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Abstract Newborns are as the primary recipients of blood transfusions. There is a possibility of an association between blood transfusion and unfavorable outcomes. Such complications not only imperil the lives of newborns but also cause long hospitalization. Our objective is to explore the predictor variables that may lead to extended hospital stays in neonatal intensive care unit (NICU) patients who have undergone blood transfusions and develop a predictive nomogram. A retrospective review of 539 neonates who underwent blood transfusion was conducted using median and interquartile ranges to describe their length of stay (LOS). Neonates with LOS above the 75th percentile (P75) were categorized as having a long LOS. The Least Absolute Shrinkage and Selection Operator (LASSO) regression method was employed to screen variables and construct a risk model for long LOS. A multiple logistic regression prediction model was then constructed using the selected variables from the LASSO regression model. The significance of the prediction model was evaluated by calculating the area under the ROC curve (AUC) and assessing the confidence interval around the AUC. The calibration curve is used to further validate the model’s calibration and predictability. The model’s clinical effectiveness was assessed through decision curve analysis. To evaluate the generalizability of the model, fivefold cross-validation was employed. Internal validation of the models was performed using bootstrap validation. Among the 539 infants who received blood transfusions, 398 infants (P75) had a length of stay (LOS) within the normal range of 34 days, according to the interquartile range. However, 141 infants (P75) experienced long LOS beyond the normal range. The predictive model included six variables: gestational age (GA) (

Abstract Background The relaxation of the “zero-COVID” policy on Dec. 7, 2022, in China posed a major public health threat recently. Complete blood count test was discovered to have complicated relationships with COVID-19 after the infection, while very few studies could track long-term monitoring of the health status and identify the characterization of hematological parameters prior to COVID-19. Methods Based on a 13-year longitudinal prospective health checkup cohort of ~ 480,000 participants in West China Hospital, the largest medical center in western China, we documented 998 participants with a laboratory-confirmed diagnosis of COVID-19 during the 1 month after the policy. We performed a time-to-event analysis to explore the associations of severe COVID-19 patients diagnosed, with 34 different hematological parameters at the baseline level prior to COVID-19, including the whole and the subtypes of white and red blood cells. Results A total of 998 participants with a positive SARS-CoV-2 test were documented in the cohort, 42 of which were severe cases. For white blood cell-related parameters, a higher level of basophil percentage (HR = 6.164, 95% CI = 2.066–18.393, P = 0.001) and monocyte percentage (HR = 1.283, 95% CI = 1.046–1.573, P = 0.017) were found associated with the severe COVID-19. For lymphocyte-related parameters, a lower level of lymphocyte count (HR = 0.571, 95% CI = 0.341–0.955, P = 0.033), and a higher CD4/CD8 ratio (HR = 2.473, 95% CI = 1.009–6.059, P = 0.048) were found related to the risk of severe COVID-19. We also observed that abnormality of red cell distribution width (RDW), mean corpuscular hemoglobin concentration (MCHC), and hemoglobin might also be involved in the development of severe COVID-19. The different trajectory patterns of RDW-SD and white blood cell count, including lymphocyte and neutrophil, prior to the infection were also discovered to have significant associations with the risk of severe COVID-19 (all P

Abstract Objective The objective of this study was to explore the associations of body mass index (BMI), fat mass index (FMI), skeletal mass index (SMI) and secondary osteoporosis (OP) in patients with rheumatoid arthritis (RA). Methods The bone mineral density (BMD) at sites of the femur neck (Neck), total hip (Hip) and lumbar vertebrae 1–4 (L1-4) was measured by dual-energy X-ray absorptiometry. The skeletal muscle index, body fat percentage and mineral content were measured by biological electrical impedance for calculating BMI, FMI and SMI. Results A total of 433 patient with RA and 158 healthy controls were enrolled. The BMDs at each site of the RA patients were lower compared with those of the healthy controls (p

AbstractBackground Robot-assisted upper-limb rehabilitation has been studied for many years, with many randomised controlled trials (RCTs) investigating the effects of robotic-assisted training on affected limbs. The current trend directs towards end-effector devices. However, most studies have focused on the effectiveness of rehabilitation devices, but studies on device sizes are relatively few.Goal Systematically review the effect of a portable rehabilitation robot (PRR) on the rehabilitation effectiveness of paralysed upper limbs compared with non-robotic therapy.Methods A meta-analysis was conducted on literature that included the Fugl-Meyer Assessment (FMA) obtained from the PubMed and Web of Science (WoS) electronic databases until June 2023.Results A total of 9 studies, which included RCTs, were completed and a meta-analysis was conducted on 8 of them. The analysis involved 295 patients. The influence on upper-limb function before and after treatment in a clinical environment is analysed by comparing the experimental group using the portable upper-limb rehabilitation robot with the control group using conventional therapy. The result shows that portable robots prove to be effective (FMA: SMD = 0.696, 95% = 0.099 to.293, p

