Correlation between abdominal computed tomography signs and postoperative prognosis for patients with colorectal cancer.

BACKGROUND: Patients with different stages of colorectal cancer (CRC) exhibit different abdominal computed tomography (CT) signs. Therefore, the influence of CT signs on CRC prognosis must be determined. AIM: To observe abdominal CT signs in patients with CRC and analyze the correlation between the CT signs and postoperative prognosis. METHODS: The clinical history and CT imaging results of 88 patients with CRC who underwent radical surgery at Xingtan Hospital Affiliated to Shunde Hospital of Southern Medical University were retrospectively analyzed. Univariate and multivariate Cox regression analyses were used to explore the independent risk factors for postoperative death in patients with CRC. The three-year survival rate was analyzed using the Kaplan-Meier curve, and the correlation between postoperative survival time and abdominal CT signs in patients with CRC was analyzed using Spearman correlation analysis. RESULTS: For patients with CRC, the three-year survival rate was 73.86%. The death group exhibited more severe characteristics than the survival group. A multivariate Cox regression model analysis showed that body mass index (BMI), degree of periintestinal infiltration, tumor size, and lymph node CT value were independent factors influencing postoperative death (P < 0.05 for all). Patients with characteristics typical to the death group had a low three-year survival rate (log-rank χ 2 = 66.487, 11.346, 12.500, and 27.672, respectively, P < 0.05 for all). The survival time of CRC patients was negatively correlated with BMI, degree of periintestinal infiltration, tumor size, lymph node CT value, mean tumor long-axis diameter, and mean tumor short-axis diameter (r = -0.559, 0.679, -0.430, -0.585, -0.425, and -0.385, respectively, P < 0.05 for all). BMI was positively correlated with the degree of periintestinal invasion, lymph node CT value, and mean tumor short-axis diameter (r = 0.303, 0.431, and 0.437, respectively, P < 0.05 for all). CONCLUSION: The degree of periintestinal infiltration, tumor size, and lymph node CT value are crucial for evaluating the prognosis of patients with CRC.

Fluoride exposure-induced gut microbiota alteration mediates colonic ferroptosis through N6-methyladenosine (m6A) mediated silencing of SLC7A11.

Fluoride exposure is widespread worldwide and poses a significant threat to organisms, particularly to their gastrointestinal tracts. However, due to limited knowledge of the mechanism of fluoride induced intestinal injury, it has been challenging to develop an effective treatment. To address this issue, we used a series of molecular biology in vitro and in vivo experiments. NaF triggered m6A mediated ferroptosis to cause intestinal damage. Mechanistically, NaF exposure increased the m6A level of SLC7A11 mRNA, promoted YTHDF2 binding to m6A-modified SLC7A11 mRNA, drove the degradation of SLC7A11 mRNA, and led to a decrease in its protein expression, which eventually triggers ferroptosis. Moreover, NaF aggravated ferroptosis of the colon after antibiotics destroyed the composition of gut microbiota. 16 S rRNA sequencing and SPEC-OCCU plots, Zi-Pi relationships, and Spearman correlation coefficients verified that Lactobacillus murinus (ASV54, ASV58, and ASV82) plays a key role in the response to NaF-induced ferroptosis. Collectively, NaF-induced gut microbiota alteration mediates severe intestinal cell injury by inducing m6A modification-mediated ferroptosis. Our results highlight a key mechanism of the gut in response to NaF exposure and suggest a valuable theoretical basis for its prevention and treatment.

Duck plague virus-encoded microRNA dev-miR-D28-3p inhibits viral replication via targeting UL27.

Herpesviruses-encoded microRNAs (miRNAs) have been discovered to be essential regulators in viral life cycle, participating in viral replication, latent or lytic infection, and immunological escape. However, the roles of miRNAs encoded by duck plague virus (DPV) are still unknown. Dev-miR-D28-3p is a miRNA uniquely encoded by DPV CHv strain. The aim of this study was to explore the effect of dev-miR-D28-3p on DPV replication and explore the potential mechanisms involved. Our findings demonstrated that transfection of dev-miR-D28-3p mimic into duck embryo fibroblasts (DEFs) effectively suppressed viral copies, viral titers and viral protein expressions during DPV infection, while the results above were reversed after transfection with dev-miR-D28-3p inhibitor. Subsequently, we further discovered that dev-miR-D28-3p specifically bound to DPV-encoded UL27 and inhibited its expression, suggesting that UL27 was the target gene of dev-miR-D28-3p. Finally, we investigated the role of UL27 in DPV replication and found the overexpression of UL27 increased viral copies, viral titers, and viral protein expressions; whereas the opposite results appear when knockdown of UL27. Our findings illustrated a novel mechanism that DPV regulated itself replication via dev-miR-D28-3p, paving the way for exploring the role of DPV-encoded miRNAs.

