Establishing and Validating an Innovative Focal Adhesion-Linked Gene Signature for Enhanced Prognostic Assessment in Endometrial Cancer.

Studies have highlighted the significant role of focal adhesion signaling in cancer. Nevertheless, its specific involvement in the pathogenesis of endometrial cancer and its clinical significance remains uncertain. We analyzed TCGA-UCEC and GSE119041 datasets with corresponding clinical data to investigate focal adhesion-related gene expression and their clinical significance. A signature, "FA-riskScore," was developed using LASSO regression in the TCGA cohort and validated in the GSE dataset. The FA-riskScore was compared with four existing models in terms of their prediction performance. We employed univariate and multivariate Cox regression analyses towards FA-riskScore to assess its independent prognostic value. A prognostic evaluation nomogram based on our model and clinical indexes was established subsequently. Biological and immune differences between high- and low-risk groups were explored through functional enrichment, PPI network analysis, mutation mining, TME evaluation, and single-cell analysis. Sensitivity tests on commonly targeted drugs were performed on both groups, and Connectivity MAP identified potentially effective molecules for high-risk patients. qRT-PCR validated the expressions of FA-riskScore genes. FA-riskScore, based on FN1, RELN, PARVG, and PTEN, indicated a poorer prognosis for high-risk patients. Compared with published models, FA-riskScore achieved better and more stable performance. High-risk groups exhibited a more challenging TME and suppressive immune status. qRT-PCR showed differential expression in FN1, RELN, and PTEN. Connectivity MAP analysis suggested that BU-239, potassium-canrenoate, and tubocurarine are effective for high-risk patients. This study introduces a novel prognostic model for endometrial cancer and offers insights into focal adhesion's role in cancer pathogenesis.

Factors Associated With Radiological Lung Growth Rate After Lobectomy in Patients With Lung Cancer.

INTRODUCTION: This study is a retrospective study. This study aims to explore the association between lobectomy in lung cancer patients and subsequent compensatory lung growth (CLG), and to identify factors that may be associated with variations in CLG. METHODS: 207 lung cancer patients who underwent lobectomy at Yunnan Cancer Hospital between January 2020 and December 2020. All patients had stage IA primary lung cancer and were performed by the same surgical team. And computed tomography examinations were performed before and 1 y postoperatively. Based on computed tomography images, the volume of each lung lobe was measured using computer software and manual, the radiological lung weight was calculated. And multiple linear regressions were used to analyze the factors related to the increase in postoperative lung weight. RESULTS: One year after lobectomy, the radiological lung weight increased by an average of 112.4 ± 20.8%. Smoking history, number of resected lung segments, preoperative low attenuation volume, intraoperative arterial oxygen partial pressure/fraction of inspired oxygen ratio and postoperative visual analog scale scores at 48 h were significantly associated with postoperative radiological lung weight gain. CONCLUSIONS: Our results suggest that CLG have occurred after lobectomy in adults. In addition, anesthetists should maintain high arterial oxygen partial pressure/fraction of inspired oxygen ratio during one-lung ventilation and improve acute postoperative pain to benefit CLG.

Serological investigation and isolation of Salmonella abortus equi in horses in Xinjiang.

