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Objective To explore the causes and nursing strategies of red blood cell spillage in apheresis platelet donors, so as to avoid adverse reactions to blood donation and platelet discarding and improve blood donation services. Methods A nursing flowchart for red blood cell spillage was developed based on literature. One case of red blood cell spillage in a apheresis platelet donor as attached, and corresponding literature review was conducted. Results After the nursing intervention through the nursing flowchart of red cell spillage, platelet apheresis was successfully conducted. The donor felt good and did not experience any adverse reaction to blood donation, and with no more red blood cell spillage. By reviewing relevant literature, the incidence, principles, causes, treatments, prevention of adverse reactions to blood donation and psychological care methods of red blood cell spillage were systematically summarized. Conclusion Red blood cell spillage in apheresis platelet donors occurs occasionally, and a flowchart of care for red blood cell spillage can help blood station staff quickly identify the cause and handle it correctly to avoid mishandling whicn can result in adverse reactions or discarding of platelets.

Background: Using Shuxuening injection (SXNI) for acute ischemic stroke (AIS) is popular in China, but its efficacy and safety remain controversial.Purpose: This study aims to assess the efficacy and safety of SXNI as an add-on therapy for AIS.Study design: Systematic review and meta-analysis.Methods: We searched for randomized controlled trials (RCTs) on SXNI for AIS in seven databases and two clinical trial registration platforms from their inception to January 2023. We used the Cochrane risk of bias tool to assess the methodological quality of the included studies and performed the meta-analysis with R software. The primary outcome was clinical efficacy, assessed by the clinical effective rate (CER). The secondary outcomes were neurological function, activities of daily living (ADL), and adverse events (AEs).Results: In total, 116 studies with 12,401 participants were included in this review. Fifteen (12.9%) studies were judged to be of moderate to high quality. SXNI plus conventional treatments (CTs) improved the CER compared with CTs alone (risk ratio [RR]: 1.21, 95% confidence interval [CI]: 1.17–1.25, p < 0.0001) or CTs plus other injections (RR: 1.18, 95% CI: 1.15–1.21, p < 0.0001). SXNI plus CTs reduced the National Institute of Health Stroke Scale score compared with CTs alone (mean difference [MD]: −4.00, 95% CI: −5.22 to −2.78, p < 0.0001) or CTs plus other injections (MD: −2.28, 95% CI: −3.41 to −1.16, p < 0.0001). SXNI plus CTs also decreased the Chinese Stroke Scale score compared with CTs alone (MD: −5.01, 95% CI: −7.38 to −2.65, p < 0.0001) or CTs plus other injections (MD: −4.31, 95% CI: −5.75 to −2.88, p < 0.0001). SXNI plus CTs was superior for increasing the Barthel index score compared with CTs alone (MD: 11.58, 95% CI: 8.27–14.90, p < 0.0001) or CTs plus other injections (MD: 5.43, 95% CI: 0.48–10.39, p = 0.0317). The level of evidence for each outcome was assessed as low to very low. The most common AEs of SXNI were cardiovascular system events, and all these AEs were mild.Conclusion: SXNI combined with CTs maybe better than CTs alone or CTs plus other injections for improving the clinical efficacy, neurological function, and ADL of AIS patients, with relatively reliable safety. However, due to the low quality of the included studies, more rigorously designed RCTs with large sample sizes should be conducted in the future.Systematic Review Registration:www.crd.york.ac.uk, identifier (CRD42023418565).

IntroductionSpontaneous intracerebral hemorrhage is the second most common subtype of stroke. Therefore, this study aimed to investigate the risk factors affecting the prognosis of patients with basal ganglia cerebral hemorrhage after neuroendoscopy.MethodsBetween January 2020 and January 2024, 130 patients with basal ganglia cerebral hemorrhage who underwent neuroendoscopy were recruited from two independent centers. We split this dataset into training (n = 79), internal validation (n = 22), and external validation (n = 29) sets. The least absolute shrinkage and selection operator-regression algorithm was used to select the top 10 important radiomic features of different regions (perioperative hemorrhage area [PRH], perioperative surround area [PRS], postoperative hemorrhage area [PSH], and postoperative edema area [PSE]). The black hole, island, blend, and swirl signs were evaluated. The top 10 radiomic features and 4 radiological features were combined to construct the k-nearest neighbor classification (KNN), logistic regression (LR), and support vector machine (SVM) models. Finally, the performance of the perioperative hemorrhage and postoperative edema machine learning models was validated using another independent dataset (n = 29). The primary outcome is mRS at 6 months after discharge. The mRS score greater than 3 defined as functional independence.ResultsA total of 12 models were built: PRH-KNN, PRH-LR, PRH-SVM, PRS-KNN, PRS-LR, PRS-SVM, PSH-KNN, PSH-LR, PSH-SVM, PSE-KNN, PSE-LR, and PSE-SVM, with corresponding areas under the curve (AUC) values in the internal validation set of 0.95, 0.91, 0.94, 0.52, 0.91, 0.54, 0.67, 0.9, 0.72, 0.92, 0.92, and 0.95, respectively. The AUC values of the PRH-KNN, PRH-LR, PRH-SVM, PSE-KNN, PSE-LR, and PSE-SVM in the external validation were 0.9, 0.92, 0.89, 0.91, 0.92, and 0.88, respectively.ConclusionThe model built based on computed tomography images of different regions accurately predicted the prognosis of patients with basal ganglia cerebral hemorrhage treated with neuroendoscopy. The models built based on the preoperative hematoma area and postoperative edema area showed excellent predictive efficacy in external verification, which has important clinical significance.

This paper investigates the speed selection mechanism for traveling wave fronts of a reaction-diffusion-advection lattice stream-population model with the Allee effect. First, the asymptotic behaviors of the traveling wave solutions are given. Then, sufficient conditions for the speed determinacy of the traveling wave are successfully obtained by constructing appropriate upper and lower solutions. We examine the model with the reaction term $ f (\psi) = \psi(1-\psi)(1+\rho\psi) $, with $ \rho $ being a nonnegative constant, as a specific example. We give a novel conjecture that there exists a critical value $ \rho_c > 1 $, such that the minimal wave speed is linearly selected if and only if $ \rho\leq\rho_c $. Finally, our speculation is verified by numerical calculations.

BackgroundOzone (O3) pollution has gradually become a primary problem of air pollution in recent years. Conducting epidemiological studies on the correlation between O3 concentration variation and risk of cardiovascular and cerebrovascular diseases can provide reference data for O3 risk assessment and related policy making. ObjectiveTo quantitatively evaluate the effects of O3 exposure on mortalities of cardiovascular and cerebrovascular diseases among residents in Minhang District, Shanghai. MethodsData of mortalities of cardiovascular and cerebrovascular diseases, air pollutants, and meteorological factors in Minhang District of Shanghai from January 1, 2016 to December 31, 2021 were collected. Associations between O3 concentration and the mortalities due to total cardiovascular and cerebrovascular diseases, coronary heart disease, and stroke were analyzed by generalized additive models with a quasi Poisson distribution with different lag patterns, such as current day effect (lag0), single-day lag effects (lag1-lag3), and cumulative lag effects (lag01-lag03). The subgroup analyses of age, sex, and season were conducted. Furthermore, temperature was divided into low, middle, and high levels based on the 25th percentile (P25) and the 75th percentile (P75) to perform hierarchical analyses. Increased excess risks (ER) of death from target diseases caused by a 10 µg·m−3 increase in daily maximum 8 h concentration of O3 (O3-8 h) and their 95% confidence intervals (CI) were used to indicate the effects of O3. ResultsThe associations between O3 and the risks of death from cardiovascular and cerebrovascular diseases were statistically significant at lag2, lag3, lag02, and lag03 (P

The type I interferon (IFN) pathway is important for eukaryotic cells to resist viral infection, as well as an impediment to efficient virus replication. Therefore, this study aims to create an IFNAR1 knockout (KO) Madin-Darby bovine kidney (MDBK) cell line using CRISPR/Cas9 and investigate its application and potential mechanism in increasing viral replication of bovines. The IFNAR1 KO cells showed increased titers of bovine viral diarrhea virus (BVDV) (1.5 log10), with bovine enterovirus and bovine parainfluenza virus type 3 (0.5–0.8 log10). RNA-seq revealed reduced expression of the genes related IFN-I pathways including IFNAR1, STAT3, IRF9, and SOCS3 in IFNAR1 KO cells compared with WT cells. In WT cells, 306 differentially expressed genes (DEGs) were identified between BVDV-infected and -uninfected cells. Of these, 128 up- and 178 down-regulated genes were mainly associated with growth cycle and biosynthesis, respectively. In IFNAR1 KO cells, 286 DEGs were identified, with 82 up-regulated genes were associated with signaling pathways, and 204 down-regulated genes. Further, 92 DEGs were overlapped between WT and IFNAR1 KO cells including ESM1, IL13RA2, and SLC25A34. Unique DEGs in WT cells were related to inflammation and immune regulation, whereas those unique in IFNAR1 KO cells involved in cell cycle regulation through pathways such as MAPK. Knocking down SLC25A34 and IL13RA2 in IFNAR1 KO cells increased BVDV replication by 0.3 log10 and 0.4 log10, respectively. Additionally, we constructed an IFNAR1/IFNAR2 double-knockout MDBK cell line, which further increased BVDV viral titers compared with IFNAR1 KO cells (0.6 log10). Overall, the IFNAR1 KO MDBK cell line can support better replication of bovine viruses and therefore provides a valuable tool for bovine virus research on viral pathogenesis and host innate immune response.

