A chitosan-based near-infrared ratiometric fluorescent nanoprobe created by molecular assembly with applications in hypochlorous acid detection in live mouse.

Hypochlorous acid (HClO/ClO-) is a key reactive oxidative species (ROS) in the body. The HClO/ClO- concentrations are imbalanced during cancer formation due to the ROS stress response. This paper introduces a novel chitosan-based self-calibration fluorescent nanoprobe (ChCyNil) constructed by molecular assembly for the ratiometric detection of HClO/ClO-. Two chromophores with different fluorescence characteristics and HClO/ClO- sensitivity were labeled on chitosan, and nanoparticles were prepared by a self-assembly strategy for HClO/ClO- detection. ChCyNil exhibits several advantages, such as dual near-infrared emissions at 670 nm and 845 nm, tunable fluorescence intensity, self-calibration fluorescence, and good biocompatibility, improving its accuracy in HClO/ClO- detection. Our study confirmed that ChCyNil exhibits a well-assembled spheroidal nanostructure and good photophysical properties in solution. The fluorescence imaging properties were further proved by detecting endogenous HClO/ClO- produced by LPS/PMA stimuli in cells and zebrafish. In addition, ChCyNil was used to detect the fluorescence behavior of HClO/ClO- in tumors of live mice. The successful design and fabrication of ChCyNil have presented a new strategy for constructing detection tools with improved fluorescence properties for HClO/ClO- in live animals.

The integrated molecular and histological analysis defines subtypes of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is highly heterogeneous. Our understanding of full molecular and immune landscape of ESCC remains limited, hindering the development of personalised therapeutic strategies. To address this, we perform genomic-transcriptomic characterizations and AI-aided histopathological image analysis of 120 Chinese ESCC patients. Here we show that ESCC can be categorized into differentiated, metabolic, immunogenic and stemness subtypes based on bulk and single-cell RNA-seq, each exhibiting specific molecular and histopathological features based on an amalgamated deep-learning model. The stemness subgroup with signature genes, such as WFDC2, SFRP1, LGR6 and VWA2, has the poorest prognosis and is associated with downregulated immune activities, a high frequency of EP300 mutation/activation, functional mutation enrichment in Wnt signalling and the highest level of intratumoural heterogeneity. The immune profiling by transcriptomics and immunohistochemistry reveals ESCC cells overexpress natural killer cell markers XCL1 and CD160 as immune evasion. Strikingly, XCL1 expression also affects the sensitivity of ESCC cells to common chemotherapy drugs. This study opens avenues for ESCC treatment and provides a valuable public resource to better understand ESCC.

[Effects of Different Nitrogen Application Measures on N2O Emissions in Wheat-maize Rotation System].