BACKGROUND: Salmonella enterica subspecies enterica serovar abortus equi (S. abortus equi) is one of the main pathogens that causes abortion in pregnant horses and donkeys, which was highly infectious and greatly restricts the healthy development of the horse industry. OBJECTIVES: In order to investigate the prevalence and biological characteristics of S. abortus equi in different regions and breeds of horses in Xinjiang. METHODS: This study conducted ELISA detection of S. abortus equi antibodies on serum samples of 971 horses collected from three large-scale horse farms and five free-range horse farms in Yili Prefecture and Bayingol Mongolian Autonomous Prefecture of Xinjiang from 2020 to 2023. On this basis, bacterial isolation, culture, identification, and drug sensitivity tests were conducted on 42 samples of aborted foal tissues and 23 mare vaginal swabs. RESULTS: The results showed that the positive rate of S. abortus equi antibody was as high as 20.91% in 971 horse serum samples. Among them, the positive rate in the Ili region (29.09%) was significantly higher than that in the Bayingole region (11.24%), and the positive rate in mares (22.45%) was higher than that in stallions (14.05%). In terms of horse breeds, the positive rates of self-propagating thoroughbred horses, half-bred horses, Ili horses and Yanqi horses were 43.22%, 28.81%, 14.72% and 11.24% respectively. In addition, S. abortus equi was more susceptible to juvenile and elderly horses, with positive rates of 70.00%and 41.86%, respectively, both of which were significantly higher than young (10.97%) and adult (19.79%) horses. Further, 9 strains of S. abortus equi were obtained through bacterial isolation, culture and identification, which were resistant to five antibiotics (Clarithromycin, Clindamycin, penicillin, Sulfamethoxazole and Rifampicin), and sensitive to 13 antimicrobial agents (Amoxicillin, Ciprofloxacin and Gentamicin, et al.). CONCLUSION: There was a high infection rate of S. abortus equi in Ili Prefecture and self-propagating thoroughbred horses, and juvenile or old mares were more susceptible, which will provide scientific basis for the prevention of S. abortus equi infection in different regions and breeds of horses in Xinjiang.

Effect of ß-alanine on the athletic performance and blood amino acid metabolism of speed-racing Yili horses.

The objective of this study was to examine the effects of supplemental ß-alanine feeding on the athletic performance of Yili horses involved in speed racing, focusing on alterations in plasma free amino acid patterns pre and post exercise. Additionally, the research aimed to evaluate the effects of carnosine on the plasma acid-base buffering capacity and antioxidant levels in these horses. Twelve Yili horse stallions, averaging 3 years in age and 346.50 ± 21.39 kg in weight, were chosen and randomly divided into two groups: a control group and a test group, each comprising six horses. The control group received a supplementation of 300 mg/kg BW/day of α-alanine, while the test group received 300 mg/kg BW/day of ß-alanine. This supplementation regimen was maintained for a 30-day supplementation trial period, under identical feeding and management conditions. Throughout the trial, the horses participated in the 1,000 Speed Race, and three distinct blood samples were gathered for assessing plasma free amino acids, blood gases, biochemical parameters, and antioxidant parameters. The outcomes indicated a considerable enhancement in the 1,000 m exercise performance of the speed racing Yili horses in the test group compared to the control group, showcasing a noteworthy improvement of 12.01%, with the test group completing the race 13.29 s faster. Notably, the α-alanine content in the plasma of the control group Yili horses remained higher than that of the test group, demonstrating a consistent increasing trend. By contrast, the plasma ß-alanine content was notably higher in the test group than in the control group. Over the course of the supplementation period, plasma ß-alanine exhibited an escalating and then stabilizing trend in the test group, whereas in the control group, although ß-alanine content also increased, the trend was less pronounced. The plasma levels of histidine and carnosine showed minimal variance between the two groups. Overall, the test group of Yili horses exhibited slightly higher plasma levels of histidine and carnosine compared to the control group. The addition of ß-alanine to their diet for a duration of 30 days notably affected the plasma levels of amino acids both pre- and post-exercise in speed-racing Yili horses. Furthermore, ß-alanine demonstrated an inhibitory effect on the catabolism of these horses' bodies during high-intensity exercise. Ten marker amino acids, including valine, leucine, ß-alanine, isoleucine, carnosine, 3-methyl-histidine, lysine, ethanolamine, argnine, and taurine, displayed statistically significant changes. ß-alanine notably increased the blood glucose levels of Yili horses and played a role in expediting the restoration of blood gas levels post-exercise. Moreover, in the test group of Yili horses, the levels of superoxide dismutase, glutathione peroxidase, and total antioxidant capacity significantly increased both before and after the race, while the content of malondialdehyde, an oxidation product, exhibited an extremely significant decrease immediately after the race. These outcomes suggest that the addition of ß-alanine significantly augmented antioxidant levels during high-intensity exercise in Yili horses. Consequently, it reduced post-exercise injuries and accelerated the recovery process after exercise.

Effects of IFN-γ on the immunological microenvironment and TAM polarity in stage IA non-small cell lung cancer and its mechanisms.

