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Clinical classification of advanced schistosomiasis japonica is important for treatment options and prognosis prediction. Network analysis was used to solve the problem of complexity and co-occurrence complications in classification of advanced schistosomiasis. A total of 4,125 retrospective patients were enrolled and divided randomly into a training cohort (n = 2,888) and a validation cohort (n = 1,237). Network analysis was used to cluster the isolated complications of advanced schistosomiasis. The accuracy of the network was evaluated. Nomograms based on the clustered complications were built to predict 1- to 5-year survival rates in advanced schistosomiasis. The predictive performance of the nomogram was also evaluated and validated. Fifteen isolated complications were identified: metabolic syndromes, minimal hepatic encephalopathy, hepatic encephalopathy, chronic obstructive pulmonary disease, pulmonary hypertension, respiratory failure, right heart failure, gastroesophageal variceal bleeding, gastrointestinal ulcer bleeding, splenomegaly, fibrosis, chronic kidney disease, ascites, colorectal polyp, and colorectal cancer. Through network analysis, three major clustered complications were achieved—namely, schistosomal abnormal metabolic syndromes (related to chronic metabolic abnormalities), schistosomal abnormal hemodynamics syndromes (related to severe portal hypertension and portosystemic shunting), and schistosomal inflammatory granulomatous syndromes (related to granulomatous inflammation). The nomograms showed a good performance in prognosis prediction of advanced schistosomiasis. The novel classification-based nomogram was useful in predicting the survival rate in advanced schistosomiasis japonica.

Adoptive therapy with cytomegalovirus (CMV)-specific cytotoxic T lymphocytes (CMV-CTLs) has emerged as an effective method for CMV infection. However, the efficacy reportedly ranges from 50% to 90%, and factors affecting anti-CMV efficacy have not been established. We investigated the safety and efficacy of adoptive therapy with CMV-CTLs for CMV infection in 190 patients after haploidentical stem cell transplantation (haplo-SCT), and importantly, we analyzed the main factors affecting antiviral efficacy. The CMV peak titer decreased from 19 (range, 1.0-503.0) × 10

The interaction of inhibitory receptors with self–MHC class I (MHC-I) molecules is responsible for NK cell education. The intensity of DNAM-1 expression correlates with NK cell education. However, whether DNAM-1 expression directly influences the functional competence of NK cells via the KIR/MHC-I interaction remains unclear. Based on allogeneic haploidentical hematopoietic stem cell transplantation, we investigated the intensity of DNAM-1 expression on reconstituted NK cells via the interaction of KIR with both donor HLA and recipient HLA at days 30, 90, and 180 after hematopoietic stem cell transplantation. The reconstituted NK cells educated by donor and recipient HLA molecules showed the highest DNAM-1 expression, whereas DNAM-1 expression on educated NK cells with only recipient HLA molecules was higher than that on educated NK cells with only donor HLA molecules, indicating that NK cells with donor or recipient HLA molecules regulate DNAM-1 expression and thereby affect NK cell education. Additionally, the effects of recipient cells on NK cell education were greater than those of donor cells. However, only when the DNAM-1, NKP30, and NKG2D receptors were blocked simultaneously was the function of educated and uneducated NK cells similar. Therefore, activating receptors may collaborate with DNAM-1 to induce educated NK cell hyperresponsiveness. Our data, based on in vitro and in vivo studies, demonstrate that the functional competence of NK cells via the KIR/MHC-I interaction correlates with DNAM-1 expression in human NK cells.