Targeted-lung delivery of bardoxolone methyl using PECAM-1 antibody-conjugated nanostructure lipid carriers for the treatment of lung inflammation.

The effective treatment of acute lung injury (ALI) remains a significant challenge. Patients with ALI demonstrate an abundance of proinflammatory mediators in both bronchoalveolar lavage fluid (BALF) and circulating plasma. Bardoxolone methyl (BM) is a semi-synthetic triterpenoid derived from oleanolic acid, a natural product known for its ability to inhibit proinflammatory signaling. GSDMD is a signaling protein involved in pyroptosis, a form of programmed cell death. It has been reported that its upstream proteins play a role in the pathogenesis of ALI. However, there is currently no research examining whether the effect of BM on the occurrence and development of ALI is associated with changes in GSDMD protein. In this study, we prepared nanostructured lipid carriers loaded with BM and conjugated with anti-PECAM-1 antibody (PECAM@BM NLCs). PECAM@BM NLCs were designed to specifically bind to pulmonary vascular endothelial cells that highly express the PECAM-1 receptors. We also aimed to investigate the protective effects of PECAM@BM NLCs on ALI and elucidate the underlying molecular mechanisms. The results demonstrated that PECAM@BM NLCs accumulated in the lung tissues and significantly alleviated the inflammatory injury of ALI. This was evidenced by the changes in the lung wet/dry ratio, the total protein concentration, proinflammatory cytokines in BALF, and the histopathological progress. Additionally, we elucidated that PECAM@BM NLCs had the ability to inhibit the assembly of NLRP3 inflammasome and pro-caspase-1 complex, thereby suppressing the induction of pyroptosis. This mechanism resulted in the inhibition of N-terminal GSDMD expression and effectively prevented the progression of ALI.

Fiber-integrated quantum microscopy system for cells.

Quantum entanglement serves as an essential resource across various fields, including quantum communication, quantum computing, and quantum precision measurement. Quantum microscope, as one of the significant applications in quantum precision measurement, could bring revolutionary advancements in both signal-to-noise ratio (SNR) and spatial resolution of imaging. Here, we present a quantum microscopy system that relies on a fully fiber-integrated high-performance energy-time entangled light source operating within the near-infrared II (NIR-II) window. Complemented by tailored real-time data acquisition and processing software, we successfully demonstrate the quantum imaging of a standard target, achieving a SNR of 131.51 ± 6.74 and a spatial resolution of 4.75 ± 0.27 µm. Furthermore, we showcase quantum imaging of cancer cells, unveiling the potential of quantum entanglement in biomedical applications. Our fiber-integrated quantum microscope, characterized by high imaging SNR, instantaneous image capture, and analysis capabilities, marks an important step toward the practical application in life sciences.

Highly selective and visual detection of vanillin based on fluorescence Cd-MOF sensor in milk powders.

Vanillin is a commonly used synthetic flavoring agent in daily life. However, excessive intake of vanillin may pose risks to human health. Therefore, there is an urgent need for rapid and sensitive detection methods for vanillin. In this study, we developed a fluorescent sensor based on Cd-MOF for the sensitive and selective recognition of vanillin. The presence of vanillin leads to significant fluorescence quenching of Cd-MOF due to competitive absorption and photoinduced electron transfer (PET). The limit of detection was determined to be 39.6 nM, which is the lowest-among the reported fluorescent probes. The sensor was successfully applied for the detection of vanillin in real samples such as powdered milk and milk, with a recovery rate ranging from 96.88 % to 104.83 %. Furthermore, by immobilizing the Cd-MOF probe into a polyvinyl alcohol (PVA) film, we achieved a portable and visual detection composite materials for vanillin.

