Novel herbicide flusulfinam: absolute configuration, enantioseparation, enantioselective bioactivity, toxicity and degradation in paddy soils.

BACKGROUND: Flusulfinam, a novel chiral herbicide, effectively controls Echinochloa crusgalli and Digitaria sanguinalis in paddy fields, indicating significant potential for practical agricultural applications. However, limited information is available on flusulfinam from a chiral perspective. A comprehensive evaluation of the enantiomeric levels of flusulfinam was performed. RESULTS: Two enantiomers, R-(+)- and S-(-)-flusulfinam, were separately eluted using a Chiralcel OX-RH column. The bioactivity of R-flusulfinam against the two was 1.4-3.1 fold that of Rac-flusulfinam against two weed species. R-flusulfinam toxicity to Danio rerio larvae and Selenastrum capricornutumwere was 0.8- and 3.0-fold higher than Rac-flusulfinam, respectively. Degradation experiments were conducted using soil samples from four Chinese provinces. The findings indicated that S-flusulfinam (half-life T1/2 = 40.8 days) exhibits preferential degradation than R-flusulfinam (T1/2 = 46.2-57.8 days) in the soils of three provinces. Under anaerobic conditions, soil from Anhui exhibited preferential degradation of R-flusulfinam (T1/2 = 46.2 days) over S-flusulfinam (T1/2 = 63 days). Furthermore, two hydrolysis products of flusulfinam (M299 and M100) are proposed for the first time. CONCLUSION: The enantioselective bioactivity, toxicity and degradation of flusulfinam were investigated. Our findings indicate that R-flusulfinam is an extremely effective and low-toxicity enantiomer for the tested species. The soil degradation test indicated that the degradation of flusulfinam was accelerated by higher organic matter content and lower soil pH. Furthermore, microbial communities may play a crucial role in driving the enantioselective degradation processes. This study lays the groundwork for the systematic evaluation of flusulfinam from an enantiomeric perspective. © 2024 Society of Chemical Industry.

Adipose-derived mesenchymal stromal cells alleviate intestinal fibrosis: The role of tumor necrosis factor-stimulated gene 6 protein.

BACKGROUND: The therapeutic potential of adipose-derived mesenchymal stromal cells (AMSCs) in the treatment of intestinal fibrosis occured in patients with Crohn's disease (CD) remains unclear. Tumor necrosis factor-stimulated gene 6 (TSG6) protein plays a critical role in inflammation regulation and tissue repair. This study aimed to determine if AMSCs attenuate intestinal fibrosis by secreting paracrine TSG6 protein and explore the underlying mechanisms. METHODS: Two murine models for intestinal fibrosis were established using 2,4,6-trinitrobenzene sulfonic acid in BALB/c mice and dextran sulfate sodium in C57BL/6 mice. Primary human fibroblasts and CCD-18co cells were incubated with transforming growth factor (TGF)-ß1 to build two fibrosis cell models in vitro. RESULTS: Intraperitoneally administered AMSCs attenuated intestinal fibrosis in the two murine models, as evidenced by significant alleviation of colon shortening, collagen protein deposits, and submucosal thickening, and also decrease in the endoscopic and fibrosis scores (P < 0.001). Although intraperitoneally injected AMSCs did not migrate to the colon lesions, high levels of TSG6 expression and secretion were noticed both in vivo and in vitro. Similar to the role of AMSCs, injection of recombinant human TSG6 attenuated intestinal fibrosis in the mouse models, which was not observed with the administration of AMSCs with TSG6 knockdown or TSG6 neutralizing antibody. Mechanistically, TSG6 alleviates TGF-ß1-stimulated upregulation of α-smooth muscle actin (αSMA) and collagen I by inhibiting Smad2 phosphorylation. Furthermore, the expression of TSG6 is lower in intestinal fibrosis tissue of patients with Crohn's disease and can reduce pro-fibrotic protein (αSMA) secretion from primary ileal fibrotic tissue. CONCLUSIONS: AMSCs attenuate intestinal fibrosis by secreting paracrine TSG6 protein, which inhibits Smad2 phosphorylation. TSG6, a novel anti-fibrotic factor, could potentially improve intestinal fibrosis treatments.

Physiological Basis for the Mechanism of Selectivity of Tripyrasulfone between Rice (Oryza sativa) and Barnyard Grass (Echinochloa crus-galli).

