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Background: Shenfu Injection (SFI) has emerged as a prevalent therapeutic intervention in clinical practice for the management of acute pancreatitis (AP). The purpose of this research was to investigate and validate the potential mechanisms of SFI in the treatment of AP through network pharmacology. Methods: Network pharmacology was adopted to investigate the potential targets and mechanisms of SFI in the treatment of AP. Molecular docking was employed to evaluate the binding affinity between active components and targets. Single-cell transcriptome analysis was conducted to explore the cell types associated with SFI treatment in AP. In vitro and in vivo models of AP were induced by caerulein. The histopathological changes were observed by HE staining. Cell apoptosis was detected using flow cytometry and Tunel staining. Cell viability was assessed using CCK-8 assay. Western blot and ELISA were used to detect the protein expression and inflammatory cytokines, respectively. Results: A total of 104 SFI active components were obtained, of which 29 targeted 76 genes. After intersecting with 3370 AP-related genes, 42 SFI treatment AP potential targets were identified. Enrichment analysis revealed that these targets were associated with cell apoptosis, necroptosis, and multiple signal transduction pathways, such as p53, IL-17 and TNF signal pathways, etc. Molecular docking demonstrated that the active components of SFI had good binding affinity with the corresponding targets and the binding ability of NGF and aromadendrene was the strongest. Bioinformatics analysis revealed that SFI treatment in AP is associated with various cell types, including acinar cells, endothelial cells, T cells, dendritic cells, ductal cells, and mesenchymal cells. Furthermore, in vitro experiments demonstrated that SFI induces acinar cell apoptosis in a dose-dependent manner, accompanied by increased expression of cleaved-caspase3/caspase3 and cleaved-caspase8/caspase8 proteins, and inhibition of inflammatory cytokine (TNF-ɑ, IL-1β, and PTGS2) expression. In vivo experiments demonstrated that SFI improved histopathological alterations, reduces inflammation, and promotes apoptosis and the expression of cleaved-casp3 and cleaved-casp8 in AP rats. Conclusions: This study elucidated the multi-component, multi-target, and multi-cellular characteristics of SFI in the treatment of AP, and confirmed its mechanism of promoting acinar cell apoptosis.

(1) Background: Weaning is a challenging and stressful event in the pig’s life, which disrupts physiological balance and induces oxidative stress. Microbiota play a significant role during the weaning process in piglets. Therefore, this study aimed to investigate key gut microbiota and metabolites associated with weaning stress in piglets. (2) Methods: A total of ten newborn piglet littermates were randomly assigned to two groups: S (suckling normally) and W (weaned at 21 d; all euthanized at 23 d). Specimens of the cecum were dehydrated with ethanol, cleared with xylene, embedded in paraffin, and cut into 4 mm thick serial sections. After deparaffinization, the sections were stained with hematoxylin and eosin (H&E) for morphometric analysis. Cecal metagenomic and liver LC-MS-based metabolomics were employed in this study. Statistical comparisons were performed by a two-tailed Student’s t-test, and p < 0.05 indicated statistical significance. (3) Results: The results showed that weaning led to intestinal morphological damage in piglets. The intestinal villi of suckling piglets were intact, closely arranged in an orderly manner, and finger-shaped, with clear contours of columnar epithelial cells. In contrast, the intestines of weaned piglets showed villous atrophy and shedding, as well as mucosal bleeding. Metagenomics and metabolomics analyses showed significant differences in composition and function between suckling and weaned piglets. The W piglets showed a decrease and increase in the relative abundance of Bacteroidetes and Proteobacteria (p < 0.05), respectively. The core cecal flora in W piglets were Campylobacter and Clostridium, while those in S piglets were Prevotella and Lactobacillus. At the phylum level, the relative abundance of Bacteroidetes significantly decreased (p < 0.05) in weaned piglets, while Proteobacteria significantly increased (p < 0.05). Significant inter-group differences were observed in pathways and glycoside hydrolases in databases, such as the KEGG and CAZymes, including fructose and mannose metabolism, salmonella infection, antifolate resistance, GH135, GH16, GH32, and GH84. We identified 757 differential metabolites between the groups through metabolomic analyses—350 upregulated and 407 downregulated (screened in positive ion mode). In negative ion mode, 541 differential metabolites were identified, with 270 upregulated and 271 downregulated. Major differential metabolites included glycerophospholipids, histidine, nitrogen metabolism, glycine, serine, threonine, β-alanine, and primary bile acid biosynthesis. The significant differences in glycine, serine, and threonine metabolites may be potentially related to dysbiosis caused by weaning stress. Taken together, the identification of microbiome and metabolome signatures of suckling and weaned piglets has paved the way for developing health-promoting nutritional strategies, focusing on enhancing bacterial metabolite production in early life stages.

BackgroundSepsis-associated encephalopathy (SAE) is one of the most ubiquitous complications of sepsis and is characterized by cognitive impairment, poor prognosis, and a lack of uniform clinical diagnostic criteria. Therefore, this study investigated the early diagnostic and prognostic value of serum neuron-specific enolase (NSE) in SAE.MethodsThis systematic review and meta-analysis systematically searched for clinical trials with serum NSE information in patients with sepsis in the PubMed, Web of Science, Embase, and Cochrane databases from their inception to April 10, 2023. Included studies were assessed for quality and risk of bias using The Quality Assessment of Diagnostic Accuracy-2 tool. The meta-analysis of the included studies was performed using Stata 17.0 and Review Manager version 5.4.FindingsEleven studies were included in this meta-analysis involving 1259 serum samples from 947 patients with sepsis. Our results showed that the serum NSE levels of patients with SAE were higher than those of the non-encephalopathy sepsis group (mean deviation, MD,12.39[95% CI 8.27–16.50, Z = 5.9, p

In this study, L-lactate dehydrogenase (Lr-L-LDH) from Lactobacillus rhamnosus was investigated. The well-known Lr-L-LDH1 was taken as the control, differences between Lr-L-LDH1 and Lr-L-LDH2 annotated from the genome of L. rhamnosus were analyzed. The primary structure, basic properties, hydrophobicity, secondary structure of Lr-L-LDH1 and Lr-L-LDH2 were predicted and analyzed using online websites and professional software. Homology modeling of the tertiary structure, molecular docking of enzymes and substrates, phylogenetic analysis, in vitro cloning, expression, and enzyme activity assays were further studied. The results showed that, in comparison to Lr-L-LDH1, although Lr-L-LHD2 had similar molecular characteristics, secondary and tertiary structures, Lr-L-LHD2 exhibited differences: A shorter sequences, low amino acid identities (48.08%), and a different phylogenetic status. Lr-L-LHD2 also contained a catalytically active site, a highly conserved NAD+ binding site sequence (GXGXXG), a three-dimensional active pocket domain, was an NAD+ dependent tetrameric L-lactate dehydrogenase, and be activated by fructose 1,6-diphosphate in the cytoplasm for catalyzing the reduction of pyruvate to L-lactic acid. In vitro enzyme activity was significantly lower than Lr-L-LDH1 (P

Abstract Background The plasma sample has emerged as a promising surrogate sample for EGFR mutation detection in advanced non‐small cell lung cancer (NSCLC). In clinical practice, whether EGFR variants in baseline plasma ctDNA of advanced NSCLC can predict prognosis in addition to guiding targeted therapy remains to be further explored. Material and Methods In total, 315 NSCLC patients were retrospectively enrolled. EGFR mutation data from tissue detected by ARMS‐PCR and paired plasma samples within 1 month of admission detected by SuperARMS or ARMS‐PCR were collected. The correlation between baseline plasma ctDNA EGFR mutation status and survival was compared. Results EGFR mutation detection rates in tumor samples and plasma samples were 65.1% (205/315) and 43.8% (138/315). Referred to tissue results, the consistent rate of test ctDNA EGFR alteration by SuperARMS was higher than that detected by ARMS (79.5% vs. 69.0%, p = 0.04), either in stage I–IIIA patients (85.7% vs. 50.0%, p = 0.4) or stage IIIB–IV patients (79.1% vs. 69.4%, p = 0.04). Patients' treatment status and pathological subtype were the two factors that affected plasma ctDNA EGFR alteration detection accuracy. The concordance in non‐adenocarcinoma patients was obviously higher than that in adenocarcinoma (p = 0.02), and the concordance in treatment naïve patients was significantly higher than that in relapse patients (p = 0.047). In treatment naïve patients, the median PFS (mPFS) in plasma ctDNA EGFR‐positive patients was shorter than that in plasma ctDNA EGFR negative patients (7.0 vs. 10.0 months, p = 0.01). In relapsed patients, the mPFS in plasma ctDNA EGFR‐positive patients was 9.0 months versus 11.0 months in plasma ctDNA EGFR negative patients (p = 0.1). Conclusions A plasma sample could be an alternative for a molecular test when tissue samples was unavailable. The SuperARMS‐PCR detection method has high sensitivity in real‐world clinical practice. Furthermore, in patients with stage IIIB‐IV, baseline plasma ctDNA EGFR mutation positivity not only guides targeted therapy but also predicts a worse prognosis.

