24-epibrassinolide as a multidimensional regulator of rice (Oryza sativa) physiological and molecular responses under isoproturon stress.

Brassinosteroids (BRs) can regulate various processes in plant development and defense against environmental stress. In this study, the contribution of BRs in the degradation of isoproturon (IPU) in rice has been established. IPU has a significant effect on rice growth, chlorophyll content, and membrane permeability. When treated with 1.0 µmol/L 24-epibrassinolide (EBR), a BR analogue, the associated symptoms of rice poisoning were alleviated as the IPU levels in the rice and growth media were decreased. In the presence of EBR, the activities of several IPU-related detoxification enzymes were enhanced to cope with the stress due to IPU. An RNA-sequencing (RNA-Seq) has been performed to determine the variation of transcriptomes and metabolic mechanisms in rice treated with EBR, IPU, or IPU+EBR. Some of the differentially expressed genes (DEGs) were Phase I-III reaction components of plants, such as cytochrome P450 (CYP450), glutathione S-transferase (GST), glycosyltransferases (GTs), and the ATP-binding cassette transporter (ABC transporter). The expression of some signal transduction genes was significantly up-regulated. The relative content of low-toxicity IPU metabolites increased due to the presence of EBR as determined by UPLC/Q-TOF-MS/MS. The IPU metabolic pathways include enzyme-catalyzed demethylation, hydroxylation, hydrolysis, glycosylation, and amino acid conjugation processes. The results suggest that EBR plays a key role in the degradation and detoxification of IPU. This study has provided evidence that BRs regulate the metabolism and detoxification of IPU in rice, and offers a new approach to ensuring cleaner crops by eliminating pesticide residues in the environment.

Sirtuin 3 ameliorates inflammatory bowel disease via inhibiting intestinal inflammation and oxidative stress.

Sirtuin 3 involved in development of various diseases, but its role in inflammatory bowel disease is still unknown. We used inflammatory bowel disease biopsies, colitis animal model, and vitro cells RAW264.7 to study the role of Sirtuin 3 in the pathophysiology of inflammatory bowel disease. Sirtuin 3 negatively correlated with intestinal TNF-α. Sirt3 was less pronounced in pediatric and adult inflammatory bowel disease patients compared with corresponding control group. Sirtuin 3 activator Honokiol suppressed dextran sulfate sodium induced colonic manifestations, while Sirt3 inhibitor caused opposite results. Honokiol inhibited colonic oxidative stress by and reduced intestinal permeability. Honokiol repressed inflammatory response by reducing macrophage infiltration, pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6 levels, and inhibiting activation of NF-κB p65 in the colitis mice. However, Sirt3 inhibitor amplified colonic oxidative stress and inflammatory response. In vitro study, Sirt3 inhibitor or siRNA Sirtuin 3 activated NF-κB p65 and enhanced TNF-α, IL-1ß, and IL-6 secretion from LPS stimulated RAW264.7, while Honokiol remarkably attenuated these pro-inflammatory cytokines secretion. Finally, knockdown of Sirt3 in Caco-2 cells enhanced TNF-α induced intestinal barrier integrity injury. Sirtuin 3 negatively regulates inflammatory bowel disease progression via reducing colonic inflammation and oxidative stress. Sirtuin 3 is a promising therapeutic target in clinical application for inflammatory bowel disease therapy.

Catalyst-Free Synthesis of Polycyclic Spiroindolines by Cascade Reaction of 3-(2-Isocyanoethyl)indoles with 1-Sulfonyl-1,2,3-triazoles.

A catalyst-free cascade reaction of 3-(2-isocyanoethyl)indoles and 1-sulfonyl-1,2,3-triazoles was realized. This dearomative spirocyclization provided an efficient protocol to synthesize a series of polycyclic indolines bearing spiro-α-carboline in moderate to high yields in one step under thermal reaction conditions.

Synthesis of 3-aminoquinolines from α-imino rhodium carbenes and 2-aminobenzaldehydes.

A facile and efficient synthetic method for 3-aminoquinolines has been reported. The straightforward process starts from easily available triazoles and 2-aminobenzaldehydes. Low catalyst loading and good functional group compatibility are the other two merits of this transformation. Easy decoration of the 3-aminoquinoline motifs enabled the convenient synthesis of bioactive molecules, demonstrating the potential of this protocol in organic synthesis.

SHP2/SPI1axis promotes glycolysis and the inflammatory response of macrophages in Helicobacter pylori-induced pediatric gastritis.

