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.

[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.

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.

Case report: Rapidly progressive desmoid tumor after surgery for esophagogastric junction cancer and slowly progressive primary desmoid tumor: a report of two cases and literature review.

Background: Desmoid tumor (DT) is a rare locally aggressive but non-metastatic mesenchymal soft tissue neoplasm that predominantly occurs in the abdominal wall, abdominal cavity, and extremities. Its occurrence in the mesentery is relatively uncommon. Case reports: This article reports two cases of desmoid tumor treated at the Department of Gastrointestinal Surgery, Weifang People's Hospital. The first case was a 59-year-old male patient who had previously undergone surgery for esophagogastric junction cancer. Postoperatively, he developed an intra-abdominal mass that rapidly increased in size within three months. The second case was a 60-year-old male patient who incidentally discovered a mass in the left lower abdomen. Both patients underwent surgical treatment, and the postoperative pathological diagnosis was mesenteric desmoid tumor. Conclusion: The treatment of desmoid tumor remains challenging. Simple surgical resection often yields unsatisfactory outcomes, and the efficacy of adjuvant radiotherapy and chemotherapy is also limited. Further research and clinical practice are necessary to improve diagnostic and therapeutic strategies, aiming to enhance patient survival and quality of life.

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.

Acquired cystic disease-associated renal cell carcinoma with PTCH1 mutation: a case report.

Acquired cystic disease-associated renal cell carcinoma (ACD-RCC) is an extremely rare kidney tumor seen mainly in patients with end-stage renal disease. Currently, there are few reports on this type of tumor. We describe the case of a 58-year-old man who had been receiving peritoneal dialysis for more than nine years due to chronic renal insufficiency and uremia. One year after undergoing left renal clear cell renal cell carcinoma resection, a space-occupying lesion was found in the right kidney for which he underwent right nephrectomy. The histopathology of this tumor showed solid or tubular cell arrangements, with some areas of cyst formation. Vacuoles of varying sizes were present in the cytoplasm, and varying amounts of calcium oxalate crystals were found in the tumor cells or interstitium. The pathological diagnosis was ACD-RCC. Next-generation sequencing detected mutations in the PTCH1, MTOR, FAT1, SOS1, RECQL4, and CDC73 genes in the right renal tumor. This is a rare case of a patient with ACD-RCC in the right kidney and clear cell renal cell carcinoma in the left kidney. The findings suggest that mutations in PTCH1 associated with ACD-RCC may have acted as oncogenic drivers for the development of ACKD-RCC, together with providing insight into mechanisms underlying ACD-RCC development, as well as diagnostic and treatment options.

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.

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.

Neutrophil-derived S100A8/A9 promotes apoptosis of intestinal epithelial cells in children with duodenal ulcers.

Duodenal ulcer significantly reduces quality of life and safety in children; however, the mechanism of the pathogenesis in children with duodenal ulcer remains unclear. S100A8/A9, which plays a critical role in the occurrence and development of inflammation, has attracted a lot of interest recently. Here, we identified that S100A8/A9 are highly expressed in the serum of children with duodenal ulcers, and this is of excellent diagnostic value. Animal experiments have proved that inhibition of S100A8/A9 can repair ulcer progression. In addition, further study has shown that S100A8/A9, mainly produced by neutrophil, can enhance the apoptosis of intestinal epithelial cells and promote the growth in children with duodenal ulcers. Thus, our research proves the value of S100A8/A9 in the diagnosis and treatment of children with duodenal ulcers.

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 Piperidin-4-one Derivatives via α-Imino Rhodium Carbene-Initiated 1,2-Aryl/Alkyl Migration and Annulation.

Valuable piperidin-4-one derivatives were synthesized in excellent yields via an α-imino carbene-initiated cascade reaction involving 1,2-aryl/alkyl migration and annulation. The excellent selectivity of alkyl migration was attributed to the neighboring group participation of 2-bromoethyl. Features such as high efficiency, excellent migrating selectivity, broad substrate scope, and convenient one-pot procedure qualified this protocol as an effective tool for piperidine derivative synthesis. The product could be transformed to a bioactive molecule easily. The migration-annulation reaction of α-imino carbene provided a powerful strategy for heterocycle construction.

Chlorpyrifos and chlorfenapyr resistance in Spodoptera frugiperda (Lepidoptera: Noctuidae) relies on UDP-glucuronosyltransferases.

Fall armyworm, Spodoptera frugiperda (J. E. Smith), has become an important agricultural pest worldwide. S. frugiperda is mainly controlled by the chemical insecticides, whereas the frequent application of insecticides would result in the resistance development. Insect uridine diphosphate-glucuronosyltransferases (UGTs), as phase II metabolism enzymes, play vital roles in the breakdown of endobiotic and xenobiotics. In this study, 42 UGT genes were identified by RNA-seq, including 29 UGT genes were elevated compared to the susceptible population, and the transcript levels of 3 UGTs (UGT40F20, UGT40R18, and UGT40D17) were increased by more than 2.0-fold in the field populations. Expression pattern analysis revealed that S. frugiperda UGT40F20, UGT40R18, and UGT40D17 were increased by 6.34-, 4.26-, and 8.28-fold, compared the susceptible populations, respectively. The expression of UGT40D17, UGT40F20, and UGT40R18 was affected after exposure to phenobarbital, chlorpyrifos, chlorfenapyr, sulfinpyrazone, and 5-nitrouracil. The induced expression of UGT genes may have improved UGT enzymatic activity, while the inhibition of UGTs genes expression may decreased UGT enzymatic activity. Sulfinpyrazone, and 5-nitrouracil, significantly increased the toxicity of chlorpyrifos and chlorfenapyr, as well as phenobarbital significantly reduced the toxicity of chlorpyrifos and chlorfenapyr against the susceptible populations and field populations of S. frugiperda. The suppression of UGTs (UGT40D17, UGT40F20, and UGT40R18) significantly increased the insensitivity of the field populations to chlorpyrifos and chlorfenapyr. These findings strongly supported our viewpoint that UGTs may play a critical role in insecticide detoxification. This study provides a scientific basis for the management of S. frugiperda.