Background: Autoimmune diseases are a group of diseases caused by abnormal immune responses to functional body parts. Single-cell RNA-sequencing (scRNA-seq) technology provides transcriptomic information at the single-cell resolution, thus offering a new way to study autoimmune diseases. Most single-cell RNA-seq studies, however, have often focused on one type of autoimmune disease. Methods: We integrated scRNA-seq data from peripheral blood cells of five different autoimmune diseases (IgA nephropathy [IgAN], Kawasaki disease [KD], multiple sclerosis [MS], Sjogren’s syndrome [SS], and systemic lupus erythematosus [SLE]). We performed dimensionality clustering, cellular communication analysis, re-clustering analysis of monocytes, NK cell populations, differential gene expression analysis, and functional enrichment for all immune cells in these data. Results: We integrated the scRNA-seq results of peripheral blood cells from five different autoimmune diseases (IgAN, KD, MS, SS, and SLE). We showed that all samples contained 18 different immune cell subsets, although the cell cluster populations were different among the 5 diseases. Through intercellular communication network analysis, we determined that the signals of classical and non-classical monocytes were significantly enhanced in patients with IgAN and SLE. The signals of naïve B cells were increased in patients KD. Interestingly, the signals of NK and NK-T cells were enhanced in patients with SS, but reduced in patients with IgAN and SLE. Transcriptomic analysis of classical and non-classical monocyte subsets further revealed that pro-inflammatory cytokines and interferon-related genes, including CCL3, IL1B, ISG15, and IFI6, were specifically increased in patients with IgAN and SLE. Unlike monocytes, the number and NK marker genes were decreased in patients with IgAN and KD, but increased in patients with SS. Meanwhile, two NK-T cell subsets were exclusively found in SS. Conclusions: In summary, based on an integration of the single-cell RNA-seq results, we demonstrated changes in the immune cell landscape of five different autoimmune diseases with respect to immune cell subsets, populations, differentially-expressed genes, and the cell-to-cell communication network. Our data provide new insight to further explore the heterogeneity and similarity among different autoimmune diseases.

Abstract. Background:. The brain is a common metastatic site in patients with non-small cell lung cancer (NSCLC), resulting in a relatively poor prognosis. Systemic therapy with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) is recommended as the first-line treatment for EGFR-mutated, advanced NSCLC patients. However, intracranial activity varies in different drugs. Thus, brain metastasis (BM) should be considered when choosing the treatment regimens. We conducted this network meta-analysis to explore the optimal first-line therapeutic schedule for advanced EGFR-mutated NSCLC patients with different BM statuses. Methods:. Randomized controlled trials focusing on EGFR-TKIs (alone or in combination) in advanced and EGFR-mutant NSCLC patients, who have not received systematic treatment, were systematically searched up to December 2021. We extracted and analyzed progression-free survival (PFS) and overall survival (OS). A network meta-analysis was performed with the Bayesian statistical model to determine the survival outcomes of all included therapy regimens using the R software. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used to compare intervention measures, and overall rankings of therapies were estimated under the Bayesian framework. Results:. This analysis included 17 RCTs with 5077 patients and 12 therapies, including osimertinib + bevacizumab, aumolertinib, osimertinib, afatinib, dacomitinib, standards of care (SoC, including gefitinib, erlotinib, or icotinib), SoC + apatinib, SoC + bevacizumab, SoC + ramucirumab, SoC + pemetrexed based chemotherapy (PbCT), PbCT, and pemetrexed free chemotherapy (PfCT). For patients with BM, SoC + PbCT improved PFS compared with SoC (HR = 0.40, 95% CI: 0.17–0.95), and osimertinib + bevacizumab was most likely to rank first in PFS, with a cumulative probability of 34.5%, followed by aumolertinib, with a cumulative probability of 28.3%. For patients without BM, osimertinib + bevacizumab, osimertinib, aumolertinib, SoC + PbCT, dacomitinib, SoC + ramucirumab, SoC + bevacizumab, and afatinib showed superior efficacy compared with SoC (HR = 0.43, 95% CI: 0.20–0.90; HR = 0.46, 95% CI: 0.31–0.68; HR = 0.51, 95% CI: 0.34–0.77; HR = 0.50, 95% CI: 0.38–0.66; HR = 0.62, 95% CI: 0.43–0.89; HR = 0.64, 95% CI: 0.44–0.94; HR = 0.61, 95% CI: 0.48–0.76; HR = 0.71, 95% CI: 0.50–1.00), PbCT (HR = 0.29, 95% CI: 0.11–0.74; HR = 0.31, 95% CI: 0.15–0.62; HR = 0.34, 95% CI: 0.17–0.69; HR = 0.34, 95% CI: 0.18–0.64; HR = 0.42, 95% CI: 0.21–0.82; HR = 0.43, 95% CI: 0.22–0.87; HR = 0.41, 95% CI: 0.22–0.74; HR = 0.48, 95% CI: 0.31–0.75), and PfCT (HR = 0.14, 95% CI: 0.06–0.32; HR = 0.15, 95% CI: 0.09–0.26; HR = 0.17, 95% CI: 0.09–0.29; HR = 0.16, 95% CI: 0.10–0.26; HR = 0.20, 95% CI: 0.12–0.35; HR = 0.21, 95% CI: 0.12–0.39; HR = 0.20, 95% CI: 0.12–0.31; HR = 0.23, 95% CI: 0.16–0.34) in terms of PFS. And, SoC + apatinib showed relatively superior PFS when compared with PbCT (HR = 0.44, 95% CI: 0.22–0.92) and PfCT (HR = 0.21, 95% CI: 0.12–0.39), but similar PFS to SoC (HR = 0.65, 95% CI: 0.42–1.03). No statistical differences were observed for PFS in patients without BM between PbCT and SoC (HR = 1.49, 95% CI: 0.84–2.64), but both showed favorable PFS when compared with PfCT (PfCT vs. SoC, HR = 3.09, 95% CI: 2.06–4.55; PbCT vs. PfCT, HR = 0.14, 95% CI: 0.06–0.32). For patients without BM, osimertinib + bevacizumab was most likely to rank the first, with cumulative probabilities of 47.1%. For OS, SoC + PbCT was most likely to rank first in patients with and without BM, with cumulative probabilities of 46.8%, and 37.3%, respectively. Conclusion:. Osimertinib + bevacizumab is most likely to rank first in PFS in advanced EGFR-mutated NSCLC patients with or without BM, and SoC + PbCT is most likely to rank first in OS.

