MV-CVIB: a microbiome-based multi-view convolutional variational information bottleneck for predicting metastatic colorectal cancer.

Introduction: Imbalances in gut microbes have been implied in many human diseases, including colorectal cancer (CRC), inflammatory bowel disease, type 2 diabetes, obesity, autism, and Alzheimer's disease. Compared with other human diseases, CRC is a gastrointestinal malignancy with high mortality and a high probability of metastasis. However, current studies mainly focus on the prediction of colorectal cancer while neglecting the more serious malignancy of metastatic colorectal cancer (mCRC). In addition, high dimensionality and small samples lead to the complexity of gut microbial data, which increases the difficulty of traditional machine learning models. Methods: To address these challenges, we collected and processed 16S rRNA data and calculated abundance data from patients with non-metastatic colorectal cancer (non-mCRC) and mCRC. Different from the traditional health-disease classification strategy, we adopted a novel disease-disease classification strategy and proposed a microbiome-based multi-view convolutional variational information bottleneck (MV-CVIB). Results: The experimental results show that MV-CVIB can effectively predict mCRC. This model can achieve AUC values above 0.9 compared to other state-of-the-art models. Not only that, MV-CVIB also achieved satisfactory predictive performance on multiple published CRC gut microbiome datasets. Discussion: Finally, multiple gut microbiota analyses were used to elucidate communities and differences between mCRC and non-mCRC, and the metastatic properties of CRC were assessed by patient age and microbiota expression.

Ligulariatinside A, a new sesquiterpene glycoside from roots of Ligularia veitchiana.

A new sesquiterpene glycoside, ligulariatinside A (1), along with nine known compounds, dibutyl phthalate (2), 1-O-(9Z,12Z-octadecadienoyl) glycerol (3), bis (2-ethylhexyl) phthalate (4), 4-hydroxy-3-methoxyphenylpropanol (5), dihydrosyringenin (6), caffeic acid (7), 6ß-hydroxy-7(11)-eremophilen-12,8α-olide (8), together with the mixture of 6ß,8ß-dihydroxyeremophil-7(11)-en-12,8α-olide (9) and 6ß,8α-dihydroxy-eremophil-7(11)-en-12,8ß-olide (10) were isolated from roots of L. veitchiana. Structures of these compounds were elucidated by comprehensive analyses of HRESIMS, 1D NMR, and 2D NMR spectroscopic data. Compounds 2 and 4 are not likely natural compounds but contaminants. All isolated compounds were tested for antibacterial activity. Compounds 1, 5, 6, together with the mixture of 9 and 10, showed mild activity against Vibrio anguillarum, with MIC values of 50, 50, 100, and 200 µg/mL, while compound 7 showed moderate activity against Vibrio anguillarum, with a MIC value of 25 µg/mL.

Functional screening and rational design of compounds targeting GPR132 to treat diabetes.

Chronic inflammation due to islet-residing macrophages plays key roles in the development of type 2 diabetes mellitus. By systematically profiling intra-islet lipid-transmembrane receptor signalling in islet-resident macrophages, we identified endogenous 9(S)-hydroxy-10,12-octadecadienoic acid-G-protein-coupled receptor 132 (GPR132)-Gi signalling as a significant contributor to islet macrophage reprogramming and found that GPR132 deficiency in macrophages reversed metabolic disorders in mice fed a high-fat diet. The cryo-electron microscopy structures of GPR132 bound with two endogenous agonists, N-palmitoylglycine and 9(S)-hydroxy-10,12-octadecadienoic acid, enabled us to rationally design both GPR132 agonists and antagonists with high potency and selectivity through stepwise translational approaches. We ultimately identified a selective GPR132 antagonist, NOX-6-18, that modulates macrophage reprogramming within pancreatic islets, decreases weight gain and enhances glucose metabolism in mice fed a high-fat diet. Our study not only illustrates that intra-islet lipid signalling contributes to islet macrophage reprogramming but also provides a broadly applicable strategy for the identification of important G-protein-coupled receptor targets in pathophysiological processes, followed by the rational design of therapeutic leads for refractory diseases such as diabetes.