Background The pandemic of COVID‐19 has a persistent impact on global health, yet its sequelae need to be addressed at a wide scale around the globe. This study aims to investigate the characteristics, prevalence, and risk factors for mid‐term (>6 months) clinical sequelae in a cohort of COVID‐19 survivors. Methods Totally 715 COVID‐19 survivors discharged before April 1, 2020, from three medical centers in Wuhan, China, were included. The longitudinal study was conducted by telephone interviews based on a questionnaire including the clinical sequelae of general, respiratory, and cardiovascular systems. Demographics and some characteristics of clinical sequelae of the survivors were recorded and analyzed. Multivariate logistic regression analysis was applied to explore the risk factors for the sequelae. Results The median time interval from discharge to telephone interview was 225.0 days. The COVID‐19 survivors' median ages were 69 years, and 51.3% were male. Among them, 29.9% had at least one clinical sequela. There were 19.2%, 22.7%, and 5.0% of the survivors reporting fatigue, respiratory symptoms, and cardiovascular symptoms, respectively. Comorbidities, disease severity, the application of mechanical ventilation and high‐flow oxygen therapy, and the history of re‐admission were associated with the presence of clinical sequelae. Conclusions Our study provides further evidence for the prevalence and characteristics of clinical sequelae of COVID‐19 survivors, suggesting long‐term monitoring and management is needed for their full recovery.

Natural killer (NK) cells exert anti-viral effects after haematopoietic stem cell transplantation (HSCT). The balance between inhibition and activation of NK cells determined by the inherited repertoire of killer cell immunoglobulin-like receptors (KIR) genes may influence Epstein-Barr virus (EBV) reactivation after transplantation. To evaluate the relative contributions of KIR genotypes to EBV reactivation, we prospectively enrolled 300 patients with malignant haematological disease who were suitable for haploidentical HSCT. Univariate analysis showed that donors with KIR2DS1, KIR2DS3 or KIR3DS1 genes were associated with an increased risk of EBV reactivation [hazard ratio (HR) 1·86, 95% confidence interval (CI) 1·19-2·9, P = 0·0067; HR 1·78, 95% CI 1·07-2·97, P = 0·027; HR 1·86, 95% CI 1·19-2·91, P = 0·0065 respectively]. Multivariate analysis revealed that the presence of KIR2DS1, KIR2DS3 or KIR3DS1 genes was associated with increased EBV reactivation after HSCT. This effect was more evident in the absence of the cognate ligands for the corresponding activating receptors. Our present data firstly showed that donors with activating KIR genes, specifically activating KIR2DS1, KIR2DS3 and KIR3DS1, had an increased risk of EBV reactivation. Precaution for patients whose donors carry activating genes will help prevent EBV reactivation and improve patient prognosis after HSCT.

To investigate the metabolic changes in rats with minimal hepatic encephalopathy (MHE) treated with oral magnesium sulphate administration.A total of 30 Sprague-Dawley rats were divided into a control group and MHE group (further divided into an MHE group and an MHE-Mg group treated with oral administration of 124 mg/kg/day magnesium sulphate). Morris water maze (MWM), Y maze and narrow beam walking (NBW) were used to evaluate cognitive and motor functions. Brain manganese and magnesium content were measured. The metabolic changes in rats with MHE were investigated using hydrogen-nuclear magnetic resonance. Metabolomic signatures were identified with enrichment and pathway analysis.A significantly decreased number of entries into the MWM within the range of interest, longer latency and total time during NBW, and higher brain manganese content were found in rats with MHE. After magnesium sulphate treatment, the rats with MHE had better behavioural performance and lower brain manganese content. The 25 and 26 metabolomic signatures were identified in the cortex and striatum of rats with MHE. The pathway analysis revealed alanine, aspartate and glutamate metabolism as the major abnormal metabolic pathways associated with these metabolomic signatures.Alanine, aspartate and glutamate metabolism are major abnormal metabolic pathways in rats with MHE, which could be restored by magnesium sulphate treatment.