OBJECTIVE: To investigate the effect of interferon-γ (IFN-γ) on the immune microenvironment and the polarity of tumor-associated macrophages (TAMs) in stage IA non-small cell lung cancer (NSCLC) and its mechanisms. METHODS: Human non-small cell lung cancer A549 cells were treated with a series of IFN-γ concentrations (0, 50, 100, 150, 200, 250, and 300 ng/mL). Tumor tissues from patients with stage IA NSCLC were cultured using the air-liquid interface culture technique to establish a tumor microenvironment (TME) organ model. The NSCLC model was constructed by subcutaneously embedding small tumor pieces into the back of nonobese diabetic severe combined immune deficiency (NOD SCID) mice. The size and weight of the tumors were recorded, and the tumor volume was calculated. CCK-8 assays were used to investigate cell proliferation, flow cytometry and TUNEL staining were used to evaluate cell apoptosis, colony formation was investigated by cloning experiments, and cell invasion and migration were evaluated by Transwell assays and scratch tests. The expression of apoptosis-related proteins (Bax, Bcl-2 and C-caspase 3), M2 polarization-related markers (CD163, CD206 and IDO1), and marker proteins of cytotoxic T cells and helper T cells (CD8 and CD4) was detected by Western blot. The expression of Ki-67 and IDO1 was detected by immunohistochemistry, and the levels of IL-6, IL-10, IL-13 and TNF-α were measured by ELISA. The expression of CD68 was measured by RT‒qPCR, and the phagocytosis of TAMs was evaluated by a Cell Trace CFSE kit and cell probe staining. RESULTS: The proliferation activity of A549 cells increased with increasing IFN-γ concentration and peaked when the concentration reached 200 ng/mL, and the proliferation activity of A549 cells was suppressed thereafter. After treatment with 200 ng/mL IFN-γ, the apoptosis rate of cells decreased, the number of cell colonies increased, the invasion and migration of cells were promoted, the expression of Bax and C-caspase 3 was downregulated, and the expression of Bcl-2 was upregulated in cells and the TME model. In the TME model, CD163, CD206, IDO1 and Ki-67 were upregulated, CD8 and CD4 were downregulated, apoptosis was reduced, the levels of IL-6 and TNF-α were decreased, and the levels of IL-10 and IL-13 were increased. IL-4 induced TAMs to express CD163 and CD206, reduced the levels of IL-6 and TNF-α, increased the levels of IL-10 and IL-13, and weakened the phagocytic function of TAMs. IFN-γ treatment further enhanced the effect of IL-4 and enhanced the viability of A549 cells. IDO1 decreased the viability of T cells and NK cells, while suppressing the effect of IFN-γ. In mice, compared with NSCLC mice, the tumor volume and weight of the IFN-γ group were increased, the expression of CD163, CD206, IDO1, Ki-67 and Bcl-2 in tumor tissue was upregulated, the expression of Bax and C-caspase 3 was downregulated, and apoptosis was reduced. The levels of IL-6 and TNF-α were decreased, and the levels of IL-10 and IL-13 were increased in the serum of mice. CONCLUSION: In stage IA NSCLC, a low concentration of IFN-γ promotes the polarization of TAMs to the M2 phenotype in the TME model by upregulating the expression of IDO1, promoting the viability of cancer cells, inhibiting the viability of T cells and NK cells, and thus establishing an immune microenvironment conducive to tumor progression.

On the Ion Coordination and Crystallization of Metal Halide Perovskites by In Situ Dynamic Optical Probing.

Controlling the crystallization to achieve high-quality homogeneous perovskite film is the key strategy in developing perovskite electronic devices. Here, an in situ dynamic optical probing technique is demonstrated that can monitor the fast crystallization of perovskites and effectively minimize the influence of laser excitation during the measurement. This study finds that the typical static probing technique would damage and induce phase segregation in the perovskite films during the excitation. These issues can be effectively resolved with the dynamic probing approach. It also found that the crystallization between MAPbI3 and MAPbI2 Br is strikingly different. In particular, MAPbI2 Br suffers from inefficient nucleation during the spin-coating that strongly affects the uniform crystal growth in the annealing process. The commonly used pre-heating process is found at a lower temperature not only can further promote the nucleation but also to complete the crystallization of MAPbI2 Br. The role of further annealing at a higher temperature is to facilitate ion-dissociation on the crystal surface to form a passivation layer to stabilize the MAPbI2 Br lattices. The device performance is strongly correlated with the film formation mechanism derived from the in situ results. This work demonstrates that the in situ technique can provide deep insight into the crystallization mechanism, and help to understand the growth mechanism of perovskites with different compositions and dimensionalities.