Clinical efficacy of Baijin pills in the treatment of generalized tonic-clonic seizure epilepsy with cognitive impairment.

BACKGROUND: The generalized tonic-clonic seizure (GTCS) is the most usual variety of epileptic seizure. It is mainly characterized by strong body muscle rigidity, loss of consciousness, a disorder of plant neurofunction, and significant damage to cognitive function. The effect of antiepileptic drugs on cognition should also be considered. At present, there is no effective treatment for patients with epilepsy, but traditional Chinese medicine has shown a significant effect on chronic disease with fewer harmful side effects and should, therefore, be considered for the therapy means of epilepsy with cognitive dysfunction. AIM: To investigate the clinical efficacy of Baijin pills for treating GTCS patients with cognitive impairment. METHODS: This prospective study enrolled patients diagnosed with GTCS between January 2020 and December 2023 and separate them into two groups (experimental and control) using random number table method. The control group was treated with sodium valproate, and the experimental group was Baijin pills and sodium valproate for three months. The frequency and duration of each seizure, the Montreal Cognitive Assessment Scale (MoCA), and the Quality of Life Rating Scale (QOLIE-31) were recorded before and after treatment. RESULTS: There were 85 patients included (42 in the control group and 43 in the experimental group). After treatment, the seizure frequency in the experimental group was significantly reduced (P < 0.05), and seizure duration was shortened (P < 0.01). The total MoCA score in the experimental group significantly increased compared to before treatment (P < 0.01), and the sub-item scores, except naming and abstract generalization ability, significantly increased (P < 0.05), whereas the total MoCA score in the control group significantly decreased after treatment (P < 0.05). The QOLIE-31 score of the experimental group increased significantly after treatment compared to before treatment (P < 0.01). CONCLUSION: Baijin pills have a good clinical effect on epilepsy with cognitive dysfunction.

Coupling Fault Diagnosis Based on Dynamic Vertex Interpretable Graph Neural Network.

Mechanical equipment is composed of several parts, and the interaction between parts exists throughout the whole life cycle, leading to the widespread phenomenon of fault coupling. The diagnosis of independent faults cannot meet the requirements of the health management of mechanical equipment under actual working conditions. In this paper, the dynamic vertex interpretable graph neural network (DIGNN) is proposed to solve the problem of coupling fault diagnosis, in which dynamic vertices are defined in the data topology. First, in the date preprocessing phase, wavelet transform is utilized to make input features interpretable and reduce the uncertainty of model training. In the fault topology, edge connections are made between nodes according to the fault coupling information, and edge connections are established between dynamic nodes and all other nodes. Second the data topology with dynamic vertices is used in the training phase and in the testing phase, the time series data are only fed into dynamic vertices for classification and analysis, which makes it possible to realize coupling fault diagnosis in an industrial production environment. The features extracted in different layers of DIGNN interpret how the model works. The method proposed in this paper can realize the accurate diagnosis of independent faults in the dataset with an accuracy of 100%, and can effectively judge the coupling mode of coupling faults with a comprehensive accuracy of 88.3%.

Core concomitant symptoms reported by the patients with breast cancer in postoperative endocrine treatment and the demand for acupuncture therapy： a network-based cross-sectional study. / ä¹³è ºç™Œæœ¯åŽå† åˆ†æ³Œæ²»ç–—æ‚£è€ æŠ¥å‘Šçš„æ ¸å¿ƒä¼´éšç—‡çŠ¶åŠå¯¹é’ˆç¸æ²»ç–—çš„éœ€æ±‚ï¼šä¸€é¡¹åŸºäºŽç½‘ç»œçš„æ¨ªæ–­é¢ç ”ç©¶.