Abstract Fresnel zone plates (FZPs) are widely used in integrated optical systems to meet new cutting-edge demands for photonic integration and device miniaturizing. However, their use in applications of cross-scale fabrication still faces several obstacles, such as low efficiency, fixed focal length, single wavelength, large size, and complicated fabrication. Here, we first examine a novel adaptive focal length in white light focusing by using reflective-type and phase-only spatial light modulator (RLC-SLM) based on a liquid crystal on silicon. The device achieves a maximum diffraction efficiency of approximately 38% at primary focal points of binary phase-type FZPs throughout the visible range (red, green, and blue wavelengths). The RLC-SLM focuses the light of the desired wavelength while other sources are defocused. White light focusing and color separation are demonstrated by sequentially and additively switching different FZPs. These recent advances show that optically tunable FRZs are promising potential candidates to enhance adaptive camera systems, microscopes, holograms, and portable and wearable devices, thereby opening up novel possibilities in optical communications and sensing.

BackgroundTraditional Chinese medicine (TCM) has been garnering ever-increasing worldwide attention as the herbal extracts and formulas prove to have potency against disease. Fuzhengjiedu San (FZJDS), has been extensively used to treat viral diseases in pigs, but its bioactive components and therapeutic mechanisms remain unclear.MethodsIn this study, we conducted an integrative approach of network pharmacology and experimental study to elucidate the mechanisms underlying FZJDS's action in treating porcine reproductive and respiratory syndrome virus (PRRSV). We constructed PPI network and screened the core targets according to their degree of value. GO and KEGG enrichment analyses were also carried out to identify relevant pathways. Lastly, qRT-PCR, flow cytometry and western blotting were used to determine the effects of FZJDS on core gene expression in PRRSV-infected monkey kidney (MARC-145) cells to further expand the results of network pharmacological analysis.ResultsNetwork pharmacology data revealed that quercetin, kaempferol, and luteolin were the main active compounds of FZJDS. The phosphatidylinositol-3-kinase (PI3K)/Akt pathway was deemed the cellular target as it has been shown to participate most in PRRSV replication and other PRRSV-related functions. Analysis by qRT-PCR and western blotting demonstrated that FZJDS significantly reduced the expression of P65, JNK, TLR4, N protein, Bax and IĸBa in MARC-145 cells, and increased the expression of Bcl-2, consistent with network pharmacology results. This study provides that FZJDS has significant antiviral activity through its effects on the PI3K/AKT signaling pathway.ConclusionWe conclude that FZJDS is a promising candidate herbal formulation for treating PRRSV and deserves further investigation.

Abstract Tiandong is a vital traditional Chinese herbal medicine. It is derived from the tuber root of the Asparagus cochinchinensis according to the Pharmacopoeia of the people’s republic of China (2020 Edition). On account of the similar morphology, Asparagus meioclados and Asparagus munitus were used as Tian-Dong in southwest China. Chloroplast (cp) genomes are highly active genetic components of plants and play an extremely important role in improving the efficiency of the identification of plant species. To differentiate the medicinal plants belonging to the genus Asparagus, we sequenced and analyzed the complete plastomes (plastid genomes) of A. meioclados and A. munitus and obtained two plastomes whose length changed to 156,515 bp and 156,381 bp, respectively. A total of 111 unique genes have been detected in plastome, which included 78 protein-coding genes, 29 tRNA genes and 4 rRNA genes. In plastomes of A. meioclados and A. munitus, 14,685 and 14,987 codons were detected, among which 9942 and 10,207 had the relative synonymous codon usage (RSCU) values higher than 1, respectively. A. meioclados and A. munitus have 26 SSRs patterns, among which A. meioclados was 25 and A. munitus 21. The average Ka/Ks value was 0.36, and positive selection was detected in genes of the photosynthetic system (ndhF and rbcL) in Asparagus species. To perform the comparative analysis of plastomes, the two newly sequenced plastomes of the A. meioclados and A. munitus species were compared with that of A. cochinchinensis, and 12 hotspots, including 5 coding regions and 7 inter-genomic regions, were identified. Based on the whole plastome of Asparagus, 2 divergent hotspots (accD and rpl32-trnL-UAG) and 1 international barcode fragment (rbcL) were screened, which may be used as particular molecular markers for the identification of Asparagus species. In addition, we determined the phylogenetic relationship between A. meioclados and A. munitus in the genus Asparagus. This study enriches our knowledge of the molecular evolutionary relationships of the Asparagus genus and provides treasured data records for species identification, molecular breeding, and evolutionary analysis of this genus.