Successful Transfection of MicroRNA Mimics or Inhibitors in a Regular Cell Line and in Primary Cells Derived from Patients with Rheumatoid Arthritis.

The transfection of microRNA (miRNA) mimics and inhibitors can lead to the gain and loss of intracellular miRNA function, helping us better understand the role of miRNA during gene expression regulation under specific physical conditions. Our previous research has confirmed the efficiency and convenience of using liposomes to transfect miRNA mimics or inhibitors. This work uses miR-424 as an example, to provide a detailed introduction for the transfection process of miRNA mimics and inhibitors in the regular SW982 cell line and primary rheumatoid arthritis synovial fibroblasts (RASF) cells from patients by using lipofection, which can also serve as a reference to miRNA transfection in other cell lines. Key features • MiRNA mimics and inhibitors transfection in regular SW982 cell line and primary RASF cells. • Treatment and culture of RASF primary cells before transfection. • Using liposomes for transfection purposes.

Predicting the outcomes of hepatocellular carcinoma downstaging with the use of clinical and radiomics features.

BACKGROUND: Downstaging of hepatocellular carcinoma (HCC) makes it possible for patients beyond the criteria to have the chance of liver transplantation (LT) and improved outcomes. Thus, a procedure to predict the prognosis of the treatment is an urgent requisite. The present study aimed to construct a comprehensive framework with clinical information and radiomics features to accurately predict the prognosis of downstaging treatment. METHODS: Specifically, three-dimensional (3D) tumor segmentation from contrast-enhanced computed tomography (CT) is employed to extract spatial information of the lesions. Then, the radiomics features within the segmented region are calculated. Combining radiomics features and clinical data prompts the development of feature selection to enhance the robustness and generalizability of the model. Finally, we adopt the support vector machine (SVM) algorithm to establish a classification model for predicting HCC downstaging outcomes. RESULTS: Herein, a comparative study was conducted on three different models: a radiomics features-based model (R model), a clinical features-based model (C model), and a joint radiomics clinical features-based model (R-C model). The average accuracy of the three models was 0.712, 0.792, and 0.844, and the average area under the receiver-operating characteristic (AUROC) of the three models was 0.775, 0.804, and 0.877, respectively. CONCLUSIONS: The novel and practical R-C model accurately predicted the downstaging outcomes, which could be utilized to guide the HCC downstaging toward LT treatment.

TDDFT study on a fluorescent probe for distinguishing analogous thiols based on smiles rearrangement.

The complete excited-state sensing mechanism of a fluorescent probe capable of distinguishing cysteine/homocysteine and glutathione from analogous biological thiols has been investigated. Using a TDDFT method, the nature of the fluorescence differences in the detection of thiols by the probe has been explained at the molecular level. Calculation results imply that the probe undergoes photoinduced electron transfer (PET) from the fluorophore to the nitrobenzooxadiazole (NBD)-based acceptor in the excited state. In the presence of a thiol, the NBD moiety is cleaved and the red fluorescence emission of the fluorophore is enhanced through inhibition of the PET process. The sulfur-substituted NBD-thiol product is predisposed to undergo excited-state torsion, leading to fluorescence quenching. However, for cysteine and homocysteine, their appropriate distances lead to Smiles rearrangements with relatively low activation energies (26.60 kJ/mol and 42.94 kJ/mol, respectively) and the emission of a distinct green fluorescence at ambient temperature. It has been theoretically confirmed that the distance between two reactive sites, such as sulfhydryl and amino moieties, can be used to distinguish different thiols, thus providing rational support for the control of fluorescence activity and the design of probe molecules.

DHHC2 regulates fear memory formation, LTP, and AKAP150 signaling in the hippocampus.