OBJECTIVES: To investigate the most common concomitant symptoms and the urgent demand of solution in the breast cancer patients undergoing postoperative endocrine treatment, as well as the acceptance and expectation of acupuncture in the patients so as to provide the scientific data for promoting the application of acupuncture in the breast cancer patients. METHODS: Breast cancer patients treated in Tianjin Medical University Cancer Institute and Hospital from January 2022 to March 2023 were randomly selected as the subjects. Using "questionnaire star" website, the questionnaire was conducted to investigate the relevant concomitant symptoms of the patients in postoperative endocrine treatment and the questions related to acupuncture treatment. RESULTS: In this study, 229 questionnaires were distributed and 211 valid ones were collected, with the response rate of 92.1%. Among these patients, the first three common symptoms were sleep disorders (157 cases, 74.4%), hot flashes (138 cases, 65.4%) and joint / muscle pain (118 cases, 55.9%)；the top three symptoms to be solved the most urgently were sleep disorders (131 cases, 62.1%), joint / muscle pain (62 cases, 29.4%) and hot flashes (45 cases, 21.3%). 79.1% of the patients (167 cases) were willing to receive acupuncture treatment because of the high expectations on its potential effect (93%). 20.9% of them (44 cases) refused acupuncture because they were worried not to be treated by the experienced physicians of TCM (52%) or afraid of needling feelings (48%). The average expectation value of acupuncture treatment was 4.02 points (5 points for the total score) among patients willing to receive acupuncture treatment. The main purposes of receiring acupuncture for the patients undergoing endocrine treatment were to strengthen the immune function (92%), reduce the adverse reactions (83%), and improve the physical condition (75%), et al. CONCLUSIONS: Sleep disorder is one of the most concerned symptoms in endocrine treatment for the patients after breast cancer surgery. The patients highly expect for acupuncture treatment even though some patients dislike the needling sensation. How to provide the acceptable and high-quality acupuncture services for cancer patients will be one of the major directions of acupuncture research in the future.

Identification of habitat suitability for the dominant zoonotic tick species Haemaphysalis flava on Chongming Island, China.

Haemaphysalis ticks are pathogenic vectors that threaten human and animal health and were identified in Chongming, the third largest island in China. To understand the distribution of these ticks and determine their potential invasion risk, this study aimed to identify the habitat suitability of the dominant tick H. flava based on natural environmental factors. Geographic information system (GIS) images were combined with sample points from tick investigations to map the spatial distribution of H. flava. Data on 19 bioclimatic variables, environmental variables, and satellite-based landscapes of Chongming Island were retrieved to create a landcover map related to natural environmental determinants of H. flava. These data included 38 sites associated with the vectors to construct species distribution models with MaxEnt, a model based on the maximum entropy principle, and to predict habitat suitability for H. flava on Chongming Island in 2050 and 2070 under different climate scenarios. The model performed well in predicting the H. flava distribution, with a training area under the curve of 0.84 and a test area under the curve of 0.73. A habitat suitability map of the whole study area was created for H. flava. The resulting map and natural environment analysis highlighted the importance of the normalized difference vegetation index and precipitation in the driest month for the bioecology of H. flava, with 141.61 km2 (11.77%), 282.94 km2 (23.35%), and 405.30 km2 (33.69%) of highly, moderately, and poorly suitable habitats, respectively. The distribution decreased by 135.55 km2 and 138.82 km2 in 2050 and 2070, respectively, under the shared socioeconomic pathway (SSP) 1.2.6 climate change scenario. However, under SSP 5.8.5, the total area will decrease by 128.5 km2 in 2050 and increase by 151.64 km2 in 2070. From a One Health perspective, this study provides good knowledge that will guide tick control efforts to prevent the spread of Haemaphysalis ticks or transmission risk of Haemaphysalis-borne infections at the human-animal-environment interface on the island.

Jellyfish Stings: A Review of Skin Symptoms, Pathophysiology, and Management.

With the surge in the human coastal population and the increasing frequency of human activities along the coast, cases of marine envenomation, particularly jellyfish envenomation, have notably risen. Jellyfish stings can induce a spectrum of symptoms that vary in severity, encompassing skin injuries, acute systemic venom effects, delayed indirect sequelae, and even fatality, causing significant distress to patients. Among these manifestations, the occurrence of skin lesions following jellyfish stings is prevalent and substantial. These lesions are characterized by evident blister formation, development of bullae, subcutaneous hemorrhage, erythema, papules, wheal, ecchymosis, and ulceration or skin necrosis. Local cutaneous manifestations may persist for several weeks or even months after the initial sting. Despite aggressive treatment, many skin injuries still result in significant pigmentation or scarring after recovery. To address this issue effectively, it is imperative to conduct comprehensive evidence-based medical research, elucidate various components within jellyfish venom, and elucidate its pathogenic mechanism to develop targeted treatment programs. This article aims to review the skin symptoms, pathophysiology, and management of jellyfish stings. Such considerations can provide comprehensive guidance to medical professionals and the public and minimize the harm caused by jellyfish stings.