Neonatal hypoxic-ischemic brain injury is the main cause of hypoxic-ischemic encephalopathy and cerebral palsy. Currently, there are few effective clinical treatments for neonatal hypoxic-ischemic brain injury. Here, we investigated the neuroprotective and molecular mechanisms of exogenous nicotinamide adenine dinucleotide, which can protect against hypoxic injury in adulthood, in a mouse model of neonatal hypoxic-ischemic brain injury. In this study, nicotinamide adenine dinucleotide (5 mg/kg) was intraperitoneally administered 30 minutes before surgery and every 24 hours thereafter. The results showed that nicotinamide adenine dinucleotide treatment improved body weight, brain structure, adenosine triphosphate levels, oxidative damage, neurobehavioral test outcomes, and seizure threshold in experimental mice. Tandem mass tag proteomics revealed that numerous proteins were altered after nicotinamide adenine dinucleotide treatment in hypoxic-ischemic brain injury mice. Parallel reaction monitoring and western blotting confirmed changes in the expression levels of proteins including serine (or cysteine) peptidase inhibitor, clade A, member 3N, fibronectin 1, 5′-nucleotidase, cytosolic IA, microtubule associated protein 2, and complexin 2. Proteomics analyses showed that nicotinamide adenine dinucleotide ameliorated hypoxic-ischemic injury through inflammation-related signaling pathways (e.g., nuclear factor-kappa B, mitogen-activated protein kinase, and phosphatidylinositol 3 kinase/protein kinase B). These findings suggest that nicotinamide adenine dinucleotide treatment can improve neurobehavioral phenotypes in hypoxic-ischemic brain injury mice through inflammation-related pathways.

As multilateralism evolves and China’s ocean awareness grows, China remains actively engaged in global ocean governance. The country has introduced the initiative of Building a Maritime Community with a Shared Future (MCSF), offering fresh perspectives for global ocean governance. The MCSF demonstrates both compatibility and adaptability with the evolving landscape of global ocean governance. This study is grounded in the historical context of the formation and evolution of China’s ocean consciousness within the broader framework of global ocean governance. Taking China’s contemporary ocean consciousness, the MCSF as the focal point, it analyzes the practical feasibility of integrating the MCSF with the evolving frameworks of global ocean governance. It is concluded that this integration process should involve ongoing review and refinement as the MCSF continues to develop.

Background: Patients with colorectal cancer commonly experience disturbances in coagulation homeostasis. Activation of the coagulation system contributes to cancer-associated thrombosis as the second risk factor for death in cancer patients. This study intended to discover coagulation-related genes and construct a risk model for colorectal cancer patients' prognosis. Methods: Coagulation-related genes were identified by searching coagulation-related pathways in the Molecular Signatures Database. Transcriptomic data and clinical data were downloaded from the Cancer Genome Atlas and Gene Expression Omnibus datasets. Univariate Cox and backward stepwise regression were utilized to identify prognosis-related genes and construct a predictive risk model for the training cohort. Next, survival analysis determines the risk model's predictive power, correlation with clinicopathological characteristics, and nomogram. Additionally, we characterized the variances in immune cell infiltration, somatic mutations, immune checkpoint molecules, biological functions, and drug sensitivity between the high- and low-score patients. Result: Eight hundred forty-five genes were obtained by searching the theme term ''coagulation'' after de-duplication. After univariate regression analysis, 69 genes correlated with prognosis were obtained from the Cancer Genome Atlas dataset. A signature consisting of 17 coagulation-related genes was established through backward stepwise regression. The Kaplan-Meier curve indicated a worse prognosis for high-score patients. Time-dependent receiver operating characteristic curve analysis demonstrated high accuracy in predicting overall survival. Further, the results were validated by two independent datasets (GSE39582 and GSE17536). Combined with clinicopathological characteristics, the risk model was proven to be an independent prognostic factor to predict poor pathological status and worse prognosis. Furthermore, high-score patients had significantly higher stromal cell infiltration. Low-score patients were associated with high infiltration of resting memory CD4+ T cells, activated CD4+ T cells, and T follicular helper cells. The low-score patients exhibited increased expression of immune checkpoint genes, and this might be relevant to their better prognosis. High-score patients exhibited lower IC50 values of Paclitaxel, Rapamycin, Temozolomide, Cyclophosphamide, etc. The differential signaling pathways mainly involve the calcium signaling pathway and the neuroactive ligand-receptor interaction. Lastly, a nomogram was constructed and showed a good prediction. Conclusion: The prognostic signature of 17 coagulation-related genes had significant prognostic value for colorectal cancer patients. We expect to improve treatment modalities and benefit more patients through research on molecular features.

Bovine respiratory disease (BRD) is one of the most common diseases in the cattle industry worldwide; it is caused by multiple bacterial or viral coinfections, of which Mycoplasma bovis (M. bovis) and bovine herpesvirus type 1 (BoHV-1) are the most notable pathogens. Although live vaccines have demonstrated better efficacy against BRD induced by both pathogens, there are no combined live and marker vaccines. Therefore, we developed an attenuated and marker M. bovis-BoHV-1 combined vaccine based on the M. bovis HB150 and BoHV-1 gG-/tk- strain previously constructed in our lab and evaluated in rabbits. This study aimed to further evaluate its safety and protective efficacy in cattle using different antigen ratios. After immunization, all vaccinated cattle had a normal rectal temperature and mental status without respiratory symptoms. CD4+, CD8+, and CD19+ cells significantly increased in immunized cattle and induced higher humoral and cellular immune responses, and the expression of key cytokines such as IL-4, IL-12, TNF-α, and IFN-γ can be promoted after vaccination. The 1.0 × 108 CFU of M. bovis HB150 and 1.0 × 106 TCID50 BoHV-1 gG-/tk- combined strain elicited the most antibodies while significantly increasing IgG and cellular immunity after challenge. In conclusion, the M. bovis HB150 and BoHV-1 gG-/tk- combined strain was clinically safe and protective in calves; the mix of 1.0 × 108 CFU of M. bovis HB150 and 1.0 × 106 TCID50 BoHV-1 gG-/tk- strain was most promising due to its low amount of shedding and highest humoral and cellular immune responses compared with others. This study introduces an M. bovis-BoHV-1 combined vaccine for application in the cattle industry.

Background/Objectives: Limited research has examined the theoretical linkages between exposure to COVID-19 vaccine information sources, vaccination-related beliefs, vaccination-induced emotions, and vaccine information engagement. Methods: An online survey was conducted with a national sample of adults (N = 630) residing in the U.S. to test these relationships, guided by the Stimulus–Organism–Response (S-O-R) framework and the Health Belief Model. Results: Study findings showed that exposure to online authority vaccine information sources was positively related to vaccination-benefit beliefs and negatively related to vaccination-barrier beliefs, in addition to hopeful feelings connected to vaccination. Exposure to non-authority sources was positively associated with vaccination-barrier beliefs, hopeful and fearful feelings connected to vaccination, and vaccine information engagement. While vaccination-benefit beliefs and vaccination-barrier beliefs were negatively and positively linked to vaccine information engagement, respectively, these beliefs were each positively connected to hopeful feelings and fearful feelings toward vaccination in that order. Both hopeful and fearful feelings toward vaccination also emerged as positive correlates of vaccine information engagement. Conclusions: This study contributes to our understanding of how cognitive appraisals of and affective responses to risk information disseminated by different types of sources may be related to risk information engagement behavior in a public health crisis. Results bring evidence-based insights to both researchers and health professionals to better equip them to counter vaccine misinformation and reduce vaccination barriers.

Big Five personality traits have been consistently shown to be important predictors of political differences. Other work found that political differences are related to geographical differences in personality. The present study extended existing work by examining the numbers and features of distinct personality profiles within different political regions of the United States using latent profile analysis (LPA). Across two large datasets (total N > 6,000), we found that while all regions shared similar numbers (3–5 profiles per region) and some overlapping patterns of personality profiles (e.g., well-adapted individuals), different political regions also showed unique personality profile patterns (e.g., “Worrisome Liberals”, “Rigid & Antisocial”). Overall, these results provide initial evidence suggesting that different personality profiles may exist among different political regions of the US, and offer insights on the interplay between personality, political ideology, and geographical differences.

