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Background: The complex tumor microenvironment of hepatocellular carcinoma (HCC) has led to a low response to immune checkpoints inhibitors (ICIs) and a poor prognosis. PD-L1, as one of the indications for ICIs, is rich in glycosylation modifications, which result in untimely ICIs. Our study constructed a prognostic model based on N-linked glycosylation related genes for predicting the prognosis and the response to ICIs. Methods: The patients in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts were enrolled. The Cox regression was performed to develop a prognostic model and patients were divided into a low-and high-risk subgroup. 21 recurrent HCC patients who received postoperative adjuvant ICIs were recruited and evaluated the response to ICIs. siRNA was used for in vitro validation. Results: 59 N-linked glycosylation related differentially expressed genes were screened from of HCC and normal tissues in the TCGA cohort. The prognostic model was developed with DDOST, STT3A and TMEM165. The risk score could be an independent prognostic factor. Patients in high-risk subgroup showed worse prognosis than patients in low-risk. ssGSEA showed that patients in the low-risk subgroup were more tend to be immune-activated state. Immunohistochemistry studies showed that DDOST, STT3A and TMEM165 are highly expressed in tumor tissues and patients with high risk score correlated with poor progression free survival and worse immunotherapeutic response. Knockdown of the three genes significantly reduce the proliferation of HCC cell lines. Conclusion: In this study, we establish that the risk model based on N-linked glycosylation related genes could efficiently predict the prognosis and tumor microenvironment immune state of HCC patients, and the risk score could serve as an indicator of ICIs.

BackgroundGallbladder carcinosarcoma (GBCS) is a rare and aggressive malignancy with extremely poor prognosis. Although surgery is regarded as the primary therapy for GBCS, the effective therapeutic strategies for unresected lesions have been poorly defined.Case PresentationWe presented a case of a 74-year-old male who underwent radical resection of gallbladder carcinoma at a local hospital. Seven months later, he was admitted to our hospital due to right upper abdominal discomfort. Postoperative radiological examinations showed multiple hepatic lesions, hilar lymph node metastasis, and main portal vein tumor thrombus. The pathological consultation results confirmed GBCS and immunohistochemical examinations revealed PD-L1 expression in 20% of tumor cells. Then, the patient received chemotherapy (Gemcitabine plus Oxaliplatin, GEMOX) in combination with anti-PD-1 therapy. After nine courses of the combination therapy, complete regression of the tumors was achieved with no evidence of relapse till now.ConclusionsWe, for the first time, reported a patient with recurrent GBCS who benefited from the combined chemotherapy and immunotherapy, providing a potential effective management strategy for the refractory malignant tumor.

In this paper, a new filtering power divider (FPD) was proposed. The proposed third-order mainly comprises only a tri-mode stub-loaded resonator (SLR) and a isolation resistor, which leading to a small circuit area. Due to the inherent characteristic of the SLR, two extra transmission zeros (TZs) were created at the lower and upper passband and, thus, a high-selectivity quasi-elliptic bandpass response can be achieved. The resistor loaded between the output feeding lines was introduced to improve the impedance matching of the output ports and the isolation between the output ports. For a demonstration, a FPD with third-order quasi-elliptic bandpass response was designed and fabricated using microstrip technology. The EM simulation results were consistent with the experiment results.

Metarhizium anisopliae, an entomopathogenic fungus, is found to contribute to plant nutrient uptake and condidered as a plant endophyte. However, there is very little visual evidence that d...

We detected and compared the mRNA and protein expression levels of immunity-associated and symbiosis-associated genes in peanut (Arachis hypogaea) roots inoculated with entomopathogenic fungus M. anisopliae or the phytopathogenic fungus Fusarium oxysporum, by RT-qPCR and parallel reaction monitoring (PRM). The selected genes were mainly associated with plant–fungus interactions, signal transduction, regulation of cell death, nitrogen or iron metabolism, nutrient acquisition or transport, and compound synthesis based on previous transcriptome analysis. The results showed that the host basal defense responses were significantly inhibited by both M. anisopliae and F. oxysporum, which suggests that both fungi actively suppress the host immunity for successful colonization and infection. However, only F. oxysporum induced a strong host hypersensitivity, which indicates that the host is strongly resisting F. oxysporum but potentially allowing M. anisopliae. Additionally, the genes (SYMRK, CaM, CCaMK, FRI2, ABCC2, F6H1, SCT, NRT24 and LTP1) related to symbiosis and growth were distinctively observed with an up-regulated expression following M. anisopliae treatment, which implies that the host was actively initiating the establishment of symbiosis with the fungus. This study revealed a synergistic relationship between host immunosuppression and the promotion of symbiosis during interactions with M. anisopliae. It suggested that M. anisopliae benefited plant for symbiotic relationship, in addition to controlling herbivorous insects as an entomopathogen.