Magnetic activated carbon from spent coffee grounds: iron-catalyzed CO2 activation mechanism and adsorption of antibiotic lomefloxacin from aqueous medium.

The facile fabrication of low-cost adsorbents possessing high removal efficiency and convenient separation property is an urgent need for water treatment. Herein, magnetic activated carbon was synthesized from spent coffee grounds (SCG) by Fe-catalyzed CO2 activation at 800 °C for 90 min, and magnetization and pore formation were simultaneously achieved during heat treatment. The sample was characterized by N2 adsorption-desorption, XRD, VSM, SEM, and FTIR. Batch adsorption experiments were conducted using lomefloxacin (LMO) as the probing pollutant. Preparation mechanism was revealed by TG-FTIR and XRD. Experimental results showed that Fe3O4 derived from Fe species can be reduced to Fe by carbon at high temperatures, followed by subsequent reoxidation to Fe3O4 by CO2, and the redox cycle between Fe and Fe3O4 favored the formation of pores. The promotion effects of Fe species on CO2 activation can be quantitatively reflected by the yield of CO as the signature gaseous product, and the suitable activation temperate range was determined to be 675 to 985 °C. The BET surface area, total pore volume, and saturated magnetization value of the product were 586 m2 g-1, 0.327 cm3 g-1, and 11.59 emu g-1, respectively. The Langmuir model was applicable for the adsorption isotherm data for LMO with the maximum adsorption capacity of 95 mg g-1, and thermodynamic analysis revealed that the adsorption process was endothermic and spontaneous. This study demonstrated that Fe-catalyzed CO2 activation was an effective method of converting SCG into magnetic separable adsorbent for LMO removal from aqueous medium.

New prediction equations for knee isokinetic strength in young and middle-aged non-athletes.

BACKGROUND: This study aimed to develop alternative prediction equations to predict isokinetic muscle strength at 60°/s based on anthropometric characteristics, including body mass, height, age, and sex for young and middle-aged non-athlete populations. METHODS: Three hundred and thirty-two healthy non-athletic participants (174 females, 158 males) between 20 and 59 years underwent a 60°/s isokinetic knee joint concentric contraction test. Forty people were randomly selected for retesting to assess the reliability of the isokinetic instrument. Multivariate linear regression was used to establish extension peak torque (EPT) and flexion peak torque (FPT) prediction equations. Sixty extra participants were used individually to validate the prediction equations, and Bland Altman plots were constructed to assess the agreement of predicted values with actual measurements. RESULTS: The result demonstrated that the instrument we used has excellent reliability. The multivariable linear regression model showed that body mass, age, and sex were significant predictors of PT (EPT: Adjusted R2 = 0.804, p < 0.001; FPT: Adjusted R2 = 0.705, p < 0.001). Furthermore, the equations we established had higher prediction accuracy than those of Gross et al. and Harbo et al. CONCLUSION: The equations developed in this study provided relatively low bias, thus providing a more suitable reference value for the knee isokinetic strength of young and middle-aged non-athletes.

Clinical analysis of renal cell carcinoma with intestinal metastasis resulting in small bowel and colon fistula.

An enteric fistula is an abnormal connection between the intestine and other organs and is often caused by inflammation or trauma. Diagnosis and treatment involve imaging and endoscopy. Treatment may include medication and surgery. This report presents a rare case of severe enteric fistula caused by colonic metastasis of clear cell renal carcinoma. The objective of this report is to increase surgeons' awareness of atypical manifestations of intestinal metastatic cancer.

Automated evaluation of retinal hyperreflective foci changes in diabetic macular edema patients before and after intravitreal injection.