To investigate the response of N2O emissions from farmland soil to different nitrogen application measures and the factors affecting it in the wheat and jade rotation system in North China, we analyzed the results of the one-time application of fertilizer in the following six treatments： without fertilization （CK）, conventional nitrogen application （urea, one instance of follow-up fertilization, U1）, optimized nitrogen application （20% nitrogen reduction, one instance of follow-up fertilization, U2）, one-time fertilization of controlled-release doped fertilizers （50% urea + controlled-release urea 50%, nitrogen reduction 20%, SRU1）, controlled-release fertilizer one-time fertilization （nitrogen reduction 20%, SRU2）, and inhibitor-type controlled-release fertilizer one-time fertilization （nitrogen reduction 20%, ISRU）, and the differences in N2O emission fluxes and soil physicochemical properties were determined. The results showed that soil N2O emission fluxes were dynamic during the wheat and jade crop rotation, and the N2O emission peaks of the CK, U1, and U2 treatments appeared in the corn season at 4-7d of basal fertilizer and 6-10d of fertilizer, and out of the wheat season its emission peaks appeared in the basal fertilizer at 4-8 d and 6-9 d of fertilizer. The emission peaks of SRU1, SRU2, and ISRU appeared in the basal fertilizer at 10-21 d, 12-20 d, and 12-20 d of fertilizer, respectively, in the corn season and the wheat season. At 21 d and 12-20 d, the application of controlled-release fertilizer significantly reduced the peak and frequency of N2O emission. Compared with those in U1, the N2O emission fluxes of the U2, SRU1, SRU2, and ISRU treatments were significantly reduced by 8.5%, 20.0%, 33.8%, and 43.6%, respectively, and the N2O emission fluxes were higher in the corn season than in the wheat season, which accounted for 58.1%-65.1% of the whole crop rotation cycle. Yield was reduced by 5.9% and 1.9% for the U2 and SRU1 treatments and increased by 1.7% and 7.0% for the SRU2 and ISRU treatments, respectively, compared to that in U1. In the maize season, the ISRU yield increased by 14.6%, the environmental benefit was $581, and the net economic benefit increased by up to 18.6% compared to that in U1, whereas the wheat season showed a decrease in yield and net economic benefit, which resulted in a one-time application of the inhibitor controlled-release fertilizers being more suitable for the maize season. Correlation analysis of N2O emission fluxes with the physicochemical indices of soil properties revealed that N2O was correlated with moisture, ammonium N, nitrate N, and microbial carbon and nitrate N and nitrogen. N2O and moisture, ammonium N, nitrate N, and microbial amount of carbon and nitrogen were significantly positively correlated. Thus, the one-time application of inhibitor-type controlled-release fertilizers played a positive role in reducing labor inputs and environmental benefits, and it could be an effective method of N fertilizer management for maize cultivation in North China.

Embryo retention and live birth in frozen embryo transfer cycles: a cohort study.

OBJECTIVE: To study the effect of embryo retention in the transfer catheter on pregnancy outcomes in frozen embryo transfer (FET) cycles. DESIGN: Retrospective cohort study. SETTING: Tertiary-care academic medical center. PATIENT(S): This retrospective study involved a total of 39,118 women who underwent FET cycles at a tertiary-care academic medical from January 2016 to December 2022. INTERVENTION(S): Women were divided into a control group (n = 38,933) and embryo retention group (n = 185). The women in the embryo retention group had been propensity scores matched with those in the control group at a 1:4 ratio. MAIN OUTCOME MEASURE(S): The primary outcome was live birth (LB). The secondary outcomes were biochemical pregnancy, clinical pregnancy (CP), miscarriage, and ectopic pregnancy. RESULT(S): The overall incidence of embryo retention in the transfer catheter was 0.47% (185/39,118). The pregnancy outcome in the embryo retention group after propensity score matching (PSM) was comparable to that before PSM, with a reduced likelihood of biochemical pregnancy (odds ratio [OR], 0.83; 95% confidence interval [CI], 0.72-0.95), CP (OR, 0.81; 95% CI, 0.69-0.96), and LB (OR, 0.80; 95% CI, 0.66-0.97). In addition, the birth weight in the embryo retention group was higher compared with the control group. However, no differences were observed in terms of miscarriage, ectopic pregnancy, cesarean delivery, as well as gestational age both before and after PSM. CONCLUSION(S): Embryo retention in the transfer catheter decreases the chance of biochemical pregnancy, CP, and LB in FET cycles.

Fatal multiple acyl-CoA dehydrogenase deficiency caused by ETFDH gene mutation: A case report.

BACKGROUND: Multiple acyl-CoA dehydrogenase deficiency (MADD) is a disease of rare autosomal recessive disorder. There are three types of MADD. Type I is a neonatal-onset form with congenital anomalies. Type II is a neonatal-onset form without congenital anomalies. Type III is considered to a milder form and usually responds to riboflavin. However, late-onset form could also be fatal and not responsive to treatments. CASE SUMMARY: We report a severe case of a young man with onset type III MADD induced by drugs and strenuous exercise characterized by rhabdomyolysis and liver dysfunction. Urine analysis indicated 12 out of 70 kinds of organic acids like glutaric acid-2 were detected. Serum analysis in genetic metabolic diseases revealed 24 out of 43 tested items were abnormal, revealing the elevation of several acylcarnitines and the reduction of carnitine in the patient. By next generation sequencing technology for gene sequencing related to fatty acid oxidation and carnitine cycle defects, a rare ETFDH gene variant was identified: NM_004453:4:C.1448C>T(p.Pro483 Leu). The patient was diagnosed with late-onset GAII. He was not responsive to riboflavin and progressively worsened into multiple organ failure that finally led to death. CONCLUSION: Type III MADD can also be fatal and not responsive to treatments.