Palmitoyl acyltransferases (PATs) have been suggested to be involved in learning and memory. However, the underlying mechanisms have not yet been fully elucidated. Here, we found that the activity of DHHC2 was upregulated in the hippocampus after fear conditioning, and DHHC2 knockdown impaired fear induced memory and long-term potentiation (LTP). Additionally, the activity of DHHC2 and its synaptic expression were increased after high frequency stimulation (HFS) or glycine treatment. Importantly, fear learning selectively augmented the palmitoylation level of AKAP150, not PSD-95, and this effect was abolished by DHHC2 knockdown. Furthermore, 2-bromopalmitic acid (2-BP), a palmitoylation inhibitor, attenuated the increased palmitoylation level of AKAP150 and the interaction between AKAP150 and PSD-95 induced by HFS. Lastly, DHHC2 knockdown reduced the phosphorylation level of GluA1 at Ser845, and also induced an impairment of LTP in the hippocampus. Our results suggest that DHHC2 plays a critical role in regulating fear memory via AKAP150 signaling.

Effects of Compound Danshen Dripping Pills on Ventricular Remodeling and Cardiac Function after Acute Anterior Wall ST-Segment Elevation Myocardial Infarction (CODE-AAMI): Protocol for a Randomized Placebo-Controlled Trial.

BACKGROUND: Ventricular remodeling after acute anterior wall ST-segment elevation myocardial infarction (AAMI) is an important factor in occurrence of heart failure which additionally results in poor prognosis. Therefore, the treatment of ventricular remodeling needs to be further optimized. Compound Danshen Dripping Pills (CDDP), a traditional Chinese medicine, exerts a protective effect on microcirculatory disturbance caused by ischemia-reperfusion injury and attenuates ventricular remodeling after myocardial infarction. OBJECTIVE: This study is designed to evaluate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function after AAMI on a larger scale. METHODS: This study is a multi-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The total of 268 patients with AAMI after primary percutaneous coronary intervention (pPCI) will be randomly assigned 1:1 to the CDDP group (n=134) and control group (n=134) with a follow-up of 48 weeks. Both groups will be treated with standard therapy of ST-segment elevation myocardial infarction (STEMI), with the CDDP group administrating 20 tablets of CDDP before pPCI and 10 tablets 3 times daily after pPCI, and the control group treated with a placebo simultaneously. The primary endpoint is 48-week echocardiographic outcomes including left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVI), and left ventricular end-systolic volume index (LVESVI). The secondary endpoint includes the change in N terminal pro-B-type natriuretic peptide (NT-proBNP) level, arrhythmias, and cardiovascular events (death, cardiac arrest, or cardiopulmonary resuscitation, rehospitalization due to heart failure or angina pectoris, deterioration of cardiac function, and stroke). Investigators and patients are both blinded to the allocated treatment. DISCUSSION: This prospective study will investigate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function in patients undergoing pPCI for a first AAMI. Patients in the CDDP group will be compared with those in the control group. If certified to be effective, CDDP treatment in AAMI will probably be advised on a larger scale. (Trial registration No. NCT05000411).

Inhibition of LPA-LPAR1 and VEGF-VEGFR2 Signaling in IPF Treatment.

Due to the complex mechanism and limited treatments available for pulmonary fibrosis, the development of targeted drugs or inhibitors based on their molecular mechanisms remains an important strategy for prevention and treatment. In this paper, the downstream signaling pathways mediated by VEGFR and LPAR1 in pulmonary cells and the role of these pathways in pulmonary fibrosis, as well as the current status of drug research on the targets of LPAR1 and VEGFR2, are described. The mechanism by which these two pathways regulate vascular leakage and collagen deposition leading to the development of pulmonary fibrosis are analyzed, and the mutual promotion of the two pathways is discussed. Here we propose the development of drugs that simultaneously target LPAR1 and VEGFR2, and discuss the important considerations in targeting and safety.

Drivers and mechanisms of spontaneous plant community succession in abandoned PbZn mining areas in Yunnan, China.