Tripyrasulfone is currently the only HPPD-inhibiting herbicide that possesses outstanding selectivity even for direct-seeded rice (Oryza sativa) when applied POST to control grass weeds; however, the underlying mechanisms remain unclear. In this study, the inhibitory effects of the real active HDT of tripyrasulfone on recombinant 4-hydroxyphenylpyruvate dioxygenase (HPPDs) from rice and barnyard grass (Echinochloa crus-galli) were similar, with consistent structural interactions and similar binding energies predicted by molecular docking. However, the HPPD expression level in rice was significantly greater than that in barnyard grass after tripyrasulfone treatment. Tripyrasulfone was rapidly taken up and hydrolyzed into HDT, which was similarly distributed within the whole plants of rice and barnyard grass at 24 h after treatment. Compared with barnyard grass, rice has more uniform epicuticular wax in the cuticle of its leaves, absorbing less tripyrasulfone and metabolizing much more tripyrasulfone. Overall, to a greater extent, the different sensitivities to tripyrasulfone between barnyard grass and rice resulted from metabolic variations.

ELMO1 ameliorates intestinal epithelial cellular senescence via SIRT1/p65 signaling in inflammatory bowel disease-related fibrosis.

Background: Intestinal fibrosis is a common complication in inflammatory bowel disease (IBD), which still lacks of reliable markers and therapeutic options. Cellular senescence has been considered an important mechanism of intestinal fibrosis, but the underlying molecular link remains elusive. Methods: Tissues were stained using α-smooth muscle actin (α-SMA), fibronectin, and collagen I as markers of myofibroblastic differentiation. Cellular senescence was confirmed through Lamin B1 staining, senescence-associated ß-galactosidase staining, and the expression of senescence-associated secretory phenotype (SASP) factors. We explored the relationship between senescence of intestinal epithelial cells (IECs) and intestinal fibrosis, as well as the molecular mechanism underlying this interaction. The effects of irisin on cellular senescence and fibrosis were determined. Results: Here, we identify engulfment and cell motility protein 1 (ELMO1) as a novel biomarker for intestinal cellular senescence and fibrosis. In fibrostrictured tissues from patients and murine models with IBD, significantly high levels of cellular senescence score and factors were noted, which positively correlated with the fibrotic regulator fibronectin. Senescent IECs, not fibroblast itself, released SASP factors to regulate fibroblast activation. Prolonging exposure to severe and persistent injurious stimuli decreased ELMO1 expression, which dampened SIRT1 deacetylase activity, enhanced NF-κB (p65) acetylation, and thereby accelerated cellular senescence. Deletion of ELMO1 led to senescent IECs accumulation and triggered premature fibrosis in murine colitis. Furthermore, irisin, inhibiting the degradation of ELMO1, could downregulate p65 acetylation, reduce IECs senescence, and prevent incipient intestinal fibrosis in murine colitis models. Conclusions: This study reveals ELMO1 downregulation is an early symbol of intestinal senescence and fibrosis, and the altered ELMO1-SIRT1-p65 pathway plays an important role in intestinal cellular senescence and IBD-related fibrosis.

Fatty Acid Oxidation Promotes Apoptotic Resistance and Proinflammatory Phenotype of CD4+ Tissue-resident Memory T cells in Crohn's Disease.

BACKGROUND & AIMS: As the most abundant memory T cells and major source of tumor necrosis factor α in the intestinal mucosa of Crohn's disease (CD) patients, CD4+ tissue-resident memory T (TRM) cells play a critical role in CD pathogenesis. We investigated the role of metabolic reprogramming in the regulation of proinflammatory and apoptosis-resistant phenotype for CD4+ TRM cells. METHODS: CD4+ TRM cells were collected from intestinal resection tissues from control and CD patients. Transcriptomic and metabolomic analysis were performed to identify metabolic characteristics of CD4+ TRM cells. Enzyme-linked immunosorbent assay and quantitative polymerase chain reaction experiments were used to assess cytokines level in CD4+ TRM cells; activation-induced cell apoptosis rate was evaluated by flow cytometry. Transwell assay and wound healing assay were performed to detect the effect of CD4+ TRM cells on the migration of normal intestinal epithelial cells. RESULTS: Transcriptomic data combined with unbiased metabolomic analysis revealed an increased fatty acid oxidation (FAO) phenotype existed in CD4+ TRM cells from CD patients. The lipidomic data and stable isotope tracer experiments demonstrated that CD4+ TRM cells up-regulated their lipid lipolysis and fatty acid uptake to fuel FAO in CD patients. Mechanistically, the activated nuclear factor kappa B signaling increased transcription of genes involved in lipid lipolysis, fatty acid uptake, and oxidation in CD4+ TRM cells from CD patients. Targeting FAO of CD4+ TRM cells reversed their apoptosis-resistant and proinflammatory phenotype in CD patients. CONCLUSIONS: CD4+ TRM cells process an accelerated FAO mediated by activated nuclear factor kappa B signaling in CD patients; targeting FAO could reverse their apoptosis-resistant and proinflammatory phenotype. These findings shed a new light on the pathogenic mechanism investigation and novel therapy development in CD patients.