Ferroptosis-related gene signature and clinical prognostic factors as prognostic marker for colon adenocarcinoma.

Aim: To build a ferroptosis-related prognostic model for patients with colon adenocarcinoma (COAD). Methods: COAD expression profiles from The Cancer Genome Atlas were used as the training set and GSE39582 from Gene Expression Omnibus as the validation set. Differentially expressed ferroptosis-related genes between patients with COAD and normal controls were screened, followed by tumor subtype exploration based on ferroptosis-related gene expression levels. A ferroptosis score (FS) model was constructed using least absolute shrinkage and selection operator penalized Cox analysis. Based on FS, patients were subgrouped into high- and low-risk subgroups and overall survival was predicted. The potential prognostic value of the FS model and the clinical characteristics were investigated using receiver operating characteristic curves. Results: Twenty-four differentially expressed ferroptosis-related genes were identified, four of which (CYBB, PRNP, ACSL4, and ACSL6) were included in the prognostic signature. Moreover, age, pathological T stage, and tumor recurrence were independent prognostic factors for COAD. The FS model combined with three independent prognostic factors showed the best prognostic value (The Cancer Genome Atlas: area under the curve = 0.897; GSE39582: area under the curve = 0.858). Conclusion: The novel prognostic model for patients with COAD constructed by pairing the FS model with three important independent prognostic factors showed promising clinical predictive value.

Revealing the role of metformin in gastric intestinal metaplasia treatment.

Objective: Gastric intestinal metaplasia (IM) is a precancerous stage associated with gastric cancer. Despite the observed beneficial effects of metformin on IM, its molecular mechanism remains not fully elucidated. This study aims to reveal the effects and potential mechanisms of metformin in treating IM based on both bioinformatics and in vivo investigations. Methods: The seven public databases (GeneCards, DisGeNET, OMIM, SuperPred, Pharm Mapper, Swiss Target Prediction, TargetNet) were used in this work to identify targeted genes related to intestinal metaplasia (IM) and metformin. The shared targeted genes between metformin and IM were further analyzed by network pharmacology, while the interactions in-between were investigated by molecular docking. In parallel, the therapeutic effect of metformin was evaluated in IM mice model, while the core targets and pathways effected by metformin were verified in vivo. Results: We screened out 1,751 IM-related genes and 318 metformin-targeted genes, 99 common genes identified in between were visualized by constructing the protein-protein interaction (PPI) network. The top ten core targeted genes were EGFR, MMP9, HIF1A, HSP90AA1, SIRT1, IL2, MAPK8, STAT1, PIK3CA, and ICAM1. The functional enrichment analysis confirmed that carcinogenesis and HIF-1 signaling pathways were primarily involved in the metformin treatment of IM. Based on molecular docking and dynamics, we found metformin affected the function of its targets by inhibiting receptor binding. Furthermore, metformin administration reduced the progression of IM lesions in Atp4a-/- mice model significantly. Notably, metformin enhanced the expression level of MUC5AC, while inhibited the expression level of CDX2. Our results also showed that metformin modulated the expression of core targets in vivo by reducing the activity of NF-κB and the PI3K/AKT/mTOR/HIF-1α signaling pathway. Conclusion: This study confirms that metformin improves the efficacy of IM treatment by regulating a complex molecular network. Metformin plays a functional role in inhibiting inflammation/apoptosis-related pathways of further IM progression. Our work provides a molecular foundation for understanding metformin and other guanidine medicines in IM treatment.