This study investigates the potential of natural products derived from two mangrove soil bacteria, GP521A and GP3R5, in anthracnose management in oil tea. Based on 16s rDNA sequencing, GP521A and GP3R5 were identified as Bacillus velezensis and Pseudoalteromonas caenipelagi, respectively. Both bacteria showed strong antagonistic effects towards multiple fungal pathogens on dual cultural plates. The ethyl acetate extracts of fermentation cultures of GP521A (FEGP5) and GP3R5 (FEGP3) significantly inhibited mycelial growth of both Colletotrichum camelliae MC171, C. fructicola CF-1 and Pyricularia oryzae P131 at 100 and 200 μg/mL, respectively. Furthermore, FEGP5 and FEGP3 significantly inhibited conidiation, conidial germination and appressorial formation in C. camelliae MC171 at 50 μg/mL, with stronger inhibitory effects observed in the latter. On detached oil tea leaves, 100 μg/mL of FEGP5 and FEGP3 resulted in ~ 98.0% and 97.5% reduction in diseased areas, respectively, when applied before MC171 inoculation, whereas the reduction was approximately 55.0% and 77.6%, respectively, in the curative treatments. In fresh fruits, both extracts also significantly inhibited disease development, either in preventative or curative treatments. Moreover, FEGP5 and FEGP3 demonstrated significantly lower aquatic toxicity than prochloraz at the same concentrations towards a commonly used bioindicator, Artemia salina. In conclusion, this study demonstrates the potential of marine microbes derived natural products in development of environmentally compatible biopesticides to control anthracnose in oil tea.

Abstract Objective We aimed to identify new classes in acute respiratory distress syndrome (ARDS) using physiological and clinical variables and to explore heterogeneity in the effects of glucocorticoid therapy between classes. Methods Using the Medical Information Mart for Intensive Care-IV database, we identified patients with ARDS. Potential profile analysis was used to identify classes with physiological and clinical data as delineating variables. Baseline characteristics and clinical outcomes were compared between classes. The effect of glucocorticoid treatment was explored by stratifying by class and glucocorticoid treatment. Results From 2008 to 2019, 1104 patients with ARDS were enrolled in the study. The 2-class potential analysis model had the best fit (P

Abstract Background Maintaining intraoperative haemodynamic stability can reduce cardiovascular complications during surgery for pheochromocytoma and paraganglioma (PPGL). Risk factors such as tumour size and catecholamine levels are reported to predict haemodynamic responses during surgery for PPGL. We hypothesized that additional factors including body composition and genetic information could further improve prediction. Methods Consecutive patients with PPGL confirmed by surgical pathology between June 2010 and June 2019 were retrospectively included. Cross‐sectional computed tomography images at the L3 level were used to assess body composition parameters including skeletal muscle area and visceral fat area. Next‐generation sequencing was performed using a panel containing susceptibility genes of PPGL. Differences in clinical‐genetic characteristics and body composition parameters were analysed and compared in patients with and without intraoperative haemodynamic instability (HDI). Results We included 221 patients with PPGL (median age 47 [38–56] years, and 52% male). Among them, 49.8% had Cluster 2 mutations (related to kinase signalling pathways), 44.8% had sarcopenia, and 52.9% experienced intraoperative HDI. Compared with patients without HDI, more patients with HDI had Cluster 2 mutations (59.8% vs. 38.5%, P = 0.002) and less had sarcopenia (35.9% vs. 54.8%, P = 0.005). Multivariate analysis showed that urine vanillylmandelic acid ≥ 58 μmol/day (adjusted odds ratio [OR] = 1.840, 95% confidence interval [CI] = 1.012–3.347, P = 0.046), tumour size ≥ 4 cm (adjusted OR = 2.278, 95% CI = 1.242–4.180, P = 0.008), and Cluster 2 mutations (adjusted OR = 2.199, 95% CI = 1.128–4.285, P = 0.021) were independent risk factors for intraoperative HDI, while sarcopenia (adjusted OR = 0.475, 95% CI = 0.266–0.846, P = 0.012) decreased the risk. Conclusions Body composition and genotype were associated with intraoperative haemodynamics in patients with PPGL. Our results indicated that inclusion of body composition and genotype in the overall assessment of patients with PPGL helped to predict HDI during surgery, which could assist in implementing preoperative and intraoperative measures to reduce perioperative complications.

Bovine parainfluenza virus type 3 (BPIV-3) is one of the major pathogens of the bovine respiratory disease complex (BRDC). BPIV-3 surveillance in China has been quite limited. In this study, we used PCR to test 302 cattle in China, and found that the positive rate was 4.64% and the herd-level positive rate was 13.16%. Six BPIV-3C strains were isolated and confirmed by electron microscopy, and their titers were determined. Three were sequenced by next-generation sequencing (NGS). Phylogenetic analyses showed that all isolates were most closely related to strain NX49 from Ningxia; the genetic diversity of genotype C strains was lower than strains of genotypes A and B; the HN, P, and N genes were more suitable for genotyping and evolutionary analyses of BPIV-3. Protein variation analyses showed that all isolates had mutations at amino acid sites in the proteins HN, M, F, and L. Genetic recombination analyses provided evidence for homologous recombination of BPIV-3 of bovine origin. The virulence experiment indicated that strain Hubei-03 had the highest pathogenicity and could be used as a vaccine candidate. These findings apply an important basis for the precise control of BPIV-3 in China.

Abstract Background Citrate Synthase (Cs) gene mutation (locus ahL4) has been found to play an important role in progressive hearing loss of A/J mice. HEI-OC1 cells have been widely used as an in vitro system to study cellular and molecular mechanisms related to hearing lose. We previously reported the increased apoptosis and the accumulation of reactive oxygen species in shRNACs-1429 cells, a Cs low-expressed cell model from HEI-OCI. The details of the mechanism of ROS production and apoptosis mediated by the abnormal expression of Cs needed to research furtherly. Methods iTRAQ proteomics was utilized to detect the differentially expressed proteins (DEPs) caused by low expression of Cs. The GO and KEGG pathways analysis were performed for annotation of the differentially expressed proteins. Protein–protein interaction network was constructed by STRING online database. Immunoblotting was utilized to confirm the protein levels of the the differentially expressed proteins. Results The differentially expressed proteins were significantly enriched in various signaling pathways mainly related to mitochondrial dysfunction diseases including Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, et al. Most noteworthy, the oxidative phosphorylation pathway was most significantly suppressed in the shRNACs-1429 cells,, in which a total of 10 differentially expressed proteins were enriched and were all downregulated by the abnormal expression of Cs. The downregulations of Ndufb5, Ndufv1 and Uqcrb were confirmed by immunoblotting. Meanwhile, the ATP levels of shRNACs-1429 cells were also reduced. Conclusions These results suggest that low level expression of Cs induces the inhibition of oxidative phosphorylation pathway, which is responsible for the high level production of reactive oxygen species and low level of ATP, leading to the apoptosis of cochlear cells. This study may provide new theories for understanding and therapy of progressive hearing loss.

Abstract Background A prospective interventional study comparing outcomes in critically ill patients receiving intermittent infusion (II) or continuous infusion (CI) of vancomycin during continuous venovenous hemofiltration (CVVH) is lacking. The objective of this study was to compare the pharmacokinetic/pharmacodynamics (PK/PD) target attainment, therapeutic efficacy and safety among critically ill patients who received CI or II of vancomycin in a prospective interventional trial and to explore the correlations of effluent flow rate (EFR) with PK/PD indices. Methods This prospective interventional study was conducted in two independent intensive care units (ICUs) from February 2021 to January 2022. Patients in one ICU were assigned to receive CI (intervention group) of vancomycin, whereas patients in the other ICU were assigned to receive II regimen (control group). The primary outcome was to compare the PK/PD target attainment, including target concentration and target area under the curve over 24 h to minimum inhibitory concentration (AUC24/MIC). Results Overall target attainment of PK/PD indices was higher with CI compared with II, irrespective of target concentration (78.7% vs. 40.5%; P