Weed biology and management in the multi-omics era: Progress and perspectives.

Weeds pose a significant threat to crop production, resulting in substantial yield reduction. In addition, they possess robust weedy traits that enable them to survive in extreme environments and evade human control. In recent years, the application of multi-omics biotechnologies has helped to reveal the molecular mechanisms underlying these weedy traits. In this review, we systematically describe diverse applications of multi-omics platforms for characterizing key aspects of weed biology, including the origins of weed species, weed classification, and the underlying genetic and molecular bases of important weedy traits such as crop-weed interactions, adaptability to different environments, photoperiodic flowering responses, and herbicide resistance. In addition, we discuss limitations to the application of multi-omics techniques in weed science, particularly compared with their extensive use in model plants and crops. In this regard, we provide a forward-looking perspective on the future application of multi-omics technologies to weed science research. These powerful tools hold great promise for comprehensively and efficiently unraveling the intricate molecular genetic mechanisms that underlie weedy traits. The resulting advances will facilitate the development of sustainable and highly effective weed management strategies, promoting greener practices in agriculture.

Features of synchronous and metachronous dual primary gastric and colorectal cancer.

BACKGROUND: Studies evaluating the characteristics of dual primary gastric and colorectal cancer (CRC) (DPGCC) are limited. AIM: To analyze the clinicopathologic characteristics and prognosis of synchronous and metachronous cancers in patients with DPGCC. METHODS: From October 2010 to August 2021, patients with DPGCC were retrospectively reviewed. The patients with DPGCC were divided into two groups (synchronous and metachronous). We compared the overall survival (OS) between the groups using Kaplan-Meier survival methods. Univariate and multivariate analyses were performed using Cox's proportional hazards model to identify the independent prognostic factors for OS. RESULTS: Of the 76 patients with DPGCC, 46 and 30 had synchronous and metachronous cancers, respectively. The proportion of unresectable CRC in patients with synchronous cancers was higher than that in patients with metachronous cancers (28.3% vs 3.3%, P = 0.015). The majority of the second primary cancers had occurred within 5 years. Kaplan-Meier survival analysis showed that the patients with metachronous cancers had a better prognosis than patients with synchronous cancers (P = 0.010). The patients who had undergone gastrectomy (P < 0.001) or CRC resection (P < 0.001) had a better prognosis than those who had not. In the multivariate analysis, synchronous cancer [hazard ratio (HR) = 6.8, 95% confidence interval (95%CI): 2.0-22.7, P = 0.002)] and stage III-IV gastric cancer (GC) [HR = 10.0, 95%CI: 3.4-29.5, P < 0.001)] were risk prognostic factor for OS, while patients who underwent gastrectomy was a protective prognostic factor for OS [HR = 0.2, 95%CI: 0.1-0.6, P = 0.002]. CONCLUSION: Regular surveillance for metachronous cancer is necessary during postoperative follow-up. Surgical resection is the mainstay of therapy to improve the prognosis of DPGCC. The prognosis appears to be influenced by the stage of GC rather than the stage of CRC. Patients with synchronous cancer have a worse prognosis, and its treatment strategy is worth further exploration.

Prognostic value of hyperthermic intraperitoneal chemotherapy in gastric cancer with synchronous peritoneal metastases: a real-world retrospective study.

PURPOSE: Peritoneal metastasis in gastric cancer (GC) is a late-stage condition with a poor prognosis. Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a popular treatment for peritoneal metastases. Here, we aim to investigate the real-world application and efficacy of HIPEC alone for GC patients with synchronous peritoneal metastases. METHODS: We conducted a retrospective analysis on GC patients with synchronous peritoneal metastasis at the Sixth Affiliated Hospital of Sun Yat-sen University between January 2011 and December 2022. Survival analyses and Cox regression models were performed based on overall survival (OS) and cancer-specific survival (CSS), and subgroup analysis was used to determine the prognostic value of HIPEC across different treatment. RESULTS: We enrolled 250 patients, of whom 120 (48%) received HIPEC while 130 (52%) did not. HIPEC showed no survival benefit for GC patients (P = 0.220 for OS and P = 0.370 for CSS). However, subgroup analysis found that HIPEC can only improve OS and CSS when combined with primary tumor resection (P = 0.034 for OS and P = 0.036 for CSS). Moreover, survival analyses also demonstrated that HIPEC independently improved OS (HR for OS = 0.58, 95% CI 0.37-0.92, P = 0.020) and CSS (HR for CSS = 0.58, 95% CI 0.37-0.93, P = 0.024) for patients who underwent primary site resection, but not for those who did not. CONCLUSION: HIPEC can improve survival in GC patients with synchronous peritoneal metastases who have primary tumor resection, but not in those without primary tumor resection.