Abstract The relation between exposure to single metal/metalloid and the risk of chronic kidney disease (CKD) remains unclear. We aimed to determine the single and mixed associations of 21 heavy metals/metalloids exposure and the risk of CKD. We performed a cross-sectional study that recruited 4055 participants. Multivariate logistic regression, linear regression and weighted quantile sum (WQS) regression were conducted to explore the possible effects of single and mixed metals/metalloids exposure on the risk of CKD, the risk of albuminuria and changes in the estimated glomerular filtration rate (eGFR). In single-metal models, Cu, Fe, and Zn were positively associated with increased risks of CKD (P-trend

Abstract Background The application of molecular targeting therapy and immunotherapy has notably prolonged the survival of patients with hepatocellular carcinoma (HCC). However, multidrug resistance and high molecular heterogeneity of HCC still prevent the further improvement of clinical benefits. Dysfunction of tumor-infiltrating natural killer (NK) cells was strongly related to HCC progression and survival benefits of HCC patients. Hence, an NK cell-related prognostic signature was built up to predict HCC patients’ prognosis and immunotherapeutic response. Methods NK cell markers were selected from scRNA-Seq data obtained from GSE162616 data set. A consensus machine learning framework including a total of 77 algorithms was developed to establish the gene signature in TCGA–LIHC data set, GSE14520 data set, GSE76427 data set and ICGC–LIRI–JP data set. Moreover, the predictive efficacy on ICI response was externally validated by GSE91061 data set and PRJEB23709 data set. Results With the highest C-index among 77 algorithms, a 11-gene signature was established by the combination of LASSO and CoxBoost algorithm, which classified patients into high- and low-risk group. The prognostic signature displayed a good predictive performance for overall survival rate, moderate to high predictive accuracy and was an independent risk factor for HCC patients’ prognosis in TCGA, GEO and ICGC cohorts. Compared with high-risk group, low-risk patients showed higher IPS–PD1 blocker, IPS–CTLA4 blocker, common immune checkpoints expression but lower TIDE score, which indicated low-risk patients might be prone to benefiting from ICI treatment. Moreover, a real-world cohort, PRJEB23709, also revealed better immunotherapeutic response in low-risk group. Conclusions Overall, the present study developed a gene signature based on NK cell-related genes, which offered a novel platform for prognosis and immunotherapeutic response evaluation of HCC patients.

Abstract Retrospective studies have identified an increased risk of ankylosing spondylitis (AS) in endometriosis patients. The purpose of this study was to investigate the causal relationship between clinical phenotypes of endometriosis and AS using mendelian randomized analysis (MR). MR was performed using data from genome-wide association studies (GWASs). Heterogeneity, pleiotropy and sensitivity analyses were performed to evaluate the robustness of the results by MR Egger and inverse variance weighted (IVW), leave-one-out analysis. IVW, IVW-MRE (inverse variance weighted multiplicative random effects), weighted median and MR Egger were used to explore the relationship between endometriosis and AS. The IVW analysis showed a causal relationship between infertile endometriosis and AS (OR = 0.8334, P = 0.02191), and the same result was observed with IVW-MRE (OR = 0.8334, P = 0.0007933). However, further stratified analysis showed that no matter which statistical method was used, ovarian endometriosis (IVW: OR = 0.1662, P = 0.4986; IVW-MRE: OR = 0.1662, P = 0.4986; MR Egger: OR = − 0.9577, P = 0.2798; Weighted median: OR = 0.2628, P = 0.3452), pelvic peritoneum endometriosis (IVW: OR = 0.4363, P = 0.225; IVW-MRE: OR = 0.4363, P = 0.225, MR Egger: OR = 4.159, P = 0.1705; Weighted median: OR = 0.4112, P = 0.2714), rectovaginal endometriosis (IVW: OR = 0.1365, P = 0.805; IVW-MRE: OR = 0.1365, P = 0.805) there was no causal relationship between endometriosis and AS. This study suggested that patients with infertility endometriosis are at increased risk for AS. This study supports clinicians to pay more attention to the occurrence of AS in endometriosis patients with infertility.