Effect of Oridonin on Experimental Animal Model of Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is a serious disease that occurs in premature and low-birth-weight infants. In recent years, the incidence of BPD has not decreased, and there is no effective treatment for it. Oridonin (Ori) is a traditional Chinese medicine with a wide range of biological activities, especially pharmacological and anti-inflammatory. It is well known that inflammation plays a key role in BPD. However, the therapeutic effect of Ori on BPD has not been studied. Therefore, in the present study, we will observe the anti-inflammatory activity of Ori in an experimental animal model of BPD. Here, we showed that Ori could significantly decrease hyperoxia-induced alveolar injury, inhibit neutrophil recruitment, myeloperoxidase concentrations, and release inflammatory factors in BPD neonatal rats. Taken together, the experimental results suggested that Ori can significantly improve BPD in neonatal rats by inhibiting inflammatory response.

Impact of inclusion of a poor-quality embryo with a good-quality embryo on pregnancy outcomes in vitrified-warmed blastocyst transfers.

RESEARCH QUESTION: Does the co-transfer of a good-quality embryo and a poor-quality embryo influence pregnancy outcomes in comparison to the transfer of a single good-quality embryo in vitrified-warmed blastocyst transfer cycles? DESIGN: This retrospective cohort study involved a total of 11,738 women who underwent IVF/intracytoplasmic sperm injection cycles and vitrified-warmed blastocyst transfer at a tertiary-care academic medical from January 2015 to June 2022. The study population was categorized into two groups: single-blastocyst transfer (SBT; participants who underwent single good-quality embryo transfer, n = 9338) versus double-blastocyst transfer (DBT; participants who underwent transfers with a poor and a good-quality embryo, n = 2400). RESULTS: The live birth rate (LBR) was significantly higher in the DBT group in comparison with the SBT group (65.6% versus 56.3%, P < 0.001). Multivariable logistic regression analysis showed that DBT was an independent predictor for LBR with a strong potential impact (adjusted odds ratio 1.55, 95% confidence interval 1.41-1.71; P < 0.001). However, the multiple birth rate was significantly higher in the good-quality embryo and poor-quality embryo group compared with patients undergoing a single good-quality embryo transfer (41.4% versus 1.8%; P < 0.001). CONCLUSIONS: In vitrified-warmed blastocyst transfer cycles, LBR was higher following DBT with one good-quality and one poor-quality embryo compared with SBT. However, this was at the expense of a marked increase in the likelihood of multiple gestations. Physicians should still balance the benefits and risks of double-embryo transfer.

Study on the Effect of Precise Prevention of H-Type Hypertension, Cardiovascular, and Cerebrovascular Risks in Qingyuan District.

Objective: To explore the relationship between controlling the development of H-type hypertension and the effectiveness of precision prevention of cardiovascular risk. Methods: 518 patients with essential hypertension with hyperhomocysteinemia diagnosed in December 2019 to February 2020 in Qingyuan District Public Hospital were recruited as the experimental sample for prospective analysis and were equally divided into control and experimental groups according to their order of admission, i.e., 259 patients in each group. The control group was treated with antihypertensive drugs only, while the experimental group was given enalapril folic acid tablets (0.8 mg/d) and vitamin B once daily in addition to antihypertensive drugs, and then monitored for plasma Hcy levels, cardiovascular event rates, and survival at one year. Results: After treatment, the plasma Hcy levels of the experimental group were significantly lower than those of the control group (P < .001). During treatment, the total incidence of cardiovascular disease in the experimental group was less than that in the control group (P < .05). One year after the end of treatment, the mortality rate due to cardiovascular disease in the control group was higher than that in the experimental group (P < .05). Conclusion: It is worthwhile to promote the use of targeted management of patients with H-type hypertension to prevent the occurrence of cardiovascular diseases, improve Hcy levels, and stabilize blood pressure levels in patients.

miR-493-5p Silenced by DNA Methylation Promotes Angiogenesis via Exosomes and VEGF-A-Mediated Intracellular Cross-Talk Between ESCC Cells and HUVECs.