Implication of perineural invasion in patients with stage II gastric cancer.

BACKGROUND: Perineural invasion (PNI) is regarded as a prognostic factor for patients with GC. However, the significance of PNI in patients with stage II GC remains unclear. This study aimed to investigate the clinical implication of PNI in patients with stage II GC undergoing curative resection. METHODS: Patients with stage II GC who underwent curative resection were retrospectively evaluated from January 2010 to July 2019. According to PNI status, all patients were divided into two groups: with or without PNI. The prognostic value of PNI was analyzed by univariate and multivariate Cox proportional hazards regression models. RESULTS: A total of 233 patients were included in this study. There were 100 patients with PNI (42.92%) and 133 patients without PNI (57.08%). The overall survival (OS) and disease-free survival (DFS) rates for patients with PNI were significantly lower than that for patients without PNI (p = 0.019 and p = 0.032, respectively). Multivariate analysis indicated that the presence of PNI was an independent risk factor for OS (hazard ratio (HR): 1.76, 95% confidence interval (CI) 1.02-3.06, p = 0.044) and DFS (HR: 1.70, 95% CI 1.04-2.80, p = 0.035), while adjuvant chemotherapy (AC) was an independent protective factor for OS (HR: 0.51, 95% CI 0.30-0.88, p = 0.016) and DFS (HR: 0.52, 95% CI 0.31-0.86, p = 0.011). Furthermore, among patients with PNI, those who received AC had better OS (p = 0.022) and DFS (p = 0.027) than their counterparts. When patients with PNI received AC, the OS (p = 0.603) and DFS (p = 0.745) appeared to be similar to those without PNI and no AC. CONCLUSION: In patients with stage II GC undergoing curative resection, the presence of PNI was associated with worse survival, which appeared to improve with the treatment of AC, indicating a potential need for more intensive AC.

Elderly patients with stage II gastric cancer do not benefit from adjuvant chemotherapy.

BACKGROUND: With the aging of the population, the burden of elderly gastric cancer (EGC) increases worldwide. However, there is no consensus on the definition of EGC and the efficacy of adjuvant chemotherapy in patients with stage II EGC. Here, we investigated the effectiveness of adjuvant chemotherapy in defined EGC patients. METHODS: We enrolled 5762 gastric cancer patients of three independent cohorts from the Sixth Affiliated Hospital of Sun Yat-sen University (local), the Surveillance, Epidemiology, and End Results (SEER), and the Asian Cancer Research Group (ACRG). The optimal age cutoff for EGC was determined using the K-adaptive partitioning algorithm. The defined EGC group and the efficacy of adjuvant chemotherapy for them were confirmed by Cox regression and Kaplan-Meier survival analyses. Furthermore, gene set variation analyses (GSVA) were performed to reveal pathway enrichment between groups. RESULTS: The optimal age partition value for EGC patients was 75. In the local, SEER, and ACRG cohorts, the EGC group exhibited significantly worse overall survival and cancer-specific survival than the non-EGC group (P < 0.05) and was an independent risk factor. Stratified analyses based on chemotherapy showed that EGC patients derived little benefit from adjuvant chemotherapy. Furthermore, GSVA analysis revealed the activation of DNA repair-related pathways and downregulation of the p53 pathway, which may partially contribute to the observed findings. CONCLUSION: In this retrospective, international multi-center study, 75 years old was identified as the optimal age cutoff for EGC definition, and adjuvant chemotherapy proved to be unbeneficial for stage II EGC patients.

Risk factors for postoperative recurrence in patients with stage II colorectal cancer.

