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.

The role of OsBZR4 as a brassinosteroid-signaling component in mediating atrazine and isoproturon degradation in rice.

Development of a biotechnological system for rapid degradation of pesticides is important to mitigate the environmental, food security, and health risks that they pose. Degradation of atrazine (ATZ) and isoproturon (IPU) in rice crops promoted by the brassinosteroid (BR) signaling component BRASSINAZOLE RESISTANT4 (OsBZR4) is explored. OsBZR4 is localized in the plasma membrane and nucleus, and is strongly induced by ATZ and IPU exposure. Transgenic rice OsBZR4-overexpression (OE) significantly enhances resistance to ATZ and IPU toxicity, improving growth, and reducing ATZ and IPU accumulation (particularly in grains) in rice crops. Genetic destruction of OsBZR4 (CRISPR/Cas9) increases rice sensitivity and leads to increased accumulation of ATZ and IPU. OE plants promote phase I, II, and III metabolic reactions, and expression of corresponding pesticide degradation genes under ATZ and IPU stress. UPLC-Q-TOF-MS/MS analysis reveals increased relative contents of ATZ and IPU metabolites and conjugates in OE plants, suggesting an increased OsBZR4 expression and consequent detoxification of ATZ and IPU in rice and the environment. The role of OsBZR4 in pesticide degradation is revealed, and its potential application in enhancing plant resistance to pesticides, and facilitating the breakdown of pesticides in rice and the environment, is discussed.

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.

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.

Cytochrome P450 CYP90D5 Enhances Degradation of the Herbicides Isoproturon and Acetochlor in Rice Plants and Grains.

The rice cytochrome P450 gene has been comprehensively studied in the present study. This gene encodes CYP90D5 in promoting the degradation of isoproturon (IPU) and acetochlor (ACT) in rice tissues and grains. It has here been found that CYP90D5 improved the resistance of the plant to IPU and ACT, which was reflected in the improvement of the growth of the overexpression (OE) lines. CYP90D5 also reduced the levels of IPU and ACT accumulation in rice, and the CRISPR-Cas9 (Cas9) lines displayed the opposite effects. This function of CYP90D5 for pesticide degradation was also confirmed by the transformation of CYP90D5 in Pichia pastoris. Compared with the control yeast, it grew better and could degrade more pesticides. In addition, the relative contents of the IPU and ACT derivatives increased in the OE rice, while they decreased in the Cas9 rice. This suggested that CYP90D5 plays a pivotal role in the pesticide detoxification and degradation.

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.

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.

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.

Synthesis of α-Amino Cyclobutanones via Formal 1,3-Hydroxy Migration Triggered by Formation of α-Imino Rhodium Carbene.

Formal intramolecular 1,3-OH migration of α-imino carbene was achieved producing a unique zwitterion, and the subsequent selective annulation afforded α-amino cyclobutanone. Features such as readily available substrates, mild reaction conditions, a time-saving procedure, excellent functional group compatibility, and valuable transformations of the products qualified this unique protocol as an efficient tool for the synthesis of strained cyclic compounds. Density functional theory calculations were in good agreement with experimental observations, and a plausible mechanism is presented.

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.

A2 adenosine receptor contributes to the development of cow's milk protein allergy via regulating regulatory T cells.

OBJECTIVES: A2 adenosine receptor (A2AR) is a novel promising target for the treatment of inflammatory and allergic diseases. However, its role in the development of cow's milk protein allergy (CMPA) has not been elucidated. The present study was designed to investigate the function of A2AR in CMPA development. MATERIALS AND METHODS: BALB/c mice were sensitized and challenged with ovalbumin (OVA) to induce allergic responses. The model was assessed by detecting allergic responses and plasma-specific IgE levels. The levels of A2AR were measured by PCR and flow cytometry. The subpopulation of Treg cells was analysed. RESULTS: The mice sensitized and challenged with OVA showed classic allergic symptoms, such as acute allergic skin responses, increased anaphylactic shock symptom scores, and higher levels of total IgE, OVA-specific IgE, IgG1 and IgG2a. OVA-sensitized mice and CMPA patients showed decreased levels of A2AR and Treg cells. Interestingly, we observed a positive correlation between A2AR expression and Treg levels in CMPA patients. Further study showed that the A2AR agonist CGS21680 blocked OVA-induced allergic reactions, and the A2AR antagonist KW-6002 amplified allergic responses. Interestingly, CGS21680 not only activated the A2AR-mediated signalling pathway but also caused an increase in the population of Treg cells. In contrast, KW-6002 therapy decreased the levels of Tregs in allergic mice. CONCLUSION: A2AR expression is downregulated in CMPA. The A2AR-mediated pathway negatively regulates the development of CMPA, at least in part, by amplifying the differentiation of Tregs.

A standardized pathological proposal for evaluating microvascular invasion of hepatocellular carcinoma: a multicenter study by LCPGC.

BACKGROUND AND AIMS: Microvascular invasion (MVI) is a key pathological factor that severely affects the postoperative prognosis of patients with hepatocellular carcinoma (HCC). However, no MVI classification schemes based on standardized gross sampling protocols of HCC are available at present. METHODS: 119 HCC specimens were sampled at multiple sites (3-, 7-, and 13 points) for the optimum MVI detection rate. 16,144 resected HCCs were graded as M0, M1 or M2 by adopting three-tiered MVI grading (MVI-TTG) scheme based on the seven-point sampling protocol (SPSP). Survival analyses were performed on 2573 patients to explore the advantages of MVI-TTG. RESULTS: The MVI detection rate determined by SPSP was significantly higher than that determined by the 3-point sampling method (34.5% vs. 47.1%, p = 0.048), but was similar to that determined by the 13-point sampling method (47.1% vs. 51.3%, p = 0.517). Among 16,144 resected HCCs, the proportions of M0, M1 and M2 specimens according to SPSP were 53.4%, 26.2% and 20.4%, respectively. Postoperative survival analysis in 2573 HCC patients showed that the 3-year recurrence rates in M0, M1 and M2 MVI groups were 62.5%, 71.6% and 86.1%, respectively (p < 0.001), and the corresponding 3-year overall survival (OS) rates were 94.1%, 87.5% and 67.0%, respectively (p < 0.001). M1 grade was associated with early recurrence, while M2 grade was associated with both early and late recurrence. MVI-TTG had a larger area under the curve and net benefit rate than the two-tiered MVI grading scheme for predicting time to recurrence and OS. CONCLUSIONS: SPSP is a practical method to balance the efficacy of sampling numbers and MVI detection rates. MVI-TTG based on SPSP is a better prognostic predictor than the two-tiered MVI scheme. The combined use of SPSP and MVI-TTG is recommended for the routine pathological diagnosis of HCC.