Background: Exosomal microRNAs (miRNAs) in the tumor microenvironment play crucial roles in tumorigenesis and tumor progression by participating in intercellular cross-talk. However, the functions of exosomal miRNAs and the mechanisms by which they regulate esophageal squamous cell carcinoma (ESCC) progression are unclear. Methods: RNA sequencing and GEO analysis were conducted to identify candidate exosomal miRNAs involved in ESCC development. Receiver operating characteristic curve analysis was performed to assess the diagnostic value of plasma exosomal miR-493-5p. EdU, tube formation and Transwell assays were used to investigate the effects of exosomal miR-493-5p on human umbilical vein endothelial cells (HUVECs). A subcutaneous xenograft model was used to evaluate the antitumor effects of miR-493-5p and decitabine (a DNA methyltransferase inhibitor). The relationship between miR-493-5p and SP1/SP3 was revealed via a dual-luciferase reporter assay. A series of rescue assays were subsequently performed to investigate whether SP1/SP3 participate in exosomal miR-493-5p-mediated ESCC angiogenesis. Results: We found that miR-493-5p expression was notably reduced in the plasma exosomes of ESCC patients, which showed the high potential value in early ESCC diagnosis. Additionally, miR-493-5p, as a candidate tumor suppressor, inhibited the proliferation, migration and tube formation of HUVECs by suppressing the expression of VEGFA and exerted its angiostatic effect via exosomes. Moreover, we found that SP1/SP3 are direct targets of miR-493-5p and that re-expression of SP1/SP3 could reverse the inhibitory effects of miR-493-5p. Further investigation revealed that miR-493-5p expression could be regulated by DNA methyltransferase 3A (DNMT3A) and DNMT3B, and either miR-493-5p overexpression or restoration of miR-493-5p expression with decitabine increased the antitumor effects of bevacizumab. Conclusion: Exosomal miR-493-5p is a highly valuable ESCC diagnosis marker and inhibits ESCC-associated angiogenesis. miR-493-5p can be silenced via DNA methylation, and restoration of miR-493-5p expression with decitabine increases the antitumor effects of bevacizumab, suggesting its potential as a therapeutic target for ESCC treatment.

Clostridium butyricum regulates intestinal barrier function via trek1 to improve behavioral abnormalities in mice with autism spectrum disorder.

BACKGROUND: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder that has been found to be associated with dysregulation of gastrointestinal functions and gut microbial homeostasis (the so-called "gut-brain axis"). ASD is often accompanied by poor performances in social interaction and repetitive behaviors. Studies on the gut-brain axis provide novel insights and candidate targets for ASD therapeutics and diagnosis. Based on the ASD mice model, this work aims to reveal the mechanisms behind the interaction of intestinal barrier function and probiotics in ASD mouse models. RESULTS: We found an altered intestinal barrier in both BTBR T+ Itpr3tf/J (BTBR) and valproic acid (VPA) mice, including increased intestinal permeability, decreased expression of intestinal tight junction proteins (claudin1, claudin3, and occludin), and increased levels of IL-6, TNF-α, and IFN-γ. Based on intestinal microbial alternation, C. butyricum can drive reduced expression of histone deacetylases 1 (HDAC1) and enhanced intestinal barrier function, significantly promoting behavioral abnormalities of ASD in BTBR mice. In parallel, we confirmed that C. butyricum was involved in the regulation of intestinal function by the Trek1 channel, indicating that it is a target of C. butyricum/butyric acid to improve intestinal barrier function in ASD mice. CONCLUSIONS: Our finding provides solid evidence for the gut microbiota involved in ASD through the brain-gut axis. In addition, the probiotics C. butyricum hold promise to improve gut health and ameliorate behavioral abnormalities associated with ASD.

Integrative nomogram model based on anoikis-related genes enhances prognostic evaluation in colorectal cancer.