Natural killer (NK) cell exhaustion is associated with a poor prognosis in persistent infection and cancer. Determination and understanding of the mechanism of NK cell exhaustion in acute myeloid leukaemia (AML) patients may provide underlying principles for enhancing AML therapy. We investigated NK cell exhaustion in relapsed AML patients post allogeneic haematopoietic stem cell transplantation (allo-HSCT) based on phenotypic, functional, and RNA-sequencing (RNA-seq) analyses. Compared with those from the complete remission control (N=30) and healthy control (N=12) groups, NK cells from the relapsed group (N=30) were less mature, with a large CD56bright subset, high NKG2A expression, poor cytotoxicity, downregulation of the transcription factors Eomesodermin (EOMES) and T-bet, and cell cycle arrest in the G1 stage. NK cell exhaustion could be reversed once relapsed patients achieved remission. Furthermore, NK cells showed high NKG2A expression but normal cytotoxicity in minimal residual disease (MRD)-positive patients post allo-HSCT. Combined with in vitro and mouse model results, the data suggested that NK cell exhaustion was induced by persistent AML stimulation. Moreover, RNA-seq and western blot analyses showed that the phosphatidylinositol-3-kinase (PI3K)-AKT inhibition in exhausted NK cells was induced by AML and that PI3K-AKT activators could reverse NK cell exhaustion in vitro. Consequently, our studies highlight that AML induces NK cell exhaustion through the PI3K-AKT pathway.

Adoptive transfer of cytomegalovirus (CMV)-specific cytotoxic T lymphocytes (CMV-CTLs) from original transplant donors or third-party donors was effective for the treatment of CMV infection after allogenic stem cell transplantation (allo-SCT), but the antiviral activity of CMV-CTL types has not been compared. To determine whether third-party CMV-CTLs provide comparable long-term antiviral efficacy to transplant donor CMV-CTLs, we first compared the antiviral abilities of transplant donors and third-party CMV-CTLs for treatment of CMV infection in two mouse models, compared the in vivo recovery of CMV-specific immunity, and analyzed the underlying mechanisms driving sustained antiviral immunity. The results showed that both donor and third-party CMV-CTLs effectively combated systemic CMV infection by reducing CMV pathology and tumor burden 28 days postinfusion. The in vivo recovery of CMV-specific immunity after CMV-CTL infusion was comparable in both groups. A detailed analysis of the source of recovered CMV-CTLs showed the proliferation and expansion of graft-derived endogenous CMV-CTLs in both groups. Our clinical study, which enrolled 31 patients who received third-party CMV-CTLs and 62 matched pairs of individuals who received transplant donor CMV-CTLs for refractory CMV infection, further showed that adoptive therapy with donor or third-party CMV-CTLs had comparable clinical responses without significant therapy-related toxicity. We observed strong expansion of CD8(+) tetramer(+) T cells and proliferation of recipient endogenous CMV-CTLs after CMV-CTL infusion, which were associated with a reduced or cleared viral load. Our data confirmed that adoptive therapy with third-party or transplant donor CMV-CTLs triggered comparable antiviral responses to CMV infection that might be mediated by restoration of endogenous CMV-specific immunity.

NKG2C+ natural killer (NK) cell plays a vital role in CMV infection control after hematopoietic stem cell transplantation (HSCT). However, the modulation on NKG2C+ NK cell reconstitution is still unclear. NK cell education is affected by the interactions of HLA-I/killer immunoglobulin receptor (KIR). Our aim is to figure out which HLA-I/KIR interaction plays a dominant role in NKG2C+ NK education. Based on allogeneic haploidentical HSCT, we investigated the expansion and function of single KIR positive NKG2C+ NK cells via the interaction of KIR with both donor HLA and recipient HLA at days 30, 90, and 180 after HSCT. KIR2DL2/L3 single-positive/NKG2C+ cells were significantly expanded compared with KIR2DL1 or KIR3DL1 single-positive/NKG2C+ cells when donors and recipients were both HLA-C1/C1 or HLA-C1C1BW4 (p < 0.05), with higher NKp30 expression (p < 0.05). Moreover, the proportion of single KIR positive NK cells increased in both NKG2C+/NKG2A- NK cells and conventional NKG2C-/NKG2A- NK cells over time. We also observed that increased proportion of KIR2DL2/L3 single-positive/NKG2C+ NK cells correlated with higher incidence of acute graft-versus-host disease (aGVHD). Our study allows a better understanding of HLA-I/KIR interaction in the NKG2C+ NK cell education after HSCT.

