Exploring Appropriate Reference Intervals and Clinical Decision Limits for Glucose-6-Phosphate Dehydrogenase Activity in Individuals From Guangzhou, China.

Background: Quantitative detection of glucose-6-phosphate dehydrogenase (G6PD) is commonly done to screen for G6PD deficiency. However, current reference intervals (RIs) of G6PD are unsuitable for evaluating G6PD-activity levels with local populations or associating G6PD variants with hemolysis risk to aid clinical decision-making. We explored appropriate RIs and clinical decision limits (CDLs) for G6PD activity in individuals from Guangzhou, China. Methods: We enrolled 5,852 unrelated individuals between 2020 and 2022 and screened their samples in quantitative assays for G6PD activity. We conducted further investigations, including G6PD genotyping, thalassemia genotyping, follow-up analysis, and statistical analysis, for different groups. Results: In Guangzhou, the RIs for the G6PD activities were 11.20-20.04 U/g Hb in male and 12.29-23.16 U/g Hb in female. The adjusted male median and normal male median (NMM) values were 15.47 U/g Hb and 15.51 U/g Hb, respectively. A threshold of 45% of the NMM could be used as a CDL to estimate the probability of G6PD variants. Our results revealed high hemolysis-risk CDLs (male: <10% of the NMM, female: <30% of the NMM), medium hemolysis-risk CDLs (male: 10%-45% of the NMM, female: 30%-79% of the NMM), and low hemolysis-risk CDLs (male: ≥ 45% of the NMM, female: ≥ 79% of the NMM). Conclusions: Collectively, our findings contribute to a more accurate evaluation of G6PD-activity levels within the local population and provide valuable insights for clinical decision-making. Specifically, identifying threshold values for G6PD variants and hemolysis risk enables improved prediction and management of G6PD deficiency, ultimately enhancing patient care and treatment outcomes.

tiRNA-Val-CAC-2 interacts with FUBP1 to promote pancreatic cancer metastasis by activating c­MYC transcription.

Cumulative studies have established the significance of transfer RNA-derived small RNA (tsRNA) in tumorigenesis and progression. Nevertheless, its function and mechanism in pancreatic cancer metastasis remain largely unclear. Here, we screened and identified tiRNA-Val-CAC-2 as highly expressed in pancreatic cancer metastasis samples by tsRNA sequencing. We also observed elevated levels of tiRNA-Val-CAC-2 in the serum of pancreatic cancer patients who developed metastasis, and patients with high levels of tiRNA-Val-CAC-2 exhibited a worse prognosis. Additionally, knockdown of tiRNA-Val-CAC-2 inhibited the metastasis of pancreatic cancer in vivo and in vitro, while overexpression of tiRNA-Val-CAC-2 promoted the metastasis of pancreatic cancer. Mechanically, we discovered that tiRNA-Val-CAC-2 interacts with FUBP1, leading to enhanced stability of FUBP1 protein and increased FUBP1 enrichment in the c-MYC promoter region, thereby boosting the transcription of c-MYC. Of note, rescue experiments confirmed that tiRNA-Val-CAC-2 could influence pancreatic cancer metastasis via FUBP1-mediated c-MYC transcription. These findings highlight a potential novel mechanism underlying pancreatic cancer metastasis, and suggest that both tiRNA-Val-CAC-2 and FUBP1 could serve as promising prognostic biomarkers and potential therapeutic targets for pancreatic cancer.

Mechanical and Architectural Changes in Animal Bone Following Fast Neutron Irradiation.

ABSTRACT: Damage to healthy bone following exposure to ionizing radiation has been well documented for at least seven decades. Among the reported effects are a transient increase in stiffness and a reduction in breaking strength. These changes have been linked to a decrease in osteoblast proliferation and differentiation, inducing cell cycle arrest, reducing collagen production, and increasing sensitivity to apoptotic agents. In this work, we analyzed some mechanical and structural changes in compact costal bovine bone (Hereford breed, n = 9) subjected to escalating doses of fast neutrons from a 7Li(p,n)7Be reaction. The mean neutron energy was 233 keV with calculated absorbed doses ranging from 0 to 4.05 ± 10% Gy. Samples were subjected to Young's Modulus (YM) and breaking strength testing with a Universal Testing Machine (UTM). We found an increase in Young's Modulus and a decrease in breaking strength as functions of increasing dose equivalent. Optical coherence tomography (OCT) revealed trabecular displacement into compact bone in an irradiated sample (D = 4.05 ± 10% Gy), with breaching of the endosteal wall. OCT further revealed a "crack-like" structure across the irradiated sample, potentially consistent with damage from a proton track resulting from an elastic (n,p) reaction. No previous report has been found on mechanical changes in large mammalian bones following fast neutron doses, nor of the OCT imaging of such samples.