Purpose: Fast and automated reconstruction of retinal hyperreflective foci (HRF) is of great importance for many eye-related disease understanding. In this paper, we introduced a new automated framework, driven by recent advances in deep learning to automatically extract 12 three-dimensional parameters from the segmented hyperreflective foci in optical coherence tomography (OCT). Methods: Unlike traditional convolutional neural networks, which struggle with long-range feature correlations, we introduce a spatial and channel attention module within the bottleneck layer, integrated into the nnU-Net architecture. Spatial Attention Block aggregates features across spatial locations to capture related features, while Channel Attention Block heightens channel feature contrasts. The proposed model was trained and tested on 162 retinal OCT volumes of patients with diabetic macular edema (DME), yielding robust segmentation outcomes. We further investigate HRF's potential as a biomarker of DME. Results: Results unveil notable discrepancies in the amount and volume of HRF subtypes. In the whole retinal layer (WR), the mean distance from HRF to the retinal pigmented epithelium was significantly reduced after treatment. In WR, the improvement in central macular thickness resulting from intravitreal injection treatment was positively correlated with the mean distance from HRF subtypes to the fovea. Conclusion: Our study demonstrates the applicability of OCT for automated quantification of retinal HRF in DME patients, offering an objective, quantitative approach for clinical and research applications.

Differences in the degradation behavior of disinfection by-products in UV/PDS and UV/H2O2 processes and the effect of their chemical properties.

In this work, sixteen typical chlorinated and brominated aromatic disinfection by-products (DBPs) were selected as examples to investigate their different degradation mechanisms initiated by HO• and SO4•-. Addition reactions were the main mode of degradation of DBPs by HO•, while SO4•- dominated H-abstraction reactions and single electron transfer reactions. Chlorinated compounds had higher reactivity than brominated compounds. Furthermore, substituents with stronger electron-donating effects promoted the electrophilic reaction of DBPs with the two radicals. In addition, we developed a model based on the chemical properties LUMO, fmax-, and hardness for predicting the average reaction energy barriers for the initial reactions of DBPs with HO• and SO4•-. The model had good predictive performance for the difficulty of degradation of different DPBs by HO• and SO4•-, with R2 values of 0.85 and 0.87, respectively. Through the degradation efficiency simulation, we found that longer reaction times, higher oxidant concentrations and lower pollutant concentrations were more favorable for the removal of DBPs. The UV/PDS process showed better degradation of DBPs than the UV/H2O2 process. In addition, most degradation products of DBPs exhibited less toxicity to aquatic organisms than their parent compounds. This study provided theoretical guidance for the degradation and removal of other aromatic DBPs at the molecular level.

Risk factor analysis for major mediastinal vessel invasion in thymic epithelial tumors based on multi-slice CT Imaging.

Objective: To explore the characteristics and risk factors for major mediastinal vessel invasion in different risk grades of thymic epithelial tumors (TETs) based on computed tomography (CT) imaging, and to develop prediction models of major mediastinal artery and vein invasion. Methods: One hundred and twenty-two TET patients confirmed by histopathological analysis who underwent thorax CT were enrolled in this study. Clinical and CT data were retrospectively reviewed for these patients. According to the abutment degree between the tumor and major mediastinal vessels, the arterial invasion was divided into grade I, II, and III (< 25%, 25 - 49%, and ≥ 50%, respectively); the venous invasion was divided into grade I and II (< 50% and ≥ 50%). The degree of vessel invasion was compared among different defined subtypes or stages of TETs using the chi-square tests. The risk factors associated with TET vascular invasion were identified using multivariate logistic regression analysis. Results: Based on logistic regression analysis, male patients (ß = 1.549; odds ratio, 4.824) and the pericardium or pleural invasion (ß = 2.209; odds ratio, 9.110) were independent predictors of 25% artery invasion, and the midline location (ß = 2.504; odds ratio, 12.234) and mediastinal lymphadenopathy (ß = 2.490; odds ratio, 12.06) were independent predictors of 50% artery invasion. As for 50% venous invasion, the risk factors include midline location (ß = 2.303; odds ratio, 10.0), maximum tumor diameter larger than 5.9 cm (ß = 4.038; odds ratio, 56.736), and pericardial or pleural effusion (ß = 1.460; odds ratio, 4.306). The multivariate logistic model obtained relatively high predicting efficacy, and the area under the curve (AUC), sensitivity, and specificity were 0.944, 84.6%, and 91.7% for predicting 50% artery invasion, and 0.913, 81.8%, and 86.0% for 50% venous invasion in TET patients, respectively. Conclusion: Several CT features can be used as independent predictors of ≥50% artery or venous invasion. A multivariate logistic regression model based on CT features is helpful in predicting the vascular invasion grades in patients with TET.