The drivers and mechanisms underlying succession and the spontaneous formation of plant communities in mining wasteland remain largely unknown. This study investigated the use of nature-based restoration to facilitate the recovery of viable plant communities in mining wasteland. It was found that scientific analyses of spontaneously formed plant communities in abandoned mining areas can provide insights for nature-based restoration. A chronosequence ("space for time") approach was used to establish sites representing three successional periods with six successional stages, and 90 quadrats were constructed to investigate changes in plant species and functional diversity during succession in abandoned PbZn mining areas. A total of 140 soil samples were collected to identify changes in soil properties, including plant nutrient and heavy metal concentrations. Then, this paper used structural equation models to analyze the mechanisms that drive succession. It was found that the functional diversity of plant communities fluctuated substantially during succession. Species had similar functional traits in early and mid-succession, but traits tended to diverge during late succession. Soil bulk density and soil organic matter gradually increased during succession. Total nitrogen (N), pH, and soil Zn concentrations first increased and then decreased during succession. Concentrations of Mn and Cd gradually decreased during succession. During early succession, soil organic matter was the key factor driving plant colonization and succession. During mid-succession, soil Zn functioned as an environmental filter factor limiting the rates of succession in mining wasteland communities. During late succession, soil bulk density and competition for nutrient resources contributed to more balanced differentiation among plant species. This thesis proposed that a nature-based strategy for the stabilization of abandoned mining lands could facilitate effective plant community restoration that promotes ecosystem services and functioning.

[Analysis and Simulation of the Spatiotemporal Evolution of Habitat Quality and Carbon Storage in the Weibei Dry Plateau Region of Shaanxi].

Exploring the spatial and temporal pattern evolution of habitat quality and carbon storage has a positive feedback effect on establishing an ecological security barrier and optimizing the spatial pattern of national land in the WeiBei Arid Plateau Region of Shaanxi. This study took the Weibei Plateau Region as a case study, simulated the spatial pattern of land use for different development scenarios of 2035 based on the PLUS model, and used the InVEST model to analyze the characteristics of habitat quality and carbon storage distribution in the study area from 1980 to 2020 and under multi-scenarios in the future. The results showed that:①the area of the low-grade habitat quality area in the study area expanded by 462.55 km2, and the carbon stock decreased by 7.85×106 t over the past 40 years, both of which showed an overall decreasing trend yearly. ②During the study period, the degraded habitat quality areas were concentrated in the northeastern part of the study area within Yan'an City, and the upgraded areas were distributed in strips near water sources or at higher elevations. The high carbon stock areas were concentrated in the complex terrain and sparsely populated areas in the study area, and the decreasing carbon stocked areas were scattered throughout the study area in a dotted pattern without obvious aggregation. ③In 2035, carbon stock decreased to different degrees in all states except for the natural development scenario. In the economic priority development scenario, the habitat quality low grade area covered 20787.41 km2, which was the simulated scenario of the fastest growth rate of low-grade area and the largest reduction of high-grade area compared with the early stage of the simulation. The results of this study can provide decision references and data support for low carbon green development and ecological restoration in the study area.

Integrated transcriptomic and proteomic analyses of plerocercoid and adult Spirometra mansoni reveal potential important pathways in the development of the medical tapeworm.

BACKGROUND: Spirometra mansoni can parasitize animals and humans through food and water, causing parasitic zoonosis. Knowledge of the developmental process of S. mansoni is crucial for effective treatment; thus, it is important to characterize differential and specific proteins and pathways associated with parasite development. METHODS: In this study, we performed a comparative proteomic analysis of the plerocercoid and adult stages using a tandem mass tag-based quantitative proteomic approach. Additionally, integrated transcriptomic and proteomic analyses were conducted to obtain the full protein expression profiles of different life cycle stages of the tapeworm. RESULTS: Approximately 1166 differentially expressed proteins (DEPs) were identified in adults versus plerocercoids, of which 641 DEPs were upregulated and 525 were downregulated. Gene Ontology (GO), Clusters of Orthologous groups (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that most DEPs related to genetic information processing and metabolism of energy in adults seem to be more activated. In the plerocercoid stage, compared to metabolism, genetic information processing appears more dynamic. Protein-protein interaction (PPI) revealed six key proteins (phosphomannomutase, glutathione transferase, malate dehydrogenase, cytoplasmic, 40S ribosomal protein S15, ribosomal protein L15 and 60S acidic ribosomal protein P2) that may play active roles in the growth and development of S. mansoni. Finally, the combination of transcriptomic and proteomic data suggested that three pathways (ubiquitin-mediated proteolysis, phagosome and spliceosome) and five proteins closely related to these pathways might have a significant influence in S. mansoni. CONCLUSIONS: These findings contribute to increasing the knowledge on the protein expression profiles of S. mansoni and provide new insights into functional studies on the molecular mechanisms of the neglected medical tapeworm.