Anoikis-related genes as potential prognostic biomarkers in gastric cancer: A multilevel integrative analysis and predictive therapeutic value.

BACKGROUND: Gastric cancer (GC) is a frequent malignancy of the gastrointestinal tract. Exploring the potential anoikis mechanisms and pathways might facilitate GC research. PURPOSE: The authors aim to determine the significance of anoikis-related genes (ARGs) in GC prognosis and explore the regulatory mechanisms in epigenetics. METHODS: After describing the genetic and transcriptional alterations of ARGs, we searched differentially expressed genes (DEGs) from the cancer genome atlas and gene expression omnibus databases to identify major cancer marker pathways. The non-negative matrix factorisation algorithm, Lasso, and Cox regression analysis were used to construct a risk model, and we validated and assessed the nomogram. Based on multiple levels and online platforms, this research evaluated the regulatory relationship of ARGs with GC. RESULTS: Overexpression of ARGs is associated with poor prognosis, which modulates immune signalling and promotes anti-anoikis. The consistency of the DEGs clustering with weighted gene co-expression network analysis results and the nomogram containing 10 variable genes improved the clinical applicability of ARGs. In anti-anoikis mode, cytology, histology, and epigenetics could facilitate the analysis of immunophenotypes, tumour immune microenvironment (TIME), and treatment prognosis. CONCLUSION: A novel anoikis-related prognostic model for GC is constructed, and the significance of anoikis-related prognostic genes in the TIME and the metabolic pathways of tumours is initially explored.

Synthesis of Diacylhydrazine Derivatives Based on Tetrazole-Focused DNA-Encoded Library.

Utilizing already existing DNA-encoded libraries (DELs) for the generation of a distinct DEL represents an expedited strategy for expanding the chemical space. Herein, we leverage the unique photoreactivity of tetrazoles to synthesize diacylhydrazines on DNA. Widely available carboxylic acids serving as building blocks were employed under the mild photomediated reaction conditions, affording diverse DNA-conjugated diacylhydrazines. This methodology also demonstrates robustness in DEL-compatible synthesis and facilitates the preparation of oligonucleotide-based chemical probes.

Application of the quality of recovery-40 questionnaire to evaluate the effectiveness of enhanced recovery after surgery protocols in gastric cancer.

Patient reported outcomes is currently considered to be an important supplement to evaluate the effectiveness of enhanced recovery after surgery (ERAS) clinical practice. The Quality of Recovery-40 Questionnaire (QoR-40) is one of the most frequently used and validation tool to assess the subjective feelings of quality of life after surgery. The present study aimed to use the QoR-40 to evaluate the effectiveness of ERAS protocols in gastric cancer from the perspective of patient-reported quality of recovery. The study was designed as a prospective, non-randomized clinical trial, conducted in a single center. Patients in our hospital who were scheduled to undergo radical surgery for gastric cancer were divided into ERAS group and control group (Contr group). The QoR-40 were administered one day before surgery (Baseline) and on postoperative day 1, 3, 6, and 30. The difference in QoR-40 scores between the ERAS and Contr groups was compared by repeated-measures ANOVA. A total of 200 patients completed the study, including 100 patients in the ERAS group and 100 patients in the Contr group. The Baseline time point QoR-40 scores of the ERAS and Contr groups were 179.68 ± 14.46 and 180.12 ± 17.12, respectively, and no significant difference was noted between the two groups (p = 0.845). The postoperative QoR-40 score of the ERAS group was significantly higher than that of the Contr group, and the difference was statistically significant (p = 0.006). This study demonstrated that, in terms of patient-reported quality of recovery, the postoperative recovery effect of ERAS protocols in gastric cancer is significantly better than that of the traditional treatment model.