Peripheral nerve injury (PNI) is a neurological disorder caused by trauma that is frequently induced by accidents, war, and surgical complications, which is of global significance. The severity of the injury determines the potential for lifelong disability in patients. Artificial nerve scaffolds have been investigated as a powerful tool for promoting optimal regeneration of nerve defects. Over the past few decades, bionic scaffolds have been successfully developed to provide guidance and biological cues to facilitate Schwann cell myelination and orientated axonal growth. Numerous assessment techniques have been employed to investigate the therapeutic efficacy of nerve scaffolds in promoting the growth of Schwann cells and axons upon the bioactivities of distinct scaffolds, which have encouraged a greater understanding of the biological mechanisms involved in peripheral nerve development and regeneration. However, it is still difficult to compare the results from different labs due to the diversity of protocols and the availability of innovative technologies when evaluating the effectiveness of novel artificial scaffolds. Meanwhile, due to the complicated process of peripheral nerve regeneration, several evaluation methods are usually combined in studies on peripheral nerve repair. Herein, we have provided an overview of the evaluation methods used to study the outcomes of scaffold-based therapies for PNI in experimental animal models and especially focus on Schwann cell functions and axonal growth within the regenerated nerve.

Context: The expression of programmed cell death ligand1 (PDL1) is a research hotspot of immunotherapy. The treatment targeted for its expression has shown effectiveness in many tumors. Objective: The aim of the study was to determine PD-L1 expression in urothelial carcinoma (UC) and to compare the PD-L1 expression in muscle invasive bladder carcinoma (MIBC) and upper urinary tract urothelial carcinoma (UTUC). The predictive value of CD8+ tumor-infiltrating lymphocyte (TIL) density for the diagnosis of PD-L1 positivity and the association between CD8+ TIL density and prognosis in MIBC were also explored. Materials and Methods: Immunohistochemistry (IHC) staining for PD-L1 (SP263), CK5/6, CK20, CD44, and p53 was carried out using a 3D Histech digital scanner to scan and determine CD8+ TIL density. Results: 122 patients received radical cystectomy, and the overall PD-L1 positivity was 34.43% (42/122). PD-L1 positivity in whole sections was higher than in tissue micro-array (TMA) (all P < 0.05). If multiple lesions were detected simultaneously, the number of patients with positive results increased from 42 to 49. The areas under the curve (AUCs) of CD8+ TIL density for the diagnosis of PD-L1 positivity were 0.739, 0.713, and 0.826. Univariate cox regression analysis demonstrated that high CD8+ TIL density and CD8highPDL1+ were protective factors of overall survival (OS), and multivariate cox analyses showed that only CD8+ TIL density was an independent prognostic factor for OS. For UTUC, the overall PD-L1 expression was 40.0% (16/40). Conclusions: Our study results emphasize the importance of detecting PD-L1 expression in multiple tumor lesions from the same patient. In MIBC, CD8+ TIL density could be used as a prognostic marker for predicting the status of PD-L1 expression.

ObjectiveThis study was designed to evaluate the suitable radiotherapy dose in SCLC patients with BM.MethodsA retrospective analysis was performed among 121 patients on the prognosis of BM of SCLC who were admitted to our hospital from 2013 to 2023. They all received first line chemotherapy. 80 patients of them received TRT after chemotherapy. The Chi square method was used to compare the categorical data. Univariate survival analysis was estimated by Kaplan Meier method and the logrank was used to compare survival curves between groups. A multivariate prognostic analysis was made by the Cox proportional hazard model. The iOS and iLC of two groups of low dose and high dose were analyzed after propensity score matching (PSM).ResultsIn all the patients, the median follow-up time was 18.6 months (range 6.30~85.7), the 2-year iOS and iLC rates were 15.4% and 70.3%, respectively, and cerebral necrosis occurred in 2 patients. In univariate analysis related to iOS, extracranial disease control (p=0.023), higher DS-GPA (≥2) (p=0.016), immunotherapy (p=0.049), low-dose(p=0.030), and WBRT+SIB (p=0.009) were significantly associated with an increase in survival rate. After PSM, the 2-year iOS of low dose (n=49) was significantly higher than that of high dose (n=49) (P=0.025), while the 2-year iLC was not significantly improved (P=0.267). In DS-GPA < 2 subgroup, the iOS of low dose group was significantly higher than that of high dose group (p=0.019). In the DS-GPA ≥ 2 subgroup, the 2-year iLC of the low dose group was significantly inferior than that of the high dose group (p=0.044).ConclusionsThe iLC was improved along with increasing radiotherapy dose, but high dose had inferior iOS compared to low dose, while there were not significantly improving iLC when radiotherapy BED >56Gy. But in patients with DS-GPA≥2 subgroup, high dose brought better iLC benefits.

Purpose: The purpose of this study was to investigate the prognostic differences between patients with small-cell lung cancer (SCLC) with different chemosensitivity to first-line chemotherapy who developed brain metastasis (BM) as the first site of progression. Methods: Patients with a BM after first-line treatment in the Tianjin Cancer Hospital were retrospectively analyzed. According to the time-free interval (TFI) between the completion of first-line chemotherapy and the onset of the BM, the patients were divided into the chemo-sensitive group (TFI ≥ 90 days, n = 145) and the chemo-resistant group (TFI < 90 days, n = 97). The survival time, which was calculated from the diagnosis of the BM, was analyzed after the onset of brain metastasis (BM-OS). Survival curves were plotted using the Kaplan–Meier method, and differences between groups were compared using the log-rank test. Results: In total, the median BM-OS was 8.4 months. The median BM-OS in the chemo-sensitive group was 8.8 months, and it was 8.0 months in the chemo-resistant group (p = 0.538). In patients without extracranial progression (n = 193), the median BM-OSes in the chemo-sensitive and chemo-resistant groups were 9.4 months and 9.7 months, respectively (p = 0.947). In patients with extracranial progression (n = 49), the median BM-OSes in the chemo-sensitive and chemo-resistant groups were 5.4 months and 4.2 months, respectively (p = 0.161). Conclusions: After the development of a BM as the first site of progression following chemotherapy in patients with SCLC, the prognosis of chemo-sensitive patients was not necessarily superior to chemo-resistant patients, especially in patients without extracranial progression.

Abstract Background Previous studies have identified the carbohydrate epitope Galα1–3Galβ1–4GlcNAc-R (termed the α-galactosyl epitope), known as the α-Gal antigen as the primary xenoantigen recognized by the human immune system. The α-Gal antigen is regulated by galactosyltransferase (GGTA1), and α-Gal antigen-deficient mice have been widely used in xenoimmunological studies, as well as for the immunogenic risk evaluation of animal-derived medical devices. The objective of this study was to develop α-Gal antigen-deficient rabbits by GGTA1 gene editing with the CRISPR/Cas9 system. Results The mutation efficiency of GGTA1 gene-editing in rabbits was as high as 92.3% in F0 pups. Phenotype analysis showed that the α-Gal antigen expression in the major organs of F0 rabbits was decreased by more than 99.96% compared with that in wild-type (WT) rabbits, and the specific anti-Gal IgG and IgM antibody levels in F1 rabbits increased with increasing age, peaking at approximately 5 or 6 months. Further study showed that GGTA1 gene expression in F2-edited rabbits was dramatically reduced compared to that in WT rabbits. Conclusions α-Gal antigen-deficient rabbits were successfully generated by GGTA1 gene editing via the CRISPR/Cas9 system in this study. The feasibility of using these α-Gal antigen-deficient rabbits for the in situ implantation and residual immunogenic risk evaluation of animal tissue-derived medical devices was also preliminarily confirmed.