Effect of Flammulina velutipes polysaccharide on mitochondrial apoptosis in lung adenocarcinoma A549 cells.

FVP is a polysaccharide extracted from Flammulina velutipes with immunomodulatory, anti-tumor, and anti-oxidation activities. In this study, we obtained the crude polysaccharide FVP-C from the water extract of Flammulina velutipes, and its main component FVP-S1 was obtained after further purification. Upon structural identification, we found that FVP-C is a neutral polysaccharide, and FVP-S1 was an acidic golden mushroom polysaccharide, consisting of glucuronic acid, xylose, and glucose. Lung adenocarcinoma (A549) was treated with FVP-S1 and FVP-C, respectively, and we found that FVP-S1 and FVP-C inhibited the proliferation and migration ability of tumor cells, as well as changed the morphology of the tumor cells and caused chromosome sheteropythosis, among which FVP-S1 had the best inhibition effect. The results of flow cytometry experiments and mitochondrial membrane potential, RT-qPCR, and Western blot showed that FVP-S1 and FVP-C were able to decrease the mitochondrial membrane potential, increase the expression level of apoptotic proteins Casepase-3 and Casepase-9 proteins, and at the same time, increase the ratio of Bax and Bcl-2, which promoted apoptosis of tumor cells. In conclusion, these data indicated that FVP-S1 and FVP-C were able to induce apoptosis in A549 cells through the mitochondrial pathway, which played an important role in inhibiting tumor cells.

Inhibition of SIRT1 relieves hepatocarcinogenesis via alleviating autophagy and inflammation.

Imbalanced Sirtuin 1 (SIRT1) levels may lead to liver diseases through abnormal regulation of autophagy, but the roles of SIRT1-regulated autophagy in hepatocellular carcinoma are still controversial. In this study, we found that SIRT1 mRNA and protein levels were upregulated in hepatocellular carcinoma, and high SIRT1 expression hinted an advanced stage and a poor prognosis. The differentially expressed proteins were significantly elevated in autophagy, cellular response to stress, and immune signaling pathways. In a thioacetamide-induced hepatocellular carcinoma mouse model, we found that SIRT1 expression was highly increased with increased autophagy and excessive macrophage inflammatory response. Next, we established a Hepa 1-6 cells and macrophage co-culture system in vitro to model the alteration of tumor microenvironment, and found that the medium from CCl4-treated or SIRT1-overexpressing Hepa 1-6 cells triggered the polarization of macrophage M1, and the culture medium derived from M1 macrophage promoted Hepa 1-6 cells growth and intracellular oxidative stress. The progression of liver fibrosis in the CCl4-induced liver fibrosis mouse model showed that inhibition of SIRT1 alleviated inflammatory response and ameliorated liver fibrosis. These findings suggest that SIRT1-regulated autophagy and inflammation are oncogenic in hepatocarcinogenesis.

Chemical composition, pharmacological effects, and parasitic mechanisms of Cistanche deserticola: An update.

