This study aimed to investigate the mechanism of liquiritin (LQ) in the improvement of ventricular remodeling (VR) after acute myocardial infarction (AMI). Molecular docking was used to predict the binding affinity of liquiritin to thioredoxin-interacting protein (TXNIP). After 2 weeks of modeling, the rats were randomly divided into a model group, a low-dose liquiritin group (20 mg/kg LQ), and a high-dose liquiritin group (40 mg/kg LQ). Liquiritin was administered by gavage once a day, and the sham group and model group were given the same volume of 0.5% sodium carboxymethylcellulose (CMC-Na), with intervention of 4 consecutive weeks. Echocardiography was employed to detect the cardiac function, HE staining was used to observe cardiological changes, ELISA was used to detect the activity of serum creatine kinase-MB (CK-MB) activity, and the colorimetric method was adopted to detect serum malondialdehyde (MDA), total superoxide dismutase (T-SOD) and catalase (CAT) activities. RT-qPCR was used to detect the gene expressions of TXNIP, thioredoxin (TRX) and NACHT, LRR, and PYD domains-containing protein 3(NLRP3). Western blot was used to detect the protein expressions of TXNIP, TRX and NLRP3 in rat myocardial tissue. Molecular docking results showed that liquiritin had a good binding affinity to TNXIP target. After 20 and 40 mg/kg liquiritin intervention, the levels of ejection fraction (EF) and fractional shortening (FS) were significantly increased (P<0.01), and the levels of LVIDs, LVIDd, LVESV, and LVEDV were decreased (P<0.01). The myocardial structure was significantly improved, the cell arrangement tended to be regular, and the area of inflammatory cell infiltration and necrosis was reduced. Liquiritin significantly reduced the level of CK-MB (P<0.01), decreased the activity of MDA, and increased the activities of CAT and T-SOD (P<0.01). Liquiritin effectively inhibited the overexpression of TXNIP and NLRP3 genes and proteins, and enhanced the expression of TRX genes and proteins in the myocardial tissues of AMI rats. In conclusion, liquiritin has a regulatory effect on the TXNIP/TRX signaling pathway, inhibits the activation of the NLRP3 inflammasome, and thus improves ventricular remodeling after acute myocardial infarction.

This study aims to establish a method for counting the viral particles in adenovirus vector-based vaccines. Nano-flow cytometry was employed to analyze the viral particles in adenovirus-based vector vaccines at the single-particle level. Monodisperse silica nanoparticles with a refractive index close to that of the virus were selected as the particle size standard to calculate the viral particle size, which was then compared with the results obtained from transmission electron microscopy (TEM) to determine the gating strategy. Subsequently, a particle count standard was employed to calculate the viral particle concentration. The established method demonstrated good linearity, accuracy, precision, and specificity. The results of determined viral particle concentration showed a good correlation with the infectious titer. Compared with the conventional OD₂₆₀ method, nano-flow cytometry can directly measure the viral particle concentration and indicate whether the sample has been disassembled according to changes in viral particle concentration and size, thus more accurately reflecting the actual infectious potency of the sample. The novel quantification method established in this study is capable of indicating the efficacy of adenovirus vector-based vaccines and provides effective technical support for the quality control of such products.
Adenoviridae/genetics* ; Genetic Vectors ; Flow Cytometry/methods* ; Virion/isolation & purification* ; Particle Size ; Nanoparticles ; Viral Vaccines

L-phosphinothricin (L-PPT) is an efficient broad-spectrum herbicide. To realize the multi-enzyme catalytic preparation of L-PPT, we constructed an engineered strain Escherichia coli YM-1 for efficient expression of D-amino acid transaminase, which could catalyze the generation of the intermediate 2-oxo-4-[(hydroxymethylphosphonyl)] butyric acid (PPO) from D-phosphinothricin (D-PPT). In addition, E. coli pLS was constructed to co-express glutamate dehydrogenase and glucose dehydrogenase, which not only catalyzed the generation of L-PPT from PPO but also regenerated the coenzyme nicotinamide adenine dinucleotide phosphate (NADPH). A fed-batch fermentation process was then established for E. coli YM-1 and pLS, and the apparent activities of D-amino acid transaminase and glutamate dehydrogenase were increased by 22.68% and 100.82%, respectively, compared with those in shake flasks. The process parameters were optimized for the catalytic preparation of L-PPT by whole-cell cascade of E. coli YM-1 and pLS with D, L-PPT as the substrate. After reaction for 8 h, 91.36% conversion of D-PPT was achieved, and the enantiomeric excess of L-PPT reached 90.22%. The findings underpin the industrial production of L-PPT.
Escherichia coli/enzymology* ; Aminobutyrates/metabolism* ; Glutamate Dehydrogenase/biosynthesis* ; Glucose 1-Dehydrogenase/biosynthesis* ; Herbicides/metabolism* ; Multienzyme Complexes/metabolism* ; Transaminases/metabolism* ; Phosphinic Acids/metabolism*