Objective: Clinical practice guidelines recommend open adrenalectomy (OA) for large pheochromocytoma (LPCC) > 6 cm in size. Although laparoscopic adrenalectomy (LA) for the treatment of LPCC has been reported, its role remains unclear. This study aimed to compare the effectiveness of LA and OA, and summary the surgical treatment experience. Methods: Data concerning LPCC, from January 2010 to June 2019 of a single institution, were retrospectively reviewed. Altogether 82 patients with a tumor larger than 6 cm were included (52 patients in LA group and 30 patients in OA group). Groups were balanced by propensity score matching (PSM) into 15 pairs. Patients’ demographics, preoperative characteristics, and prognosis were analyzed. Results: Before PSM, the OA group had larger tumor sizes (median [interquartile range, IQR]: 8.9 [7.3–10.3] vs. 7.2 [6.7–8.0] cm; p=0.000) and higher vanillylmandelic acid level (median [IQR]: 114.3 [67.8–326.4] vs. 66.6 [37.8–145.8] μmol/24 h; p =0.004) and needed a higher cumulative dose of prazosin (median [IQR]: 83.5 [37.0–154.0] vs. 38.0 [21.0–81.0] mg; p=0.028). After PSM, the baseline data showed no significant differences between both groups. The LA group had relatively more stable blood pressure in surgery, with a lower fluctuation of systolic blood pressure (mean±standard deviation [SD]: 70.9±25.1 vs. 107.4±46.2 mmHg, p=0.012) and a lower percentage of hemodynamic instability (46.7% vs. 86.7%, p=0.020). The LA group had shorter postoperative hospital stays (mean±SD: 6.4±2.7 vs. 10.1±3.4 days; p=0.003) than the OA group. Differences regarding metastasis rate (6.7% vs. 0, p=1.000) were not statistically significant between LA and OA groups. The median (IQR) follow-up time of 82 patients was 72.5 (47.0–103.5) months. Binary logistic regression showed that right-side tumors or those >8 cm in size were independent risk factors of OA. Conclusion: LA is a safe, minimally invasive procedure for LPCC and has relatively better perioperative characteristics in large medical centers. Patients with tumors on the right side or larger than 8 cm are more likely to undergo OA initially.

Abstract Background and Aims The annual incidence of early‐onset colorectal cancer (EOCRC) is increasing at an alarming rate. The prognosis of EOCRC remains controversial, and whether the early onset is a risk factor for colorectal cancer remains unclear. Methods We searched four electronic bibliographic databases from database inception to April 25, 2022 for studies that included both early‐ and later‐onset patients and performed a prognostic analysis. Random‐effects models were used to summarize the prognostic information extracted by the investigators, including overall survival (OS), cancer‐special survival (CSS), and disease‐free survival (DFS). Network meta‐analysis (NMA) was used to compare patients' long‐term prognoses in different age subgroups. Results After 694 reports were screened, 13 studies were included in the final analysis, with a total of 448,781 CRC cases. In the meta‐analysis of the 5‐year OS, EOCRC had a better prognosis compared to LOCRC (hazard ratio [HR] 0.87, 95% confidence interval [CI], 0.74–0.99; relative risk [RR] 0.83, 95% CI, 0.78–0.89). No difference in prognosis was found between the two groups in terms of 5‐year CSS (RR 0.99, 95% CI, 0.93–1.05), 5‐year DFS (RR 0.90, 95% CI, 0.74–1.09), and short‐term OS. In the NMA, patients aged

Satellite-based quantum communication is critical in establishing a global quantum network for its ability to achieve thousand-kilometer-level tasks without the requirement of quantum relay. The free-space channel, however, is affected by diffraction, regular refraction, and atmospheric turbulence, which induce random wandering and broadening of the transmitted beam, resulting in the transmittance of fluctuation. In such a scenario, the ability to predict the unknown situation has become a problem worth considering. In this paper, we suggest a machine learning (ML) assisted prediction of continuous-variable quantum teleportation (CVQT) over satellite-ground channel. We apply the prediction algorithm, which involves $k$-nearest neighbor (KNN) algorithm and decision tree (DT) algorithm, to the squeezing parameter and the satellite altitude. Numerical analysis shows that the predicted parameter can reflect the actual derivation and calculation under certain circumstances within the allowable range of error. Moreover, we apply the prediction algorithm to the case affected by the fluctuating parameter transmittance. The results show that the ML-assisted prediction results are consistent with the actual data when zenith angles, turbulence strengths, and wavelengths are taken into account. It demonstrates the high identifying accuracy without increasing the complexity of the system.

In this paper, an off-set fin heat exchanger (OSFHE) and a flying-wing fin heat exchanger (FWFHE) were developed for the condenser of a condensing clothes dryer. They were used to replace the slit fin heat exchanger (SFHE), which is the prototype condenser. Performance parameters, like condensation rate, IEC energy efficiency index (EEI) and specific moisture extraction rate (SMER), were used to assess the dehumidification performance of the heat exchangers and the drying performance of the dryer. Though the fin areas of OSFHE and FWFHE are 20% and 34.2% less than that of SFHE, the experiment results indicated that OSFHE and FWFHE had a faster condensation rate than SFHE during the main drying stage. And the heat exchanger with a faster condensation rate also led to less power consumption of the dryer in most tests. Compared with using SFHE, using OSFHE could decrease the EEI of the dryer by 0.43%. Using FWFHE could reduce the EEI of the dryer by 1.19% and improve the EU energy efficiency class of the dryer from Class C to Class B. Both OSFHE and FWFHE are able to replace SFHE and become a new generation of condensers for clothes dryers.

The synthesis and single-crystal X-ray structures of three N-(pyridine-2-carbonyl)pyridine-2-carboxamide imides, with or without F atoms on the 3-position of the pyridine rings are reported, namely, N-(pyridine-2-carbonyl)pyridine-2-carboxamide, C12H9N3O2 (1), N-(3-fluoropyridine-2-carbonyl)pyridine-2-carboxamide, C12H8FN3O2 (2), and 3-fluoro-N-(3-fluoropyridine-2-carbonyl)pyridine-2-carboxamide, C12H7F2N3O2 (3). The above-mentioned compounds were synthesized by a mild, general procedure with an excellent yield, providing straightforward access to symmetrical and/or asymmetrical heterocyclic ureas. The crystal structures of 1 and 2 are isomorphous, showing similar packing arrangements, i.e. double layers of parallel (face-to-face) molecules alternating with analogous, but perpendicularly oriented, double layers. In contrast, the crystal structure of 3, containing a fluoro- group at the 3-position of both pyridine rings, shows molecular arrangements in a longitudinal, tubular manner along the c axis, with the aromatic pyridine and carbonyl/fluorine moieties facing towards each other.

Abstract Background Coronary heart disease (CHD) has become one of the biggest health problems in the world. Stable angina is a common clinical type of CHD with poor prognosis and high mortality. Although there are various interventions for stable angina, none of them can significantly reduce mortality. Both basic and clinical research have shown that Suxiao Jiuxin Pill (SJP) can relieve the symptoms of angina pectoris and improve the clinical efficacy, but there is a lack of high-quality clinical research to provide research-based evidence. We design a randomized, double-blind, placebo-controlled trial to evaluate the efficacy of SJP for stable angina. Methods/design This is a prospective, randomized, double-blind, placebo-controlled, and multicenter trial. The trial will enroll 324 participants with chronic stable angina (Qi Stagnation and Blood Stasis syndrome). All participants will have received the conventional therapy of chronic stable angina. Participants will be randomized into two groups, conventional therapy plus SJP group and conventional therapy plus placebo group. Eligible participants will receive either SJP or placebo (five pills administered orally, three times daily) in addition to conventional treatment for 24 weeks. The primary outcomes are the symptom improvement rate of angina from baseline to 4 weeks after inclusion and major adverse cardiovascular events (MACE). The secondary outcomes are angina classification (CCS), improvement of traditional Chinese medicine (TCM) syndromes, Seattle Angina Scale score, the dosage of emergency drugs and the stopping rate, and electrocardiogram (EKG) efficacy. Adverse events will be monitored throughout the trial. Discussion Integrated traditional Chinese and Western Medicine is commonly used for angina in China. This study will evaluate the clinical effectiveness and safety of SJP for angina. The results of the trial will provide high-level clinical research-based evidence for the application of SJP instable angina. Trial registration This study protocol was registered on 14 March 2019. The registration number is ChiCTR1900021876 on the Chinese Clinical Trial Registry.

Isoprocarb is a widely used carbamate insecticide in agriculture and aquaculture. Overuse of isoprocarb always leaves toxic residues in soil and water, however, the potential ecotoxicity of isoprocarb to organisms is still confusing. In this study, zebrafish embryo was used as a model to evaluate the toxicity of isoprocarb. Zebrafish embryos (96 hpf) were separately exposed at different concentrations of isoprocarb. The mortality rate, hatchability rate, average heart beat of the zebrafish embryo were separately calculated. Our results suggested that exposure to isoprocarb induced developmental toxicity in zebrafish embryos. HE staining showed that exposure to isoprocarb caused developmental defect in the hindbrain of zebrafish embryos. As expected, the behavioral analysis also showed that the motor ability of zebrafish embryos were significantly inhibited following exposure to isoprocarb. In terms of mechanism, The expressions of genes involved in neurodevelopment signaling pathways, such as foxo3a, gfap, syn2a, elavl3 and sox19b, were inhibited in zebrafish embryos after exposure to isoprocarb. The acetylcholinesterase (AChE) activity was also reduced in isoprocarb-treated zebrafish embryos. Moreover, oxidative stress was induced by increasing the reactive oxygen species (ROS) level and decreasing the activity of antioxidant enzyme (SOD) after exposure to isoprocarb. Expectedly, acridine orange (AO) staining and the detection of some apoptosis-related genes revealed that oxidative stress resulted in apoptosis. In short, the expressions of genes associated with the neurodevelopmental signaling pathway are inhibited, and oxidative stress is also induced in zebrafish embryos after exposure to isoprocarb, which may be the molecular basics of isoprocarb-induced neurotoxicity in zebrafish embryos.