BACKGROUND: C. deserticola, a highly esteemed medicinal herb in China, commonly referred to as "desert ginseng", has been renowned for its unique pharmacological properties in clinical use for countless centuries. Despite its long-standing reputation, our current comprehension of its active components and pharmacological effects remains shallow and incomplete. Moreover, the unclear mechanism underlying its pharmacological actions hinders the advancement and utilization of novel drug formulations derived from C. deserticola. Furthermore, as a unique parasitic plant, the current research on its parasitic mechanisms is limited, hampering efforts to enhance both its medicinal composition and overall yields. PURPOSE: The objective of this review is to meticulously assess, condense, and evaluate the salient aspects pertaining to the chemical composition, pharmacological impacts, and parasitic mechanisms of C. deserticola. Furthermore, the aim is to furnish valuable references that can inform and guide future research endeavors and developmental activities related to C. deserticola. METHODS: This review adheres to the rigorous standards outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A thorough examination and analysis of pertinent research findings, published up to February 6, 2024, has been conducted. Databases such as PubMed, Scopus, Web of Science, Cochrane, and Science Direct were exhaustively searched using targeted keywords and operators to delve into the chemical constituents, pharmacological effects, and parasitic mechanisms exhibited by C. deserticola. RESULTS: The review comprehensively summarizes the advancements in research regarding the chemical composition, pharmacological impacts, and toxicological safety of C. deserticola. It delves into the parasitic mechanisms of C. deserticola from three distinct angles: seed germination, haustorium induction, and recognition of signal substances. Furthermore, the review pinpoints pertinent issues and offers insightful recommendations for future exploration and research pertaining to C. deserticola. CONCLUSION: In recent years, C. deserticola has garnered considerable attention due to its distinctive pharmacological properties. This comprehensive review aims to establish a scientific foundation for the development of potential novel drugs and the enhancement of both the quantity and quality of C. deserticola. It accomplishes this by meticulously analyzing and evaluating the latest research findings pertaining to its chemical composition, pharmacological impacts, and parasitic mechanisms.

Bile acid profiles and classification model accuracy for inflammatory bowel disease diagnosis.

To investigate the utility of serum bile acid profiling for the diagnosis of inflammatory bowel disease (IBD). We analyzed 15 specific bile acids in the serum of 269 IBD patients, 200 healthy controls (HC), and 174 patients with other intestinal diseases (OID) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Serum bile acid levels were compared between IBD group, HC group, and OID group. Binary logistic regression-based models were developed to model the bile acids and diagnose IBD. Furthermore, receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic accuracy of each bile acid and the model. Compared to HC group, IBD group exhibited significantly lower levels of chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), glycodeoxycholic acid (GDCA), taurodeoxycholic acid (TDCA), lithocholic acid (LCA), glycolithocholic acid (GLCA), taurolithocholic acid (TLCA), and an elevated primary-to-secondary bile acid ratio. DCA had an area under the curve (AUC) of 0.860 for diagnosing IBD, with a sensitivity of 80.67% and a specificity of 82.50%. A model Y0 combining DCA and CDCA to distinguish between IBD group and HC group further improved accuracy (AUC = 0.866, sensitivity = 76.28%, specificity = 89.37%). Compared to non-IBD group (which combined healthy controls and those with other intestinal diseases), IBD group had significantly lower levels of DCA, GDCA, TDCA, LCA, GLCA, and TLCA, and elevated levels of glycocholic acid (GCA) and glycochenodeoxycholic acid (GCDCA). A model Y1 incorporating GCDCA, DCA and TLCA to distinguish between IBD group and non-IBD group yielded an AUC of 0.792, with a sensitivity of 77.67% and specificity of 71.91%. IBD patients exhibit decreased serum secondary bile acid levels and an elevated primary-to-secondary bile acid ratio. Serum bile acid alterations are associated with the onset of IBD. A model consisting of CDCA and DCA has potential for distinguishing between IBD group and HC group, while a model incorporating GCDCA, DCA and TLCA may be suitable for distinguishing between IBD group and non-IBD group.

Resveratrol activates MAPK/ERK pathway to regulate oestrogen metabolism in type I endometrial cancer.