BACKGROUND: Macrophages, as innate immune cells, were reported to participate in the pathogenesis of Helicobacter pylori (H. pylori)-induced gastritis. However, the role and mechanism of macrophage dysfunction in H. pylori-associated pediatric gastritis remain unclear. MATERIALS AND METHODS: An RNA-sequencing assay was used to examine the differential gene expression in normal gastric antrum, non-H. pylori-infected tissue, and H. pylori-infected pediatric gastritis tissue. qPCR assays were applied to verify the expression of target genes. HE staining was performed to identify the occurrence of inflammation in the normal gastric antrum, non-H. pylori-infected tissue, and H. pylori-infected pediatric gastritis tissue. Western blotting was used to measure the expression of SHP2 in pediatric gastritis tissue. The metabolic profile of macrophages was determined via Seahorse metabolic analysis. Flow cytometry analysis was used to examine the level of reactive oxygen species (ROS). RESULTS: We found that H. pylori -infected gastritis tissue exhibited many differentially expressed genes (DEGs) compared to gastritis tissue without H. pylori infection. Moreover, H. pylori -infected gastritis tissue showed many DEGs annotated with an overactive immune response. We identified that tyrosine-protein phosphatase nonreceptor type 11 (PTPN11), which encodes SHP2, was significantly increased in macrophages of H. pylori -infected gastritis tissue. Furthermore, we revealed that SHP2 could activate the glycolytic function of macrophages to promote H. pylori -induced inflammation. The transcription factor SPI1 , as the downstream molecule of SHP2, could be responsible for the regulation of metabolism-associated gene expression and inflammation. CONCLUSION: Our study illustrated the molecular landscape of H. pylori-infected gastritis tissue in children and suggested that the SHP2/SPI1axis could be a novel therapeutic target in H. pylori-induced pediatric gastritis.

Access to tetrahydrocarbazoles and pyrrolo[3,4-b]carbazoles through sequential reactions of triazoles and indoles.

Tetrahydrocarbazoles and pyrrolo[3,4-b]carbazoles could be synthesized conveniently through sequential reactions of ester-tethered 1-sulfonyl-1,2,3-triazoles and indoles. The reaction conditions were mild and the procedures were quite simple. Moreover, the key intermediate α,ß-unsaturated imine acted as a [2C] synthon in the [4 + 2] cycloaddition reaction, and the imino group could be used as a nucleophile to construct the fourth ring.

Synthesis of benzothiazonine by rhodium-catalyzed denitrogenative transannulation of 1-sulfonyl-1,2,3-triazole and thiochromone.

A facile synthesis of multi-functionalized benzothiazonine was achieved by the rhodium-catalyzed denitrogenative annulation of 1-sulfonyl-1,2,3-triazole and thiochromone. In view of the excellent atom economy, broad substrate scope and easy availability of starting materials, the protocol provided an efficient strategy for the construction of medium N,S-heterocycles.

Asymmetric Synthesis and Application of Chiral Spirosilabiindanes.

Reported here is the development of a class of chiral spirosilabiindane scaffolds by Rh-catalyzed asymmetric double hydrosilation, for the first time. Enantiopure SPSiOL (spirosilabiindane diol), a new type of chiral building block for the preparation of various chiral ligands and catalysts, was readily prepared on greater than 10 gram scale using this protocol. The potential of this new spirosilabiindane scaffold in asymmetric catalysis was preliminarily demonstrated by development of the corresponding monodentate phosphoramidite ligands (SPSiPhos), which were used in both a Rh-catalyzed hydrogenation and a Pd-catalyzed intramolecular carboamination.

Integrated transcriptome, small RNA and degradome sequencing approaches provide insights into Ascochyta blight resistance in chickpea.

Ascochyta blight (AB) is one of the major biotic stresses known to limit the chickpea production worldwide. To dissect the complex mechanisms of AB resistance in chickpea, three approaches, namely, transcriptome, small RNA and degradome sequencing were used. The transcriptome sequencing of 20 samples including two resistant genotypes, two susceptible genotypes and one introgression line under control and stress conditions at two time points (3rd and 7th day post inoculation) identified a total of 6767 differentially expressed genes (DEGs). These DEGs were mainly related to pathogenesis-related proteins, disease resistance genes like NBS-LRR, cell wall biosynthesis and various secondary metabolite synthesis genes. The small RNA sequencing of the samples resulted in the identification of 651 miRNAs which included 478 known and 173 novel miRNAs. A total of 297 miRNAs were differentially expressed between different genotypes, conditions and time points. Using degradome sequencing and in silico approaches, 2131 targets were predicted for 629 miRNAs. The combined analysis of both small RNA and transcriptome datasets identified 12 miRNA-mRNA interaction pairs that exhibited contrasting expression in resistant and susceptible genotypes and also, a subset of genes that might be post-transcriptionally silenced during AB infection. The comprehensive integrated analysis in the study provides better insights into the transcriptome dynamics and regulatory network components associated with AB stress in chickpea and, also offers candidate genes for chickpea improvement.