Unexpected Cyclization Product Discovery from the Photoinduced Bioconjugation Chemistry between Tetrazole and Amine.

Bioconjugation chemistry has emerged as a powerful tool for the modification of diverse biomolecules under mild conditions. Tetrazole, initially proposed as a bioorthogonal photoclick handle for 1,3-dipolar cyclization with alkenes, was later demonstrated to possess broader photoreactivity with carboxylic acids, serving as a versatile bioconjugation and photoaffinity labeling probe. In this study, we unexpectedly discovered and validated the photoreactivity between tetrazole and primary amine to afford a new 1,2,4-triazole cyclization product. Given the significance of functionalized N-heterocycles in medicinal chemistry, we successfully harnessed the serendipitously discovered reaction to synthesize both pharmacologically relevant DNA-encoded chemical libraries (DELs) and small molecule compounds bearing 1,2,4-triazole scaffolds. Furthermore, the mild reaction conditions and stable 1,2,4-triazole linkage found broad application in photoinduced bioconjugation scenarios, spanning from intramolecular peptide macrocyclization and templated DNA reaction cross-linking to intermolecular photoaffinity labeling of proteins. Triazole cross-linking products on lysine side chains were identified in tetrazole-labeled proteins, refining the comprehensive understanding of the photo-cross-linking profiles of tetrazole-based probes. Altogether, this tetrazole-amine bioconjugation expands the current bioconjugation toolbox and creates new possibilities at the interface of medicinal chemistry and chemical biology.

Hydrogel-Based Therapeutics for Pancreatic Ductal Adenocarcinoma Treatment.

Pancreatic ductal adenocarcinoma (PDAC), one of the deadliest malignancies worldwide, is characteristic of the tumor microenvironments (TME) comprising numerous fibroblasts and immunosuppressive cells. Conventional therapies for PDAC are often restricted by limited drug delivery efficiency, immunosuppressive TME, and adverse effects. Thus, effective and safe therapeutics are urgently required for PDAC treatment. In recent years, hydrogels, with their excellent biocompatibility, high drug load capacity, and sustainable release profiles, have been developed as effective drug-delivery systems, offering potential therapeutic options for PDAC. This review summarizes the distinctive features of the immunosuppressive TME of PDAC and discusses the application of hydrogel-based therapies in PDAC, with a focus on how these hydrogels remodel the TME and deliver different types of cargoes in a controlled manner. Furthermore, we also discuss potential drug candidates and the challenges and prospects for hydrogel-based therapeutics for PDAC. By providing a comprehensive overview of hydrogel-based therapeutics for PDAC treatment, this review seeks to serve as a reference for researchers and clinicians involved in developing therapeutic strategies targeting the PDAC microenvironment.

Case Report: A rare case of recurrent ascites after anti-Claudin18.2 antibody therapy for metastatic gastric cancer while responding sustainingly.

Background: Gastric cancer remains one of the deadliest malignancies in the world, thus urgently requiring effective and safe therapeutics. Claudin18.2 is a member of the tight junction protein family specifically expressed in gastric cancer cells. Monoclonal antibodies targeting Claudin18.2 have been receiving increasing attention recently. ASKB589 is a humanized monoclonal antibody targeting Claudin18.2. Case presentation: This case described a 65-year-old Chinese man diagnosed with gastric cancer metastasizing to the liver and multiple lymph nodes. The biomarker examination revealed that he had proficient mismatch repair (pMMR), human epidermal growth factor receptor 2 (HER2) was negative, and the combined proportion score (CPS) of PD-L1 (22C3) was 1. After being proven to be moderately positive for Claudin18.2 expression, he received ASKB589 and CAPOX (oxaliplatin and capecitabine) chemotherapy. After a six-cycle therapy (from 14 July 2022 to 29 November 2022), the target tumor was evaluated for partial response (PR) by the investigator based on the enhanced CT scan according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. However, this patient also suffered from intolerable ascites that gradually aggravated during the therapy, which was not controlled well by the supporting therapy. Therefore, the patient stopped receiving the combined therapy in our hospital and did not receive any other anti-tumor treatment. After 4 months of discontinuation of the drug, the patient's ascites almost disappeared, while the tumor continued to reduce and almost achieved clinically complete relapse (cCR). His progression-free survival (PFS) reached at least 10 months. Conclusion: This is the first case of severe ascites reported after anti-Claudin18.2 monoclonal antibody treatment for advanced gastric cancer. At the same time, the patient still benefited significantly from this incomplete treatment even after discontinuation of the drug and the PFS reached at least 10 months. The ascites might be an immune adverse effect related to the monoclonal antibody-induced antibody-dependent cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Further mechanisms remain to be investigated.