Objective:To determine the actual metastasis rate of paracolic lymph nodes (PCN) more than 10 cm proximal to rectal tumors and explore the significance of PCN dissection in the prognosis of patients with rectal cancer. ?Methods:This was a prospective observational cohort study. The clinical data of 457 consecutive patients with rectal cancer who underwent radical surgery at the Colorectal Tumor Center of West China Hospital, Sichuan University from January 2015 to May 2022 were included. Inclusion criteria: (1) Pathologically confirmed rectal adenocarcinoma (anal margin ≤ 12 cm); (2) R0 resection was performed with a proximal margin ≥ 10 cm (measured on the in vivo specimen during surgery after intestinal mobilization); (3) For stage IV patients, only those with resectable metastatic lesions by R0 were included; (4) Patients who completed the full course of neoadjuvant therapy (TNT) must meet the surgical window of 8-12 weeks after radiotherapy. Exclusion criteria: tumors located more than 15 cm from the anal margin, synchronous multiple primary colorectal cancers, positive tumor margins, preoperative imaging suggesting lateral lymph node metastasis (LLNM), presence of Lynch syndrome or familial adenomatous polyposis, emergency surgery, recurrence after rectal cancer surgery, T4b tumors requiring combined organ resection, previous radiotherapy and chemotherapy for non-rectal cancer, and those with cardiac, pulmonary, renal and other organ dysfunction that could not tolerate surgery. After standard total mesorectal excision (TME), the proximal intestinal tube was transected at a level more than 10 cm above the lesion, and then intestinal anastomosis or enterostomy was completed. The distance from the tumor edge was marked and measured in vivo during the operation, and lymph nodes were harvested from the fresh specimen. Patients with PCN metastasis beyond 10 cm proximal to the tumor were classified into the positive lymph node group (pPCN group), while those without PCN metastasis beyond 10 cm proximal to the tumor were classified into the negative lymph node group (nPCN group). The differences in clinicopathological characteristics, overall survival (OS) and disease-free survival (DFS) between the two groups were compared, and risk factor analysis and survival analysis of pPCN were performed.Results:There were 16 cases (3.5%) in the pPCN group, 15 cases (3.3%) had central lymph node metastasis; the nPCN group included 441 cases. When comparing the baseline characteristics between the pPCN group and the nPCN group, there was no statistically significant difference in other aspects except that the cN stage was more advanced in the pPCN group ( P=0.006) (all P>0.05). The number of positive mesenteric lymph nodes in the pPCN group was higher than that in the nPCN group ( P<0.001), and the proportion of patients with a total number of harvested lymph nodes ≥12 and the number of lymph nodes with a short diameter >5 mm were both higher (all P<0.05). The proportion of patients with positive lymph nodes within 10 cm and the number of positive lymph nodes within 10 cm were also higher in the pPCN group (both P<0.001). Similar to the clinical TNM staging, the proportions of patients with pT3 and N2 stages, as well as the incidence of poorly differentiated tumors (G3, G4) were higher in the pPCN group ( P<0.001). The results of multivariate analysis showed that among the preoperative pathological characteristic variables, the presence of positive lymph nodes within 10 cm (OR=14.869, 95%CI: 2.993-73.858, P=0.001) and low tumor differentiation grade (OR=7.189, 95%CI: 2.091- 24.714, P=0.002) were independent risk factors for pPCN. The median follow-up time of the patients in this group was 63 (0-63) months. No local recurrence occurred in the pPCN group, and the 5-year OS was 50.0%, which was significantly lower than 78.0% in the nPCN group (HR=2.496, 95%CI: 1.263-4.930, P=0.008). The 3-year DFS was 43.8%, also significantly lower than 77.7% in the nPCN group (HR=2.950, 95%CI:1.488-5.846, P=0.002). Multivariate Cox prognostic analysis suggested that age ≥65 years (HR=2.041, 95%CI: 1.375-3.031, P<0.001), female (HR=1.838, 95%CI: 1.171-2.884, P=0.008), tumor length ≥3 cm (HR=1.747, 95%CI: 1.076-2.834, P=0.024), more advanced cT stage (HR=2.865, 95%CI: 1.234-6.653, P=0.014), and cM1 (HR=4.368, 95%CI: 2.480-7.694, P<0.001) were independent risk factors affecting OS. No neoadjuvant therapy (HR=0.636, 95%CI: 0.413-0.980, P=0.040) and cM1 (HR=5.556, 95%CI: 3.335-9.256, P<0.001) were independent risk factors affecting DFS. pPCN showed a tendency to be an independent risk factor for DFS (HR=1.942, 95%CI: 0.966-3.906, P=0.063). Conclusion:The incidence of pPCN is higher than expected, and the prognosis of patients is poor. Patients with high-risk factors may benefit from extended proximal intestinal resection (>10 cm) to avoid residual positive PCN, thereby reducing local recurrence.