Metal-free synthesis of imidazole by BF3·Et2O promoted denitrogenative transannulation of N-sulfonyl-1,2,3-triazole.

BF3·Et2O promoted metal-free denitrogenative transannulation of N-sulfonyl-1,2,3-triazole was reported. Rather than transition metals, BF3·Et2O was employed for the first time to promote the formation of α-diazoimines from N-sulfonyl-1,2,3-triazoles in nitriles, leading to the synthesis of various imidazoles. The protocol tolerates a broad range of functional groups and could also be applied to the late-stage modification of bioactive molecules, demonstrating the potential of this protocol in organic synthesis. A plausible mechanism was proposed.

Therapy with omeprazole modulates regulatory T cell/T helper 17 immune response in children with duodenal ulcers.

The purpose of this study was to determine the effect of omeprazole on the regulatory T cell (Treg) and T helper 17 (Th17)-mediated response in patients with duodenal ulcers (DUs). DU patients were randomly divided into omeprazole and colloid bismuth subcitrate treatment groups. The ratios of Th17 and Treg in peripheral blood mononuclear cells (PBMCs) were measured. Cytokine production and Foxp3+- and RORγt-positive cells were detected. The expressions of STAT3, p-STAT3, STAT5 and p-STAT5 were detected by Western blot. The results showed that DU patients had an imbalanced Treg/Th17 response, as reflected by the higher IL-17 level and Th17 ratio and lower IL-10 level and Treg proportion in serum compared with those in the healthy volunteers. The administration of omeprazole to the patients significantly increased Treg and IL-10 levels and reduced Th17 and IL-17 levels. Omeprazole markedly increased the number of Foxp3-positive cells, decreased the number of RORγt-positive cells and restored the balanced ratio of IL-10/IL-17 in the ulcer tissue. Interestingly, we observed a negative correlation between the ratios of Treg/Th17 and the pathological scores in damaged tissues. Of note, H. pylori-infected PBMCs showed decreased Treg and an increased Th17 proportion, which could be reversed by omeprazole. Finally, omeprazole increased the expression of p-STAT5 and reduced the level of p-STAT3 without any effects on the total expression of STAT5 and STAT3. Our data suggest that omeprazole treatment restores the equilibrium of the Treg/Th17-mediated response in DU patients. Moreover, the modulation of p-STAT3 and p-STAT5 expression by omeprazole induced balanced polarisation of Treg/Th17.

Metal-free synthesis of 2-aminonaphthalenes by intramolecular transannulation of 1-sulfonyl-4-(2-alkenylphenyl)-1,2,3-triazoles.

A facile metal-free synthesis of naphthalenes by intramolecular transannulation of 1-sulfonyl-4-(2-alkenylphenyl)-1,2,3-triazoles was realized. The in situ formed ketenimine was proposed as the key intermediate, and the desired 2-aminonaphthalenes were generated in up to 87% yield in refluxing 1,2-dichloroethane without any catalyst or additive.

Human mammaglobin: A specific marker for breast cancer prognosis.

PURPOSE: In this study, we examined the expression of human mammaglobin (hMAM) mRNA and the protein levels in patients with breast cancer and their relationship with prognostic clinicopathological parameters. METHODS: hMAM mRNA expression in leucocytes from peripheral blood samples from patients diagnosed with primary invasive breast cancer (IC), carcinoma in situ (CIS), or benign breast diseases was analyzed using RT-PCR. The hMAM protein levels and expression patterns in tissue from 3 patient groups were evaluated by immunohistochemical staining, and several non-breast neoplasms were selected as negative controls, undergoing the same examination. RESULTS: The expression of hMAM mRNA was significantly higher in patients with IC or CIS compared to those with benign tumors (both<0.01). Immunohistochemical staining revealed similar results, where patients with IC or CIS had higher levels of hMAM protein (p<0.01 and p<0.01, respectively), while none of the negative controls expressed hMAM. Further analyses showed a strong correlation between hMAM protein/mRNA expression and clinicopathological factors, such as histological grade, clinical stage, and lymph node status, in patients with IC. CONCLUSION: The hMAM mRNA and protein expression profiles validate the potential of hMAM as a specific marker for breast cancer diagnosis and target treatment delivery.