Infectious hematopoietic necrosis virus (IHNV) is an important pathogen that causes significant economic losses to salmon trout farming. Although vaccines have been invented for the treatment of IHNV, findings from our previous survey show that breeding enterprises and farmers require effective oral drugs or immune enhancers. However, studies on the development of oral drugs are limited. In the present study, we used bioinformatics methods to predict the protein targets of andrographolide (Andro) in IHNV. Cells were infected with IHNV, and the effect of andrographolide was explored by evaluating the expression levels of genes implicated in oxidative stress, activities of antioxidant enzymes, and the expression of genes implicated in apoptosis and necrosis. In the present study, cells were divided into NC, IHNV, IHNV+10 μM andrographolide, and IHNV+20 μM andrographolide groups. qRT-PCR was performed to determine the expression level of genes, and an antioxidant enzyme detection kit was used to evaluate the activities of antioxidant enzymes. Fluorescent staining was performed using a reactive oxygen species detection kit (ROS) and Hoechst 33342/PI double staining kit, and the mechanism of alleviation of apoptosis and oxidative stress andrographolide after IHNV infection was determined. The results indicated that andrographolide inhibits viral growth by binding to the NV protein of IHNV and increasing the antioxidant capacity of the body through the CTSK/BCL2/Cytc axis, thereby inhibiting the occurrence of IHNV-induced apoptosis. This is the first study to explore the antagonistic mechanism of action of andrographolide in alleviating IHNV infection. The results provide valuable information on alternative strategies for the treatment of IHNV infection during salmon family and provide a reference for the use of andrographolide as an antioxidant agent in agricultural settings.

In order to increase the comprehensive utilization rate of green Sichuan pepper and improve economic benefits, the slag material with higher quality was screened out to develop related products. This study used ultraviolet-visible spectroscopy scanning, principal component factor analysis, correlation analysis and cluster analysis to comprehensively evaluate the green Sichuan pepper slag from five different origins (Sichuan Han, Sichuan Hongya, Sichuan Jinyang, Chongqin Jiangjin, Yunnan Zhaotong). The results showed that the similarity of the five types of green Sichuan pepper in the early soaking period was between 0.994 and 0.997, and the similarity after the extraction was between 0.980 and 0.991, indicating that the extraction process had a certain influence on the quality of green Sichuan pepper. The hydroxy-β-sanshool content, opening ratio, ash, moisture, chlorophyll, △L*, △b* and sensory score of the green Sichuan pepper showed a downward trend，△a* and △E*showed an upward trend. The overall quality of the slag after the leaching of green Sichuan pepper was as follows: Sichuan Jinyang, Sichuan Hongya, Chongqing Jiangjin, Yunnan Zhaotong and Sichuan Hanyuan. When the threshold was less than 35.54, there were significant differences between Sichuan Jinyang and the other four producing origins of green Sichuan pepper. This study could provide a theoretical reference for the comprehensive utilization of raw materials and product development of green Sichuan pepper residue.

Abstract Background Cyclin-dependent kinase 16 (CDK16) is an atypical PCTAIRE kinase, and its activity is dependent on the Cyclin Y (CCNY) family. Ccnys have been reported to regulate mammary stem cell activity and mammary gland development, and CCNY has been recognized as an oncoprotein in various cancers, including breast cancer. However, it remains unclear whether CDK16 has a role in breast cancer and whether it can be used as a therapeutic target for breast cancer. Methods Publicly available breast cancer datasets analyses and Kaplan-Meier survival analyses were performed to reveal the expression and clinical relevance of atypical CDKs in breast cancer. CDK16 protein expression was further examined by immunohistochemical and immunoblot analyses of clinical samples. Cell proliferation was measured by colony formation and MTT analyses. Cell cycle and apoptosis were examined by fluorescence-activated cell sorting (FACS) analysis. Wound-healing and trans-well invasion assays were conducted to test cell migration ability. The functions of CDK16 on tumorigenesis and metastasis were evaluated by cell line-derived xenograft, patient-derived organoid/xenograft, lung metastasis and systemic metastasis mouse models. Transcriptomic analysis was performed to reveal the potential molecular mechanisms involved in the function of CDK16. Pharmacological inhibition of CDK16 was achieved by the small molecular inhibitor rebastinib to further assess the anti-tumor utility of targeting CDK16. Results CDK16 is highly expressed in breast cancer, particularly in triple-negative breast cancer (TNBC). The elevated CDK16 expression is correlated with poor outcomes in breast cancer patients. CDK16 can improve the proliferation and migration ability of TNBC cells in vitro, and promote tumor growth and metastasis of TNBC in vivo. Both genetic knockdown and pharmacological inhibition of CDK16 significantly suppress the tumor progression of TNBC. Mechanistically, CDK16 exerts its function by phosphorylating protein regulator of cytokinesis 1 (PRC1) to regulate spindle formation during mitosis. Conclusion CDK16 plays a critical role in TNBC and is a novel promising therapeutic target for TNBC.

Wild type (WT) animals cannot be used to objectively assess the immunogenicity of animal tissue-derived biomaterials when used as recipients due to difference with human in α-Gal expression. The purpose of this study is to compare the differences of immunological responses between the GGTA1 gene-knockout (GTKO) rabbits and WT rabbits after implantation with animal tissue-derived biomaterials. The porcine-derived decellularized bone matrix (natural bone material, NBM) and fresh porcine cancellous bone (PCB) were implanted in GTKO rabbits and WT rabbits, respectively, and sham operation was used as control (Con). At 2- and 6-week post-implantation, the related immunological items including antibody levels, serum-mediated cell lysis, cytokines, lymphocyte subtypes, and histopathological changes were assessed.GTKO rabbits exhibited more sensitive immune responses than WT rabbits after PCB implantation, resulted from a significant increase of antibodies (except total antibodies) and cytokines levels, cell lysis ratios, CD4/CD8 proportions, and inflammatory cells infiltration. Immunological factors and inflammatory cells infiltrate in GTKO rabbits after NBM implantation were significantly lower than those in the PCB group. Among the three groups, the NBM group showed the highest contents of new bone formation elements.In conclusion, the GTKO rabbit is a more sensitive alternative model than WT rabbit for preclinical study of xenografts via in situ implantation. Studies on multiple gene-edited animals are also necessary for more comprehensively evaluating xenoimmunologen risks of animal tissue-derived biomaterials in the future. Additionally, the immunogenicity of NBM was remarkably decreased compared to PCB.

Abstract Medical image generation from diagnostic report has important research significance for medical‐aided diagnosis. This research can improve the diagnosis speed and accuracy of doctors and effectively save the storage resources of hospitals. The research has made significant progress in the field of natural images, but rarely used in medical images. Medical images have higher requirements for image quality. In this paper, a method based on attention mechanism and content preservation loss to improve image quality is proposed. The model consists of three stages, and each stage generates feature map of different scale combined with attention features as the input of the next stage to optimise semantic consistency between image and text. The last stage will generate an image, whose size is 256 × 256. And the content preservation loss can optimise the similarity between the generated image and the real image by low‐level and high‐level features to meet the high requirements of medical image for texture details. The content preservation loss consists of MSE loss, VGG loss and TV loss. The experiments on two datasets prove that the method can achieve excellent results.

ABSTRACT Previous inactivated vaccines against infectious hematopoietic necrosis (IHN) usually had a strong early immune protective effect but failed to provide long-term protection in rainbow trout (Oncorhynchus mykiss). To find a method for stabilizing the desired protective effect of IHN vaccines, we assessed the immune enhancement effect of four adjuvants on formaldehyde inactivated vaccine for IHN at 60 days postvaccination (dpv). The efficacy of a two-dose vaccination with the candidate adjuvant-formaldehyde inactivated vaccine for IHN was evaluated in terms of early protection and long-term protection (30 to 285 dpv). Neutralizing antibody titers were also measured at each time point. The Montanide GEL 02 PR (Gel 02) adjuvant significantly enhanced the immune protection provided by the IHN inactivated vaccine, whereas the immune-boosting effect of the other tested adjuvants lacked statistical significance. Both tested Gel 02-adjuvanted IHN inactivated vaccine dosages had a strong immune protection effect within 2 months postvaccination, with a relative percent of survival (RPS) of 89.01% to 100%, and the higher dosage provided complete protection at 204 dpv and a RPS of 60.79% on 285 dpv by reducing viral titers in rainbow trout. The neutralizing antibodies were observed only in vaccinated fish on 30 and 60 dpv. Through compatibility with an appropriate adjuvant, the highly immune protective effect of an IHN inactivated vaccine was prolonged from 60 dpv to at least 284 dpv; this novel adjuvant-IHN inactivated vaccine has promise as a commercial vaccine that provides the best available and longest duration of protection against IHN to rainbow trout. IMPORTANCE Infectious hematopoietic necrosis virus (IHNV) is one of the most serious pathogens threatening the global salmon and trout industry. However, there is currently only one commercialized infectious hematopoietic necrosis (IHN) vaccine, and it is inadequate for solving the global IHN problem. In this study, a promising adjuvanted inactivated vaccine with long-term protection was developed and comprehensively studied. We confirmed the presence of a late antiviral response stage in vaccinated rainbow trout that lacked detectable neutralizing antibodies, which are commonly recognized to be responsible for long-term specific protection in mammals. These findings further our understanding of unique features of fish immune systems and could lead to improved prevention and control of fish diseases.