PurposeThe purpose of this study was to establish a model for predicting early recurrence (≤2 years) of hepatocellular carcinoma (HCC) after anatomical hepatectomy based on the hepatobiliary phase (HBP) imaging characteristics of gadobenate-enhanced MRI.MethodsA total of 155 patients who underwent anatomical hepatectomy HCC therapy and gadobenate-enhanced MRI were included retrospectively. The patients were divided into the early recurrence-free group (n = 103) and the early recurrence group (n = 52). Univariate and multivariate Cox regression analysis was used to determine the independent risk factors related to early recurrence, and four models were established. The preoperative model with/without HBP imaging features (HBP-pre/No HBP-pre model) and the postoperative model with/without HBP imaging features (HBP-post/No HBP-post model). Bootstrap resampling 1,000 times was used to verify the model and displayed by nomograms. The performance of nomograms was evaluated by discrimination, calibration, and clinical utility. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used to evaluate the differences between models and to select the optimal model.ResultsShape, arterial peritumoral enhancement, AFP-L3, and peritumoral hypointensity on HBP were identified as independent risk factors. Prothrombin time (PT) and r-glutamyltransferase (GGT) were selected by multivariate Cox regression. These six factors construct the HBP-pre model. Removing peritumoral hypointensity on HBP was the No HBP-pre model. Adding microvascular invasion (MVI) and microscopic capsule factors were the HBP-post and No HBP-post model. The C-index was 0.766, 0.738, 0.770, and 0.742, respectively. The NRI and IDI of the HBP-pre vs. the No HBP-pre model and the HBP-post vs. the No HBP-post model significantly increased 0.258, 0.092, 0.280, and 0.086, respectively. The calibration curve and decision curve analysis (DCA) had good consistency and clinical utility. However, the NRI and IDI of the No HBP-post vs. the No HBP-pre model and the HBP-post vs. the HBP-pre model did not increase significantly.ConclusionsPreoperative gadobenate-enhanced MR HBP imaging features significantly improve the model performance while the postoperative pathological factors do not. Therefore, the HBP-pre model is selected as the optimal model. The strong performance of this model may help hepatologists to assess the risk of recurrence in order to guide the selection of treatment options.

Subjective cognitive decline (SCD) is considered the first stage of Alzheimer’s disease (AD). Accurate diagnosis and the exploration of the pathological mechanism of SCD are extremely valuable for targeted AD prevention. However, there is little knowledge of the specific altered morphological network patterns in SCD individuals. In this present study, 36 SCD cases and 34 paired-matched normal controls (NCs) were recruited. The Jensen-Shannon distance-based similarity (JSS) method was implemented to construct and derive the attributes of multiple brain connectomes (i.e., morphological brain connections and global and nodal graph metrics) of individual morphological brain networks. A t-test was used to discriminate between the selected nodal graph metrics, while the leave-one-out cross-validation (LOOCV) was used to obtain consensus connections. Comparisons were performed to explore the altered patterns of connectome features. Further, the multiple kernel support vector machine (MK-SVM) was used for combining brain connectomes and differentiating SCD from NCs. We showed that the consensus connections and nodal graph metrics with the most discriminative ability were mostly found in the frontal, limbic, and parietal lobes, corresponding to the default mode network (DMN) and frontoparietal task control (FTC) network. Altered pattern analysis demonstrated that SCD cases had a tendency for modularity and local efficiency enhancement. Additionally, using the MK-SVM to combine the features of multiple brain connectomes was associated with optimal classification performance [area under the curve (AUC): 0.9510, sensitivity: 97.22%, specificity: 85.29%, and accuracy: 91.43%]. Therefore, our study highlighted the combination of multiple connectome attributes based on morphological brain networks and offered a valuable method for distinguishing SCD individuals from NCs. Moreover, the altered patterns of multidimensional connectome attributes provided a promising insight into the neuroimaging mechanism and early intervention in SCD subjects.

As one of the Mex3 family members, Mex3A is crucial in cell proliferation, migration, and apoptosis in mammals. In this study, a novel gene homologous to mammalian Mex3A (named CiMex3A, MW368974) was cloned and identified in grass carp, which is 1,521 bp in length encoding a putative polypeptide of 506 amino acids. In CIK cells, CiMex3A is upregulated after stimulation with LPS, Z-DNA, and especially with intracellular poly(I:C). CiMex3A overexpression reduces the expressions of IFN1, ISG15, and pro-inflammatory factors IL8 and TNFα; likewise, Mex3A inhibits IRF3 phosphorylation upon treatment with poly(I:C). A screening test to identify potential targets suggested that CiMex3A interacts with RIG-I exclusively. Co-localization analysis showed that Mex3A and RIG-I are simultaneously located in the endoplasmic reticulum, while they rarely appear in the endosome, mitochondria, or lysosome after exposure to poly(I:C). However, RIG-I is mainly located in the early endosome and then transferred to the late endosome following stimulation with poly(I:C). Moreover, we investigated the molecular mechanism underlying CiMex3A-mediated suppression of RIG-I ubiquitination. The results demonstrated that Mex3A truncation mutant (deletion in the RING domain) can still interact physically with RIG-I, but fail to degrade it, suggesting that Mex3A also acts as a RING-type E3 ubiquitin ligase. Taken together, this study showed that grass carp Mex3A can interact with RIG-I in the endoplasmic reticulum following poly(I:C) stimulation, and then Mex3A facilitates the ubiquitination and degradation of RIG-I to inhibit IRF3-mediated innate antiviral immune response.

Abstract Background Developmental dysplasia of the hip (DDH) is a complex hip joint deformity with effects ranging from acetabulum malformation to irreversible hip dislocation. Previous studies suggest a significant association of four variations, teneurin transmembrane protein 3 (TENM3, OMIM * 610083) (chr4:183721398), heparan sulfate proteoglycan 2 (HSPG2, OMIM * 142461) (chr1:22201470), ATPase plasma membrane Ca2+ transporting 4 (ATP2B4, OMIM * 108732) (chr1:203682345), and prostaglandin F receptor (PTGFR, OMIM * 600563) (chr1:79002214), with DDH susceptibility in families with segregating DDH. However, the association was not validated in sporadic cases and remains controversial. To confirm the association of the reported variations in these four genes with DDH, we conducted replicative verification in 250 sporadic samples with DDH from a Chinese Han population. Methods We conducted Sanger sequencing after amplifying the variation sites. The results were compared with the reference sequence from the GRCh37 assembly in UCSC ( http://genome.ucsc.edu ). Results Replication analysis of 250 sporadic samples by Sanger sequencing indicated that the four variations, TENM3 (OMIM * 610083, chr4:183721398), HSPG2 (OMIM * 142461, chr1:22201470), ATP2B4 (OMIM * 108732, chr1:203682345), and PTGFR (OMIM * 600563, chr1:79002214), were not associated with the susceptibility to DDH in the Chinese Han population. Conclusions Further studies should be performed to identify other variations of these four genes that are potentially associated with DDH by whole-exome sequencing and the results should be verified in different populations.

To eliminate the disadvantages of both the uncontrollability in the magnetic field of a permanent magnet excitation system and the high energy consumption of an electric excitation system in a traditional magnetically rotating arc plasma generator, a novel topology of a hybrid permanent magnet and electrically excited coil system is proposed. The proposed system will generate a large enough magnetic field to drive the arc rotation with a minimum consumption of materials and electric energy in the normal operation duty, and will guarantee a nearly zero magnetic field in the arc triggering stage. To optimize the hybrid excitation system, a comprehensive analysis and an optimization methodology; by combining finite element analysis, the moving the least squares approximation and an adaptive weighted particle swarm optimization, are proposed. Finally, a prototype hybrid excitation system is optimized with promising results in views of both saving a huge amount of electric power consumptions and ensuring a nearly zero magnetic field in the arc triggering.