Identification of a Phase I mechanism gene of rice (OsCYP1) in response to isoproturon.

The long-term use of isoproturon may threaten food security and human health. Cytochrome P450 (CYP or P450) can catalyze the biosynthetic metabolism, and play a crucial role in the modification of plant secondary metabolites. Therefore, it is of great importance to explore the genetic resources for isoproturon degradation. This research focused on a phase I metabolism gene (OsCYP1) with significant differential expression in rice under isoproturon pressure. Specifically, the high-throughput sequencing results of rice seedling transcriptome in response to isoproturon stress were analyzed. The molecular information and tobacco subcellular localization of OsCYP1 were studied. The subcellular localization of OsCYP1 in tobacco was assessed, where it is located in the endoplasmic reticulum. To analyze the expression of OsCYP1 in rice, the wild-type rice was treated with 0-1 mg/L isoproturon for 2 and 6 days, and qRT-PCR assays were conducted to detect the transcription levels. Compared with the control group, the expression of OsCYP1 in shoots was progressively upregulated after exposure to isoproturon, with 6.2-12.7-fold and 2.8-7.9-fold increases in transcription levels, respectively. Moreover, treatment with isoproturon upregulated the expression of OsCYP1 in roots, but the upregulation of transcripts was not significant except for 0.5 and 1 mg/L isoproturon at day 2. To confirm the role of OsCYP1 in enhancing isoproturon degradation, the vectors overexpressing OsCYP1 were transformed into recombinant yeast cells. After exposure to isoproturon, the growth of OsCYP1-transformed cells was better than the control cells, especially at higher stress levels. Furthermore, the dissipation rates of isoproturon were increased by 2.1-, 2.1- and 1.9-fold at 24, 48 and 72 h, respectively. These results further verified that OsCYP1 could enhance the degradation and detoxification of isoproturon. Collectively, our findings imply that OsCYP1 plays vital role in isoproturon degradation. This study provides a fundamental basis for the detoxification and regulatory mechanisms of OsCYP1 in crops via enhancing the degradation and/or metabolism of herbicide residues.

Diverse Synthesis of Alkenylsilanes via Pd-Catalyzed Alkenyl C-H Silylation.

Here, we disclose a general approach for the diverse synthesis of alkenylsilanes in a highly efficient, stereoselective, and atom-economic manner by leveraging the palladium-catalyzed disilylation reaction of 2-bromostyrene derivatives with hexamethyldisilane, which is suitable for the preparation of a series of disubstituted, trisubstituted, and tetrasubstituted alkenylsilanes. Furthermore, the resulting tetrasubstituted alkenylsilanes could be readily transformed into the corresponding diarylated benzosiloles, which have been proven to be a potential AIE material and a fluorene material.

Synthesis of dihydropyrroles from in situ-generated zwitterions via Rh2(adc)4/TBAI dual catalysis.

Triggered by formation of α-imino carbene, the regioselective synthesis of dihydropyrroles was achieved via a cascade 1,3-sulfinate migration/annulation. The sulfinate group was converted into sulfone during the group migration, and a stable anion bearing two electron-withdrawing groups was thus formed. The addition of a catalytic amount of iodide is believed to assist the cleavage of the C-O bond, and the formation of a more stable carbocation. Thermodynamic product dihydropyrroles were produced efficiently rather than kinetic product cyclopropanes. This dual catalysis system would afford chemists a new strategy to control the annulation selectivity of zwitterions bearing multiple reactive sites and may be employed in flexible and divergent synthesis of different ring systems.

Visible-Light-Initiated Difunctionalization of Quinoxalin-2(1H)-ones with Acyloxy Nitroso Compounds.

Herein, a photoinitiated radical relay reaction of quinoxalin-2(1H)-ones, with acyloxy nitroso compounds as a source of radicals, is described. Although the C-H functionalization of quinoxalin-2(1H)-ones has been investigated, its difunctionalization, the simultaneous construction of C-C and N-N bonds directly via the radical relay reaction, has rarely been reported. Moreover, the obtained products underwent sequential reactions to access C7-NO2 of quinoxalin-2(1H)-ones under mild conditions.

Synthesis of Azepane Derivatives via Formal 1,3-Migration of Hydroxy and Acyloxy Groups and Selective Annulation.

Formal 1,3-migration of hydroxy and acyloxy groups initiated by α-imino rhodium carbene was achieved, and the following selective annulations of the corresponding zwitterions could efficiently afford azepane derivatives. Benefiting from a time-saving procedure as well as a good functional group tolerance, this unique migration-annulation protocol could provide an efficient tool for synthesizing seven-membered N-heterocycles. The plausible mechanism is discussed.

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.