BACKGROUND: Recurrences are the main reasons for unfavorable outcomes for patients with stage II colorectal cancer (CRC). To obtain a clear understanding of the high-risk factors, further investigation is warranted. The present study aimed to analyze the risk factors associated with postoperative recurrence in patients with stage II CRC. METHODS: Eligible patients with pathologically confirmed stage II CRC were enrolled in the study retrospectively based on a prospectively maintained database from April 2008 to March 2019. The Kaplan-Meier method were used to calculate the overall survival (OS) rate and the cumulative recurrence rate. Univariate and multivariable Cox regression analyses were performed to identify risk factors for recurrence. RESULTS: There were 2515 patients included, of whom 233 (9.3%) developed local or distant recurrence. Recurrence was associated with a significantly worse 5-year OS (45.4% vs. 95.5%, p < 0.0001). The 5-year cumulative recurrence rate was 13.0% in patients with stage II CRC. On multivariable Cox analysis, tumor size (Hazard Ratio (HR) [95% confidence interval (CI)] = 1.79[1.38, 2.33]), preoperative carbohydrate antigen (CA) 125 level (HR [95% CI] = 1.78[1.17, 2.70]), preoperative CA 199 level (HR [95% CI] = 1.56[1.09, 2.22]), and ulcerating tumor (HR [95% CI] = 1.61[1.19, 2.17]) were found to be associated with postoperative recurrence. Adjuvant chemotherapy was associated with a lower cumulative recurrence rate in patients with these risk factors (p = 0.00096). CONCLUSION: The tumor diameter, preoperative CA125 level, preoperative CA199 level, and an ulcerative tumor can predict postoperative recurrence in patients with stage II CRC, and postoperative chemotherapy could reduce the cumulative recurrence rate in patients with these high-risk factors.

Cypyrafluone, a 4-Hydroxyphenylpyruvate Dioxygenase Inhibitor to Control Weed in Wheat Fields.

As a bleaching herbicide, cypyrafluone was applied postemergence in wheat fields for annual weed control; especially, this herbicide possesses high efficacy against cool-season grass weed species such as Alopecurus aequalis and Alopecurus japonicus. In this study, the target of action of cypyrafluone on 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibition was confirmed. This herbicide caused severe foliar whitening symptoms at 5-7 days after treatment (DAT) and death of the whole plant within 10 DAT. Significant increases in phytoene content and significant decreases in kinds of carotenoid and chlorophyll pigments were observed. The content of chlorophyll pigments in cypyrafluone-treated Spirodela polyrhiza decreased upon the addition of homogentisic acid (HGA), which indicated that cypyrafluone prevents the HGA production, possibly by inhibiting the catalytic activity of 4-HPPD. Indeed, cypyrafluone strongly inhibited the catalytic activity of Arabidopsis thaliana HPPD produced by Escherichia coli, which was approximately 2 times less effective than mesotrione. In addition, overexpression of Oryza sativa HPPD in rice and A. thaliana both conferred a high tolerance level to cypyrafluone on them. Molecular docking found that cypyrafluone bonded well to the active site of the HPPD and formed a bidentate coordination interaction with the Fe2+ atom, with distances of 2.6 and 2.7 Å between oxygen atoms and the Fe2+ atom and a binding energy of -8.0 kcal mol-1.

Induction of filopodia formation by α-Actinin-2 via RelA with a feedforward activation loop promoting overt bone marrow metastasis of gastric cancer.

BACKGROUND: Bone marrow metastasis (BMM) is underestimated in gastric cancer (GC). GC with BMM frequently complicate critical hematological abnormalities like diffused intravascular coagulation and microangiopathic hemolytic anemia, which constitute a highly aggressive GC (HAGC) subtype. HAGC present a very poor prognosis with peculiar clinical and pathological features when compared with not otherwise specified advanced GC (NAGC). But the molecular mechanisms underlying BMM from GC remain rudimentary. METHODS: The transcriptomic difference between HAGC and NAGC were analyzed. Genes that were specifically upregulated in HAGC were identified, and their effect on cell migration and invasion was studied. The function of ACTN2 gene were confirmed by GC cell lines, bone-metastatic animal model and patients' tissues. Furthermore, the molecular mechanism of ACTN2 derived-BMM was explored by multiple immunofluorescence staining, western blot, chromatin immunoprecipitation, and luciferase reporter assays. RESULTS: We elucidated the key mechanisms of BMM depending on the transcriptomic difference between HAGC and NAGC. Five genes specifically upregulated in HAGC were assessed their effect on cell migration and invasion. The ACTN2 gene encoding protein α-Actinin-2 was detected enhanced the metastatic capability and induced BMM of GC cells in mouse models. Mechanically, α-Actinin-2 was involved in filopodia formation where it promoted the Actin filament cross-linking by replacing α-Actinin-1 to form α-Actinin-2:α-Actinin-4 complexes in GC cells. Moreover, NF-κB subunit RelA and α-Actinin-2 formed heterotrimers in the nuclei of GC cells. As a direct target of RelA:α-Actinin-2 heterotrimers, the ACTN2 gene was a positive auto-regulatory loop for α-Actinin-2 expression. CONCLUSIONS: We demonstrated a link between filopodia, BMM and ACTN2 activation, where a feedforward activation loop between ACTN2 and RelA is established via actin in response to distant metastasis. Given the novel filopodia formation function and the new mechanism of BMM in GC, we propose ACTN2 as a druggable molecular vulnerability that may provide potential therapeutic benefit against BMM of GC.