The objective of this experiment was to investigate the inhibitory effect and mechanism of mammary-derived extracellular vesicles(MmEVs)from mastitis dairy cows on the biofilm for-mation of Staphylococcus aureus SA1.The biofilm-forming ability of Staphylococcus aureus SA1 was confirmed using Congo red staining,and the biofilm growth curve of S.aureus SA1 was plot-ted using the crystal violet staining method.The minimum inhibitory concentration(MIC)and minimum biofilm inhibitory concentration(MBIC)of MmEVs against S.aureus SA1 were deter-mined.After treating S.aureus SA1 with different concentrations of MmEVs,the cell morphology of S.aureus SA1 was observed using transmission electron microscopy.The effects of MmEVs on S.aureus SA1 under low pH(pH value=5)or heat stress(58℃)were investigated.The hydro-phobicity index was explored using the microbial adhesion to hydrocarbons(MATH)assay.Bacte-rial conductivity was measured.The expression levels of biofilm-related genes(SarA,icaB,FnbA,ClfB,CidA,and gyrB)were detected using quantitative real-time PCR(qPCR).The results showed that MIC of MmEVs against the biofilm of S.aureus SA1 was 1 000 mg/L,and the MBIC was 500 mg/L.Under the influence of MmEVs,the internal substances of S.aureus SA1 leaked,the biofilm boundary became blurred,and the cell wall separated.At the MBIC concentration,MmEVs significantly reduced the tolerance of S.aureus SA1 to low pH(P＜0.001)and high tem-perature(P＜0.001),decreased hydrophobicity(P＜0.001),and increased bacterial conductivity(P＜0.001).At the MBIC concentration,MmEVs significantly downregulated the gene expression of Sa rA(P＜0.001),icaB(P＜0.001),FnbA(P＜0.001),ClfB(P＜0.001),and CidA(P＜0.001)in S.aureus SA1,while no significant effect was observed on the expression of the gyrB gene.In summary,MmEVs inhibit the formation of Staphylococcus aureus SA1 biofilms by sup-pressing the gene expression of SarA,icaB,FnbA,ClfB,and CidA within the biofilm.This dis-ruption damages the biofilm's morphological structure,reduces its tolerance to low pH and high temperature,decreases hydrophobicity,and increases bacterial conductivity,thereby ultimately in-hibiting the formation of S.aureus SA1 biofilms.

Malignant intestinal obstruction is one of the common clinical symptoms of peritoneal metastasis of colorectal cancer, and its pathophysiological mechanism involves various factors such as local invasion and compression of tumors, intestinal adhesions caused by the formation of scattered nodules in the abdominal cavity, inflammatory response in the abdominal cavity, and neuromodulation disorders. Patients with traditional intestinal obstruction are generally treated with surgery, but patients with malignant intestinal obstruction associated with peritoneal metastasis of colorectal cancer can present with multi-level obstruction, complex and diverse symptoms. Combined with multiple metastases in the abdominal cavity and even accompanied by cachexia, malignant intestinal obstruction as a major treatment problem in the field of colorectal surgery is often difficult to be treated by surgery. What's more, it is worth noting that new progress and breakthroughs have been made in the diagnosis and treatment of peritoneal metastasis of colorectal cancer, and the treatment of cancerous intestinal obstruction has also begun to receive extensive attention. Therefore, this article summarizes the clinical features of peritoneal metastasis-related malignant intestinal obstruction in colorectal cancer and looks forward to its treatment challenges.

Iron,a vital trace element and redox-active metal in the human body,is pivotal in cellular processes and en-gages in a multitude of biological reactions.Ferroptosis,an emerging form of regulated cell death,is predominantly instiga-ted by the excessive free iron that catalyzes reactive oxygen species(ROS)production via the Fenton reaction.This process results in the peroxidation of polyunsaturated fatty acids within the cellular lipid membrane,compromising the membrane's integrity and thereby inducing ferroptosis.In the context of diabetic retinopathy(DR),ferroptosis plays a sig-nificant role.The disruption of iron metabolism,the excessive accumulation of ROS,and the imbalance of the antioxidant system are key mechanisms contributing to ferroptosis in retinal tissues and the exacerbation of DR's pathological progres-sion.This review provides a systematic summary and in-depth discussion of the advancements in understanding the role of ferroptosis in DR pathogenesis,intending to offer valuable insights for future research endeavors in this field.