With the upgrading of production technology and design aesthetic of textile products, the development and application of double-sided digital printing technology have been gradually proposed in recent years. The production of double-sided heterochromatic digital printing requires high accuracy for color management, as in the production process, different input devices, display devices, and output devices each have varying color processing capabilities and color performance characteristics, which leads to the transfer of color between different devices and not being accurately reproduced. However, there is little research involved in the color formation laws in the design and production of double-sided heterochromatic digital printing. The purpose of this paper is to explore the prediction model of color presentation in double-sided heterochromatic digital printing. Due to the influence of the fabric thickness, the gap between the textile structure, and the infiltration rate of the printing pigments, the color of each side in double-sided, heterochromatic printing results often differs from the designed color. In this paper, taking chiffon fabric, which is one of the thinnest and has the strongest permeability in silk fabric, as an example fabric base, 24 colors from six hue angles and four chromas were selected as experimental colors. According to the color gamut of the digital printing machine, 15 out of 24 colors were selected as experimental colors. These 15 colors were printed on two sides in pairs to generate 225 color pairs as double-sided experimental samples. For these experimental samples, this paper conducts experiments from both subjective and objective aspects through the combination of subjective evaluation of psychophysics experiments and objective instrument measurement. Through the analysis of experimental data, the color difference prediction under the subjective model (R2 = 0.74) and objective model (R2 = 0.85) are given, respectively. The dominant color prediction model (R2 = 0.75) during double-sided heterochromatic digital printing has also been built. The combination of the three models can predict the color regularity of double-sided heterochromatic digital printing on silk, which may have a certain significance for the design and development of silk double-sided heterochromatic digital printing products.

The prevalence of Helicobacter pylori (H. pylori) infection has exceeded 50% worldwide, and it is considered a high-risk factor for chronic gastritis, peptic ulcer, gastric adenocarcinoma, gastroesophageal reflux disease and functional dyspepsia. H. pylori drug resistance is a common problem worldwide. In recent years, the relationship between H. pylori infection and gastrointestinal microecology has received much attention. H. pylori infection changes the structure and composition of gastrointestinal microflora by regulating the gastrointestinal microecological environment, local pH value, cytokines and antimicrobial peptides, and immune response and then plays a crucial role in the occurrence and development of digestive system tumors, liver metabolism and extragastrointestinal diseases. The quadruple strategy of H. pylori eradication can also aggravate gastrointestinal microflora disorder. However, probiotics can reduce intestinal flora changes and imbalances through different mechanisms, thus enhancing the efficacy of H. pylori eradication therapy and reducing adverse reactions caused by eradication therapy. Therefore, this paper reviews the relationship between H. pylori infection and gastrointestinal microecology and its clinical application, providing a basis for clinical treatment.

Background and PurposeOn the basis of the promising clinical study results, thoracic radiotherapy (TRT)1 has become an integral part of treatment of synchronous oligometastatic non–small cell lung cancer (SOM-NSCLC). However, some of them experienced rapid disease progression after TRT and showed no significant survival benefit. How to screen out such patients is a more concerned problem at present. In this study, we developed a risk-prediction model by screening hematological and clinical data of patients with SOM-NSCLC and identified patients who would not benefit from TRT.Materials and MethodsWe investigated patients with SOM-NSCLC between 2011 and 2019. A formula named Risk-Total was constructed using factors screened by LASSO-Cox regression analysis. Stabilized inverse probability treatment weight analysis was used to match the clinical characteristics between TRT and non-TRT groups. The primary endpoint was overall survival (OS).ResultsWe finally included 283 patients divided into two groups: 188 cases for the training cohort and 95 for the validation cohort. Ten prognostic factors included in the Risk-Total formula were age, N stage, T stage, adrenal metastasis, liver metastasis, sensitive mutation status, local treatment status to metastatic sites, systemic inflammatory index, CEA, and Cyfra211. Patients were divided into low- and high-risk groups based on risk scores, and TRT was found to have improved the OS of low-risk patients (46.4 vs. 31.7 months, P = 0.083; 34.1 vs. 25.9 months, P = 0.078) but not that of high-risk patients (14.9 vs. 11.7 months, P = 0.663; 19.4 vs. 18.6 months, P = 0.811) in the training and validation sets, respectively.ConclusionWe developed a prediction model to help identify patients with SOM-NSCLC who would not benefit from TRT, and TRT could not improve the survival of high-risk patients.

(1) Background: Piglet diarrhea is one of the most serious diseases in pigs and has brought great economic losses to the pig industry. Alteration of the gut microbiota is an important factor in the etiology of piglet diarrhea. Therefore, this study aimed to analyze the differences in the gut microbial structures and fecal metabolic profile between post-weaning diarrhea and healthy Chinese Wannan Black pigs. (2) Methods: An integrated approach of 16S rRNA gene sequencing combined with LC/MS-based metabolomics was employed in this study. (3) Results: We found an increase in the relative abundance of the bacterial genus Campylobacter and a decrease in phylum Bacteroidetes and the species Streptococcus gallolyticus subsp. macedonicus. (S. macedonicus) in piglet diarrhea. Meanwhile, obvious changes in the fecal metabolic profile of diarrheic piglets were also detected, particularly higher levels of polyamines (spermine and spermidine). Moreover, there were substantial associations between the disturbed gut microbiota and the altered fecal metabolites, especially a strong positive relationship between spermidine and Campylobacter. (4) Conclusions: These observations may provide novel insights into potential etiologies related to post-weaning diarrhea and further enhance our understanding of the role of gut microbiota in host homeostasis and in modulating gut microbial structure.

Abstract When colorectal subepithelial lesions occur in ovarian carcinoma patients, EUS‐FNA may help to diagnose colorectal metastasis, thereby guiding clinicians to select appropriate treatment and improve the overall outcome.

BackgroundMolecular information about bladder cancer is significant for treatment and prognosis. The immunohistochemistry (IHC) method is widely used to analyze the specific biomarkers to determine molecular subtypes. However, procedures in IHC and plenty of reagents are time and labor-consuming and expensive. This study established a computer-aid diagnosis system for predicting molecular subtypes, p53 status, and programmed death-ligand 1 (PD-L1) status of bladder cancer with pathological images.Materials and MethodsWe collected 119 muscle-invasive bladder cancer (MIBC) patients who underwent radical cystectomy from January 2016 to September 2018. All the pathological sections are scanned into digital whole slide images (WSIs), and the IHC results of adjacent sections were recorded as the label of the corresponding slide. The tumor areas are first segmented, then molecular subtypes, p53 status, and PD-L1 status of those tumor-positive areas would be identified by three independent convolutional neural networks (CNNs). We measured the performance of this system for predicting molecular subtypes, p53 status, and PD-L1 status of bladder cancer with accuracy, sensitivity, and specificity.ResultsFor the recognition of molecular subtypes, the accuracy is 0.94, the sensitivity is 1.00, and the specificity is 0.909. For PD-L1 status recognition, the accuracy is 0.897, the sensitivity is 0.875, and the specificity is 0.913. For p53 status recognition, the accuracy is 0.846, the sensitivity is 0.857, and the specificity is 0.750.ConclusionOur computer-aided diagnosis system can provide a novel and simple assistant tool to obtain the molecular subtype, PD-L1 status, and p53 status. It can reduce the workload of pathologists and the medical cost.