Manipulations of multi-frequency waves and signals via multi-partition asynchronous space-time-coding digital metasurface.

Manipulations of multiple carrier frequencies are especially important in a variety of fields like radar detection and wireless communications. In conventional radio-frequency architecture, the multi-frequency control is implemented by microwave circuits, which are hard to integrate with antenna apertures, thus bringing the problems of expensive system and high power consumption. Previous studies demonstrate the possibility to jointly control the multiple harmonics using space-time-coding digital metasurface, but suffer from the drawback of inherent harmonic entanglement. To overcome the difficulties, we propose a multi-partition asynchronous space-time-coding digital metasurface (ASTCM) to generate and manipulate multiple frequencies with more flexibility. We further establish an ASTCM-based transmitter to realize wireless communications with frequency-division multiplexing, where the metasurface is responsible for carrier-wave generations and signal modulations. The direct multi-frequency controls with ASTCM provides a new avenue to simplify the traditional wireless systems with reduced costs and low power consumption.

Copper catalyzed Shono-type oxidation of proline residues in peptide.

Since the initial report in 1975, the Shono oxidation has become a powerful tool to functionalize the α position of amines, including proline derivatives, by electrochemical oxidation. However, the application of electrochemical Shono oxidations is restricted to the preparation of simple building blocks and homogeneous Shono-type oxidation of proline derivatives remains challenging. The late-stage functionalization at proline residues embedded within peptides is highly important as substitutions about the proline ring are known to affect biological and pharmacological activities. Here, we show that homogenous copper-catalyzed oxidation conditions complement the Shono oxidation and this general protocol can be applied to a series of formal C-C coupling reactions with a variety of nucleophiles using a one-pot procedure. This protocol shows good tolerance toward 19 proteinogenic amino acids and was used to functionalize several representative bioactive peptides, including captopril, enalapril, Smac, and endomorphin-2. Last, peptide cyclization can also be achieved by using an appropriately positioned side-chain hydroxyl moiety.

Perinatal Outcomes of Pregnancy in Women with Scarred Uteri.

Objective: Uterine scarring is risky for the pregnancy and is closely associated with adverse pregnancy outcomes. Here, we investigated risk factors and associated perinatal outcomes in singleton pregnant women with uterine scars. Methods: This retrospective cohort study was conducted on singleton pregnant women who delivered at the West China Second University Hospital between January 1, 2021, and December 31, 2021. Results: The control group included 13,433 cases without uterine scars. The study group involved 2397 cases with one previous cesarean delivery (PCD), 163 cases with two PCDs, 12 cases with three PCDs, and 184 cases with non-cesarean uterine scars. The study group had a significantly higher incidence of placenta previa (6.4%), placenta percreta (5.3%), preterm delivery (10.3%), postpartum hemorrhage (3.4%), uterine rupture (9.4%), hysterectomy (0.18%), and bladder injury (0.4%) when compared with the control group (P <0.05). The scarred uterus cases with 1, 2, or 3 PCDs had significantly different complications, with the higher PCD frequency correlating with increased rates of placenta previa, placenta percreta, postpartum hemorrhage, uterine rupture, and uterine resection. Moreover, the hospitalization time, cesarean operation time, and intrapartum bleeding in the current pregnancy significantly increased with increasing PCD frequency (P <0.05). Analysis of the association between the duration of the interval between PCD and re-pregnancy and pregnancy complication revealed that the incidence of pernicious placenta previa was statistically higher in cases with intervals of <2 years or ≥5 years (4.7%) than in cases with 2 years ≤ interval time <5 years (2.5%) (P <0.05). Conclusion: Pregnancies with uterine scars may experience higher rates of adverse perinatal outcomes. This calls for increased observation during pregnancy and delivery to reduce maternal and fetal complications.