Background: Revealing the role of anoikis resistance plays in CRC is significant for CRC diagnosis and treatment. This study integrated the CRC anoikis-related key genes (CRC-AKGs) and established a novel model for improving the efficiency and accuracy of the prognostic evaluation of CRC. Methods: CRC-ARGs were screened out by performing differential expression and univariate Cox analysis. CRC-AKGs were obtained through the LASSO machine learning algorithm and the LASSO Risk-Score was constructed to build a nomogram clinical prediction model combined with the clinical predictors. In parallel, this work developed a web-based dynamic nomogram to facilitate the generalization and practical application of our model. Results: We identified 10 CRC-AKGs and a risk-related prognostic Risk-Score was calculated. Multivariate COX regression analysis indicated that the Risk-Score, TNM stage, and age were independent risk factors that significantly associated with the CRC prognosis(p < 0.05). A prognostic model was built to predict the outcome with satisfied accuracy (3-year AUC = 0.815) for CRC individuals. The web interactive nomogram (https://yuexiaozhang.shinyapps.io/anoikisCRC/) showed strong generalizability of our model. In parallel, a substantial correlation between tumor microenvironment and Risk-Score was discovered in the present work. Conclusion: This study reveals the potential role of anoikis in CRC and sets new insights into clinical decision-making in colorectal cancer based on both clinical and sequencing data. Also, the interactive tool provides researchers with a user-friendly interface to input relevant clinical variables and obtain personalized risk predictions or prognostic assessments based on our established model.

Site-specific N-glycoproteomic analysis reveals up-regulated fucosylation in seminal plasma of asthenozoospermia.

N-linked glycoproteins are rich in seminal plasma, playing essential roles in supporting sperm function and fertilization process. The alteration of seminal plasma glycans and its correspond glycoproteins may lead to sperm dysfunction and even infertility. In present study, an integrative analysis of glycoproteomic and proteomic was performed to investigate the changes of site-specific glycans and glycoptoteins in seminal plasma of asthenozoospermia. By large scale profiling and quantifying 5,018 intact N-glycopeptides in seminal plasma, we identified 92 intact N-glycopeptides from 34 glycoproteins changed in asthenozoospermia. Especially, fucosylated glycans containing lewis x, lewis y and core fucosylation were significantly up-regulated in asthenozoospermia compared to healthy donors. The up-regulation of fucosylated glycans in seminal plasma may interfere sperm surface compositions and regulation of immune response, which subsequently disrupts sperm function. Three differentiated expression of seminal vesicle-specific glycoproteins (fibronectin, seminogelin-2, and glycodelin) were also detected with fucosylation alteration in seminal plasma of asthenozoospermia. The interpretation of the altered site-specific glycan structures provides data for the diagnosis and etiology analysis of male infertility, as well as providing new insights into the potential therapeutic targets for male infertility.

A comparative study of sampling methods in the detection of esophageal cancer-related microbiota.

Esophageal cancer (EC) is a multifaceted disease. Our understanding of the involvement of esophageal microbiota in its pathogenesis and progression is limited, which is due to the lack of proper endoscopic sampling methods. Hereby, we conducted a comparative analysis of paired samples obtained through endoscopic brushing and cytosponge, aiming at assessing the feasibility of using cytosponge as a minimally invasive sampling way for studying esophageal microbiota. Our findings suggest that cytosponge sampling yielded significantly superior community richness and diversity compared to endoscopic brushing in both controls (non-cancerous) and EC individuals. The analysis of beta-diversity revealed distinct microbial community pattern in the genus diversity between the two sampling methods, underscoring the importance of selecting appropriate sampling methods to effectively characterize the esophageal microbiota. Specifically, Lactococcus and Serratia showed higher abundance in the samples collected by endoscopic brushing, while Alloprevotella and Leptotrichia were more enriched in the samples collected by cytosponge. These differences in dominant microbes were associated with metabolic pathways that particularly were related to host inflammation, such as pyruvate and glucose metabolisms. Notably, the phylogenetic levels of the microbiota indicated varied explanatory power for different detection purposes. This study underscores the substantial impact of sampling method selection on the acquisition of esophageal microbiota associated with the EC development, encompassing considerations of both abundance and diversity. This highlights the significance of selecting an appropriate sampling method for investigating the esophageal microbial status and studying the micro-environment in EC-related individuals. IMPORTANCE: This study addresses a critical issue in esophageal cancer study by comparing two different sampling methods, endoscopic brushing and cytosponge, for investigating the esophageal microbiota. Our work highlights the suitability of the cytosponge technique as a minimally invasive sampling method for studying the esophageal microbiota and emphasizes the importance of selecting an appropriate sampling method to characterize the microbial community. Our findings have significant implications for advancing the understanding of the role of the esophageal microbiota in cancer development and will inform future research and clinical approaches in this field.