The effects of crude lentinan (CLNT) on the intestinal microbiota and the immune barrier were evaluated in rainbow trout (Oncorhynchus mykiss) infected by infectious hematopoietic necrosis virus (IHNV). The results showed that supplementary CLNT declined the rainbow trout mortality caused by IHNV, which suggested that CLNT has preventive effects on IHNV infection. IHNV destroyed intestinal integrity, as well as caused the intestinal oxidative and damage in rainbow trout. Supplementary CLNT significantly strengthened the intestinal immune barrier by declining intestinal permeability, as well as enhancing intestinal antioxidant and anti-inflammatory abilities in IHNV-infected rainbow trout (P

Targeted therapy has made breakthrough progress in the treatment of advanced non–small cell lung cancer (NSCLC) in the last 20 years. Despite that, acquired resistance of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is an urgent clinical problem. Our study established an acquired gefitinib-resistant cell line, which exhibited epithelial–mesenchymal transition (EMT) and stem cell–like properties. Transcriptional sequencing and bioinformatics analysis revealed that TROY was significantly increased in gefitinib-resistant cells. Gene set enrichment analysis (GSEA) showed EMT was the core enriched hallmark in the resistant cells. TROY siRNA interference could overcome the gefitinib resistance with the downregulated expression of EMT and CSC markers. In addition, immunohistochemistry indicated that TROY was overexpressed in tumor samples from patients who acquired resistance to first-generation EGFR-TKI without T790M mutation and the expression of TROY was associated with poor prognosis in LUAD. Here, we provided the potential role of TROY in the resistance of targeted therapy and a new strategy to overcome the acquired resistance to EGFR-TKI in NSCLC.

Based on the cores from 47 wells and logging data of 130 wells, the main types of sand bodies in the shallow water delta of the Chang 82 sub-member in the Triassic Yanchang Formation, Longdong Area, Ordos Basin were comprehensively analyzed, the distribution characteristics of sand bodies more than 20 m thick were identified, and the genetic types of the thick sand bodies were sorted out. In this region, thick-bed sand bodies can be divided into two types according to the shape and position: type 1 is the sand body in wide strip and is distributed between the average high water mark and the average low water mark; type 2 is distributed on both sides of the average low water mark and is in irregular lump shape. Based on the principle of the volume distribution of sediments and the change rule of accommodation space, the genetic models of two types of thick-bed sand bodies in the Chang 82 sub-member are superimposed distributary channel sand bodies in high accommodation space and superimposed composite sand bodies in low accommodation space.

Befitting from the interpretability and the capacity in capturing the underlying manifold structure, diffusion process (DP) has attracted increasing attention in the field of image retrieval. Within it, hierarchical diffusion process (HDP) has achieved satisfactory results in retrieved performance and complexity. However, the existing hierarchical diffusion process methods only diffuse the affinity values in low-level visual space without considering the high-level semantic information, which cause the problem of semantic gap. To overcome these problems, we propose a Graph Regularized Hierarchical Diffusion Process (GRHDP) method with relevance feedback, and apply it to retrieve medical images. The proposed algorithm firstly establishes a hierarchical structure of the images in medical image database and spreads the affinity values among query images and top-layer images by graph regularization diffusion. Then relevance feedback is introduced to adjust the similarity between query images and retrieved images in top layer, and the affinity values are diffused again according to labeled information of feedback. Finally, the similarity between queries and others in database can be obtained by interpolating the diffused results on the top layer from top to bottom. The experimental results show that our proposed GRHDP with relevance feedback has achieved better retrieval performance than manifold ranking and regularized diffusion process (RDP) when returning top retrieved images.

N-hexane, a common industrial organic solvent, causes multiple organ damage owing to its metabolite, 2,5-hexanedione (2,5-HD). To identify and evaluate the effects of 2,5-HD on sows’ reproductive performance, we used porcine ovarian granulosa cells (pGCs) as a vehicle and carried out cell morphology and transcriptome analyses. 2,5-HD has the potential to inhibit the proliferation of pGCs and induce morphological changes and apoptosis depending on the dose. RNA-seq analyses identified 4817 differentially expressed genes (DEGs), with 2394 down-regulated and 2423 up-regulated following 2,5-HD exposure treatment. The DEG, cyclin-dependent kinase inhibitor 1A (CDKN1A), according to the Kyoto Encyclopedia of Genes and Genomes enrichment analysis, was significantly enriched in the p53 signaling pathway. Thus, we evaluated its function in pGC apoptosis in vitro. Then, we knocked down the CDKN1A gene in the pGCs to identify its effects on pGCs. Its knockdown decreased pGC apoptosis, with significantly fewer cells in the G1 phase (p < 0.05) and very significantly more cells in the S phase (p < 0.01). Herein, we revealed novel candidate genes that influence pGCs apoptosis and cell cycle and provided new insights into the role of CDKN1A in pGCs during apoptosis and cell cycle arrest.

The purpose of this study was to establish a collagen determination method based on an isotope-labeled collagen peptide as an internal reference via high-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS), and using the established method to evaluate the degradation process of collagen-based implants in vivo. The specific peptide (GPAGPQGPR) of bovine type I collagen was identified with an Orbitrap mass spectrometer. Then, the quantification method based on the peptide detection with HPLC-MS/MS was established and validated, and then further used to analyze the degradation trend of the collagen sponge and acellular matrix (ACM) in vivo at 2, 4, 6, 8, 12, 16, and 18 weeks after implantation. The results indicate that the relative standard deviation (RSD) of the detection precision and repeatability of the peptide-based HPLC-MS/MS quantification method were 3.55% and 0.63%, respectively. The limitations of quantification and detection were 2.05 × 10−3 μg/mL and 1.12 × 10−3 μg/mL, respectively. The collagen sponge and ACM were completely degraded at 10 weeks and 18 weeks, respectively. Conclusion: A specific peptide (GPAGPQGPR) of bovine type I collagen was identified with an Orbitrap mass spectrometer, and a standardized HPLC-MS/MS-based internal reference method for the quantification of bovine type I collagen was established. The method can be used for the analysis of the degradation of collagen-based implants in vivo.

This study is aimed at investigating the role of β-galactoside-α2,3-sialyltransferase III (ST3GAL3) in fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA), as well as its potential mechanism of action. The Gene Expression Omnibus (GEO) database and gene set enrichment analysis (GSEA) were used to analyse the expression of ST3GAL3 and the enrichment signalling pathways associated with ST3GAL3 in RA. The effects of ST3GAL3 on tumour necrosis factor- (TNF-) α and interleukin- (IL-) 1β-treated MH7A cells were determined using methyl thiazolyl tetrazolium (MTT), transwell, and enzyme-linked immunosorbent assays (ELISA). The expression of proliferation-associated proteins and Toll-like receptor (TLR) pathway-enriched proteins was analysed using western blotting. As a main result, ST3GAL3 was screened as an overlapping upregulated gene from GSE101193 and GSE94519 datasets. ST3GAL3 expression in MH7A cells significantly increased with increasing treatment time with TNF-α or IL-1β. TLR9/myeloid differentiation primary response protein 88 (MyD88) is a downstream activation pathway of ST3GAL3. ST3GAL3 overexpression promoted MH7A cell proliferation and migration. Additionally, ST3GAL3 overexpression upregulated the expression of proliferation-associated proteins (cyclinD, cyclinE, and proliferating cell nuclear antigen) and TLR pathway enrichment factors (TLR9 and MyD88) and increased the production of matrix metallopeptidase (MMP) 1, MMP3, interleukin- (IL-) 6, and IL-8, whereas si-ST3GAL3 had the opposite effect. The addition of TLR9 agonists (CpG 2216 and CpG 2006) reversed the effects of si-ST3GAL3 on MH7A cell proliferation, migration, and inflammation. TLR9-specific siRNA reversed the effects of ST3GAL3 overexpression on MH7A cell proliferation, migration, and inflammation. In conclusion, ST3GAL3 is likely involved in RA pathogenesis by activating the TLR9/MyD88 pathway.