Abstract Background Non-recombining regions of the Y-chromosome recorded the evolutionary traces of male human populations and are inherited haplotype-dependently and male-specifically. Recent whole Y-chromosome sequencing studies have identified previously unrecognized population divergence, expansion and admixture processes, which promotes a better understanding and application of the observed patterns of Y-chromosome genetic diversity. Results Here, we developed one highest-resolution Y-chromosome single nucleotide polymorphism (Y-SNP) panel targeted for uniparental genealogy reconstruction and paternal biogeographical ancestry inference, which included 639 phylogenetically informative SNPs. We genotyped these loci in 1033 Chinese male individuals from 33 ethnolinguistically diverse populations and identified 256 terminal Y-chromosomal lineages with frequency ranging from 0.0010 (singleton) to 0.0687. We identified six dominant common founding lineages associated with different ethnolinguistic backgrounds, which included O2a2b1a1a1a1a1a1a1-M6539, O2a1b1a1a1a1a1a1-F17, O2a2b1a1a1a1a1b1a1b-MF15397, O2a2b2a1b1-A16609, O1b1a1a1a1b2a1a1-F2517, and O2a2b1a1a1a1a1a1-F155. The AMOVA and nucleotide diversity estimates revealed considerable differences and high genetic diversity among ethnolinguistically different populations. We constructed one representative phylogenetic tree among 33 studied populations based on the haplogroup frequency spectrum and sequence variations. Clustering patterns in principal component analysis and multidimensional scaling results showed a genetic differentiation between Tai-Kadai-speaking Li, Mongolic-speaking Mongolian, and other Sinitic-speaking Han Chinese populations. Phylogenetic topology inferred from the BEAST and Network relationships reconstructed from the popART further showed the founding lineages from culturally/linguistically diverse populations, such as C2a/C2b was dominant in Mongolian people and O1a/O1b was dominant in island Li people. We also identified many lineages shared by more than two ethnolinguistically different populations with a high proportion, suggesting their extensive admixture and migration history. Conclusions Our findings indicated that our developed high-resolution Y-SNP panel included major dominant Y-lineages of Chinese populations from different ethnic groups and geographical regions, which can be used as the primary and powerful tool for forensic practice. We should emphasize the necessity and importance of whole sequencing of more ethnolinguistically different populations, which can help identify more unrecognized population-specific variations for the promotion of Y-chromosome-based forensic applications.

Abstract Lung adenocarcinoma (LUAD) is the most common form of non-small cell lung cancer (NSCLC). Hypoxia has been found in 50–60% of locally advanced solid tumors and is associated with poor prognosis in various tumors, including NSCLC. This study focused on hypoxia-associated molecular hallmarks in LUAD. Fifteen hypoxia-related genes were selected to define the hypoxia status of LUAD by ConsensusClusterPlus based on data from The Cancer Genome Atlas (TCGA). Then, we investigated the immune status under different hypoxia statuses. Subsequently, we constructed prognostic models based on hypoxia-related differentially expressed genes (DEGs), identified hypoxia-related microRNAs, lncRNAs and mRNAs, and built a network based on the competing endogenous RNA (ceRNA) theory. Two clusters (Cluster 1 and Cluster 2) were identified with different hypoxia statuses. Cluster 1 was defined as the hypoxia subgroup, in which all 15 hypoxia-associated genes were upregulated. The infiltration of CD4+ T cells and Tfh cells was lower, while the infiltration of regulatory T (Treg) cells, the expression of PD-1/PD-L1 and TMB scores were higher in Cluster 1, indicating an immunosuppressive status. Based on the DEGs, a risk signature containing 7 genes was established. Furthermore, three differentially expressed microRNAs (hsa-miR-9, hsa-miR-31, hsa-miR-196b) associated with prognosis under different hypoxia clusters and their related mRNAs and lncRNAs were identified, and a ceRNA network was built. This study showed that hypoxia was associated with poor prognosis in LUAD and explored the potential mechanism from the perspective of the gene signature and ceRNA theory.

Abstract The purpose of this study was to explore the differences between the prevalence and impact factors of adolescent dissociative symptoms (ADSs) by using sex-stratification during the coronavirus disease 2019 (COVID-19) pandemic. A school-based, two-center cross-sectional study was conducted in Hangzhou City, China, between January 1, 2021 and April 30, 2022. The sample included 1,916 adolescents aged 13–18 years that were randomly selected using a multiphase, stratified, cluster sampling technique. A two-stage assessment procedure was used to find out the ADSs. We used a multivariate logistic regression analysis to assess the impact factors of ADSs during the COVID-19 pandemic. The adolescent dissociative scores (t = 4.88, P

Objective To analyze the causes of staff burnout and various errors during group blood donation in blood centers, and to explore the significance of overall planning to improve above problems. Methods Various errors occurred during group blood donation from January 2016 to December 2020 in a blood center were selected as the research object. Job burnout related survey data including emotional exhaustion (MBI-EE), work attitude (MBI-DP), sense of achievement (MBI-PA) etc. were collected. The influence of six variables, including blood collection quantity, staff, order control, plan compliance, overload blood collection and over-stock blood collection, on the occurrence of errors was analyzed, and an ordered logistic regression model was established. After optimizing overall planning measures, the occurrence of errors and the improvement of burnout were compared. Results In addition to the volume of blood collected (P>0.05), the other five variables had significant influence on the occurrence of errors (P0.05). Conclusion Scientific inventory management and effective blood collection assessment measures are helpful to improve work quality, and the ordered Logistic regression model has a good fitting degree for error rectification. Analyzing the occurrence of errors during blood collection and supply from the influencing factors is conducive to formulate corrective and preventive measures and promote the continuous improvement of work quality.