Comparison of Epidemiological Characteristics Between ESBL and Non-ESBL Isolates of Clinically Isolated Escherichia coli from 2014 to 2022: A Single-Center Study.

Purpose: This single-center study aims to investigate the epidemiological characteristics of clinically isolated Escherichia coli from 2014 to 2022. Methods: In vitro drug sensitivity of E. coli to 20 antibiotics was examined using the microbroth dilution method. A total of 7580 clinical E. coli strains were isolated from 2014 to 2022, among which 56.9% were identified as extended spectrum beta-lactamase-producing strains. The data were analyzed using the software WHONET5.6 and the R language platform. Results: Over the study period, carbapenem resistance rates increased by more than 50% (2022 [1.34%] vs 2014 [0.8%]) and the annual number of isolates showed an upward trend (1264 in 2022 vs 501 in 2014). Drug resistance rates were the highest for penicillin (75-85%) and lowest for imipenem (1%). The resistance rate of strains isolated from male patients and sputum was found to be higher than that of female patients and urine, except for quinolones (p <0.05). The drug resistance rates from high to low were penicillins (75-85%), tetracycline (64%), quinolones (64-67%), sulfamethoxazole (59.3%), cephalosporins (22-72%), aztreonam (34%), chloramphenicol (21%), amikacin (2.8%), colistin (1.4%), meropenem (1.1%), and imipenem (1%). Urine, sputum, and blood accounted for 51%, 16.6%, and 10.6% of the samples, respectively. A greater number of female patients were included more than male patients (4798[63.3%] vs 2782[26.7%]). Patients aged 50-80 accounted for 64.2% of those surveyed. Conclusion: Carbapenems remain the optimal choice for treating extended spectrum beta-lactamase-producing E. coli infections (sensitivity rate: 98%). Colistin (87.7%) and amikacin (87%) exhibited good antibacterial activities against carbapenem-resistant E. coli. Long-term and continuous epidemiological surveillance of E. coli can facilitate the development of preventive strategies and control policies.

Elevation of preoperative serum hs-CRP is an independent risk factor for malnutrition in patients with gastric cancer.

Background: Recent studies have reported hypersensitive C-reactive protein (hs-CRP) linked to clinicopathological characteristics and nutritional status of the tumor, but its clinical significance in GC remains unclear. This study aimed to investigate the relationship between preoperative serum hs-CRP level and clinicopathological features and nutritional status in gastric cancer (GC) patients. Methods: The clinical data of 628 GC patients who met the study criteria were analyzed retrospectively. The preoperative serum hs-CRP level was divided into two groups (<1 mg/L and ≥1 mg/L) to evaluate clinical indicators. Nutritional Risk Screening and nutritional assessment of GC patients were performed by the Nutritional Risk Screening 2002 (NRS2002) and the Patient-Generated Subjective Global Assessment (PG-SGA), respectively. The data were subjected to chi-square test, univariate and multivariate logistic regression analyses, respectively. Results: The analysis of 628 GC cases revealed that 338 patients (53.8%) were on malnutrition risk(NRS2002≥3 points), and 526(83.8%) had suspected/moderate to severe malnutrition(PG-SGA≥ 2 points). Preoperative serum hs-CRP level was significantly correlated with age, tumor maximum diameter (TMD), peripheral nerve invasion (PNI), lymph-vascular invasion (LVI), depth of tumor invasion (DTI), lymph node metastasis (LNM), pTNM stage, body weight loss (BWL), body mass index (BMI), NRS2002 score, PG-SGA grade, hemoglobin (HB), total protein (TP), albumin (ALB), prealbumin (PAB) and total lymphocyte count (TLC). Multivariate logistic regression analysis revealed that hs-CRP (OR=1.814, 95%CI=1.174-2.803; P=0.007), age, ALB, BMI, BWL and TMD were independent risk factors for existing malnutritional risk in GC. Similarly, non-malnutrition and suspected/moderate to severe malnutrition groups presented that hs-CRP (OR=3.346, 95%CI=1.833-6.122; P< 0.001), age, HB, ALB, BMI and BWL were independent risk factors for malnutrition in GC. Conclusion: In addition to the generally used nutritional evaluation indicators such as age, ALB, BMI, and BWL, the hs-CRP level may be used as a nutritional screening and evaluation indicator for GC patients.