Prognostic factors and the necessity of chemotherapy for stage II gastric cancer: a model based on multicenter retrospective study.

BACKGROUND: This study aimed to construct a prognostic model for prognosis prediction and assess the response to adjuvant chemotherapy (ACT) of stage II gastric cancer (GC) patients on high and low survival risk stratifications. METHODS: We retrospectively reviewed 547 stage II gastric cancer patients who underwent D2 radical gastrectomy from January 2009 to May 2017 in Sixth Affiliated Hospital of Sun Yat-Sen University (SAH-SYSU), the Fujian Medical University Union Hospital (FJUUH), and the Sun Yat-Sen University Cancer Center (SYSUCC).The propensity score matching (PSM) of all variables was performed to balance selective bias between ACT and surgery alone (SA) groups. Kaplan-Meier survival and multivariate Cox regression analyses were carried out to identify independent prognostic factors. Independent factors selected by the Cox regression were integrated into the nomogram. The nomogram points stratified patients into high-risk and low-risk groups by the optimal cut-off value. RESULTS: 278 patients were selected after PSM. Age, tumor site, T stage and lymph-nodes-examined (LNE) selected by Cox regression as independent prognostic factors were integrated into the nomogram. The nomogram performed well with a C-index of 0.76 and with C-indexes of 0.73 in and 0.71 in two validate cohorts. AUCs of the 3 year and 5 year ROC curves were 0.81 and 0.78. High- and low-risk groups stratified by the cut-off value demonstrated different responses to ACT. CONCLUSIONS: The nomogram performed well in prognosis prediction. Patients in high- and low-risk groups demonstrated different responses to ACT, and high-risk patients might need ACT.

Metabolic resistance to acetolactate synthase inhibitors in Beckmannia syzigachne: identification of CYP81Q32 and its transcription regulation.

Frequent herbicide use selects for herbicide resistance in weeds. Cytochrome P450s are important detoxification enzymes responsible for herbicide resistance in plants. We identified and characterized a candidate P450 gene (BsCYP81Q32) from the problematic weed Beckmannia syzigachne to test whether it conferred metabolic resistance to the acetolactate synthase-inhibiting herbicides mesosulfuron-methyl, bispyribac-sodium, and pyriminobac-methyl. Transgenic rice overexpressing BsCYP81Q32 was resistant to the three herbicides. Equally, rice overexpressing the rice ortholog gene OsCYP81Q32 was more resistant to mesosulfuron-methyl. Conversely, an OsCYP81Q32 gene knockout generated using CRISPR/Cas9 enhanced mesosulfuron-methyl sensitivity in rice. Overexpression of the BsCYP81Q32 gene resulted in enhanced mesosulfuron-methyl metabolism in transgenic rice seedlings via O-demethylation. The major metabolite, demethylated mesosulfuron-methyl, was chemically synthesized and displayed reduced herbicidal effect in plants. Moreover, a transcription factor (BsTGAL6) was identified and shown to bind a key region in the BsCYP81Q32 promoter for gene activation. Inhibition of BsTGAL6 expression by salicylic acid treatment in B. syzigachne plants reduced BsCYP81Q32 expression and consequently changed the whole plant response to mesosulfuron-methyl. Sequence polymorphisms in an important region of the BsTGAL6 promoter may explain the higher expression of BsTGAL6 in resistant versus susceptible B. syzigachne plants. Collectively, the present study reveals the evolution of an herbicide-metabolizing and resistance-endowing P450 and its transcription regulation in an economically important weedy plant species.

Advanced lung cancer inflammation index predicts the outcomes of patients with non-metastatic gastric cancer after radical surgical resection.