Rhodium-Catalyzed Synthesis of 4-Bromo-1,2-dihydroisoquinolines: Access to Bromonium Ylides by the Intramolecular Reaction of a Benzyl Bromide and an α-Imino Carbene.

Highly functionalized 4-bromo-1,2-dihydroisoquinolines were synthesized from readily available 4-(2-(bromomethyl)phenyl)-1-sulfonyl-1,2,3-triazoles. A bromonium ylide is proposed as the key intermediate, which can be formed by the intramolecular nucleophilic attack of the benzyl bromide on the α-imino rhodium carbene formed in the presence of the rhodium catalyst.

Synthesis of ß-Amino-α,ß-unsaturated Ketone Derivatives via Sequential Rhodium-Catalyzed Sulfur Ylide Formation/Rearrangement.

In the presence of a Rh(II) catalyst and ß-(methylthio)-α,ß-unsaturated ketones, 1-sulfonyl-1,2,3-triazoles can be converted into functionalized ß-amino-α,ß-unsaturated ketones via formation of α-imino rhodium carbene/sulfur ylide and subsequent rearrangement. The products decompose to useful 2-methylthiopyrrole derivatives conveniently in high yield.

[Predictive value of albumin-to-fibrinogen ratio for acute kidney injury in infants undergoing ventricular septal defect repair with cardiopulmonary bypass].

OBJECTIVE: To investigate the predictive value of albumin-to-fibrinogen ratio (AFR) for postoperative acute kidney injury (AKI) in infants with ventricular septal defect repair under cardiopulmonary bypass (CPB). METHODS: A retrospective analysis was conducted on infants diagnosed with ventricular septal defect in Anhui Children's Hospital from January 2019 to July 2023. The infants were divided into AKI group and non-AKI group according to whether AKI occurred in hospital after operation. Demographic data, preoperative data, intraoperative data, postoperative data and laboratory results during CPB were collected. Multivariate Logistic regression analysis was used to find the factors of AKI after ventricular septal defect repair with CPB. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of AFR for postoperative AKI after ventricular septal defect repair with CPB. RESULTS: A total of 215 children were collected, including 28 in AKI group and 187 in non-AKI group. There were no significant differences in age, gender, body weight, height, history of pneumonia and history of chronic heart failure between the two groups, but the left ventricular ejection fraction (LVEF) in the AKI group was significantly lower than that in the non-AKI group (0.526±0.028 vs. 0.538±0.030, P = 0.048). The duration of CPB (minutes: 74.1±12.1 vs. 65.8±11.3, P < 0.001), aortic cross-clamping (minutes: 41.7±9.7 vs. 37.2±9.4, P = 0.021) and hypothermic circulation arrest (21.4% vs. 8.6%, P = 0.047) in AKI group were significantly higher than those in non-AKI group, but there were no significant differences in the proportion of ultrafiltration and urine volume between the two groups. The length of intensive care unit (ICU) stay in AKI group was significantly longer than that in non-AKI group (days: 5.3±2.0 vs. 4.0±1.7, P < 0.001), but there were no significant differences in duration of mechanical ventilation and the proportion of postoperative hypotension between the two groups. During CPB, the levels of blood glucose (mmol/L: 9.4±1.3 vs. 8.8±0.8, P < 0.001), blood lactic acid (mmol/L: 2.2±0.3 vs. 2.0±0.3, P = 0.015) and serum creatinine (µmol/L: 79.7±11.5 vs. 74.4±10.9, P = 0.018) in AKI group were significantly higher than those in non-AKI group, while the AFR was significantly lower than that in non-AKI group (8.5±1.3 vs. 10.2±1.6, P < 0.001), but there were no significant differences in the levels of hemoglobin, blood urea nitrogen, alanine aminotransferase and aspartate aminotransferase between the two groups during CPB. Multivariate Logistic regression showed that AFR was a protective factor for AKI after ventricular septal defect repair with CPB [odds ratio (OR) = 0.439, 95% confidence interval (95%CI) was 0.288-0.669, P < 0.001]. Blood glucose (OR = 2.133, 95%CI was 1.239-3.672, P = 0.006) and blood lactic acid (OR = 5.568, 95%CI was 1.102-28.149, P = 0.038) were risk factors for AKI after ventricular septal defect repair with CPB. ROC curve analysis showed that the area under the curve (AUC) of AFR in predicting AKI after ventricular septal defect repair with CPB was 0.804 (95%CI was 0.712-0.897, P < 0.001). When the optimal cut-off value was less than 9.05, the corresponding sensitivity was 75.0% and the specificity was 72.7%. CONCLUSIONS: Low AFR (≤9.05) during CPB is an independent risk factor for AKI after ventricular septal defect repair with CPB. AFR during CPB has a high predictive value for postoperative AKI after ventricular septal defect repair with CPB.