Background 17α-hydroxylase deficiency is a rare autosomal recessive disorder caused by mutations in the cytochrome P450 family 17 subfamily A member 1 gene. The major clinical presentation includes hypertension, hypokalemia, male pseudohermaphroditism and female gonadal dysplasia. Hundreds of pathogenic variants have been reported in this disorder, and some common mutations were found to be race-specific. Case presentation In this study, we reported 5 Chinese girls with 17α-hydroxylase deficiency from Henan Province. The patients all came to the hospital for hypertension, and they also presented with sexual infantilism. The average age of the patients was 14 years old, ranging from 12 to 17 years old. They all had reduced blood cortisol, estradiol (E2), and testosterone (TESTO) and increased adrenocorticotropic hormone (ACTH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). They all had the appearance of females; however, three of the chromosome karyotypes were 46XX, and two were 46XY. Conclusions All of the patients carried a mutation on the 329 amino acid of CYP17A1 exon 6. By summarizing the currently known pathogenic mutations of 17α-hydroxylase deficiency, we demonstrated the prevalence of these gene mutations in Chinese Han and non-Chinese populations.

PtPd nanoflowers (PtPd NFs) exhibit intrinsic peroxidase-like activity as nanozymes, but the nanozymes lack substrate specificity and have low catalytic activity. Herein, a molecularly imprinted nanogel on PtPd NFs was prepared by using 3,3′,5,5′-tetramethylbenzidine (TMB) as the template through the aqueous precipitation polymerization method. After the TMB was washed out, many substrate binding pockets were retained in the PtPd NFs. Scanning electron microscopy (SEM), transmission electron microscopy (TEM) and powder X-ray diffraction (XRD) were employed to characterize the molecularly imprinted polymer (MIP) PtPd nanoflowers (T-MIP-PtPd NFs). The obtained T-MIP-PtPd NFs exhibited enhanced catalytic activity and specific recognition for TMB. Compared with PtPd NFs, T-MIP-PtPd NFs showed a linear range from 0.01–5000 μM and a detection limit of 0.005 μM toward the detection of H2O2. Glucose can also be sensitively detected through cascade reaction by the T-MIP-PtPd NFs and glucose oxidase. Therefore, molecular imprinting on nanozymes technology shows promising application in biocatalysis and sensing fields.

Efficacy of Metarhizium anisopliae strain (IMI330189) and Mad1 protein alone or in combination by feeding method to overcome immune-related enzymes and Toll-like pathway genes was investigated in migratory locust. M. anisopliae (IMI330189) is a potent and entomopathogenic fungal strain could be effectively used against insect pests. Similarly, Mad1 protein adheres to insect cuticle, causing virulence to insects. We confirmed maximum 55% of mortality when M. anisopliae (IMI330189) and Mad1 was applied in combination. Similarly, increased PO activity was observed in locust with combined dose of Mad1 + IMI330189 whereas PO, POD, and SOD activities reduced using Mad1 independently. Four Toll-like signaling pathway genes (MyD88, Cactus, Pelle, and CaN) were investigated from midgut and body of the migratory locust after 72 h of treatments. Subsequently, the expression of MyD88 in the midgut and body significantly decreased with the application of Mad1 and Mad1 + IMI330189. Performance of these treatments was absolutely non-consistent in both parts of insects. Meanwhile, IMI330189 significantly raised the expression of Cactus in both midgut and body. However, the combined treatment (Mad1 + IMI330189) significantly reduced the Cactus expression in both body parts. Pelle expression was significantly increased in the midgut with the application of independent treatment of Mad1 and IMI330189 whereas the combined treatment (Mad1 + IMI330189) suppressed the Pelle expression in midgut. Its expression level was absolutely higher in body with the application of IMI330189 and Mad1 + IMI330189 only. On the other hand, Mad1 significantly increased the expression of CaN in midgut. However, all three treatments significantly affected and suppressed the expression of CaN gene in body of locust. This shows that the applications of M. anisopliae and Mad1 protein significantly affected Toll signaling pathway genes, which ultimately increased level of susceptibility of locust. However, their effect was significantly different in both parts of locust which recommends that the Toll-related genes are conserved in midgut instead of locust body.