Long Term Characteristics of Clinical Distribution and Resistance Trends of Carbapenem-Resistant and Extended-Spectrum ß-Lactamase Klebsiella pneumoniae Infections: 2014-2022.

Purpose: Through long-term and large sample size statistical analysis, we revealed the pattern of Klebsiella pneumoniae (KP) infection and drug resistance and provided epidemiological data for the treatment and prevention and control of multidrug-resistant bacterial infection in our hospital. Patients and Methods: Strains were identified using the BD PhoenixTM100 system, minimal inhibitory concentration of antibiotics were determined by the broth method, and data were statistically analyzed using WHONET 5.6 and SPSS27.0. Results: The isolation rate of KP from Enterobacteriaceae (26.2%, 4547/17358) in our hospital showed an increasing annual trend, ranking second only to Escherichia coli. Carbapenem-resistant KP (CRKP) accounted for the highest proportion of carbapenem-resistant Enterobacteriaceae (72.2%, 431/597), showing an upward trend. Infected patients had a male-to-female ratio of approximately 2:1 and were mainly >60 years of age (66.2%), with intensive care units being the most commonly distributed department. Sputum was the most common specimen type (74.0%). Compared with spring and summer, autumn and winter were the main epidemic seasons for KP and extended-spectrum ß-lactamase KP (ESBL-KP). The resistance rate of KP to common antibiotics was low, but all showed an increasing trend each year. ESBL-KP was >90% resistant to piperacillin, amoxicillin/clavulanic acid, and cefotaxime and less resistant to other common antibiotics, but showed an increasing trend in resistance to most antibiotics. CRKP resistance to common antibiotics was high, with resistance rates >90%, excluding amikacin (64.1%), gentamicin (87.4%), cotrimoxazole (44.3%), chloramphenicol (13.6%), and tetracycline (30.5%). Conclusion: KP in our hospital mainly caused pulmonary infection in older men, which occurred frequently in autumn and winter, and the isolation and drug resistance rates showed an increasing trend. Age over 70 years, admission to intensive care unit, and urinary tract infection were found to be the risk factors for CRKP and ESBL-KP-resistance.

In vitro susceptibility profiles of Candida parapsilosis species complex subtypes from deep infections to nine antifungal drugs.