Theoretical Prediction of Strengthening in Nanocrystalline Cu with Multi-Element Grain Boundary Segregation Decoration.

The composition of grain boundaries (GBs) determines their mechanical behavior, which in turn affects the mechanical properties of nanocrystalline materials. Inspired by GB segregation and the concept of high-entropy alloys (HEAs), we investigated, respectively, the mechanical responses of nanocrystalline Cu samples with and without multi-element GBs, as well as the grain size effects, aiming to explore the effects of GB composition decoration on mechanical properties. Our results show that introducing multi-element segregation GBs can significantly improve the mechanical properties of nanocrystalline Cu by effectively inhibiting GB migration and sliding. Additionally, we proposed an improved a theoretical model that can reasonably describe the strengths of the materials with multi-element or single-element segregation GBs. Notably, the introduction of multi-element segregation GBs inhibits both migration and sliding behavior, with migration being more effectively suppressed than sliding. These results present a novel approach for designing high-performance nanometallic materials and offer valuable insights into the role of GB composition decoration in enhancing mechanical properties.

Laparoscopic repair of perineal hernia and unilateral inguinal hernia after rectal cancer surgery: A case report.

INTRODUCTION: Perineal hernia (PH) is a rare complication that can occur after abdominoperineal resection for rectal cancer. Laparoscopic repair of PHs has gained increasing popularity compared to open approaches due to advantages such as superior visualization, decreased invasiveness, and faster recovery. This case report highlights the successful use of laparoscopic tension-free mesh repair for concurrent perineal and inguinal hernias after rectal cancer surgery. CASE DESCRIPTION: A 51-year-old man underwent laparoscopic-assisted abdominoperineal resection for rectal cancer. About 2 months postoperatively, he developed reducible masses in the perineal and left groin regions, associated with urinary symptoms and sensation of prolapse. Physical exam revealed protruding masses that enlarged with Valsalva. Pelvic CT confirmed PH and left inguinal hernia. INTERVENTIONS: Laparoscopic tension-free repair of the PH and inguinal hernia was performed on this patient. The repair was completed by the steps of adhesion separation, mesh placement, and fixation. OUTCOMES: The 98-minute surgery was successful without complications. The patient recovered well, ambulating on postoperative day 2 and getting discharged on day 6. CONCLUSION: This case demonstrates that laparoscopic tension-free repair with mesh is an effective approach for treating PH and concurrent inguinal hernia following rectal cancer surgery, resulting in successful outcomes and low recurrence rates. The laparoscopic technique provides benefits of minimal invasiveness and rapid recovery.

Photoredox-Catalyzed Defluorinative Carboxylation of gem-Difluorostyrenes with Formate Salt.

Herein, we present a transition-metal-free, easy handling protocol for regioselective carboxylation of gem-difluorostyrenes with sodium formate as the C1 source. 30 examples of α-fluoracrylates were obtained in yields of 30 to 80% under these conditions. A defluorinative monofluorovinyl intermediate and consecutive photoinduced electron transfer mechanism were proposed after mechanism investigation.

Copper-Catalyzed Synthesis of Furan-Tethered Benzocyclobutenes via Carbene-Mediated 1,4-Sulfinate Migration-Annulation.

A copper-catalyzed intramolecular cascade reaction of conjugated enynones has been achieved via a pivotal 1,4-sulfinate migration step. This process leverages a cost-effective and ecofriendly copper salt as catalyst, enabling the efficient construction of five- and four-membered rings in a rapid, sequential manner, producing furan-tethered benzocyclobutenes in good to excellent yields under mild conditions. The reaction is characterized by 100% atom economy, outstanding efficiency, and excellent diastereoselectivity in the cases studied. The robustness of this method is evidenced by its compatibility with air exposure and the use of undistilled, commercially available solvents, further enhancing its practicality.