ObjectiveAutism spectrum disorder (ASD) is a common neurodevelopmental disorder characterized by the development of multiple symptoms, with incidences rapidly increasing worldwide. An important step in the early diagnosis of ASD is to identify informative biomarkers. Currently, the use of functional brain network (FBN) is deemed important for extracting data on brain imaging biomarkers. Unfortunately, most existing studies have reported the utilization of the information from the connection to train the classifier; such an approach ignores the topological information and, in turn, limits its performance. Thus, effective utilization of the FBN provides insights for improving the diagnostic performance.MethodsWe propose the combination of the information derived from both FBN and its corresponding graph theory measurements to identify and distinguish ASD from normal controls (NCs). Specifically, a multi-kernel support vector machine (MK-SVM) was used to combine multiple types of information.ResultsThe experimental results illustrate that the combination of information from multiple connectome features (i.e., functional connections and graph measurements) can provide a superior identification performance with an area under the receiver operating characteristic curve (ROC) of 0.9191 and an accuracy of 82.60%. Furthermore, the graph theoretical analysis illustrates that the significant nodal graph measurements and consensus connections exists mostly in the salience network (SN), default mode network (DMN), attention network, frontoparietal network, and social network.ConclusionThis work provides insights into potential neuroimaging biomarkers that may be used for the diagnosis of ASD and offers a new perspective for the exploration of the brain pathophysiology of ASD through machine learning.

ObjectiveWe aimed to retrospectively collect pathologically identified pheochromocytoma and paraganglioma (PPGL) tumor tissues from our center and investigate the expression of apelin and succinyl-CoA synthetase subunit beta (SUCLG2), human epidermal growth factor receptor-2 (HER2 or ERBB-2), contactin 4 (CNTN4), chromogranin B (CHGB), and succinate dehydrogenase B (SDHB) in metastatic and non-metastatic PPGLs, for exploring their roles in the diagnosis of metastatic PPGLs.MethodsA total of 369 patients with pathologically and surgically confirmed PPGLs at Xiangya Hospital, Central South University, between June 2010 and June 2020 were retrospectively included. Sixty patients—12 patients with metastatic PPGLs and 48 patients with non-metastatic PPGLs—were selected through propensity score matching (1:4) to reduce the effect of PPGL type, sex, and age. We observed and quantified the expression of apelin, SDHB, CHGB, ERBB-2, CNTN4, and SUCLG2 in paraffin-embedded samples using immunohistochemical staining.ResultsNo significant differences were observed between the metastatic group and non-metastatic group with respect to the expression of CNTN4 and SUCLG2. The expression of apelin, SDHB, CHGB, and ERBB-2 was significantly different between the two groups. The expression of apelin, SDHB, and CHGB was significantly lower in the metastatic group than that in the non-metastatic group (P < 0.001). ERBB-2 expression was significantly higher in the metastatic group than in the non-metastatic group (P = 0.042). Kaplan–Meier analysis revealed that patients with negative expression of apelin, SDHB, and CHGB showed significantly lower metastasis-free survival than those with positive expression. Multivariate Cox analysis revealed that SDHB and CHGB levels were independently associated with metastasis-free survival.ConclusionThe expression levels of apelin, CHGB, SDHB, and ERBB-2 may be predictive biomarkers for the diagnosis of metastatic PPGLs. Patients with negative expression of apelin, CHGB, and SDHB should be subjected to frequent postoperative follow-up procedures

Abstract Background and purpose Targeted therapy and immunotherapy have led to dramatic change in the treatment of lung cancer, however, the overall 5-year survival rate of lung cancer patients is still suboptimal. It is important to exploit new potential of molecularly targeted therapies. High-frequency somatic mutations in KEAP1/NRF2 (27.9%) have been identified in lung squamous cell carcinoma. In this research, we explored the role of KEAP1 somatic mutations in the development of LSCC and whether a nuclear factor erythroid 2-related factor 2(NRF2) inhibitor be potential to target lung cancer carrying KEAP1/NRF2 mutations. Methods Lung cancer cell lines A549 and H460 with loss-of-function mutations in KEAP1 stably transfected with wild-type (WT) KEAP1 or somatic mutations in KEAP1 were used to investigate the functions of somatic mutations in KEAP1. Flow cytometry, plate clone formation experiments, and scratch tests were used to examine reactive oxygen species, proliferation, and migration of these cell lines. Results The expression of NRF2 and its target genes increased, and tumor cell proliferation, migration, and tumor growth were accelerated in A549 and H460 cells stably transfected with KEAP1 mutants compared to control cells with a loss-of-function KEAP1 mutation and stably transfected with WT KEAP1 in both in vitro and in vivo studies. The proliferation of A549 cell line trasfected with the R320Q KEAP1 mutant was inhibited more apparent than that of the A549 cell line trasfected with WT KEAP1 after treatment with NRF2 inhibitor ML385. Conclusion Somatic mutations of KEAP1 identified from patients with LSCC likely promote tumorigenesis mediated by activation of the KEAP1/NRF2 antioxidant stress response pathway. NRF2 inhibition with ML385 could inhibit the proliferation of tumor cells with KEAP1 mutation. Video abstract

The aim of this study was to investigate the extraction of antibacterial substances from Galla chinensis (ASGC) that act against the aquatic pathogen Vibrio harveyi, to identify the chemical composition and explore the mechanism of action. The optimal extraction process was as follows: anhydrous methanol, liquid/material ratio (mL/g) 26:1, extraction temperature 98 °C and extraction time 157 min. The diameter of the inhibition zones (21.31 ± 0.51 mm) under the optimal conditions agreed with the predicted value by experimental rechecking. The yield of ASGC was 39.39% ± 0.69%, and two compounds including gallic acid (GA) and penta-O-galloyl-β-d-glucose (5GG) were identified in ASGC. The minimal inhibitory concentration (MIC) values of ASGC and GA were 0.50 and 0.25 mg/mL, respectively. Meanwhile, 5GG and other chemical constituents did not exert antibacterial activities against V. harveyi (MICs > 1 mg/mL). Further investigation of the mechanisms of action of ASGC and GA against V. harveyi revealed their strong destructive effects on the growth of bacterial cells, the integrity and permeability of the cell membrane, and morphological alterations. The report provides a favorable prospect of GA as a potential control agent against V. harveyi in aquaculture.

It is important for large scale scientific simulations to read and write data from parallel file system efficiently. To decrease the I/O bottleneck of scientific simulations, many middle-ware solutions had been developed, and the two-phase scheme is one well-known I/O algorithm designed for collective I/O operations. During two-phase I/O based operations, a subset of processes is selected to aggregate non-contiguous pieces of data in the shuffle phase before doing collective reads/writes in the I/O phase. In the meantime, the tapered hierarchical network has long been proposed in order to decrease procurement and power cost. Higher bandwidth and lower latency can be provided in the low levels of tapered hierarchical network. In this paper, we presented a new implementation of two-phase I/O algorithm which takes into consideration the communication pattern and the topology of tapered hierarchical network when scheduling the inter-process communications during the shuffle phase. We validated the new algorithm on our high performance computers and obtained the experimental data on the I/O kernels of some simulations. A significant improvement of the shuffle phase performance was achieved by our new algorithm when compared with the previous two-phase I/O implementations.

Background: Due to the lack of updated information on teicoplanin (TEI) for continuous renal replacement therapy (CRRT), no exact dosage regimen has been recommended. The aim of this study was to optimize the dosage regimen of TEI in renal dysfunction patients with or without CRRT, evaluate the influence factors of the eradication of Gram-positive bacteria, and evaluate the effect of CRRT on the clearance of TEI.Methods: Patients with renal dysfunction receiving TEI treatment in the ICU were prospectively recruited and divided into CRRT and non-CRRT groups. Logistic regression analysis was used to screen the factors affecting the eradication of Gram-positive bacteria. The filtrate concentration of the CRRT group was measured at the time of TEI Cmin, and the filtration coefficient of TEI was calculated to evaluate the effect of CRRT on the clearance of TEI.Results: A total of 106 patients were included, 40 cases in the CRRT group and 66 cases in the non-CRRT group. After giving high-loading doses of TEI, 75.8 and 70% of TEI Cmin in the non-CRRT and CRRT groups reached the range of 10–30 mg/L before the 3rd dose, respectively. The risk of G+ bacteria being uneradicated was higher while the APACHEⅡscore was higher than 22.5. The albumin level before the start of TEI administration and before the 6th–8th dose was lower than 32.8 g/L and 29.3 g/L, respectively, and Cmin before the 3rd dose and 6th–8th dose was lower than 13.2 mg/L and 17.1 mg/L, respectively, with the duration of TEI therapy shorter than 10.5 days. The correlation coefficient (r) was 0.6490 between Cmin before the 3rd dose and the albumin level (p < 0.001). The filtration coefficient of TEI was 10.7 ± 2.4% at Cmin and 11.1 ± 2.5% at Cmax. The GFR had no correlation with the filtration coefficient (r = −0.06204; r = −0.08059). The clearance of TEI in CRRT patients was negatively correlated with the albumin level (r = −0.6305, p = 0.0013).Conclusion: The early stage of the albumin level can significantly affect the initial Cmin and clinical efficacy of TEI, and also had effect on the clearance of TEI by CRRT. The filtration coefficient of TEI was stable, even with a higher ultrafiltration rate.