Introduction. The Candida parapsilosis complex can be divided into C. parapsilosis sensu stricto, C. orthopsilosis, and C. metapsilosis subtypes. It is uncommon for drug sensitivity tests to type them.Gap Statement. In routine susceptibility reports, drug susceptibility of C. parapsilosis complex subtypes is lacking.Aim. The aim of this study is to investigate the antifungal susceptibility and clinical distribution characteristics of the C. parapsilosis complex subtypes causing deep infection in patients.Methodology. Non-repetitive strains of C. parapsilosis complex isolated from deep infection from 2017 to 2019 were collected. Species-level identification was performed using a matrix-assisted laser desorption/ionization time-of-flight mass spectrometer and confirmed using ITS gene sequencing, when necessary. Antifungal susceptibility testing was performed using the Sensititre YeastOne system method.Results. A total of 244 cases were included in the study, including 176 males (72.13 %, 60.69±13.43 years) and 68 females (27.87 %, 60.21±10.59 years). The primary diseases were cancer (43.44 %), cardiovascular disease (25.00 %), digestive system diseases, (18.44 %), infection (6.97 %), and nephropathy (6.15 %). Strains were isolated from the bloodstream (63.11 %), central venous catheters (15.16 %), pus (6.56 %), ascites (5.74 %), sterile body fluid (5.33 %), and bronchoalveolar lavage fluid (BALF, 4.09 %). Of the 244 C. parapsilosis complex strains, 179 (73.26 %) were identified as C. parapsilosis sensu stricto, 62 (25.41 %) were C. orthopsilosis, and three (1.23 %) were C. metapsilosis. Only one C. parapsilosis sensu stricto strain was resistant to anidulafungin, micafungin, caspofungin, and voriconazole, and it was non-wild-type (NWT) to amphotericin B. Furthermore, six C. parapsilosis sensu stricto strains were resistant to fluconazole, and one was dose-dependent susceptible. Five C. parapsilosis sensu stricto strains were NWT to posaconazole. Only one C. orthopsilosis strain was NWT for anidulafungin, micafungin, caspofungin, fluconazole, voriconazole, amphotericin B, and posaconazole, while the rest of the strains were wild-type.Conclusion. C. parapsilosis sensu stricto was the main clinical isolate from the C. parapsilosis complex in our hospital. Most strains were isolated from the bloodstream. The susceptibility rate to commonly used antifungal drugs was more than 96 %. Furthermore, most of the infected patients were elderly male cancer patients.

Performance analysis for OFDM-based multi-carrier continuous-variable quantum key distribution with an arbitrary modulation protocol.

Multi-carrier continuous-variable quantum key distribution (CV-QKD) is considered to be a promising way to boost the secret key rate (SKR) over the existing single-carrier CV-QKD scheme. However, the extra excess noise induced in the imperfect multi-carrier quantum state preparation process of N subcarriers will limit the performance of the system. Here, a systematic modulation noise model is proposed for the multi-carrier CV-QKD based on the orthogonal frequency division multiplexing (OFDM). Subsequently, the performance of multi-carrier CV-QKD with arbitrary modulation protocol (e.g. QPSK, 256QAM and Gaussian modulation protocol) can be quantitatively evaluated by combining the security analysis method of the single-carrier CV-QKD. Under practical system parameters, the simulation results show that the SKR of the multi-carrier CV-QKD can still be significantly improved by increasing the carrier number N even with imperfect practical modulations. Specifically, the total SKR of multi-carrier CV-QKD can be optimized by carefully choosing N. The proposed model provides a feasible theoretical framework for the future multi-carrier CV-QKD experimental implementation.

Effects of T-2 toxin on growth performance, feather quality, tibia development and blood parameters in Yangzhou goslings.

T-2 toxin is a dangerous natural pollutant and widely exists in animal feed, often causing toxic damage to poultry, such as slow growth and development, immunosuppression, and death. Although geese are considered the most sensitive poultry to T-2 toxin, the exact damage caused by T-2 toxin to geese is elusive. In the present study, a total of forty two 1-day-old healthy Yangzhou male goslings were randomly allotted seven diets contaminated with 0, 0.2, 0.4, 0.6, 0.8, 1.0, or 2.0 mg/kg T-2 toxin for 21 d, and the effects of T-2 toxin exposure on growth performance, feather quality, tibia development, and blood parameters were investigated. The results showed that T-2 toxin exposure significantly inhibited feed intake, body weight gain, shank length growth, and organ development (e.g., ileum, cecum, liver, spleen, bursa, and tibia) in a dose-dependent manner. In addition, the more serious feathering abnormalities and feather damage were observed in goslings exposed to a high dose of T-2 toxin (0.8, 1.0, and 2.0 mg/kg), which were mainly sparsely covered with short, dry, rough, curly, and gloss-free feathers on the back. We also found that hypertrophic chondrocytes of the tibial growth plate exhibited abnormal morphology and nuclear consolidation or loss, accompanied by necrosis and excessive apoptosis under 2.0 mg/kg T-2 toxin exposure. Moreover, 2.0 mg/kg T-2 toxin exposure triggered erythropenia, thrombocytosis, alanine aminotransferase, and aspartate aminotransferase activity, as well as high blood urea nitrogen, uric acid, and lactic dehydrogenase levels. Collectively, these data indicate that T-2 toxin had an adverse effect on the growth performance, feather quality, and tibia development, and caused liver and kidney damage and abnormal blood parameters in Yangzhou goslings, providing crucial information toward the prevention and control of T-2 toxin contamination in poultry feed.