Background Understanding the long-term effects of coronavirus disease 2019 (COVID-19) on cognitive function is essential for monitoring the cognitive decline in the elderly population. This study aims to assess the current cognitive status and the longitudinal cognitive decline in elderly patients recovered from COVID-19. Methods This cross-sectional study recruited 1539 COVID-19 inpatients aged over 60 years who were discharged from three COVID-19-designated hospitals in Wuhan, China, from February 10 to April 10, 2020. In total, 466 uninfected spouses of COVID-19 patients were selected as controls. The current cognitive status was assessed using a Chinese version of the Telephone Interview of Cognitive Status-40 (TICS-40) and the longitudinal cognitive decline was assessed using an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Cognitive assessments were performed 6 months after patient discharge. Results Compared with controls, COVID-19 patients had lower TICS-40 scores and higher IQCODE scores [TICS-40 median (IQR): 29 (25 to 32) vs. 30 (26 to 33), p p p p p p p p p p Conclusions Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with an increased risk of long-term cognitive decline in elderly population. COVID-19 patients, especially severe patients, should be intensively monitored for post-infection cognitive decline.

Background: Understanding the long-term effects of coronavirus disease 2019 (COVID-19) on cognitive function is essential for the prevention of cognitive decline in elderly population. This study aims to assess cognitive status and longitudinal decline at 6 months post-infection in elderly patients recovered from COVID-19. Methods: This cross-sectional study recruited 1013 COVID-19 inpatients aged over 60 years who were discharged from three COVID-19-designated hospitals in Wuhan, China, from February 10 to March 13, 2020. In total, 262 uninfected living spouses of COVID-19 patients were selected as controls. Subjects were examined for their current cognitive status using a Chinese version of the Telephone Interview of Cognitive Status-40 (TICS-40) and longitudinal cognitive decline using an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Cognitive assessments were performed 6 months after patient discharge. Findings: COVID-19 patients had significantly lower TICS-40 scores (patients: 29.73±6.13; controls: 30.74±5.95, p=0.016) and higher IQCODE scores (patients: 3.40±0.81; controls: 3.15±0.39, p

The Contact Graph Routing (CGR) algorithm uses the scheduled contact between nodes to calculate the route. When the contact plan and the actual situation are inconsistent, the CGR will be invalid. In addition, CGR does not consider the link state and queuing delay, which may lead to excessive end-to-end delay or even bundle expired. In view of the above problems, this paper proposes a CGR routing decision mechanism that considers the link state, queuing delay and the reliability of contact plan, and determines the best path by defining a delay factor. The simulation results show that the improved algorithm has a great improvement in both end-to-end delay and packet loss rate, especially in the case of limited resources, the performance is better.

The effect of chitosan–ergothioneine coating (CHER) on the post-mortem quality and shelf life of Japanese sea bass (Lateolabrax japonicas) stored at 4 ± 1 °C for 16 days was investigated. Four different treatments were used: control without coating, CH with chitosan coating, ER with 0.3 % ergothioneine immersion, and CHER with chitosan containing 0.3 % ergothioneine coating. Sea bass pH value, total volatile basic nitrogen, peroxide value, thiobarbituric acid-reactive substances, biogenic amines, color, texture profile, and microbiological and sensory qualities were measured. The results indicate that treatment with CHER coating inhibited increase of total volatile basic nitrogen, peroxide value, and TBA value; maintained tissue hardness; and reduced microorganism counts, such as Pseudomonas, compared with control treatment. The efficiency was better than that of ER or CH treatment. Furthermore, sea bass treated with chitosan–ergothioneine coating also exhibited a positive effect, causing low biogenic amine content, especially putrescine, cadaverine, and histamine. Sensory evaluation proved the efficacy of chitosan–ergothioneine coating by maintaining the overall quality of sea bass during the storage period. Our study suggests that chitosan–ergothioneine coating might be a promising candidate for maintaining sea bass quality and extending their shelf life.