Exploring the potential of thiophene derivatives as dual inhibitors of ß-tubulin and Wnt/ß-catenin pathways for gastrointestinal cancers in vitro.

Background: Gastrointestinal cancer poses a considerable global health risk, encompassing a heterogeneous spectrum of malignancies that afflict the gastrointestinal tract. It is significant to develop efficacious therapeutic agents, as they are indispensable for both the treatment and prevention of this formidable disease. Methods: In this study, we synthesized a novel thiophene derivative, designated as compound 1312. An assessment was performed to investigate its anti-proliferative activity in several cancer cell lines (GES-1, EC9706, SGC7901, and HT-29). Furthermore, we performed molecular biology techniques to investigate the inhibitory impact of compound 1312 on gastrointestinal cell lines SGC-7901 and HT-29. Results: Our findings reveal that compound 1312 exhibits significant efficacy in suppressing colony formation of cancer cells. Notably, it triggers cell cycle arrest at the G2/M phase in gastrointestinal cell lines SGC7901 and HT-29. Compound 1312 was confirmed to exert inhibitory effects on cell migration and invasion in SGC7901. Additionally, the compound elicits apoptotic cell death through the activation of the DNA repair enzyme poly (ADP-ribose) polymerase (PARP) and the caspase signaling cascade. Furthermore, in vitro experiments revealed that compound 1312 effectively suppresses both the ß-tubulin cytoskeletal network and the Wnt/ß-catenin signaling pathway. These multifaceted anti-cancer activities highlight the potential of compound 1312 as a promising therapeutic agent for the treatment of gastrointestinal malignancies. Conclusion: This study indicates the promising potential of compound 1312 as a prospective candidate agent for gastrointestinal cancer treatment. Further comprehensive investigations are needed to explore its therapeutic efficacy in greater detail.

Esophageal squamous cell carcinoma metastases to kidney and renal hilar lymph nodes through epithelial-mesenchymal transition: a case report and literature review.

BACKGROUND: Esophageal cancer (EC) metastasized to the kidney is extremely rare clinically. Here, we present a case of metachronous renal metastasis of esophageal squamous cell carcinoma (ESCC) through epithelial-mesenchymal transition (EMT). CASE PRESENTATION: A 60-year-old patient, male, complained of left waist pain for 5 days, 11 months after radical esophagectomy. Laboratory tests revealed haematuria. Both CT and PET-CT scan showed retroperitoneal lymph nodes and left renal masses. Subsequently the patient received a left nephrectomy and lymph nodes resection, and squamous cell carcinoma of kidney and renal hilar lymph nodes was diagnosed, combined with morphology, medical history and immunophenotype, it was presumed to be metastasis of ESCC through the EMT pathway. CONCLUSIONS: The renal metastasis of squamous cell carcinoma should be considered in patients with history of EC, although this is very rare. Histopathological examination combined with immunochemical detection is helpful in differential diagnosis.

Baicalin Prevents Colon Cancer by Suppressing CDKN2A Protein Expression.

