure rates of the ESIN group and the ABM + ESIN group were higher than that of the ABM group (P < 0.05, respectively). The cure time in the ESIN group was lower than that of the other two groups (P < 0.05, respectively). The times for admission were 2.0 ± 0.0 in the ESIN group, 5.7 ± 1.9 in the ABM group, and 4.7 ± 2.4 in the ABM + ESIN group (P < 0.05 when compared with each other). CONCLUSIONS: The method of ABM combined with ESIN for children's bone cyst has the highest effective rate and curative rate. For the individual method, ESIN has a higher effective rate and curative rate than that of ABM. Meanwhile, it has the fewest time of hospitalization.

Synaptic remodeling in mouse motor cortex after spinal cord injury.

Spinal cord injury dramatically blocks information exchange between the central nervous system and the peripheral nervous system. The resulting fate of synapses in the motor cortex has not been well studied. To explore synaptic reorganization in the motor cortex after spinal cord injury, we established mouse models of T12 spinal cord hemi-section and then monitored the postsynaptic dendritic spines and presynaptic axonal boutons of pyramidal neurons in the hindlimb area of the motor cortex in vivo. Our results showed that spinal cord hemi-section led to the remodeling of dendritic spines bilaterally in the motor cortex and the main remodeling regions changed over time. It made previously stable spines unstable and eliminated spines more unlikely to be re-emerged. There was a significant increase in new spines in the contralateral motor cortex. However, the low survival rate of the new spines demonstrated that new spines were still fragile. Observation of presynaptic axonal boutons found no significant change. These results suggest the existence of synapse remodeling in motor cortex after spinal cord hemi-section and that spinal cord hemi-section affected postsynaptic dendritic spines rather than presynaptic axonal boutons. This study was approved by the Ethics Committee of Chinese PLA General Hospital, China (approval No. 201504168S) on April 16, 2015.

Cloning and characterization of Methoprene-tolerant (Met) and Krüppel homolog 1 (Kr-h1) genes in the wheat blossom midge, Sitodiplosis mosellana.

Juvenile hormone (JH), a growth regulator, inhibits ecdysteroid-induced metamorphosis and controls insect development and diapause. Methoprene-tolerant (Met) and Krüppel homolog 1 (Kr-h1) are two proteins involved in JH action. To gain some insight into their function in development of Sitodiplosis mosellana, an insect pest undergoing obligatory larval diapause at the mature 3rd instar stage, we cloned full-length complementary DNAs of Met and Kr-h1 from this species. SmMet encoded a putative protein, which contained three domains typical of the bHLH-PAS family and eight conserved amino acid residues important for JH binding. SmKr-h1 encoded a protein showing high sequence homology to its counterparts in other species, and contained all eight highly conserved Zn-finger motifs for DNA-binding. Expression patterns of SmMet and SmKr-h1 were developmentally regulated and JH III responsive as well. Their mRNA abundance increased as larvae entered early 3rd instar, pre-diapause and maintenance stages, and peaked during post-diapause quiescence, a pattern correlated with JH titers in this species. Different from reduced expression of SmMet, SmKr-h1 mRNA increased at mid-to-late period of post-diapause development. Topical application of JH III on diapausing larvae also induced the two genes in a dose-dependent manner. Expression of SmMet and SmKr-h1 clearly declined in the pre-pupal phase, and was significantly higher in female adults than male adults. These results suggest that JH-responsive SmMet and SmKr-h1 might play key roles in diapause induction and maintenance as well as in post-diapause quiescence and adult reproduction, whereas metamorphosis from larvae to pupae might be correlated with their reduced expression.

Enantioselective Radical Hydroacylation of Enals with α-Ketoacids Enabled by Photoredox/Amine Cocatalysis.

A photoredox/amine-cocatalyzed enantioselective radical hydroacylation of enals with α-ketoacids is described. Acyl radicals generated from α-ketoacids act as the acylation reagent with the iminium ions. This strategy provides an efficient way to access synthetically challenging 1,4-dicarbonyl compounds in an enantioselective manner. The reactions of various enals with α-ketoacids show the generality and limitations of this method.

Enantioselective Allylic Alkylation with 4-Alkyl-1,4-dihydro-pyridines Enabled by Photoredox/Palladium Cocatalysis.

Highly regio- and enantioselective allylic alkylation has been achieved enabled by the merger of photoredox and palladium catalysis. In this dual catalytic process, alkyl radicals generated from 4-alkyl-1,4-dihydropyridines act as the coupling partners of the π-allyl palladium complexes. The generality of this method has been illustrated through the reaction of a variety of allyl esters with 4-alkyl-1,4-dihydropyridines. This mechanistically novel strategy expands the scope of the traditional Pd-catalyzed asymmetric allylic alkylation reaction and serves as its alternative and potential complement.

Photoredox-Catalyzed Intermolecular Remote C-H and C-C Vinylation via Iminyl Radicals.

A unified strategy for intermolecular remote C(sp3)-H and C-C vinylation of O-acyl oximes with vinyl boronic acids has been achieved. This strategy is enabled by photoreductive generation of iminyl radicals from O-acyl oximes under irradiation by visible light. The translocated carbon-centered radicals, which are generated from the iminyl radicals through 1,5-hydrogen atom transfer or C-C cleavage, can be vinylated with vinyl boronic acids. This strategy opens up a new approach to remote functionalization via C(sp3)-H and C-C cleavage and provides an efficient and versatile solution to the synthesis of γ-vinylation of ketones and nitriles.

ß-Ecdysterone accumulation and regulation in Ajuga multiflora Bunge suspension culture.

Ajuga multiflora Bunge cells contain ß-ecdysterone (ß-EC) that regulates the molting process of insect larvae. In this study, different conditions of culture have been studied to optimize the production of ß-EC. A. multiflora Bunge growth fitted the curve of logistic equation with one growth cycle of 17 days. The electric conductivity of medium had a negative correlation with not only the weight of dry cell but also the ß-EC accumulation, and thus, could be used for monitoring the peak of both cell growth and ß-EC accumulation. The pH value of the culture medium varied from 4.67 to 5.84 and reached the maximum at the end of the culture (on the 17th day). The relation of cell growth and nutrient consumption in A. multiflora Bunge cell suspension culture was distinctly correlated. Continuous subculture caused a reduction in ß-EC synthesis; passages 7-15, the ß-EC content declined (p < 0.05). At passage 11, the ß-EC content was only 42.72% of that at passage 5. Additives such as mevalonic acid (MVA), l-phenylalanine (l-Phe), α-pinene, terpineol, and nitric oxide (NO) in the suspension culture medium, could significantly promote the cell growth and stimulate ß-EC accumulation. The optimal concentrations of l-Phe, MVA, terpineol, and α-pinene were 0.2 mmol/l, 10 mg/l, 1 mmol/l and 6 mmol/l, respectively, with the ß-EC concentrations as 1.914 ± 0.1948 mg/g (p < 0.01), 6.012 ± 0.4252 mg/g (p < 0.01), 5.147 ± 0.4819 mg/g (p < 0.01), 2.801 ± 0.1253 mg/g (p < 0.01), respectively. The optimal concentration of sodium nitroprusside, the provider of NO, was 3 mmol/l with the ß-EC concentration 2.87 ± 0.2493 mg/g (p < 0.01). The results offer a strategy for massive production of ß-EC.