Microbial-derived metabolites are important mediators of host-microbial interactions. In recent years, the role of intestinal microbial metabolites in colorectal cancer has attracted considerable attention. These metabolites, which can be derived from bacterial metabolism of dietary substrates, modification of host molecules such as bile acids, or directly from bacteria, strongly influence the progression of colitis-associated cancer (CAC) by regulating inflammation and immune response. Here, we review how microbiome metabolites short-chain fatty acids (SCFAs), secondary bile acids, polyamines, microbial tryptophan metabolites, and polyphenols are involved in the tumorigenesis and development of CAC through inflammation and immunity. Given the heated debate on the metabolites of microbiota in maintaining gut homeostasis, serving as tumor molecular markers, and affecting the efficacy of immune checkpoint inhibitors in recent years, strategies for the prevention and treatment of CAC by targeting intestinal microbial metabolites are also discussed in this review.
Humans ; Gastrointestinal Microbiome/physiology* ; Animals ; Carcinogenesis/metabolism* ; Colitis-Associated Neoplasms/microbiology* ; Fatty Acids, Volatile/metabolism* ; Bile Acids and Salts/metabolism* ; Colitis/microbiology*

To achieve efficient and rapid detection of duck astrovirus type 2(DAstV-2),RPA prim-ers and crRNA were designed and synthesized based on the conserved sequence of the ORF2 gene of DAstV-2.A detection method for DAstV-2 was constructed,integrating RPA nucleic acid ampli-fication,LwCas13a cleavage,and colloidal gold lateral flow dipstick visualization.The specificity,sensitivity,and concordance of this detection method were evaluated.The experimental results showed that the detection limit for the DAstV-2 recombinant plasmid standard was 1.2×101 cop-ies/μL,which is superior to the conventional RT-PCR method.The method can specifically detect DAstV-2 pathogenic nucleic acids without cross-reactivity with DAstV-1,DAstV-3,DAstV-4,duck plague virus(DEV),and duck tembusu virus(DTMUV).When testing liver tissue samples from ducks suspected of being infected with DAstV-2,the results obtained using this method were com-pletely consistent with those from real-time quantitative PCR,with a 100％concordance rate.How-ever,this method is simpler and faster to perform.The research indicates that the established RPA-CRISPR/Cas13a-LFD detection system has high sensitivity,strong specificity,and high accuracy,capable of completing rapid visual detection of DAstV-2 nucleic acids within 1 h at a constant tem-perature of 37 ℃,providing a new technical platform for the rapid diagnosis of DAstV-2.

Objective To systematically evaluate the efficacy and safety of proximal gastrectomy (PG) versus total gastrectomy (TG) for the treatment of Siewert type Ⅱ/Ⅲ adenocarcinoma of the esophagogastric junction (AEG). Methods PubMed, The Cochrane Library, Web of Science, EMbase, CNKI, Wanfang, and VIP databases were searched for literature comparing the efficacy and safety of PG and TG for the treatment of Siewert type Ⅱ/Ⅲ AEG. The search period was from database inception to March 2023. Meta-analysis was performed using Review Manager 5.4 software. Results A total of 23 articles were included, including 16 retrospective cohort studies, 5 prospective cohort studies, and 2 randomized controlled trials. The total sample size was 2 826 patients, with 1 389 patients undergoing PG and 1 437 patients undergoing TG. Meta-analysis results showed that compared with TG, PG had less intraoperative blood loss [MD=−19.85, 95%CI (−37.20, −2.51), P=0.02] and shorter postoperative hospital stay [MD=−1.23, 95%CI (−2.38, −0.08), P=0.04]. TG had a greater number of lymph nodes dissected [MD=−6.20, 95%CI (−7.68, −4.71), P<0.001] and a lower incidence of reflux esophagitis [MD=3.02, 95%CI (1.24, 7.34), P=0.01]. There were no statistically significant differences between the two surgical approaches in terms of operative time, postoperative survival rate (1-year, 3-year, 5-year), and postoperative overall complications (P>0.05). Conclusion PG has advantages in terms of intraoperative blood loss and postoperative hospital stay, while TG has advantages in terms of the number of lymph nodes dissected and the incidence of reflux esophagitis. There is no significant difference in long-term survival between the two surgical approaches.