OBJECTIVE: To observe the therapeutic effects and underlying mechanism of baicalin against colon cancer. METHODS: The effects of baicalin on the proliferation and growth of colon cancer cells MC38 and CT26. WT were observed and predicted potential molecular targets of baicalin for colon cancer therapy were studied by network pharmacology. Furthermore, molecular docking and drug affinity responsive target stability (DARTS) analysis were performed to confirm the interaction between potential targets and baicalin. Finally, the mechanisms predicted by in silico analyses were experimentally verified in-vitro and in-vivo. RESULTS: Baicalin significantly inhibited proliferation, invasion, migration, and induced apoptosis in MC38 and CT26 cells (all P<0.01). Additionally, baicalin caused cell cycle arrest at the S phase, while the G0/G1 phase was detected in the tiny portion of the cells. Subsequent network pharmacology analysis identified 6 therapeutic targets associated with baicalin, which potentially affect various pathways including 39 biological processes and 99 signaling pathways. In addition, molecular docking and DARTS predicted the potential binding of baicalin with cyclin dependent kinase inhibitor 2A (CDKN2A), protein kinase B (AKT), caspase 3, and mitogen-activated protein kinase (MAPK). In vitro, the expressions of CDKN2A, MAPK, and p-AKT were suppressed by baicalin in MC38 and CT26 cells. In vivo, baicalin significantly reduced the tumor size and weight (all P<0.01) in the colon cancer mouse model via inactivating p-AKT, CDKN2A, cyclin dependent kinase 4, cyclin dependent kinase 2, interleukin-1, tumor necrosis factor α, and activating caspase 3 and mouse double minute 2 homolog signaling (all P<0.05). CONCLUSION: Baicalin suppressed the CDKN2A protein level to prevent colon cancer and could be used as a therapeutic target for colon cancer.

Biodegradation of phenol-contaminated soil and plant growth promotion by Myroides xuanwuensis H13.

Physicochemical methods for remediating phenol-contaminated soils are costly and inefficient, making biodegradation an environmentally friendly alternative approach. This study aims to screen for potential phenol-degrading bacteria and to verify the removal capacities of a selected strain in a bioaugmentation experiment at the greenhouse level using Brassica chinensis L. (Chinese cabbage) as the model plant and phenol-contaminated soil. In parallel, pot experiments were conducted using a collaborative approach based on this model system. We found that Myroides xuanwuensis strain H13 showed a high degradation capability, with a 97.67% efficiency in degrading 100 mg/L phenol. Under shaking flask conditions, H13 facilitated the solubilization of tricalcium phosphate and potassium feldspar powder. Pot experiments suggested a phenol removal percentage of 89.22% and enhanced availability of soil phosphorus and potassium for plants with H13 inoculation. In this case, the abundance of soil microbes and the activity of soil enzymes significantly increased as well. Furthermore, both photosynthesis and the antioxidant system in Chinese cabbage were enhanced following H13 inoculation, resulting in its increased yield and quality. Partial least squares path modeling revealed that H13 can primarily affect plant root growth, with a secondary impact on photosynthesis. These findings highlight the potential of biodegradation from phenol-degrading bacteria as a promising strategy for efficient phenol removal from soil while promoting plant growth and health.IMPORTANCEThis study is significant for environmental remediation and agriculture by its exploration of a more environmentally friendly and cost-effective bio-strategy in treating phenol-contaminated soil. These findings have essential implications for environmental remediation efforts and sustainable agriculture. By utilizing the biodegradation capabilities of Myroides xuanwuensis strain H13, it is possible to remove phenol contaminants from the soil efficiently, reducing their negative effects. Furthermore, the enhanced growth and health of the Chinese cabbage plants indicate the potential of this approach to promote sustainable crop production.

Prenylated indole diketopiperazine alkaloids as phosphatase inhibitors from the marine-derived fungus Talaromyces purpureogenus.

Six previously undescribed prenylated indole diketopiperazine alkaloids, talaromyines A-F (1-6), were isolated from the marine-derived fungus Talaromyces purpureogenus SCSIO 41517. Their structures including absolute configurations were elucidated on the basis of comprehensive spectroscopic data including NMR, HR-ESI-MS, and electronic circular dichroism calculations, together with chemical analysis of hydrolysates. Compounds 1-5 represent the first example of spirocyclic indole diketopiperazines biosynthesized from the condensation of L-tryptophan and L-alanine. Compounds 2 and 4-5 showed selective inhibitory activities against phosphatases TCPTP and MEG2 with IC50 value of 17.9-29.7 µM, respectively. Compounds 4-5 exhibited mild cytotoxic activities against two human cancer cell lines H1975 and HepG-2.