Background: The prognostic value of the advanced lung cancer inflammation index (ALI) has been demonstrated in various tumors. However, the prognostic significance of ALI in non-metastatic gastric cancer (GC) remains unclear. This study aimed to identify the prognostic values of ALI in patients with non-metastatic GC who underwent radical surgical resection. Methods: Patients who underwent radical surgery for non-metastatic GC from January 2008 to September 2020 were enrolled in this study. The preoperative ALI was calculated as follows: body mass index × serum albumin/neutrophil to lymphocyte ratio. The primary outcomes were overall survival (OS) and cancer-specific survival (CSS). Cox regression analyses were performed to assess the association between ALI and survival. The potential of ALI was supported by sensitivity testing based on the propensity score matching (PSM) analysis. Results: Low preoperative ALI was significantly correlated with male gender (P=0.037), older age (P=0.004), T3/4 stage (P=0.001), lymph node metastasis (P=0.030), Tumor Node Metastasis (TNM) stage classification progression (P=0.004), and vessel invasion (P=0.001). Patients with low ALI showed worse OS (P<0.001) and CSS (P=0.001) compared to those with high ALI. Multivariable analysis showed that ALI was an independent prognostic factor for both OS [hazard ratio (HR) =1.55; 95% confidence interval (CI), 1.11-2.16]; P=0.010] and CSS (HR =1.46; 95% CI, 1.01-2.10; P=0.043) in non-metastatic GC patients who underwent radical surgical resection. Further PSM analysis confirmed the prognostic value of ALI in the PSM cohort. Conclusions: The preoperative ALI is associated with survival outcomes in patients who have undergone radical surgical resection for non-metastatic GC. Low ALI appears to predict a worse prognosis.

Lymphovascular or perineural invasion is associated with lymph node metastasis and survival outcomes in patients with gastric cancer.

BACKGROUND: Lymphovascular invasion (LVI) and perineural invasion (PNI) are associated with poorer prognosis in several human malignancies, but their significance in gastric cancer (GC) remains to be clearly defined. Our study aimed to investigate the prognostic value of LVI/PNI in patients with curative resected GC. METHODS: Records of 1488 patients with stage I--III GC and 3327 patients with stage I-III colorectal cancer (CRC) were reviewed retrospectively, and difference in the incidence of LVI/PNI between GC and CRC was compared. Univariate and multivariate analyses were used to evaluate whether LVI/PNI was an independent risk factor for lymph node metastasis (LNM) and overall survival (OS) in GC. RESULTS: Patients with stage I-III GC had a significantly higher incidence of LVI/PNI than patients with stage I-III CRC (50.54% vs. 21.91%, p < 0.001). LVI/PNI was significantly associated with higher CEA, higher CA199, deeper tumor invasion, more lymph node metastasis, and advanced TNM stage in GC ( p < 0.05). Multivariate logistic regression analysis identified LVI/PNI (OR = 2.64, 95%CI: 2.05-3.40, p < 0.001) as an independent risk factor for LNM in GC. The OS rate was significantly lower in the LVI/PNI-positive GC group than that in the LVI/PNI-negative GC group ( p < 0.001). On multivariate Cox regression analysis, LVI/PNI (HR = 1.34, 95%CI: 1.04-1.71, p  = 0.023) was an independent prognostic factor for OS in GC. CONCLUSION: GC has a high incidence of LVI/PNI, which was closely associated with disease progression. LVI/PNI could serve as an independent risk factor for LNM and the prognosis of patients with curative resected GC. These findings will be helpful in predicting survival outcomes more accurately and establishing individualized treatment plans.

Comparison of The Toronto IBD Global Endoscopic Reporting (TIGER) score, Mayo endoscopic score (MES), and ulcerative colitis endoscopic index of severity (UCEIS) in predicting the need for ileal pouch-anal anastomosis in patients with ulcerative colitis.

BACKGROUND: Total proctocolectomy (TPC) with ileal pouch-anal anastomosis (IPAA) has been accepted as a radical surgery for refractory ulcerative colitis (UC). We aimed to assess the predictive value of several novel and widely used endoscopic core systems, The Toronto IBD Global Endoscopic Reporting (TIGER) score, Mayo endoscopic score (MES), and ulcerative colitis endoscopic index of severity (UCEIS) in guiding the need for IPAA. METHODS: Data on patients with UC from June 1986 and June 2022 at our institute were collected. The endoscopic evaluation was recorded according to the first colonoscopy after hospitalization. Primary outcome was the need for IPAA during admission and follow-up. RESULTS: A total of 313 patients with a median follow-up time and a median TIGER score of 12.0 years (interquartile range (IQR): 6.0-17.0) and 212.0 (IQR: 7.0-327.0) were enrolled. IPAA was conducted in 110 (35.1%) patients, which significantly improved the long-term quality of life. TIGER score had the biggest area under the receiver-operating characteristic curve of 0.810 with a sensitivity of 75.0% and specificity of 87.1% at the cut-off value of 315 (p < 0.001). TIGER score ≥ 315 was an independent risk factor with the highest odds ratio for the need for IPAA and associated with the shortest IPAA-free survival time compared with UCEIS and MES. CONCLUSION: TIGER score was superior to UCEIS and MES in predicting the need for IPAA. For colorectal surgeons, three or more segments with moderate-to-severe endoscopic activity should be considered as a threshold value for decision-making for IPAA.