BackgroundThe optimal number of concurrent chemotherapy cycles during thoracic radiotherapy (RT) in patients with limited stage-small cell lung cancer (LS-SCLC) is not well defined. The purpose of this study was to evaluate the impact of the number of concurrent chemotherapy cycles on prognosis of LS-SCLC.Material and MethodsPatients with LS-SCLC treated with concurrent chemo-radiotherapy from May 2008 to December 2020 in our hospital were retrospectively analyzed. The prescribed radiation dose was 60Gy administrated with conventional RT in 30 fractions within 6 weeks. The prognostic role of cycle number of chemotherapy administrated concurrently with RT were analyzed. All patients were followed up at one month after the treatment, then once every three months until two years after the treatment, and every six months thereafter. Propensity score matching (PSM) was performed to reduce confounding factors. The primary endpoint was overall survival (OS). Survival analysis was performed with Kaplan-Meier and multivariate analysis was performed with Cox regression model.ResultsAmong the 370 patients who received radical radiotherapy, 206 patients received concurrent chemo-radiotherapy and were included for the analysis. Multivariate analysis showed that stage and PCI were independent prognostic factors for OS. The median OS in patients who received one cycle and two cycles of chemotherapy concurrently with RT were 32.9 months and 31.6 months, respectively (P = 0.241). And the median PFS were 20.6 months and 18.4 months, respectively (P = 0.764). After PSM, no statistical differences in OS and PFS were observed between patients who received one cycle and those who received two cycles of concurrent chemotherapy.ConclusionTwo cycles of concurrent chemotherapy during RT were not necessarily superior compared to one cycle in LS-SCLC. The optimal cycle number of concurrent chemotherapy during RT needs to be further studied.

Polyindole (PIn) has attracted extensive interest as promising energy storage materials owing to fairly good thermal stability, high redox activity and stability, however, it is challenging to prepare high-quality PIn in neutral solvents by electrochemical method. Herein, a simple route, based on MoS2 nanosheets as electrolytes, has been developed for the electrochemical preparation of PIn/MoS2 nanocomposite in acetonitrile solution. Due to the coordination interaction between indole and MoS2, the onset oxidation potential of indole in this medium was reduced to 0.5 V from 0.75 V determined in acetonitrile/LiClO4. The morphologies and structures of as-obtained PIn/MoS2 nanocomposite were characterized using SEM, TEM, XRD, Raman and XPS. The results of thermal analysis indicated that the PIn/MoS2 nanocomposite had an improved thermal stability relative to PIn and MoS2 nanosheets. Moreover, the specific capacitance of PIn/MoS2 nanocomposite was 8.3 times higher than that of PIn prepared acetonitrile/LiClO4. To the best of our knowledge, this is the first report on the high-efficiency electrodeposition of PIn/MoS2 nanocomposite in MoS2-based acetonitrile solution, which will be a promising candidate as a high efficient electrode material in the application of supercapacitors.

Abstract Background Detection of programmed cell death ligand-1 (PD-L1) by immunohistochemistry (IHC) has been commonly used to predict the efficacy of treatment with PD-1/PD-L1 inhibitors. However, there is limited literature regarding the reliability of PD-L1 testing using malignant pleural effusion (MPE) cell blocks. Here, we assess PD-L1 expression in sections from MPE cell blocks and evaluate the value of IHC double staining in the interpretation of PD-L1 expression. Methods In all, 124 paired formalin-fixed tissues from advanced NSCLC patients, including MPE cell blocks and matched histology samples, were included. PD-L1 expression was assessed using the SP263 assay, and the tumor proportion score (TPS) and the staining intensity were evaluated. PD-L1 staining results were also compared between IHC double and single staining techniques. Results PD-L1 expression was concordant in most paired cases (86/101, 85.1%) among three TPS cut-offs (

The existing medical imaging technologies have little consideration on color information, thus most of medical images are gray. Classical hand-craft features-based methods have obtained unsatisfactory results in colorizing medical images. Moreover, these methods ignore the deep feature of medical images that represent pathology and color information. In this paper, we propose a novel method that iteratively colorizes grayscale medical images under preserving content in fine-tuned deep neural network. To the best of our knowledge, there is no currently work that attempts to colorize the medical image by using deep neural network. Specifically, we propose Y-loss which is defined as nonlinear combination of ℓ1 and ℓ2 norm to preserve content invariance between target and colorized medical image. Then, adaptive reference image search algorithm is introduced to code reference and target medical image with D-hash and search reference image in hash code automatically, which free the manual selection of the reference image. Extensive experiment results show that the proposed method can generate higher quality colored medical image than recent state-of-the-art methods, and can be approved by the doctor. The objective evaluation (PSNR and SSIM) outperform an average increment 24% and 47% than baseline method, respectively. Our code is available at: https://github.com/Tongshiyue/Adaptive-medical-image-deep-color-perception-algorithm.

Context Thoracic trauma results in multiple rib fractures (MRF), and surgical stabilisation of rib fractures (SSRF) can relieve fracture pain. Epigallocatechin-3-gallate (EGCG) is reported to exhibit beneficial effects in bone-related metabolic and differentiation processes. Objective To study the clinical effect of EGCG on regional analgesia for pain relief in MRF patients after SSRF. Materials and methods Ninety-seven MRF patients (61 males, 36 females) who were on epidural catheter analgesia after SSRF were recruited. They were randomly divided into: oral EGCG 100 mg (oral grade) twice daily for 10 days and placebo groups. Pain scores, incentive spirometry (IS) volumes, respiratory rate and oxygen saturation (SpO2) were assessed day 10 after SSRF. Results Comparing results from the placebo and EGCG group, in the 10-day intervention course, oral EGCG reduced pain score (8 at base line vs. 4 at end of intervention in EGCG group, p 0.05). Discussion and conclusions Although the study is limited by a relatively small sample size and lack of serum factor analysis, the key results and the study design, for the first time, nevertheless pave the way for trials with larger number of patients to understand the effect of EGCG in MRF patients that are undergoing SSRF.

BackgroundAccumulated evidence for systemic inflammation response in several solid tumors prompts a possibility of prediction of patients’ prognosis in a more accessible and valuable manner. However, the prognostic value of peripheral blood inflammatory markers in limited-stage small cell lung cancer (LS-SCLC) remains unclear. Therefore, we investigated the prognostic values of pretreatment inflammatory indexes in LS-SCLC patients.MethodsWe retrospectively identified 334 patients with LS-SCLC and collected their pretreatment serum levels of neutrophil, platelet, lymphocyte, leukocyte, hemoglobin, and albumin, then neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic inflammation index (SII) were calculated. Patients were dichotomized as low-Risk or high-Risk group based on their corresponding cutoff values. Univariate and multivariate analyses were conducted with a Cox proportional hazards model. The least absolute shrinkage and selection operator (LASSO)-Cox regression analysis was performed to construct the inflammation-related prognostic scoring system named Risk for OS. Nomograms were established to provide prognostic information, allowing for more individualized prediction of survival.ResultsHigher pretreatment platelet, lymphocyte, and albumin were indicators of favorable overall survival (OS), whereas higher NLR and SII were accompanied by inferior OS. The prognosis of patients with high Risk was significantly worse than that with low Risk in both the training group and the validation group (both p < 0.001). Comparable area under the curve (AUC) values between the training group and the validation group were observed, yielding 1-, 3-, and 5-year OS rates of 67.3% vs. 69.2%, 66.8% vs. 69.5%, and 66.7% vs. 71.4%, respectively. Multivariate analyses revealed that Risk [hazard ratio (HR) = 0.551, p < 0.001] was an independent negative prognostic indicator for OS, which was further verified in the validation set. The addition of Risk to nomogram (C-index = 0.643) harbored improved predictive accuracy for OS when compared with that of clinical factors alone (C-index = 0.606); the AUC values of 1-, 3-, and 5-year OS rates were 71.7% vs. 66.4%, 73.5% vs. 66.6%, and 71.9% vs. 65.6%, respectively.ConclusionsPretreatment peripheral blood inflammatory indexes may be a noninvasive serum biomarker for poor prognosis in LS-SCLC. The addition of Risk to the nomogram model could serve as a more powerful, economical, and practical method to predict survival for patients with LS-SCLC.