With the rapid development of new rural construction, rural areas have been changed enormously. At the same time, the ecological environment of rural areas has suffered a lot, especially, for the water environment and the rural landscape. In this paper, Yansaihu greenway planning of Qinhuangdao City has been used as an example, to demonstrate how to combine the nature, the Yansaihu water, the fields, and the rural areas in series by means of the greenway planning. While using and protecting Yansaihu natural landscape, it promotes agricultural leisure industry and extends the historical and cultural context, protects water resources in the ecological environment, and promotes the purpose of harmonization of nature, landscapes, farmland, and rural landscape, in order to achieve both of the rural environment and ecology landscape as well as rural economic development.

Pneumatic position servo is a rapidly growing-up technology, control strategy play a key role in system performance. This article studies pneumatic position servo system, through applying the control algorithm of intelligent fuzzy PID, it has settled the difficulties of building precise mathematics model by traditional control methods and the problems of exceeding or lagging in the control process. The experiments show that, the control has achieved the expected results, and has large prospects for application in the area of industry automatization.

Acute gastroenteritis caused by pathogenic Vibrio parahaemolyticus is one of the major factors affecting the development of aquaculture and the safety of seafood. Using the antagonism of probiotics against pathogens is an alternative strategy to antibiotics and a common trend to control food-borne pathogenic bacteria. In this study, a total of 249 isolates were isolated from four types of seafood (Litopenaeus vannamei, Oratosquilla oratoria, Mactra veneriformis and Portunus trituberculatus) and coastal sediment from Liaodong Bay in the Bohai Sea, China with five different separation agars. The most isolates came from the sample of coastal sediment and on agar of 2216E, which accounted for 36.14 and 54.62 % respectively. Twenty-four among 249 isolates displayed direct antimicrobial activity to V. parahaemolyticus with spot inoculation. Sixteen active isolates were selected for extracellular antimicrobial activity using the Oxford cup method. Only strains of B16 and J7 showed extracellular antimicrobial activity and were identified as Bacillus pumilus and Bacillus mojavensis respectively based on the physiological identification and 16S rRNA sequence analysis. Both of the strains B16 and J7 exhibited extracellular hydrolytic enzyme activity and antagonism against more than one indicator bacteria in vitro, which indicates that the two strains have broad potential application as suitable probiotic candidates in aquaculture while B. mojavensis was first reported to inhibit pathogenic Vibrio spp. in vitro. There is no particular trait as to antagonism of B. pumilus B16 or B. mojavensis J7 to Gram-positive or Gram-negative indicator bacteria.

Using neuronal NO synthase (nNOS)-specific antisense oligonucleotides, we examined the role of nitric oxide (NO) in the paraventricular nucleus (PVN) on control of blood pressure and heart rate (HR) in conscious sham rats and rats with chronic heart failure (CHF). After 6–8 wk, rats with chronic coronary ligation showed hemodynamic and echocardiographic signs of CHF. In sham rats, we found that microinjection of sodium nitroprusside (SNP, 20 nmol, 100 nl) into the PVN induced a significant decrease in mean arterial pressure (MAP). SNP also induced a significant decrease in HR over the next 10 min. In contrast, the NOS inhibitor NG-monomethyl-l-arginine (l-NMMA, 200 pmol, 100 nl) significantly increased MAP and HR over the next 18–20 min. After injection of nNOS antisense, MAP was significantly increased in sham rats over the next 7 h. The peak response was 27.6 ± 4.1% above baseline pressure. However, in the CHF rats, only MAP was significantly increased. The peak magnitude was 12.9 ± 5.4% of baseline, which was significantly attenuated compared with sham rats ( P < 0.01). In sham rats, the pressor response was completely abolished by α-receptor blockade. HR was significantly increased from hour 1 to hour 7 in sham and CHF rats. There was no difference in magnitude of HR responses. The tachycardia could not be abolished by the β1-blocker metoprolol. However, the muscarinic receptor antagonist atropine did not further augment the tachycardia. We conclude that NO induces a significant depressor and bradycardiac response in normal rats. The pressor response is mediated by an elevated sympathetic tone, whereas the tachycardia is mediated by withdrawal of parasympathetic tone in sham rats. These data are consistent with a downregulation of nNOS within the PVN in CHF.