Ras and Rab interactor 3 (RIN3) functions as a Guanine nucleotide Exchange Factor (GEF) for some members of the Rab family of small GTPase. By promoting the activation of Rab5, RIN3 plays an important role in regulating endocytosis and endocytic trafficking. In addition, RIN3 activates Ras, another small GTPase, that controls multiple signaling pathways to regulate cellular function. Increasing evidence suggests that dysregulation of RIN3 activity may contribute to the pathogenesis of several disease conditions ranging from Paget’s Disease of the Bone (PDB), Alzheimer’s Disease (AD), Chronic Obstructive Pulmonary Disease (COPD) and to obesity. Recent genome-wide association studies (GWAS) identified variants in the RIN3 gene to be linked with these disease conditions. Interestingly, some variants appear to be missense mutations in the functional domains of the RIN3 protein while most variants are located in the noncoding regions of the RIN3 gene, potentially altering its gene expression. However, neither the protein structure of RIN3 nor its exact function(s) (except for its GEF activity) has been fully defined. Furthermore, how the polymorphisms/variants contribute to disease pathogenesis remain to be understood. Herein, we examine, and review published studies in an attempt to provide a better understanding of the physiological function of RIN3; More importantly, we construct a framework linking the polymorphisms/variants of RIN3 to altered cell signaling and endocytic traffic, and to potential disease mechanism(s).

BackgroundSubjective cognitive decline (SCD) was considered to be the preclinical stage of Alzheimer’s disease (AD). However, less is known about the altered rich-club organizations of the morphological networks in individuals with SCD.MethodsThis study included 53 individuals with SCD and 54 well-matched healthy controls (HC) from the Alzheimer’s disease Neuroimaging Initiative (ADNI) database. Individual-level brain morphological networks were constructed by estimating the Jensen-Shannon distance-based similarity in the distribution of regional gray matter volume. Rich-club properties were then detected, followed by statistical comparison.ResultsThe characteristic rich-club organization of morphological networks (normalized rich-club coefficients > 1) was observed for both the SCD and HC groups under a range of thresholds. The SCD group showed a reduced normalized rich-club coefficient compared with the HC group. The SCD group exhibited the decreased strength and degree of rich-club connections than the HC group (strength: HC = 79.93, SCD = 74.37, p = 0.028; degree: HC = 85.28, SCD = 79.34, p = 0.027). Interestingly, the SCD group showed an increased strength of local connections than the HC group (strength: HC = 1982.16, SCD = 2003.38, p = 0.036).ConclusionRich-club organization disturbances of morphological networks in individuals with SCD reveal a distinct pattern between the rich-club and peripheral regions. This altered rich-club organization pattern provides novel insights into the underlying mechanism of SCD and could be used to investigate prevention strategies at the preclinical stage of AD.

Post-translational modifications (PTMs), such as phosphorylation and ubiquitination, etc., have been reported to modulate the activities of IRF3 and IRF7. In this study, we found an acetyltransferase KAT8 in grass carp (CiKAT8, MW286472) that acetylated IRF3/IRF7 and then resulted in inhibition of IFN 1 response. CiKAT8 expression was up-regulated in the cells under poly I:C, B-DNA or Z-DNA stimulation as well as GCRV(strain 873) or SVCV infection. The acetyltransferase domain (MYST domain) of KAT8 promoted the acetylation of IRF3 and IRF7 through the direct interaction with them. So, the domain is essential for KAT8 function. Expectedly, KAT8 without MYST domain (KAT8-△264-487) was granularly aggregated in the nucleus and failed to down-regulate IFN 1 expression. Subcellular localization analysis showed that KAT8 protein was evenly distributed in the nucleus. In addition, we found that KAT8 inhibited the recruitment of IRF3 and IRF7 to ISRE response element. Taken together, our findings revealed that grass carp KAT8 blocked the activities of IRF3 and IRF7 by acetylating them, resulting in a low affinity interaction of ISRE response element with IRF3 and IRF7, and then inhibiting nucleic acids-induced innate immune response.

The Ti-48Al-2Cr-2Nb alloy was fabricated using laser directed energy deposition(LDED), and the impact of various process parameters on the macroscopic crack morphology was analyzed. The mechanism of crack formation was investigated through the analysis of crack microstructure, phase composition, crystal orientation, and elemental composition. The process parameters were optimized by response surface methodology(RSM) and the laser remelting method was used to suppress the crack formation. The results showed that the cracks were mainly caused by lack of fusion, residual stress during LDED and stress between different phases of TiAl alloy. The mismatch of process parameters results in insufficient energy for powder melting, ultimately leading to lack of fusion occurrence. To minimize crack formation, the response surface method was employed to optimize process parameters and reduce crack generation. The higher temperature gradient led to the existence of residual stress in the sample, and the higher stress between α _2 phase and B _2 phase formed in the deposition process due to the difference of thermal expansion coefficients. The region where the two phases converge was the region with the highest crack sensitivity, and cracks occured in the region where α _2 phase and B _2 phase converge in the form of excellent transgranular fracture. The samples prepared by using the optimized parameters can effectively restrain the cracks caused by lack of fusion, but can not restrain the cracks caused by the stress between phases. Laser remelting after LDED can not only reduce the temperature gradient and residual stress, but also remelt the unmelted powder on the surface of the as-deposited samples, effectively inhibiting the generation of cracks, and preparing crack-free samples.

Ethoprophos is an effective and widely pesticide that used in controlling nemathelminth and soil insect. However, ethoprophos has been frequently detected in environment and freshwater. The potential toxicity to aquatic organisms is still not be explored. In this study, zebrafish embryo model was used to evaluated the toxicity of ethoprophos during cardiovascular developmental process of zebrafish. Zebrafish embryos were separately exposed to 10 mg/L, 20 mg/L, 30 mg/L, 40 mg/L and 50 mg/L of ethoprophos exposure at 96 h post-fertilization (hpf), which induced cardiac defects, such as low heart rate, pericardium edema and long SV-BA distance, but had no influence to vascular development. Mechanistically, the expression of cardiac-related genes were abnormal. Moreover, ethoprophos exposure significantly increased oxidative stress in zebrafish embryos by inhibiting the production of antioxidant enzyme (SOD) and activating reactive oxygen species. Expectedly, some apoptosis genes were induced and the apoptotic cardiomyocytes were detected by acridine orange staining. In addition, ethoprophos exposure also inhibited the expression of genes in wnt signaling pathway, such as β-catenin, Axin2, GSK3β and Sox9b. BML284, an activator of wnt signaling pathway, can rescue the cardiotoxic effect of embryos. These results indicated that oxidative stress and blocking wnt signaling pathway were molecular basis of ethoprophos-induced injure in zebrafish. Generally, our study showed that ethoprophos exposure led to severe cardiotoxicity to zebrafish embryo.

SHP2 mediates signaling from multiple receptor tyrosine kinases (RTKs) to extracellular signal-regulated kinase (ERK) and Ser and Thr kinase AKT, and its inhibitors offer an unprecedented opportunity for cancer treatment. Although the ERK signaling variation after SHP2 inhibition has been well investigated, the AKT signaling variation in colorectal carcinoma (CRC) is still unknown. Therefore, we performed immunohistochemistry and bioinformatics analyses to explore the significance of p-SHP2 in CRC. A panel of CRC cell lines with the SHP2 inhibitor, SHP099, was used to assess the effects on viability and signaling. The inhibitors of AKT and focal adhesion kinase (FAK) signaling were examined in combination with SHP099 as potential strategies to enhance the efficacy and overcome resistance. Frequent resistance to the SHP2 inhibitor was observed in CRC cells, even in those without RAS mutations. We observed rapid adaptive reactivation of the AKT pathway in response to SHP2 inhibition, possibly driven by the reactivation of RTKs or released p-FAK. High baseline p-FAK may also be associated with CRC cell resistance to SHP2 inhibition. Co-inhibition of FAK abrogated the feedback reactivation of AKT in response to SHP2 inhibition. Moreover, the combined inhibition of SHP2 with AKT or FAK resulted in sustained AKT pathway suppression and improved antitumor efficacy in vitro and in vivo. Our study found that reactivation of the AKT pathway is a key mechanism of adaptive resistance to SHP2 inhibition, highlighting the potential significance of AKT and FAK inhibition strategies to enhance the efficacy of SHP2 inhibitors in CRC treatment.