Abstract Cardiovascular diseases are the most common cause of death globally. Accurately modeling cardiac homeostasis, dysfunction, and drug response lies at the heart of cardiac research. Adult human primary cardiomyocytes (hPCMs) are a promising cellular model, but unstable isolation efficiency and quality, rapid cell death in culture, and unknown response to cryopreservation prevent them from becoming a reliable and flexible in vitro cardiac model. Combing the use of a reversible inhibitor of myosin II ATPase, (-)-blebbistatin (Bleb), and multiple optimization steps of the isolation procedure, we achieved a 2.74-fold increase in cell viability over traditional methods, accompanied by better cellular morphology, minimally perturbed gene expression, intact electrophysiology, and normal neurohormonal signaling. Further optimization of culture conditions established a method that was capable of maintaining optimal cell viability, morphology, and mitochondrial respiration for at least 7 days. Most importantly, we successfully cryopreserved hPCMs, which were structurally, molecularly, and functionally intact after undergoing the freeze-thaw cycle. hPCMs demonstrated greater sensitivity towards a set of cardiotoxic drugs, compared to human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Further dissection of cardiomyocyte drug response at both the population and single-cell transcriptomic level revealed that hPCM responses were more pronouncedly enriched in cardiac function, whereas hiPSC-CMs responses reflected cardiac development. Together, we established a full set of methodologies for the efficient isolation and prolonged maintenance of functional primary adult human cardiomyocytes in vitro, unlocking their potential as a cellular model for cardiovascular research, drug discovery, and safety pharmacology.

Objective(s): Cigarette smoke may play a direct role in proliferation of human pulmonary artery smooth muscle cells (HPASMCs). However, the mechanism involved and the effect of interventions remain unclear. We aimed to evaluate the effect of cigarette smoke extract (CSE) on HPASMCs, explore the role of inflammation and oxidative stress, and the effects of Tempol and PDTC in this process.Materials and Methods: HPASMCs were subjected to normal control (NC), CSE, CSE+Tempol (CSE+T), and CSE+PDTC (CSE+P) groups. Proliferation of HPASMCs was measured by CCK-8 and Western blot. TNF-α, IL-6, MDA, and SOD levels were determined by ELISA and commercial kits. Nuclear translocation of NF-κB p65 was evaluated by western blot.Results: 1%, 2.5%, and 5% CSE all promoted proliferation of HPASMCs, and effect of 1% CSE was the most significant, however, 7.5% and 10% CSE inhibited viability of cells (all P

Objective To investigate the effect of propofol (Pro) on cardiomyocyte damage induced by anoxia-reoxygenation through regulating JNK/p38 MAPK pathway. Methods Divided the cells into control group, anoxia-reoxygenation (A/R) group, anoxia-reoxygenation+propofol of low, medium and high dose (A/R+Pro-L, A/R+Pro-M, A/R+Pro-H) group, anoxia-reoxygenation+propofol+p38 MAPK pathway inhibitor (A/R+Pro+SB203580) group. Flow cytometry was used to detect cell apoptosis; Western blot was used to detect the expression of Bcl-2, Bax, cleaved caspase-3 and JNK/p38 MAPK signaling pathway related proteins; ELISA was applied to detect LDH content, MDA content, SOD activity and CAT activity. Results In A/R group Bcl-2 protein expression SOD and CAT activity were significantly inhibited cell apoptosis rate, Bax protein, cleaved caspase-3 protein expression, LDH, MDA, p-JNK protein, p-p38 MAPK protein expression were promoted(P＜0.05). Compared with A/R group, A/R+Pro-L group, A/R+Pro-M group, A/R+Pro-H group all showed significantly promoted cell Bcl-2 protein expression, SOD, CAT activity; inhibition of cell apoptosis, Bax protein, cleaved caspase-3 protein, LDH, MDA, p-JNK protein and p-p38 MAPK protein(P＜0.05). Compared with the A/R+Pro group, the A/R+Pro+SB203580 group showed significantly promoted cell Bcl-2 protein expression, SOD, CAT activity and inhibited cell apoptosis, p-JNK protein, p-p38 MAPK protein, Bax protein, cleaved caspase-3 protein, LDH and MDA (P＜0.05). Conclusions Propofol may slow down anoxia-reoxygenation induced cardiomyocyte apoptosis and oxidative stress through regulating the JNK/p38 MAPK pathway.

At present, there are some problems in underwater low light image, such as low contrast, blurred details, color distortion. In the process of low illumination image enhancement, there are often problems such as artifacts, loss of edge details and noise amplification in the enhanced image. In this paper, we propose an underwater low-light enhancement algorithm based on U-shaped generative adversarial network, combined with bright channel prior and attention mechanism, to address the problems. For the problems of uneven edges and loss of details that occurred in traditional enhanced images, we propose a two-channel fusion technique for the input channel. Aiming at the problems of brightness, texture and color distortion in enhanced images, we propose a feature extraction technique based on the attention mechanism. For the problems of noise in enhanced output images, we propose a multi-loss function to constrain the network. The method has a wide range of applications in underwater scenes with large depth. This method can be used for target detection or biological species identification in underwater low light environment. Through the enhancement experiment of underwater low light image, the proposed method effectively solves the problems of low contrast, blurred details, color distortion, etc. of underwater low light image. Finally, we performed extensive comparison experiments and completed ablation experiments on the proposed method. The experimental results show that the proposed method is optimal in human visual experience and underwater image quality evaluation index.