Background To study the correlation between blood pressure variability (BPV) and plasma renin activity (PRA), angiotensin II (AngII), aldosterone levels in patients with essential hypertension. Methods A total of 300 patients with mild to moderate essential hypertension were analyzed retrospectively. The subjects were divided into 3 age groups: 100 patients aged 18–44 years (young group), 110 patients aged 45–64 years (middle-aged group), and 90 patients aged over 65 years (elderly group). PRA, AngII, and aldosterone levels were assessed. Blood pressure (BP) was measured by 24-hour ambulatory BP monitoring. The relationships between BP variability and the PRA, AngII, aldosterone levels were compared among the 3 groups. Results Supine and upright PRA and aldosterone levels were significantly higher in the young group than those in the middle-aged and elderly groups. The coefficient of variation (CV) of 24-hour systolic (24hSBPCV), diastolic BP (24hDBPCV), CV of daytime systolic (dSBPCV), diastolic (dDBPCV), and nighttime systolic BP (nSBPCV) in the elderly group was higher than those in the young group and the middle-aged group (all P < 0.05). Spearman correlation analysis showed that in the young and middle-aged groups, BPV was significantly correlated with the levels of PRA, AngII, and aldosterone (all P < 0.05). In the elderly group however, only 24hDBPCV, nDBPCV, and nSBPCV were correlated with AngII and aldosterone levels (all P < 0.05). Conclusions BPV is correlated with plasma renin–angiotensin–aldosterone levels in young and middle-aged patients with mild to moderate essential hypertension.

To evaluate the characteristics of microbiological contamination in donor corneas preserved for medium-term. A total of 82 donated corneas from June 1, 2014 to November 30, 2014 were retrospectively analyzed. The corneas were preserved in cornea chambers medium-term solution at 4–8 °C for keratoplasty. After removal of the central corneas for transplantation, the corneoscleral rims were put back into the medium for 1 month at room temperature (20–25 °C). The suspicious contaminated storage solutions indicated with transparency or color change were examined with bacteria and fungi cultivation for strain identification. The data collected included gender, age, procurement site and causes of death of donors, and follow-up of recipients. Statistical analysis was performed using Microsoft Excel and SPSS 24.0. Significance level was set at a P value

Methanol-water as solvent, transition metal Y-type zeolite as catalyst, L-lysine was synthesized laminin. Explores the methylation process factors, and the structure of the compound by IR, NMR and elemental analysis were characterized.

Introduction Genetic studies restricted to young adult ischemic stroke patients may help in excluding the potentially confounding variables encountered with advanced age; thus, allowing a more precise risk evaluation derived from the inherited mutations alone. Through meta-analysis, this study was conducted to determine the genetic risk contributed by each susceptibility gene polymorphism, particularly in adult early-onset ischemic stroke patients. Materials and Methods Electronic databases were searched for all the case-control studies relating to any candidate genes for ischemic stroke. The range of age was 18–50 years for cases. Fixed or random effects model was used depending on the heterogeneity between studies. Results Twenty-six studies were finally included in this meta-analysis; these studies focused on 7 candidate genes. A significant but modest association was identified for 2 polymorphisms, namely, methylenetetrahydrofolate reductase (MTHFR) C677T (OR=1.44, 95% CI=1.14–1.80) and apolipoprotein E (ApoE) e2–4 (OR=2.53, 95% CI=1.71–3.73). Although the pooled analysis for platelet glycoprotein Ia (GPIa) C807T showed a positive association (OR=1.50, 95% CI=1.10–2.05), the Egger's test indicated the existence of publication bias ( t =5.27, P>|t|=0.034). Conclusions Genetic abnormalities specific to homocysteine and lipid metabolism increase the risk for ischemic stroke at an early age. These data may offer important implications for future genetic association studies for stroke.