Type I interferon and apoptosis elicit multifaceted effects on host defense and various diseases, such as viral infections and cancers. However, the gene/protein network regulating type I interferon and apoptosis has not been elucidated completely. In this study, we selected grass carp (Ctenopharyngodon idella) as an experimental model to investigate the modulation of RNASEK on the secretion of type I interferon and apoptosis. We first cloned two paralogs RNASEK-a and -b in grass carp, defined three exons in each gene, and found the length of both coding regions is 306 bp with 73.27% of protein homology. The protein sequences of the two paralogs are highly conserved across species. Two proteins were mainly localized in early and late endosomes and endoplasmic reticulum. Further, quantitative real-time PCR demonstrated that dsRNA poly I:C and grass carp reovirus upregulated RNASEK-a and -b in grass carp cells and tissues. Overexpression of RNASEK-a and -b individually induced type I interferon expression and the phosphorylation of IRF3/IRF7 shown by Western blot and immunofluorescent staining, increased Bax/Bcl-2 mRNA ratio, DNA fragmentations, TUNEL-positive cells, and the proportion of Annexin V-positive signals in flow cytometry, and activated eIF2α, opposite to that observed when RNASEK-a and -b were knocked down in multiple cell types. Taken together, we claim for the first time that fish paralog proteins RNASEK-a and -b enhance type I interferon secretion and promote apoptosis, which may be involved in the phosphorylation of IRF3/IRF7 and eIF2α, respectively. Our study reveals a previously unrecognized role of RNASEK as a new positive regulator of type I interferon and apoptosis.

Mild cognitive impairment (MCI) is generally considered to be a key indicator for predicting the early progression of Alzheimer’s disease (AD). Currently, the brain connection (BC) estimated by fMRI data has been validated to be an effective diagnostic biomarker for MCI. Existing studies mainly focused on the single connection pattern for the neuro-disease diagnosis. Thus, such approaches are commonly insufficient to reveal the underlying changes between groups of MCI patients and normal controls (NCs), thereby limiting their performance. In this context, the information associated with multiple patterns (e.g., functional connectivity or effective connectivity) from single-mode data are considered for the MCI diagnosis. In this paper, we provide a novel multiple connection pattern combination (MCPC) approach to combine different patterns based on the kernel combination trick to identify MCI from NCs. In particular, sixty-three MCI cases and sixty-four NC cases from the ADNI dataset are conducted for the validation of the proposed MCPC method. The proposed method achieves 87.40% classification accuracy and significantly outperforms methods that use a single pattern.

Subjective cognitive decline (SCD) is considered the earliest stage of the clinical manifestations of the continuous progression of Alzheimer’s Disease (AD). Previous studies have suggested that multimodal brain networks play an important role in the early diagnosis and mechanisms underlying SCD. However, most of the previous studies focused on a single modality, and lacked correlation analysis between different modal biomarkers and brain regions. In order to further explore the specific characteristic of the multimodal brain networks in the stage of SCD, 22 individuals with SCD and 20 matched healthy controls (HCs) were recruited in the present study. We constructed the individual morphological, structural and functional brain networks based on 3D-T1 structural magnetic resonance imaging (sMRI), diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rs-fMRI), respectively. A t-test was used to select the connections with significant difference, and a multi-kernel support vector machine (MK-SVM) was applied to combine the selected multimodal connections to distinguish SCD from HCs. Moreover, we further identified the consensus connections of brain networks as the most discriminative features to explore the pathological mechanisms and potential biomarkers associated with SCD. Our results shown that the combination of three modal connections using MK-SVM achieved the best classification performance, with an accuracy of 92.68%, sensitivity of 95.00%, and specificity of 90.48%. Furthermore, the consensus connections and hub nodes based on the morphological, structural, and functional networks identified in our study exhibited abnormal cortical-subcortical connections in individuals with SCD. In addition, the functional networks presented more discriminative connections and hubs in the cortical-subcortical regions, and were found to perform better in distinguishing SCD from HCs. Therefore, our findings highlight the role of the cortical-subcortical circuit in individuals with SCD from the perspective of a multimodal brain network, providing potential biomarkers for the diagnosis and prediction of the preclinical stage of AD.

Abstract The aim of this study was to explore the feasibility of using different 3D printed internal geometries as tablet formulations to obtain controlled release profiles. In order to obtain controllable release profiles, three types of tablet models (Cylinder, Horn and Reversed Horn) with controlled structures were designed. The cylinder model shows a constant release profile and can keep the drug concentration within a certain range. The horn model exhibits an increasing release profile, which is suitable for the patients who have the drug resistance in the course of medication. The reversed horn model has a decreasing release profile that would be applied to hypertension cure. Furthermore, three types of tablets were fabricated successfully by a fused deposition modeling three-dimensional (3D) printer and injected with paracetamol (APAP) -containing gels. The results of in vitro drug release demonstrate that tablets with three kinds of structures can produce constant, gradually increasing, and gradually decreasing release profiles, respectively. The release attributes can be controlled by using different 3D printed geometries as tablet formulations. More importantly, there are no residues after dissolution. The method of preparing customized tablets with distinguished release profiles presented in this study has the promising potential in the fabrication of patient-tailored medicines.

Accumulating evidence indicates that mammalian NIMA (never in mitosis, gene A)-related kinase 6 (NEK6) plays potential roles during the course of tumorigenesis, but little is known about NEK6 in lower vertebrates. Herein, we reported a mammalian ortholog of NEK6 in grass carp (Ctenopharyngodon idellus) (CiNEK6). Multiple alignment of amino acid sequences and phylogenetic analysis showed that CiNEK6 shares a high level of sequence similarity with its counterparts in birds. CiNEK6 was ubiquitously expressed in all tested tissues, and its expression level was increased under treatment with GCRV (dsRNA virus) or poly I:C (dsRNA analog). Q-PCR and dual-luciferase assays suggested that CiNEK6 overexpression suppressed IFN I activity in CIK cells treated with poly I:C. Knockdown of CiNEK6 resulted in a higher level of IFN I expression in CIK cells treated with poly I:C compared to those which received PBS. Interestingly, analysis of subcellular localization demonstrated that CiNEK6 protein scattered throughout the cytoplasm is gradually congregated together at the edges of karyotheca upon stimulation with poly I:C. Co-IP and co-localization assays suggested that CiNEK6 interacts with CiIRF3 after poly I:C challenge. In poly I:C-treated cells, the phosphorylation of CiIRF3 was increased by CiNEK6 knockdown, but was suppressed by CiNEK6 overexpression, suggesting that CiNEK6 decreases IFN I expression through inhibiting CiIRF3 activity. Cell viability assay, crystal violet staining, and detection of Vp5 also showed that CiNEK6 plays an inhibitory role in IRF3-mediated antiviral responses.

Compound Anoectochilus roxburghii (Wall.) Lindl. (A. roxburghii) oral liquid (CAROL) is a hospital preparation of A. roxburghii and Ganoderma lucidum (G. lucidum), which have hepatoprotective effects. Eight active components (five nucleosides/nucleobases and three triterpenoid acids) in CAROL, A. roxburghii, and G. lucidum were simultaneously detected by high-performance liquid chromatography–tandem mass spectrometry (LC–MS/MS). The multiple reaction monitoring (MRM) mode was applied for the detection of analytes. These eight compounds were separated well within 12 min and quantified using the internal standard working curve method. The method showed good linearity (R2 > 0.9935) and high sensitivity (limit of detection = 0.29 ng/mL). The analyte recovery ranged from 85.07% to 97.50% (relative standard deviation < 3.31%). The content of the target analytes in four batches of CAROL, and the raw materials of G. lucidum and A. roxburghii from the five regions was determined using this method. The contents of guanosine and ganoderic acid A in four batches of oral liquid were high and stabilized and could be recommended as quality markers (Q-marker) for CAROL. Simultaneous qualitative and quantitative analysis of nucleosides and triterpenoid acids in CAROL, A. roxburghii, and G. lucidum by LC–MS/MS based on the MRM model was reported for the first time. The proposed method provides a sensitive, rapid, and reliable approach for the quality control of Chinese medicinal products.

Subjective cognitive decline (SCD) is considered the earliest preclinical stage of Alzheimer’s disease (AD) that precedes mild cognitive impairment (MCI). Effective and accurate diagnosis of SCD is crucial for early detection of and timely intervention in AD. In this study, brain functional connectome (i.e., functional connections and graph theory metrics) based on the resting-state functional magnetic resonance imaging (rs-fMRI) provided multiple information about brain networks and has been used to distinguish individuals with SCD from normal controls (NCs). The consensus connections and the discriminative nodal graph metrics selected by group least absolute shrinkage and selection operator (LASSO) mainly distributed in the prefrontal and frontal cortices and the subcortical regions corresponded to default mode network (DMN) and frontoparietal task control network. Nodal efficiency and nodal shortest path showed the most significant discriminative ability among the selected nodal graph metrics. Furthermore, the comparison results of topological attributes suggested that the brain network integration function was weakened and network segregation function was enhanced in SCD patients. Moreover, the combination of brain connectome information based on multiple kernel-support vector machine (MK-SVM) achieved the best classification performance with 83.33% accuracy, 90.00% sensitivity, and an area under the curve (AUC) of 0.927. The findings of this study provided a new perspective to combine machine learning methods with exploration of brain pathophysiological mechanisms in SCD and offered potential neuroimaging biomarkers for diagnosis of early-stage AD.