OBJECTIVE: Endometrial cancer (EC) is an oestrogen-dependent tumour, the occurrence of which is closely related to an imbalance of oestrogen homeostasis. Our previous studies explored the effects of Resveratrol(Res) on oestrogen metabolism. However, systematic research on the exact mechanism of action of Res is still lacking. Based on network pharmacology, molecular docking and animal experiments, the effects and molecular mechanisms of Res on endometrial cancer were investigated. METHODS: The target of Res was obtained from the high-throughput experiment and reference-guided database of TCM (HERB) and the Encyclopedia of Traditional Chinese Medicine (ETCM) databases, and the target of endometrial cancer was obtained by using the Genecards database. Venny map was used to obtain the intersection target of Res in the treatment of endometrial cancer, and the protein interaction network of the intersection target was constructed by importing the data into the STRING database. Then, the drug-disease-target interaction network was constructed based on Cytoscape 3.9.1 software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for intersection targets using the OmicShare cloud platform. Res and core targets were analysed by molecular docking. EC model mice induced by MNNG were randomly divided into the control group, Res group, MNNG group, MNNG + Res group, and MNNG + Res + MAPK/ERKi group. The protein levels of ERK and p-ERK in the mouse uterus were detected by Western blot. The levels of E1, E2, E3, 16-epiE3, 17-epiE3, 2-MeOE1, 4-MeOE1, 2-MeOE2, 4-MeOE2, 3-MeOE1, 2-OHE1, 4-OHE1, 2-OHE2, 4-OHE2, and 16α-OHE1 in the serum and endometrial tissue of mice were measured by LC‒MS/MS. RESULTS: A total of 174 intersection targets of Res anti-endometrial cancer were obtained. The signalling pathways analysed by KEGG enrichment included the AGE-RAGE signalling pathway in diabetic complications, the PI3K-Akt signalling pathway and the MAPK signalling pathway. The top 10 core targets were MAPK3, JUN, TP53, CASP3, TNF, IL1B, AKT1, FOS, VEGFA and INS. Molecular docking showed that in addition to TNF, other targets had good affinity for Res, and the binding activity with MAPK3 was stable. Western blot results showed that Res increased the phosphorylation level of ERK and that MAPK/ERKi decreased ERK activation. In the LC-MS/MS analysis, the levels of 2-MeOE1, 2-MeOE2 and 4-MeOE1 in serum and uterine tissue showed a significantly decreasing trend in the MNNG group, while that of 4-OHE2 was increased (P < 0.05). The concentrations of 4-MeOE1 in serum and 2-MeOE1 and 2-MeOE2 in the endometrial tissue of mice were significantly increased after Res treatment, and those of 4-OHE2 in the serum and uterus of mice were significantly decreased (P < 0.05). Meanwhile, in the MAPK/ERKi intervention group, the effect of Res on the reversal of oestrogen homeostasis imbalance was obviously weakened. CONCLUSION: Res has multiple targets and multiple approaches in the treatment of endometrial cancer. In this study, it was found that Res regulates oestrogen metabolism by activating the MAPK/ERK pathway. This finding provides a new perspective for subsequent research on the treatment of endometrial cancer.

Screening of environmental stimuli for the positive regulation of stomatal aperture in centipedegrass.

Grasslands, the largest carbon pool in China, possess enormous potential for carbon sequestration. Increasing the stomatal aperture to increase the CO2 absorption capacity is a potential method to improve plant photosynthetic efficiency and ultimately enhance the carbon sequestration capacity of grass plants. Research on stomatal aperture regulation has focused mostly on Arabidopsis or crops, while research on grass plants in these areas is scarce, which seriously restricts the implementation of this grassland carbon sequestration strategy. Here, a widely used ecological grass, centipedegrass, was used as the experimental material. First, a convenient method for observing the stomatal aperture was developed. The leaves were floated in a potassium ion-containing open solution (67 mM KCl, pH 6.0) with the adaxial surface rather than the abaxial surface in contact with the solution and were cultivated under light for 1.5 h. Then, nail polish was applied on the adaxial surface, and a large number of open stomata were imprinted. Second, with the help of this improved method, the concentration‒response characteristics of the stomatal aperture to eleven environmental stimuli were tested. The stomatal aperture is dependent on these environmental stimuli in a concentration-dependent manner. The addition of 100 µM brassinolide led to the maximal stomatal aperture. This study provided a technical basis for manipulating stomatal opening to increase the carbon sequestration capacity of centipedegrass.

Mucoadhesive chitosan-catechol as an efficient vaccine delivery system for intranasal immunization.

The mucosal barrier and scavenging effect of the mucosal layer are two main obstacles in inducing mucosal immunization. To overcome these obstacles, we synthesized a bio-inspired mucoadhesive material, chitosan-catechol (ChiC), for surface modification of inactive porcine epidemic diarrhea virus (PEDV). Studies have revealed that PEDV particles can be facilely and mildly modified by Chi-C forming Chi-C-PEDV nanoparticles (Chic-Ps) through the covalent and electrostatic bond, which effectively prolongs the retention time of PEDV in the nasal mucosa. The cell co-culture model demonstrated that Chic-Ps exhibit enhanced recruitment of dendritic cells via the secretion of stimulating chemokine CCL20 and improving antigen permeability by disruption the distribution of ZO-1 protein in epithelial cells. Additionally, the flow cytometry (FCM) analysis revealed that Chic-Ps facilitate trafficking to lymph nodes and induce stronger cellular and humoral immune responses compared to unmodified PEDV. Notably, Chic-Ps induced a higher level of PEDV neutralizing antibody was induced by Chic-Ps in the nasal washes, as confirmed by a plaque reduction neutralization test. These results demonstrate that Chi-C is a promising nasal delivery system for vaccines. Proof of principle was obtained for inactivated PEDV, but similar delivery mechanisms could be applied in other vaccines when intranasal administration is needed.