Terpenoid compounds from the fruits of Solanum virginianum.

Eleven compounds were isolated and identified from ethanolic extracts of Solanum virginianum fruits, including two new compounds (1-2) and nine known compounds (3-11). Their structures were determined to be melongenaterpene C15-O-ß-D-glucopyranoside (1), (9Z)-3,7,11,15-tetramethyl -hexadeca-1,6,10-triene-3,5,14,15-tetraol-5-O-ß-D-glucopyranoside (2), actini-dioionoside A (3), byzantionoside B (4), citroside A (5), 7Z-roseoside (6), matenoside A (7), megastigmane (8), dihydrophaseic acid 3'-O-ß-D-glucopyranoside (9), taraxerol (10), and huzhangoside C (11). In this paper, NMR spectroscopy was used to study the structures of the compounds, comparing their data with those in the literature. In addition, the potential anti-inflammatory activity of the compounds was also evaluated using the RAW264.7 cell inflammation model induced by lipopolysaccharide (LPS). The terpenoids showed no significant anti-inflammatory activity.

A mannitol-modified emodin nano-drug restores the intestinal barrier function and alleviates inflammation in a mouse model of DSS-induced ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is an inflammatory disease of the colon that is characterized by mucosal ulcers. Given its increasing prevalence worldwide, it is imperative to develop safe and effective drugs for treating UC. Emodin, a natural anthraquinone derivative present in various medicinal herbs, has demonstrated therapeutic effects against UC. However, low bioavailability due to poor water solubility limits its clinical applications. METHODS: Emodin-borate nanoparticles (EmB) were synthesized to improve drug solubility, and they modified with oligomeric mannitol into microgels (EmB-MO) for targeted delivery to intestinal macrophages that express mannose receptors. UC was induced in a mouse model using dextran sulfate sodium (DSS), and different drug formulations were administered to the mice via drinking water. The levels of inflammation-related factors in the colon tissues and fecal matter were measured using enzyme-linked immunosorbent assay. Intestinal permeability was evaluated using fluorescein isothiocyanate dextran. HE staining, in vivo imaging, real-time PCR, and western blotting were performed to assess intestinal barrier dysfunction. RESULTS: Both EmB and EmB-MO markedly alleviated the symptoms of UC, including body weight loss, stool inconsistency, and bloody stools and restored the levels of pro- and anti-inflammatory cytokines. However, the therapeutic effects of EmB-MO on the macroscopic and immunological indices were stronger than those of EmB and similar to those of 5-aminosalicylic acid. Furthermore, EmB-MO selectively accumulated in the inflamed colon epithelium and restored the levels of the gut barrier proteins such as ZO-1 and Occludin. CONCLUSIONS: EmB-MO encapsulation significantly improved water solubility, which translated to greater therapeutic effects on the immune balance and gut barrier function in mice with DSS-induced UC. Our findings provide novel insights into developing emodin-derived drugs for the management of UC.

Selective Reduction of NO into N2 Catalyzed by Rh1-Doped Cluster Anions RhCe2O3-5.

Catalytic conversion of toxic nitrogen oxide (NO) and carbon monoxide (CO) into nitrogen (N2) and carbon dioxide (CO2) is imperative under the weight of the increasingly stringent emission regulations, while a fundamental understanding of the nature of the active site to selectively drive N2 generation is elusive. Herein, in combination with state-of-the-art mass-spectrometric experiments and quantum-chemical calculations, we demonstrated that the rhodium-cerium oxide clusters RhCe2O3-5- can catalytically drive NO reduction by CO and give rise to N2 and CO2. This finding represents a sharp improvement in cluster science where N2O is commonly produced in the rarely established examples of catalytic NO reduction mediated with gas-phase clusters. We demonstrated the importance of the unique chemical environment in the RhCe2O3- cluster to guide the substantially improved N2 selectivity: a triatomic Lewis "acid-base-acid" Ceδ+-Rhδ--Ceδ+ site is proposed to strongly adsorb two NO molecules as well as the N2O intermediate that is attached on the Rh atom and can facilely dissociate to form N2 assisted by both Ce atoms.