Infectious pancreatic necrosis virus (IPNV) is the causative agent of rainbow trout (Oncorhynchus mykiss) IPN and causes significant loss of fingerlings. The currently prevalent IPNV genogroups in China are genogroups 1 and 5. However, in this study, we isolated and identified a novel IPNV, IPNV-P202019, which belonged to genogroup 7. Here, a total of 200 specific-pathogen-free rainbow trout (10 g average weight) were divided randomly into four groups to investigate the distribution of different IPNV strains (genogroups 1, 5, and 7) in 9 tissues of rainbow trout by means of intraperitoneal (ip) injection. Fish in each group were monitored after 3-, 7-, 14-, 21- and 28- days post-infection (dpi). The study showed no mortality in all groups. The distribution of IPNV genogroups 1 and 5 was similar in different tissues and had a higher number of viral loads after 3, 7, or 14 dpi. However, the distribution of IPNV genogroup 7 was detected particularly in the spleen, head kidney, and feces and had a lower number of viral loads. The results of this study provide valid data for the distribution of IPNV in rainbow trout tissues and showed that IPNV genogroups 1 and 5 were still the prevalent genogroups of IPNV in China. Although rainbow trout carried IPNV genogroup 7, the viral load was too low to be pathogenic.

Both infectious hematopoietic necrosis virus (IHNV) and infectious pancreatic necrosis virus (IPNV) are the causative agents of acute and highly contagious diseases of juvenile salmonids, resulting in severe economic losses to these cold-water fish globally. There is an urgent need to explore antiviral agents against IHNV and IPNV due to the lack of commercially available vaccines and antiviral drugs. More importantly, the co-infection of IHNV and IPNV is prevalent in nature, which not only aggravates extensive damage to the salmonids but also poses challenges to its prevention and control. The antiviral effects of a crude polysaccharide derived from seaweed (CSP) on IHNV and IPNV were evaluated in this study separately. Furthermore, the underlying antiviral mechanisms of CSP to IHNV and IPNV were analyzed, respectively. The results showed that CSP possessed excellent safety and good ability to inhibit IHNV, IPNV, and their co-infection. CSP preferred to act at the early stage of viral infection. The antiviral mechanism of CSP on IHNV is possibly involved in preventing viral attachment and release, while in IPNV, it is involved in suppressing viral attachment, entry, and release. Taken together, the results of this study shed new light on developing novel agents against viral infection in salmonid fish.

Infectious hematopoietic necrosis (IHN) and infectious pancreatic necrosis (IPN) are the most common viral diseases of salmon in aquaculture worldwide. The co-infection of rainbow trout (Oncorhynchus mykiss) with IHN virus (IHNV) and IPN virus (IPNV) is known to occur. To determine the influence of IPNV on IHNV in co-infection, rainbow trout were intraperitoneally (i.p.) injected with IPNV at different time intervals prior to, simultaneously to, or after IHNV infection. The replication of IHNV in the brain, gill, heart, liver, spleen, and head kidney was detected by real-time quantitative polymerase chain reaction (qRT-PCR). The results showed that when rainbow trout were i.p. injected with IPNV prior to, simultaneously to, or after IHNV on 2 day (d), IHNV replication was inhibited (p < 0.05) in all collected tissues. Nevertheless, when rainbow trout were i.p. injected with IPNV after IHNV on 7 d (H7P), IHNV replication was only inhibited (p < 0.05) in the liver 14 d post-IHNV infection. Moreover, stronger antiviral responses occurred in all challenge groups. Our results suggest that IPNV can inhibit IHNV replication before or simultaneously with IHNV infection, and induce a stronger antiviral response, and that this inhibition is most sensitive in the liver. Early i.p. injection of IPNV can significantly reduce the mortality of rainbow trout, compared with the group only injected with IHNV.

HR3C (25Cr-20Ni-Nb-N) is a key material used in heat exchangers in supercritical power plants. Its creep properties and microstructural evolution has been extensively studied at or below 650 °C. The precipitation evolution in HR3C steel after creep rupture at elevated temperatures of 700 °C and 750 °C with a stress range of 70~180 MPa is characterized in this paper. The threshold strength at 700 °C and 750 °C were determined by extrapolation method to be σ105700= 57.1 MPa and σ105750=37.5 MPa, respectively. A corresponding microstructure investigation indicated that the main precipitates precipitated during creep exposure are Z-phase (NbCrN), M23C6, and σ phase. The dense Z-phase precipitated dispersively in the austenite matrix along dislocation lines, and remained stable (both size and fraction) during long-term creep exposure. M23C6 preferentially precipitated at grain boundaries, and coarsening was observed in all creep specimens with some continuous precipitation of granular M23C6 in the matrix. The brittle σ phase formed during a relatively long-term creep, whose size and fraction increased significantly at high temperature. Moreover, the σ phases, grown and connected to form a large “island” at triple junctions of grain boundaries, appear to serve as nucleation sites for high stress concentration and creep cavities, weakening the grain boundary strength and increasing the sensitivity to intergranular fracture.

A new strategy for designing low side-lobe level (SLL) antenna array is presented. This strategy utilizes special arrangement of antenna elements rather than direct tapered excitation amplitude to obtain an equivalent desired amplitude distribution in the main planes and thus achieve low SLL and high gain concurrently. To illustrate the strategy, 9-element microstrip antennas are arranged in four manners. An equivalent analysis method is also proposed to predict the SLL of the arrays. Using this method, a fast analysis of the trend of a microstrip array for a low SLL can be performed and thus a proper array-element arrangement is acquired. Both numerical and experimental results demonstrate that the SLLs in E and H planes of the novel array are fairly low. Meanwhile, the main beam of the novel array is almost the same with that of a conventional high-gain array. The antenna arrangement manner and the proposed strategy are particularly suitable for applications when low SLL and high gain are both demanded.

Magnesium alloys exhibit superior biocompatibility and biodegradability, which makes them an excellent candidate for artificial implants. However, these materials also suffer from lower corrosion resistance, which limits their clinical applicability. The corrosion mechanism of Mg alloys is complicated since the spontaneous occurrence is determined by means of loss of aspects, e.g., the basic feature of materials and various corrosive environments. As such, this study provides a review of the general degradation/precipitation process multifactorial corrosion behavior and proposes a reasonable method for modeling and preventing corrosion in metals. In addition, the composition design, the structural treatment, and the surface processing technique are involved as potential methods to control the degradation rate and improve the biological properties of Mg alloys. This systematic representation of corrosive mechanisms and the comprehensive discussion of various technologies for applications could lead to improved designs for Mg-based biomedical devices in the future.

Paleo-sedimentary environment of Chang 7 Member of Upper Triassic Yanchang Formation in Ordos Basin, including the paleoclimate, paleo-salinity and paleo-redox conditions were restored through geochemical elements analysis of 289 samples collected from the outcrop sections around and wells drilled in the basin and using a series of identification indexes of paleo-climate, paleo-salinity and paleo-redox conditions, such as CaO/MgO·Al2O3, Sr/Cu, Rb/Sr, Rb/K2O, Th/U, V/(V+Ni), the content of element B tested from the mudstone. Comprehensive analysis shows that in sedimentary period of the Chang 7, the paleo-climate was warm temperate to subtropical climate with temperature higher than 15 °C, the water body was continental brackish water to freshwater, and the sediments were deposited under strong reduction conditions. Suitable temperature, extensively deep lake basin and strongly reductive paleo-sedimentary environment led to the blooming, enrichment and preservation of organic matter in the submember Chang 73. As a result, a set of high-quality source rock was formed, laying material foundation for large-scale accumulation of shale oil. Key words: paleo-climate, paleo-salinity, paleo-redox conditions, element geochemistry, paleo-sedimentary environment, Chang 7 Member, Upper Triassic, Ordos Basin

Abstract Background The role of the dose escalation strategy in brain radiotherapy for small cell lung cancer (SCLC) patients with brain metastases (BMs) has not been identified. This study aims to determine whether an additional radiation boost to whole brain radiation therapy (WBRT) has beneficial effects on overall survival (OS) compared with WBRT-alone. Methods A total of 82 SCLC patients who were found to have BMs treated with WBRT plus a radiation boost (n = 33) or WBRT-alone (n = 49) from January 2008 to December 2015 were retrospectively analyzed. All patients were limited-stage (LS) SCLC at the time of the initial diagnosis, and none of them had extracranial metastases prior to detection of BMs. The primary end point was OS. Results The median OS for all of the patients was 9.6 months and the 6-, 12- and 24-months OS rates were 69.1, 42.2 and 12.8%, respectively. At baseline, the proportion of more than 3 BMs was significantly higher in the WBRT group than in the WBRT plus boost group (p = 0.0001). WBRT plus a radiation boost was significantly associated with improved OS in these patients when compared with WBRT-alone (13.4 vs. 8.5 months; p = 0.004). Further, the survival benefit still remained significant in WBRT plus boost group among patients with 1 to 3 BMs (13.4 vs. 9.6 months; p = 0.022). Conclusion Compared with WBRT-alone, the use of WBRT plus a radiation boost may prolong survival in SCLC patients with BMs. The dose escalation strategy in brain radiotherapy for selected BMs patients with SCLC should be considered.