Homogeneous and heterogeneous atmospheric ozonolysis of chlorobenzene:Mechanism, kinetics and ecotoxicity assessment.

The reactions between chlorobenzene(CB) and ozone have been studied comprehensively in this paper. Chlorobenzene is a commonly found chlorinated aromatic volatile organic compound(VOC), and its emission into the atmosphere can cause harm to the ecosystem and human health. The frequent occurrence of mineral particles from sandstorms exerts a significant influence on the atmospheric chemistry of the troposphere. Mineral particles are abundant in SiO2 and Al2O3 content. Therefore, we investigated the homogeneous and heterogeneous reaction processes of CB and ozone in the atmosphere by using density functional theory (DFT) method at the M06-2X/6-311++g(3df,2p)//M06-2X/6-31+g(d,p) level. The atmospheric fate, reaction rate and toxicity evaluation of CB ozonation were studied in the gas-phase section. Toxicity evaluation results showed that ozonation of CB could effectively reduce its toxicity. For the heterogeneous process, we simulated three types of SiO2 clusters and nine types of (Al2O3)n clusters, and studied the configurations of CB adsorbed on the cluster surfaces. We found that adsorption of CB on the SiO2 clusters was achieved through hydrogen bonding, while adsorption of CB on the Al2O3 clusters was achieved through both hydrogen bonding and metal bonding. The energy for CB adsorption on the (Al2O3)n cluster surface was higher than that for the SixOy(OH)z cluster surface, and both types of clusters exhibited efficient adsorption of CB. As the SixOy(OH)z clusters grew larger, the rates for the reactions between O3 and CB increased. CB travelled long distances along the Al2O3 clusters, leading to an extended influence range.

Effects of Lactobacillus rhamnosus Supplementation on Growth Performance, Immune Function, and Antioxidant Capacity of Newborn Foals.

This study aimed to explore the effects of Lactobacillus rhamnosus GG (LGG) supplementation on the growth performance, immune function, and antioxidant capacity of foals. Fifteen newborn foals with similar birth weight (51.67 ± 6.07 kg) and good health were randomly assigned to three groups: control group and test groups I and II, which were supplemented with 5.0 × 109 CFU/day and 1.0 × 1010 CFU/day LGG, respectively, for 150 days. LGG intake increased the daily body height (P < .01) and weight (P < .01) gain of foals aged 120 to 150 days. The foals' IgA (P < .05) and IgG (P < .01) plasma levels increased at 30 and 150 days, respectively, and IL-6 plasma level increased at 90 days (P < .01). Plasma total antioxidant capacity level was significantly higher in test group I than in the control and test group II at 30 days (P < .01), whereas glutathione peroxidase level was significantly higher in test group II than in the control and test group I at 30 days (P < .01). Both test groups had significantly higher superoxide dismutase level than the control group (P < .01) and significantly decreased malondialdehyde plasma level at 90 and 150 days (P < .05). Overall, our findings indicate that dietary supplementation of LGG can improve the growth performance, immune function, and antioxidant capacity of newborn foals.

Interaction of Cerium Oxide Nanoparticles and Ionic Cerium with Duckweed (Lemna minor L.): Uptake, Distribution, and Phytotoxicity.