Intraoperative crystalloid-colloid infusion ratio associated with the development of early surgical complications after ileal pouch-anal anastomosis in ulcerative colitis: a multicenter long-term follow-up study.

BACKGROUND: Intraoperative intravenous fluid administration proves to be associated with surgical patients' postoperative outcomes. Few studies reported the relationship between intraoperative crystalloid-colloid infusion ratio and early surgical complications after ileal pouch-anal anastomosis (IPAA) in ulcerative colitis (UC). METHODS: Data on patients with underwent IPAA from January 2008 to March 2022 at our three inflammatory bowel disease (IBD) surgery centers were retrospectively collected. Intraoperative anesthetic data were recorded and later evaluated by our team anesthesiologist. RESULTS: A total of 140 eligible patients with a median follow-up time of 6.0 years [interquartile range (IQR): 2.0-8.0] were enrolled. Among all enrolled patients, 34 (24.3%) developed early surgical complications after IPAA. Greater blood loss and lower crystalloid-colloid infusion ratio were observed in patients with early surgical complications. Crystalloid-colloid infusion ratio < 2 and blood loss ≥ 200 ml had the most significant area under the receiver-operating characteristic curve (AUC) of 0.664 and 0.674 in predicting early surgical complications. Crystalloid-colloid infusion ratio < 2 [odds ratio (OR), 2.571; 95% confidence intervals (CI), 1.067-6.195, p = 0.035] and blood loss ≥ 200 ml (OR, 3.165; 95% CI, 1.288-7.777, p = 0.012) were independent risk factors for the development of early post-IPAA complications. CONCLUSION: Intraoperative crystalloid-colloid infusion ratio < 2 and blood loss volume over 200 ml during IPAA contribute to the occurrence of early surgical complications. Early attentions and necessary interventions are warranted to avoid these risk factors during the IPAA surgery in order to prevent the development of early surgical complications.

Risk Factors and Quality of Life in Patients with Diffuse Pouchitis After Ileal Pouch Anal Anastomosis According to the Chicago Classification for J Pouch: a Retrospective Multicenter Cohort Study in China.

BACKGROUND: Pouchitis is a common late complication in patients with ulcerative colitis (UC) who undergo ileal pouch-anal anastomosis (IPAA). The heterogeneous nature of the clinical and endoscopic presentations could affect the evaluation of therapeutic interventions for pouchitis. Thus, identifying the risk factors and clinical outcomes of pouch inflammation at different sites and severity is becoming increasingly important for colorectal surgeons. METHODS: Data on patients who underwent IPAA January from 2008 to June 2022 in our three pouch centers affiliated with the China UC Pouch Center Union were retrospectively collected. Pouchitis was categorized as a different phenotype according to the Chicago Classification. J pouches were classified into short (14 ± 2 cm) and long pouches (22 ± 2 cm) according to the distribution of ileal pouch length in our institute. RESULTS: Altogether, 143 patients with a median follow-up time of 5.0 years (interquartile range: 2.0-8.0) were enrolled. Among them, 41 patients (28.7%) developed pouchitis and 32 patients (78%) had diffuse inflammation of the pouch. Patients with diffuse pouchitis had a higher pouchitis disease activity index and more seriously impaired improvement of long-term quality of life than those with pouch phenotypes. A short J pouch, recurrent UC, and preoperative high white blood cell count were independent risk factors for diffuse pouchitis. Furthermore, a short J pouch could effectively predict the occurrence of diffuse pouchitis with an area under the receiver-operating characteristic curve of 0.614, a sensitivity of 62.5%, and a specificity of 60.4% (p = 0.049) and significantly decreased the overall diffuse pouchitis-free survival compared to a long J pouch (p = 0.0002). CONCLUSION: Diffuse pouchitis is a common phenotype of pouchitis that seriously impairs long-term prognosis. For colorectal surgeons, decision-making regarding pouch construction with an appropriate length should be considered to prevent the development of diffuse pouchitis.