Tissue slicing-assisted digestion (TSAD) of adult cardiomyocytes has shown significant improvements over conventional chunk methods. However, it remains unclear how this method compares to Langendorff perfusion, the current standard of adult cardiomyocyte isolation. Using adult Bama minipigs, we performed cardiomyocyte isolation via these two distinct methods, and compared the resulting cellular quality, including viability, cellular structure, gene expression, and electrophysiological properties, of cardiomyocytes from 3 distinct anatomical regions, namely the left ventricle, right ventricle, and left atrial appendage. Our results revealed largely indistinguishable cell quality in all of the measured parameters. These findings suggest that that TSAD can be reliably used to isolate adult mammalian cardiomyocytes as a reliable alternative to perfusion in cardiomyocyte isolation from larger mammals, particularly when Langendorff perfusion is not feasible.

FOXP1, known as a Forkhead-box (FOX) family protein, plays an important role in human tumorigenesis. However, the function and molecular mechanism of FOXP1 in pancreatic cancer (PC) remain unclear. Here, we report that PC patients with FOXP1 overexpression had a higher survival rate compared to patients with low- FOXP1 expression. Additionally, high expression of FOXP1 can markedly inhibit the growth of pancreatic cancer in vivo and in vitro, whereas low expression of FOXP1 effectively promoted the tumorigenesis. Mechanistically, FOXP1 could directly bind the IRF1 promoter, which triggered the transcriptional activity of IRF1. Taken together, FOXP1 suppressed PC growth via IRF1-dependent manner, serving as a potential prognostic biomarker for patients with PC.

During the production of electronic panels, surface defects will inevitably appear. How to quickly and accurately detect these defects is very important to improve product quality. However, some problems such as high cost and low accuracy are still prominent when existing manual detection and traditional techniques are used to solve such problems. Therefore, more and more computer vision techniques are proposed to solve such problems, but the current application of deep learning-based object detection networks for surface defect detection of electronic panels is in a gap. The analysis found that there are two main reasons for this phenomenon. On the one hand, the surface defects of electronic panels have their unique characteristics such as multi-scale and irregular shape, and the current object detection networks cannot effectively solve these problems. On the other hand, the regression and classification tasks coupled in the current computational mechanism of each network are commonly found to cause the problem of conflict between them, which makes it more difficult to adapt these network models to the detection tasks in this scenario. Based on this, we design a supervised object detection network for electronic panel surface defect detection scenario for the first time. The computational mechanism of this network includes a prediction box generation strategy based on the double branch structure and a detection head design strategy that decouples the regression task from the classification task. In addition, we validated the designed network and the proposed method on our own collected dataset of surface defects in electronic panels. The final results of the comparative and ablation experiments show that our proposed method achieves an average accuracy of 78.897% for 64 surface defect categories, proving that its application to electronic panel surface defect detection scenarios can achieve better results.

Automatic detection of surface defects in electronic panels is receiving increasing attention in the quality control of products. The surface defect detection of electronic panels is different from other target detection scenarios and is a meaningful and challenging problem. Its main manifestation is that surface defects of electronic panels usually exhibit extreme irregularity and small target characteristics, which bring great difficulties to the task of surface defect target detection including feature extraction and so on. The traditional methods can only detect a very small number of defect classes under specific detection conditions. And due to the weak robustness of these methods, they cannot be applied in real production scenarios on a large scale. Based on this, this paper applies the target detection technique under deep learning to the surface defect detection scenario of electronic panels for the first time. At the same time, in order to make the designed target detection network applicable to the electronic panel surface defect detection scenario and to enhance the interpretability of the designed target detection network in terms of computer mechanism. We design a deformable convolution module with a convolutional self-attentive module to learn the offset and a dual detection head incorporating the SE (Squeeze-and-Excitation) mechanism for the irregular characteristics of electronic panel surface defects and the small target characteristics, respectively. Finally, we carried out a series of experiments on our own electronic panel defect data set, including comparison with the most advanced target detection algorithms and a series of ablation experiments against our proposed method. The final experimental results prove that our method not only has better interpretability, but also has better metric performance, in which the map_0.5 metric reaches 78.257%, which is an increase of 13.506 percentage points over YOLOV5 and 33.457 percentage points higher than Retinanet. The results prove the proposed method is effective.

We investigated a case of cutaneous infection in an immunocompromised patient in China that was caused by a novel species within the Mycobacterium gordonae complex. Results of whole-genome sequencing indicated that some strains considered to be M. gordonae complex are actually polyphyletic and should be designated as closely related species.