Effects of chitosan (CS) and hawthorn flavonoid coating on quality and shelf life in flounder (Paralichthys olivaceus) fillets during refrigerated storage were investigated. Fish samples were treated with 0.5% acetic aqueous, 1% CS, 1% CS + 0.3% hawthorn flavonoids, then stored at 4–8C for 14 days. All the samples were analyzed periodically for microbiological (total plate count and psychrotrophic count), chemical (pH, TVB-N, K-value, TABRS), physical quality (hardness, color), and sensory evaluation. Compared with the other two groups, treated with CS, CS and hawthorn flavonoids (CS + HF) were found to extend the shelf life by 4–6 days during refrigerated storage. The results showed that CS and hawthorn flavonoid coating on fish samples could retain part of good quality characteristics and extend the shelf life of fish samples during refrigerated storage, which was supported by the results of microbiological, chemical, physical, and sensory evaluation analyses. Practical Applications Flounder (Paralichthys olivaceus) is an important marine-cultured fish species in China, which was an appreciated fish for its less muscle connective tissue and high endogenous activity during refrigerated storage. In this study, CS and hawthorn flavonoid coating has been found to be effectively extending the shelf life of fish samples by 4-6 days during refrigerated storage. Thus, CS and hawthorn flavonoid coating can be commercially applied in fish processing factory or aquatic market to extend the shelf life of fish samples.

Aim The aim of this study was to investigate whether human fetal hepatocytes are amenable to simian virus 40 large T-antigen (SV40Tag) mediated immortalization and whether the immortalized cells rescue mice with acute liver failure induced by 90% hepatectomy. Methods We constructed a retroviral vector expressing a thermolabile mutant SV40Tag for transfer into primary human fetal hepatocytes. We quantitatively detected the synthetic ability for albumin and urea by the immortalized cells, which were subcutaneously inoculated into mice with severe combined immunodeficiency (SCID) to evaluate tumorigenzcity. The immortalized cells were also transplanted into the spleens of mice with acute liver failure. Results One clone resulting after selection, referred to as HepCL, was highly differentiated, growing steadily in a chemically defined serum-free medium. HepCL cells were positive for albumin, cytokeratin 18, and cytokeratin 19 immunocytochemical staining. The average synthetic efficacies of HepCL cells for albumin and urea were comparable to that of unmodified primary human fetal hepatocytes. The population doubling time of HepCL cells in the logarithmic growth phase was approximately 17 hours. HepCL cells showed no oncogenicity in immunodeficient mice at 16 months. Mice receiving HepCL cells (G1) and primary human fetal hepatocytes (G2) showed significantly lower blood ammonia levels after 90% hepatectomy. Pairwise comparisons between the 4 groups showed that xenotransplantation of HepCL (G1) or primary fetal hepatocytes (G2) significantly improved survivals of recipient mice. Conclusions HepCL may be useful as a source of hepatic function for cell-based therapeutics in acute liver failure.

Myocyte-specific enhancer factor 2A (MEF2A) regulates a broad range of fundamental cellular processes including cell division, differentiation and death. Here, we tested the hypothesis that MEF2A is required in cardiac contractility employing zebrafish as a model organism. MEF2A is highly expressed in heart as well as somites during zebrafish embryogenesis. Knock-down of MEF2A in zebrafish impaires the cardiac contractility and results in sarcomere assembly defects. Dysregulation of cardiac genes in MEF2A morphants suggests that sarcomere assembly disturbances account for the cardiac contractile deficiency. Our studies suggested that MEF2A is essential in cardiac contractility.