Effect of different free-range systems on the growth performance, carcass traits, and meat quality of Yangzhou geese.

This study was conducted to investigate the effects of different free-range systems on the growth performance, carcass traits, and meat quality of geese. Grass pasture zones in the study area were selected, and 28 d-old male Yangzhou geese with similar body weights (1.57 ± 0.12 kg) were randomly allocated to one of three conditions: (A) free-range conditions in the apron area during 9:00 a.m.-4:00 p.m. (10-20 m from shed with grass pasture); (B) free-range conditions in the outer range from 9:00 a.m. to 4:00 p.m. (beyond 50 m from shed with grass pasture); and (C) barn system. Free range-reared geese had higher weight gain after 42 days of age than barn-reared geese, regardless of the range area. A lower feed conversion ratio was found in outer range-reared and apron area-reared geese from 28 to 63 days of age. In addition, the highest percentages of leg and breast muscle weights were observed in outer range-reared and apron area-reared geese, respectively. Finally, outer-range rearing resulted in a lower pH and lower moisture content. Therefore, these data suggest that the outer range system benefits growth performance and feed conversion ratio of geese and results in a higher percentage of leg muscle weight, lower pH, and lower moisture content.

The TRIM25 Gene in Ducks: Cloning, Characterization and Antiviral Immune Response.

TRIM25, as a significant member of the TRIM family, has been frequently demonstrated in regulating the host's antiviral response by activating innate immunity. Ducks are often asymptomatic carriers of influenza A viruses, but the beneficial roles of TRIM25 in modulating the immune response remain largely unknown in ducks. In this study, we characterized the TRIM25, which contains a 16 bp 5'-UTR, a 279 bp 3'-UTR and a 2052 bp ORF that encodes 683 amino acid residues. In addition, we found that duTRIM25 transcripts were widely expressed in the 10 tissues tested, with higher expression levels in the kidney, liver, muscle and spleen and lower expression levels in the duodenum and blood. In addition, the six kinds of virus- or bacteria-mimicking stimuli were transfected into DEFs, and duTRIM25 was induced significantly with 5'ppp dsRNA stimulation. Furthermore, overexpression of duTRIM25 followed by treatment with 5'ppp dsRNA resulted in an increase in IFN-ß. The SPRY domain of duTRIM25 contributed to promoting IFN-ß activity in DEFs challenged with 5'ppp dsRNA. Taken together, our findings suggest that duck TRIM25 can induce the production of IFN-ß against double-stranded RNA virus stimuli and that the SPRY domain of duTRIM25 was critical for the infection.

Identification of the Hub Genes and Potential Regulation Network in Chronic Hepatitis B via Bioinformatics Analysis.

Background: Chronic hepatitis B (CHB) is a serious infectious disease which is induced by hepatitis B virus (HBV) infection. This project was conducted to reveal the potential mechanism in CHB development via analyzing the public clinical data. Methods: GSE33857 and GSE110217, obtained from the GEO database, were used for bioinformatics excavation. Briefly, the raw data of GSE33857 and GSE110217 were analyzed with the GEO2R, and then the expressed matrix files were generated. The matrix files was visualized as heat map with R software. The targets of the miRNAs were analyzed with the miRDIP database. The functional annotation and pathway enrichment were performed using "clusterProfiler" package in R software. The STRING database was utilized to analyze the interaction of the DEGs, and the PPI and miRNA-mRNA network were established according to the related results. Results: 93 downregulated genes and 17 upregulated genes in GES33857, and 111 downregulated and 40 upregulated genes in GSE110217 were identified as the hub nodes. The targets of the DEGs in the datasets were enriched in PI3K/AKT and MAPK pathways and associated with transcriptional regulation. Moreover, PPI and miRNA-mRNA networks were also established with the DEGs and related targets in the datasets. miR-122-5p, miR-125b-5p, miR-136-5p, miR-194-5p, miR-139-5p, miR-140-5p, miR-181a-5p, and miR-29b-3p were identified as the potential biomarkers in CHB. Conclusion: Eight miRNAs, including miR-122-5p, miR-125b-5p, miR-136-5p, miR-194-5p, miR-139-5p, miR-140-5p, miR-181a-5p, and miR-29b-3p, were identified as the potential biomarkers in CHB, and the PPI and miRNA-mRNA networks were also established.