Pathogen-Mimicking Nanoparticles Based on Rigid Nanomaterials as an Efficient Subunit Vaccine Delivery System for Intranasal Immunization.

Despite the safety profile of subunit vaccines, the inferior immunogenicity hinders their application in the nasal cavity. This study introduces a novel antigen delivery and adjuvant system utilizing mucoadhesive chitosan-catechol (Chic) on silica spiky nanoparticles (Ssp) to enhance immunity through multiple mechanisms. The Chic functionalizes the Ssp surface and incorporates with SARS-CoV-2 spike protein receptor-binding domain (RBD) and toll-like receptor (TLR)9 agonist unmethylated cytosine-guanine (CpG) motif, forming uniform virus-like nanoparticles (Ssp-Chic-RBD-CpG) via electrostatic and covalent interactions. Ssp-Chic-RBD-CpG, mimicking the morphology and function of inactive virions, effectively prolongs the retention time of RBD in the nasal mucosa by 3.92-fold compared to RBD alone, enhances the maturation of dendritic cells (DCs), and facilitates the antigen trafficking to the draining lymph nodes, which subsequently induces a stronger mucosal immunity. Mechanistically, the enhanced chemokine chemokine (C-C motif) ligand 20 (CCL20)-driven DCs recruitment and maturation by Ssp-Chic-RBD-CpG are evidenced by a cell co-culture model. In addition, the overexpression of TLR4/9 and activation of MYD88/NF-κB signaling pathway in activation of DCs are observed. Proof of principle is obtained for RBD, but similar delivery mechanisms can be applied in other protein-based subunit vaccines as well when intranasal administration is needed.

[Prognostic analysis of childhood T-lymphoblastic lymphoma treated with leukemia regimen]. / 儿童Tæ·‹å·´æ¯ç»†èƒžæ·‹å·´ç˜¤é‡‡ç”¨ç™½è¡€ç— æ–¹æ¡ˆæ²»ç–—çš„é¢„åŽåˆ†æž.

OBJECTIVES: To investigate the prognosis of childhood T-lymphoblastic lymphoma (T-LBL) treated with acute lymphoblastic leukemia (ALL) regimen and related influencing factors. METHODS: A retrospective analysis was performed for the prognostic characteristics of 29 children with T-LBL who were treated with ALL regimen (ALL-2009 or CCCG-ALL-2015 regimen) from May 2010 to May 2022. RESULTS: The 29 children with T-LBL had a 5-year overall survival (OS) rate of 84%±7% and an event-free survival (EFS) rate of 81%±8%. The children with B systemic symptoms (unexplained fever >38°C for more than 3 days; night sweats; weight loss >10% within 6 months) at initial diagnosis had a lower 5-year EFS rate compared to the children without B symptoms (P<0.05). The children with platelet count >400×109/L and involvement of both mediastinum and lymph nodes at initial diagnosis had lower 5-year OS rates (P<0.05). There were no significant differences in 5-year OS and EFS rates between the children treated with CCCG-ALL-2015 regimen and those treated with ALL-2009 regimen (P>0.05). Compared with the ALL-2009 regimen, the CCCG-ALL-2015 regimen reduced the frequency of high-dose methotrexate chemotherapy and the incidence rate of severe infections (P<0.05). CONCLUSIONS: The ALL regimen is safe and effective in children with T-LBL. Children with B systemic symptoms, platelet count >400×109/L, and involvement of both mediastinum and lymph nodes at initial diagnosis tend to have a poor prognosis. Reduction in the frequency of high-dose methotrexate chemotherapy can reduce the incidence rate of severe infections, but it does not affect prognosis.