AIM:To investigate the influence of minTBP-1-PRGDN on the attachment, proliferation and collagen I synthesis of human keratocyte on titanium (Ti) surface.METHODS:The chimeric peptide RKLPDAPRGDN (minTBP-1-PRGDN) was synthesized by connecting RKLPDA (minTBP-1) to the N-terminal of PRGDN , the influence of minTBP-1-PRGDN on the attachment, proliferation and collagen I synthesis of human keratocyte on Ti surface were tested using PRGDN and minTBP-1as controls. The keratocytes attached to the surface of Ti were either stained with FITC-labeled phalloidin and viewed with fluorescence microscope or quantified with alamar Blue method. The proliferation of keratocytes on Ti were quantified with 3-(4,5-dim- ethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide up-taking methods. The secretion of type I collagen were determined using an ELISA kit.RESULTS:The results showed that minTBP-1-PRGDN at a concentration of 100ng/mL was the most potent peptide to enhance the attachment of human keratocytes to the surface of Ti (1.40±0.03 folds, P=0.003), to promote the proliferation (1.26±0.05 folds, P=0.014) and the synthesis of type I collagen (1.530±0.128, P=0.008). MinTBP-1 at the same concentration could only promote the attachment (1.13±0.04 folds, P=0.020) and proliferation(1.15±0.06 folds, P=0.021), while PRGDN had no significant influence (P＞0.05).CONCLUSION:Our data shows that the novel chimeric peptide minTBP-1-PRGDN could promote the attachment, proliferation and type I collagen synthesis of human keratocytes on the surface of Ti.

The effects of different concentrations of vascular endothelial cell growth factor (VEGF) on the fibrovascular ingrowth into rabbits hydroxyapatite orbital implant were investigated. Twelve New Zealand white rabbits were divided into 3 groups and received hydroxyapatite orbital implant surgery in their right eyes. Before and after the operation, the implants were treated with 10 ng/ml VEGF, 100 ng/ml VEGF, or normal saline as control group. The animals received technetium bones scan at 2, 4, and 6 weeks postoperatively. The mean radioactivity counts within region of interest (ROI) of the surgery eye (R) and the non-surgery eye (L) in the same animal were tested, and the R/L ratios were calculated. The implants were harvested at 6th weeks and examined histopathologically. The results showed that at second week, there was no significant difference in mean R/L ratios between VEGF group and control group (F=2.83, P=0.111); At 4th week (F=7.728, P=0.011) and 6th week (F=7.831, P=0.011) postoperatively, the mean ratios in VEGF groups were significantly higher than that in control group. At 6th week postoperatively, the fibrovascularization rates in VEGF groups were higher than in control group significantly (F=8.711, P=0.008). It was suggested that VEGF could promote the fibrovascular ingrowth into hydroxyapatite orbital implant, thus might shorten the time required for complete vascularization of the HA orbital implant.

To investigate the prevalence and anatomy features of iridociliary body cysts in patients with narrow anterior chamber angle.Retrospective case series study. The prevalence and anatomy features of iridociliary body cysts in 223 patients (402 eyes) were analyzed retrospectively with ultrasound biomicroscopy (UBM). All of the patients were examined for susceptive narrow anterior chamber angle without complaint. The age of the patients, the site, diameter and number of cysts, the anterior chamber angle and the central anterior chamber depth were measured.Iridociliary body cysts were found in 19 patients (23 eyes) out of 223 patients (402 eyes), the prevalence is 5.7%. Fifteen patients were unilateral and four patients bilateral. Two cases originated from the ciliary process, eighteen cases from the iris root, and three from both the root and posterior surface of the iris. Twenty one cases were single cysts while two cases were multiple cysts. The diameter of the cysts ranged from 0.5 to 3.1 mm, averaged (0.71 ± 0.53) mm. The average age and the central anterior chamber depth of the eyes with iridociliary body cysts were (55.32 ± 10.74) years and (2.25 ± 0.39) mm, with no significant difference (t = 0.534, 0.783; P0.05) as compared to that of patients without cysts, which were (57.46 ± 10.52) years and (2.14 ± 0.34) mm. The anterior chamber angle in iridociliary body cysts group was 8.2° (21.0°, 0.0°), with no significant difference (Z = -0.062, P0.05) as compared to that of patients without cysts, which was 8.9° (21.4°, 0.0°).The prevalence rate of iridociliary body cysts in this study is 5.7%, central anterior chamber depth and anterior chamber angle in patients with cysts do not differ form patients without cysts.