Circ_0008287 promotes immune escape of gastric cancer cells through impairing microRNA-548c-3p-dependent inhibition of CLIC1.

BACKGROUND: Analyses in silico suggested the upregulation of a circular RNA (circRNA), circ_0008287, in gastric cancer and possible interactions among microRNA (miR)-548c-3p, circ_0008287, and intracellular chloride channel protein 1 (CLIC1). This study aims to testify whether circ_0008287 can affect the immune escape of gastric cancer cells by regulating miR-548c-3p and CLIC1. METHODS: RT-qPCR was performed to determine the expression pattern of circ_0008287 in gastric cancer cells. Gain- and loss-of function assays were then performed to assess the effects of circ_0008287 on malignant phenotypes of cancer cells. Interactions among circ_0008287, miR-548c-3p and CLIC1 were verified by dual luciferase reporter gene, RIP and FISH assays. Effects of CLIC1 on IFN-γ secretion and apoptosis in CD8 + T cells were evaluated by flow cytometry following co-culture of CD8 + T cells with cancer cells overexpressing/silencing CLIC1. A gastric cancer mouse model was further developed for in vivo investigation on effects of circ_0008287 on tumorigenesis and tumor metastasis. RESULTS: circ_0008287, an upregulated circRNA in gastric cancer cells, augmented the viability as well as invasive and migratory potentials of gastric cancer cells. By competitively binding to miR-548c-3, circ_0008287 increased the expression of CLIC1, which impaired the function of CD8 + T cells and promoted their apoptosis. After downregulation of circ_0008287, in vivo tumorigenesis and metastasis were suppressed. CONCLUSION: Hence, this study suggests the promotive role of circ_0008287 in gastric cancer progression and immune escape and further elucidates the underlying circ_0008287/miR-548c-3p/CLIC1 regulatory axis.

Serum Nardilysin as a Prognostic Biomarker in Pancreatic Ductal Adenocarcinoma.

Background: Nardilysin, (N-arginine dibasic convertase, NRDC) has been reported to play an important role in cancer progression, and is associated with tumor proliferation signals and inflammatory signals, such as tumor necrosis factor-a (TNF-a) and heparin-binding epidermal growth factor-like growth factor (HB-EGF), through the activation of disintegrin and metalloproteinase (ADAM) proteases. NRDC has recently been revealed to be involved in the tumorigenesis of various types of cancer, including intrahepatic cholangiocarcinoma, malignant cerebral infarction, esophageal squamous cell carcinoma, and gastric cancer. However, the expression profiles and biological relevance of NRDC in pancreatic ductal adenocarcinoma have rarely been reported. Methods: We analyzed the NRDC expression profile in pancreatic ductal adenocarcinoma by enzyme-linked immunosorbent assay (ELISA) and identified NRDC as a circulating biomarker in the serum of 112 pancreatic ductal adenocarcinoma patients. The diagnostic value of NRDC was analyzed by the area under the curve (AUC) and the receiver operating characteristic (ROC) test. Results: Our results demonstrated that the clinical prognosis significance of NRDC with the clinical characteristics in pancreatic ductal adenocarcinoma (PDAC). NRDC was notably decreased in PDAC patient serum compared with the control group (p < 0.001). Furthermore, the present study found that the NRDC expression level was correlated with T grade (p < 0.001), metastasis(p < 0.001), differentiation(p < 0.001), and TNM stage (p = 0.011). Further bioinformatics analysis revealed that NRDC correlated with proliferation and migration pathways; in particular, it mediated cell-matrix adhesion-dependent activation in pancreatic ductal adenocarcinoma. Conclusions: Serum NRDC may play a useful diagnostic biomarker to evaluate the aggressive clinical features in PAAD patients.