As one of the most widely used nanomaterials, CeO2 nanoparticles (NPs) might be released into the aquatic environment. In this paper, the interaction of CeO2 NPs and Ce3+ ions (0~10 mg/L) with duckweed (Lemna minor L.) was investigated. CeO2 NPs significantly inhibited the root elongation of duckweed at concentrations higher than 0.1 mg/L, while the inhibition threshold of Ce3+ ions was 0.02 mg/L. At high doses, both reduced photosynthetic pigment contents led to cell death and induced stomatal deformation, but the toxicity of Ce3+ ions was greater than that of CeO2 NPs at the same concentration. According to the in situ distribution of Ce in plant tissues by µ-XRF, the intensity of Ce signal was in the order of root > old frond > new frond, suggesting that roots play a major role in the uptake of Ce. The result of XANES showed that 27.6% of Ce(IV) was reduced to Ce(III) in duckweed treated with CeO2 NPs. We speculated that the toxicity of CeO2 NPs to duckweed was mainly due to its high sensitivity to the released Ce3+ ions. To our knowledge, this is the first study on the toxicity of CeO2 NPs to an aquatic higher plant.

Identification of vaccine candidates against rhodococcus equi by combining pangenome analysis with a reverse vaccinology approach.

Rhodococcus equi (R. equi) is a zoonotic opportunistic pathogen that can cause life-threatening infections. The rapid evolution of multidrug-resistant R. equi and the fact that there is no currently licensed effective vaccine against R. equi warrant the need for vaccine development. Reverse vaccinology (RV), which involves screening a pathogen's entire genome and proteome using various web-based prediction tools, is considered one of the most effective approaches for identifying vaccine candidates. Here, we performed a pangenome analysis to determine the core proteins of R. equi. We then used the RV approach to examine the subcellular localization, host and gut flora homology, antigenicity, transmembrane helices, physicochemical properties, and immunogenicity of the core proteins to select potential vaccine candidates. The vaccine candidates were then subjected to epitope mapping to predict the exposed antigenic epitopes that possess the ability to bind with major histocompatibility complex I/II (MHC I/II) molecules. These vaccine candidates and epitopes will form a library of elements for the development of a polyvalent or universal vaccine against R. equi. Sixteen R. equi complete proteomes were found to contain 6,238 protein families, and the core proteins consisted of 3,969 protein families (∼63.63% of the pangenome), reflecting a low degree of intraspecies genomic variability. From the pool of core proteins, 483 nonhost homologous membrane and extracellular proteins were screened, and 12 vaccine candidates were finally identified according to their antigenicity, physicochemical properties and other factors. These included four cell wall/membrane/envelope biogenesis proteins; four amino acid transport and metabolism proteins; one cell cycle control, cell division and chromosome partitioning protein; one carbohydrate transport and metabolism protein; one secondary metabolite biosynthesis, transport and catabolism protein; and one defense mechanism protein. All 12 vaccine candidates have an experimentally validated 3D structure available in the protein data bank (PDB). Epitope mapping of the candidates showed that 16 MHC I epitopes and 13 MHC II epitopes with the strongest immunogenicity were exposed on the protein surface, indicating that they could be used to develop a polypeptide vaccine. Thus, we utilized an analytical strategy that combines pangenome analysis and RV to generate a peptide antigen library that simplifies the development of multivalent or universal vaccines against R. equi and can be applied to the development of other vaccines.

COTE-1 promotes the proliferation and invasion of small cell lung cancer by regulating autophagy activity via the AMPK/mTOR signaling pathway.

BACKGROUND: COTE-1 has been found to promote the proliferation and invasion of non-small cell lung cancer. However, the mechanism of COTE-1 in SCLC is still unclear. Exploring the role of COTE-1 in SCLC is expected to provide a potential target for the prognosis and treatment of SCLC. METHODS: The expression of COTE-1 and ki-67 was detected by immunohistochemical staining. PCR detected COTE-1 expression level. Cell proliferation activity was detected by CCK8 assay. A wound healing test detected cell migrative ability. Transwell invasion assay detected cell invasive ability. The numbers of autophagosomes were observed by transmission electron microscopy. WB detected the expression levels of autophagy-related proteins and AMPK/mTOR pathway-related proteins. The effect of COTE-1 expression level on the proliferation of SCLC tumor tissues was investigated by establishing a mouse SCLC xenograft tumor model. RESULTS: The expression of COTE-1 in SCLC tissues and cells was higher than that in normal tissues and cells. In SCLC cells with high COTE-1 expression, the expression level of autophagy proteins was notably increased, the number of intracellular autophagosomes increased, and the proliferative activity, migration and invasion abilities were enhanced. COTE-1 promotes autophagy, proliferation, and invasion of SCLC cells under nutrient deprivation by activating the AMPK/mTOR signaling pathway. Activation of autophagy by COTE-1 promotes the proliferation and development of xenograft tumors in a mouse model of SCLC. CONCLUSION: COTE-1 promotes the proliferation, migration and invasion of small cell lung cancer by mediating autophagy based on the AMPK/mTOR pathway.