Patients with advanced-stage natural killer/T-cell lymphoma (NKTCL) usually have a poor prognosis. However, there is limited data of comprehensive analysis on this particular patient population due to the rarity of the disease. The present study aimed to investigate the treatment models, survival outcomes, and prognosis of advanced-stage NKTCL. Data from 336 patients with advanced-stage NKTCL diagnosed between 2006 and 2015 in the China Lymphoma Collaborative Group database were retrospectively analyzed. The median age was 42 years and the male/female ratio was 2.4:1. About 97% of patients had stage IV disease and 77% had >1 extranodal involvement site. All patients received chemotherapy, with the most common option being asparaginase (Asp)-containing regimens (n=146; 43.5%). Among 286 patients with available response data, the overall response rate (ORR) was 57.3% with a complete remission (CR) rate of 35.7%. Asp-containing regimens led to better ORRs (86/132, 65.2% vs. 54/113, 47.8%, P = 0.006) and CR rates (60/132, 45.5% vs. 27/113, 23.9%, P < 0.001) than non-Asp-containing regimens. The expected 5-year progression-free survival (PFS) and overall survival (OS) rates were 22.6 and 32.0%, respectively, for the whole cohort. Compared to non-Asp-containing chemotherapy, Asp-containing chemotherapy improved 5-year PFS (34.2 vs. 17.1%, P < 0.001) and OS (45.3 vs. 27.8%, P < 0.001). A trend toward improvement in OS was observed when gemcitabine was added to Asp-containing chemotherapies. Moreover, those undergoing autologous hematopoietic stem cell transplantation had prolonged survival time. In conclusion, Asp-containing chemotherapy could improve the prognosis of advanced-stage NKTCL, and refinement of treatment models is warranted in the future.

BackgroundGastric cancer (GC) is one of the most common malignancies in the world, and the fourth most frequent malignancy worldwide. YTHDF2 (YTH domain family 2, YTHDF2) binds to mRNA containing m6A, thereby regulating the localization and stability of the bound mRNA. YTHDF2 was shown to be associated with some cancer patient prognosis. However, the effect of YTHDF2 on gastric cancer and the molecular mechanism of this effect have not been documented.MethodsTo conduct this research, YTHDF2 expression levels in public databases and gastric cancer patient samples were analyzed. The effects of YTHDF2 on the growth of gastric cancer cells were detected in vivo and in vitro. RNA-seq was used to analyze the signal pathways regulated by YTHDF2, and experiments were carried out for verification.ResultsIn our study, we found that YTHDF2 has lower expression in GC tissues and GC cells, and inhibits the growth of GC cells. In addition, the analysis of clinical data found that the expression level of YTHDF2 is closely related to the stage of GC and the survival of patients with GC. RNA sequencing results showed that overexpression of YTHDF2 significantly reduced protein expression in the FOXC2 (Forkhead box protein C2, FOXC2) signaling pathway. Finally, we found that knockout of FOXC2 reversed the inhibitory effect of YTHDF2 on GC cells.ConclusionIn summary, YTHDF2 inhibits the growth of GC cells by negatively regulating FOXC2 and may serve as a prognostic marker in GC.

The common bean (Phaseolus vulgaris L.) is the most important legume crop directly used for human consumption worldwide. Bean rust, caused by Uromyces appendiculatus, is a devastating disease and usually causes severe loss of seed yield and pod quality. Deployment of resistant cultivars is the best strategy to combat this disease. However, despite being the largest snap bean-producing country, the genetic basis research of rust resistance has largely lagged in China. In this study, an RIL population and a diversity panel were evaluated for rust resistance against a purified rust isolate Cua-LS using a detached leaf assay. Deploying a QTL-Seq analysis in the RIL population, a 1.81 Mb interval on chromosome 4, a 2.73 Mb interval on chromosome 5 and a 1.26 Mb interval on chromosome 6 were identified as major QTLs for rust resistance, designated as Qur-1, Qur-2 and Qur-3, respectively. Through a GWAS diversity panel, 64 significant SNPs associated with rust resistance were detected, distributed in all 11 chromosomes and explaining 19–49% of the phenotypic variation. Synteny analysis showed that Qur-2 was validated in GWAS, but the rust QTL/SNPs detected in our study were different from the known genes, except Ur-11. A total of 114 candidate genes, including the typical NBS-LRR genes, protein kinase superfamily proteins and ABC transporter family proteins, were identified and proposed as the likely candidates. The identified 17 resistant accessions will enrich the resistant germplasm resources, and the detected QTLs/SNPs will facilitate the molecular breeding of rust resistance in the common bean.

Abstract The low specific capacitance and energy density of carbon electrode has extremely limited the wide application of supercapacitors. For developing a high‐performance carbon electrode using a simple and effective method, a fishnet‐like, N‐doped porous carbon (FNPC) film is prepared by calcining the KOH‐activated polyindole precoated on carbon cloths. The FNPC film is tightly anchored on carbon cloths without any binder. The FNPC film with 3.8 at% N content exhibits a fairly high specific capacitance of 416 F g−1 at 1.0 A g−1. Moreover, the assembled button‐type cell with two FNPC film electrodes shows a high energy density of 16.4 Wh kg−1, a high power density of 67.4 kW kg−1, and long‐term cyclic stability of 92% of the initial capacitance after 10 000 cycles at 10 A g−1. The high performances mainly came from the integration of pseudocapacitance and electrical double‐layer capacitance behavior, wettability, fishnet‐like nanostructure, as well as the low interfacial resistivity. This strategy provides a practical, uncomplicated, and low‐cost design of binder‐free flexible carbon materials electrode for high‐performance supercapacitors.

Objectives: The characteristics and prognostic factors of small-cell lung cancer (SCLC) patients with bone metastases at first diagnosis have scarcely been reported. This study aimed to analyze the prognostic factors of these patients and to develop a scoring system for survival to provide evidence for clinical treatment decisions. Materials and Methods: The records of 102 SCLC patients with bone metastasis at the time of diagnosis who were seen in our hospital between May 2010 and May 2015 were retrospectively reviewed. The log-rank test and multivariate Cox regression analysis were used to evaluate potential clinical predictors of survival. A scoring system was developed based on the hazard ratios of significant independent prognostic factors. Result: The most common site of bone metastases was the spine (64.7%), and 26 patients (25.6%) had a single bone metastasis. The median survival was 10.4 months, and the 2-year survival rate was 10.3%. Age, number of bone metastases, and occurrence of extraosseous distant metastases were significant independent prognostic factors for overall survival. Based on their scores, patients were divided into three groups. The median survival times of the three groups were 6.4 months, 8.5 months and 12.4 months, and the 2-year survival rates were 0%, 2.9%, and 19.3% (p=0.000). Twenty-six patients (25.5%) developed skeletal-related events (SREs), and the most common SREs were radiation to the bone (22.5%) and spinal cord compression (11.8%). Conclusion: This study includes preliminary clinical data of SCLC patients with bone metastases at the time of diagnosis, and more studies are needed. Keywords: small-cell lung cancer, bone metastases, prognosis, scoring system

Shot peening can be an effective solution for the prevention or retardation of scale formation, and subsequent exfoliation, upon exposure of the inner tube to steam in coal-fired power plants. In this study, specimens of T91 tubes were shot peened and then exposed to 1-bar steam for 100–1000 h at 650 °C, and were then analyzed using Vickers hardness test and microscopic techniques OM, SEM, TEM, etc. The analysis indicates that the oxide scales are typically Fe2O3 on the topmost layer, Fe3O4 below, and a FeCr2O4 spinel on the bottom in both shot peening treated and untreated specimens. However, the oxide scale thicknesses of shot peened specimens are thinner, indicating that shot peened specimens have better oxidation resistance. In addition, numerous defects, such as voids and micro-cracks, were found in the untreated specimens, which are believed to cause exfoliation of the uppermost Fe2O3 layers of the specimens exposed to steam for 800 and 1000 h. By contrast, the shot peened specimens maintained a dense contact oxide scale with fewer defects.