Prognostic significance of the novel nutrition-inflammation marker of lymphocyte-C-reactive protein ratio in patients with nasopharyngeal carcinoma receiving concurrent chemoradiotherapy.

Background: Recent studies indicate that the novel lymphocyte-C-reactive protein ratio (LCR) is strongly associated with the survival of various tumors, but its prognostic value in nasopharyngeal carcinoma (NPC) is understudied. This study aimed to explore the relationship between LCR and overall survival (OS) in NPC and develop a predictive model. Methods: A total of 841 NPC patients who received concurrent chemoradiotherapy (CCRT) between January 2010 and December 2014 were retrospectively enrolled and randomly divided into a training cohort (n = 589) and a validation cohort (n = 252), and 122 patients between January 2015 and March 2015 were included as an additional validation cohort. Univariate and multivariate Cox analyses were performed to identify variables associated with OS and construct a predictive nomogram. The predictive accuracy of the nomogram was evaluated and independently validated. Results: The LCR score differentiated NPC patients into two groups with distinct prognoses (HR = 0.53; 95% CI: 0.32-0.89, P = 0.014). Multivariate analysis showed that age, T stage, N stage, EBV-DNA status, and LCR score were independently associated with OS, and a predictive nomogram was developed. The nomogram had a good performance for the prediction of OS [C-index = 0.770 (95% CI: 0.675-0.864)]. and outperformed the traditional staging system [C-index = 0.589 (95% CI: 0.385-0.792)]. The results were internally and additionally validated using independent cohorts. Conclusion: The pretreatment LCR could independently predict the overall survival in NPC patients. A novel LCR-based prognostic model of an easy-to-use nomogram was established, and it outperformed the conventional staging system in terms of predictive power. Further external verification remains necessary.

Electroconvulsive Therapy Reduces Protein Expression Level of EP300 and Improves Psychiatric Symptoms and Disturbance of Thought in Patients with Schizophrenia.

Objective: Although electroconvulsive therapy (ECT) has been employed as an effective treatment strategy and to improve mental symptoms in schizophrenia (SCZ), its action mechanisms remain unclear. Our previous study found that some genes and biological pathways were closely related to ECT through genetic technology analysis, such as LTP pathway and EP300. This study combined with healthy controls and symptomatology analysis to further explore the changes of expression of EP300 protein in treatment and related symptoms of SCZ. Methods: One hundred and one patients with SCZ and 45 healthy controls (HCs) were enrolled in this study. Patients with SCZ received acute courses of 6 times bilateral ECT. The peripheral blood of patients with SCZ (BECT: before ECT; AECT: after ECT) and the HCs was collected to calculate the changes of expression level of EP300 protein by enzyme-linked immunosorbent assay. The Positive and Negative Symptoms Scale (PANSS) was used to evaluate the severity of symptoms of SCZ patients and the efficiency of the ECT. Results: There was a statistical difference of EP300 protein expression in patients with SCZ (BECT and AECT) (F = 114.5, p < 0.05). ECT reduced plasma expression level of EP300 protein in patients with SCZ, which was not statistically different from that in HCs (t = 4.47, p = 0.20). The change of the expression level of EP300 protein in patients with SCZ (BECT and AECT) has a positive correlation with reduction rate of positive symptoms (r = 0.228, p < 0.05) and disturbance of thought (r = 0.219, p < 0.05). Conclusion: Our study suggests that the expression level of EP300 protein has a significant change in patients with SCZ treating with ECT, and EP300 may have some connections with positive symptoms and disturbance thought of patients with SCZ.