StruNet: Perceptual and low-rank regularized transformer for medical image denoising.

BACKGROUND: Various types of noise artifacts inevitably exist in some medical imaging modalities due to limitations of imaging techniques, which impair either clinical diagnosis or subsequent analysis. Recently, deep learning approaches have been rapidly developed and applied on medical images for noise removal or image quality enhancement. Nevertheless, due to complexity and diversity of noise distribution representations in different medical imaging modalities, most of the existing deep learning frameworks are incapable to flexibly remove noise artifacts while retaining detailed information. As a result, it remains challenging to design an effective and unified medical image denoising method that will work across a variety of noise artifacts for different imaging modalities without requiring specialized knowledge in performing the task. PURPOSE: In this paper, we propose a novel encoder-decoder architecture called Swin transformer-based residual u-shape Network (StruNet), for medical image denoising. METHODS: Our StruNet adopts a well-designed block as the backbone of the encoder-decoder architecture, which integrates Swin Transformer modules with residual block in parallel connection. Swin Transformer modules could effectively learn hierarchical representations of noise artifacts via self-attention mechanism in non-overlapping shifted windows and cross-window connection, while residual block is advantageous to compensate loss of detailed information via shortcut connection. Furthermore, perceptual loss and low-rank regularization are incorporated into loss function respectively in order to constrain the denoising results on feature-level consistency and low-rank characteristics. RESULTS: To evaluate the performance of the proposed method, we have conducted experiments on three medical imaging modalities including computed tomography (CT), optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). CONCLUSIONS: The results demonstrate that the proposed architecture yields a promising performance of suppressing multiform noise artifacts existing in different imaging modalities.

Joint conditional generative adversarial networks for eyelash artifact removal in ultra-wide-field fundus images.

Background: Ultra-Wide-Field (UWF) fundus imaging is an essential diagnostic tool for identifying ophthalmologic diseases, as it captures detailed retinal structures within a wider field of view (FOV). However, the presence of eyelashes along the edge of the eyelids can cast shadows and obscure the view of fundus imaging, which hinders reliable interpretation and subsequent screening of fundus diseases. Despite its limitations, there are currently no effective methods or datasets available for removing eyelash artifacts from UWF fundus images. This research aims to develop an effective approach for eyelash artifact removal and thus improve the visual quality of UWF fundus images for accurate analysis and diagnosis. Methods: To address this issue, we first constructed two UWF fundus datasets: the paired synthetic eyelashes (PSE) dataset and the unpaired real eyelashes (uPRE) dataset. Then we proposed a deep learning architecture called Joint Conditional Generative Adversarial Networks (JcGAN) to remove eyelash artifacts from UWF fundus images. JcGAN employs a shared generator with two discriminators for joint learning of both real and synthetic eyelash artifacts. Furthermore, we designed a background refinement module that refines background information and is trained with the generator in an end-to-end manner. Results: Experimental results on both PSE and uPRE datasets demonstrate the superiority of the proposed JcGAN over several state-of-the-art deep learning approaches. Compared with the best existing method, JcGAN improves PSNR and SSIM by 4.82% and 0.23%, respectively. In addition, we also verified that eyelash artifact removal via JcGAN could significantly improve vessel segmentation performance in UWF fundus images. Assessment via vessel segmentation illustrates that the sensitivity, Dice coefficient and area under curve (AUC) of ResU-Net have respectively increased by 3.64%, 1.54%, and 1.43% after eyelash artifact removal using JcGAN. Conclusion: The proposed JcGAN effectively removes eyelash artifacts in UWF images, resulting in improved visibility of retinal vessels. Our method can facilitate better processing and analysis of retinal vessels and has the potential to improve diagnostic outcomes.