Abstract Plant kinases containing the LysM domain play important roles in pathogen recognition and self-defense reactions. And it could recognize microbe-associated molecules including chitin and other polypeptides. The white tip nematode Aphelenchoides besseyi is a migratory parasitic nematode that infects plant shoots. It is distributed over almost all rice-producing areas and causes up to 50% economic losses. The rice OsRLK3 gene was a defense-related LysM kinase gene of rice. This study showed that the rice LysM kinase OsRLK3 could be induced by flg22, jasmonic acid, salicylic acid, and chitin. An interaction gene, Ab-atps from A. besseyi, was identified by screening the interaction between the rice gene OsRLK3 and an A. besseyi cDNA library using yeast two-hybrid screening. Ab-atps is a novel ATP synthase gene with a full length of 1341 bp, coding for 183 amino acids. The mRNA of Ab-atps was located in the esophagus and reproductive system of A. besseyi. The expression of Ab-atps was assessed at different developmental stages of the nematode and found to be the highest in the juvenile, followed by the egg, female, and male. Reproduction was significantly decreased in nematodes treated with Ab-atps double-stranded RNA (dsRNA) (p

Abstract. Backgrounds:. Cancer is one of the main causes of death worldwide, seriously threatening human health and life expectancy. We aimed to analyze the cancer incidence and mortality rates during 2016 in Zhejiang Province, Southeast China. Methods:. Data were collected from 14 population-based cancer registries across Zhejiang Province of China. Cancer incidence and mortality rates stratified by sex and region were analyzed. The crude rate, age-standardized rate, age-specific and region-specific rate, and cumulative rate were calculated. The proportions of 10 common cancers in different groups and the incidence and mortality rates of the top five cancers in different age groups were also calculated. The Chinese national census of 2000 and the world Segi population was used for calculating the age-standardized incidence and mortality rates. Results:. The 14 cancer registries covered a population of 14,250,844 individuals, accounting for 29.13% of the population of Zhejiang Province. The total reported cancer cases and deaths were 55,835 and 27,013, respectively. The proportion of morphological verification (MV%) was 78.95% of the population, and percentage of incident cases identified through death certificates only (DCO%) was 1.23% with a mortality-to-incidence ratio (M/I ratio) of 0.48. The crude incidence rate in Zhejiang cancer registration areas was 391.80/105; the age-standardized incidence rate of the Chinese standard population (ASIRC) and the age-standardized incidence rate of the world standard population (ASIRW) were 229.76/105 and 220.96/105, respectively. The incidence rate in men was higher than that in women. The incidence rate increased rapidly after 45 years of age and peaked in individuals aged 80 to 84 years. The top 10 incidence rates of cancers were lung cancer, female breast cancer, thyroid cancer, colorectal cancer, stomach cancer, liver cancer, prostate cancer, cervical cancer, esophageal cancer, and pancreatic cancer (from highest to lowest). The crude mortality rate in Zhejiang cancer registration areas was 189.55/105; the age-standardized mortality rate of the Chinese standard population (ASMRC) and the age-standardized mortality rate of the world standard population (ASMRW) were 94.46/105 and 93.42/105, respectively. The mortality rate in men was higher than that in women, and the male population in rural areas was higher than that in urban areas. The cancer mortality rate increased rapidly after 50 years of age and peaked in individuals aged 85+ years. The top 10 mortality rates of cancers were lung cancer, liver cancer, stomach cancer, colorectal cancer, pancreatic cancer, esophageal cancer, female breast cancer, prostate cancer, lymphoma, and leukemia (from highest to lowest). Conclusions:. Lung cancer, female breast cancer, thyroid cancer, colorectal cancer, prostate cancer, liver cancer, and stomach cancer were the most common cancers in Zhejiang Province. Effective prevention and control measures should be established after considering the different characteristics of cancers in urban and rural areas.

Objectives Over the past decade, the incidence and global burden of coronary heart disease (CHD) have increased in the young population. We aimed to identify patient characteristics and risk factors for premature CHD, including single-vessel disease (SVD) and multivessel disease (MVD).Design Retrospective, cross-sectional study.Setting Demographic and clinical data of patients with CHD were collected from the patient medical records of a tertiary hospital in Tianjin, China, between 2014 and 2017.Participants A total of 2846 patients were enrolled in the study.Primary and secondary outcome measures Premature CHD, which is the primary outcome, was defined as men

Abstract. Treatment-emergent central sleep apnea (TECSA) is a specific form of sleep-disordered breathing, characterized by the emergence or persistence of central apneas during treatment for obstructive sleep apnea. The purpose of this review was to summarize the definition, epidemiology, potential mechanisms, clinical characteristics, and treatment of TECSA. We searched for relevant articles up to January 31, 2020, in the PubMed database. The prevalence of TECSA varied widely in different studies. The potential mechanisms leading to TECSA included ventilatory control instability, low arousal threshold, activation of lung stretch receptors, and prolonged circulation time. TECSA may be a self-limited disorder in some patients and could be resolved spontaneously over time with ongoing treatment of continuous positive airway pressure (CPAP). However, central apneas persist even with the regular CPAP therapy in some patients, and new treatment approaches such as adaptive servo-ventilation may be necessary. We concluded that several questions regarding TECSA remain, despite the findings of many studies, and it is necessary to carry out large surveys with basic scientific design and clinical trials for TECSA to clarify these irregularities. Further, it will be vital to evaluate the baseline demographic and polysomnographic data of TECSA patients more carefully and comprehensively.

Introduction Nucleotide-binding and oligomerization domain like receptors protein 3 (NLRP3) inflammasome-mediated interleukin (IL)-1β secretion plays an important role in the progression of Alzheimer’s disease (AD). Curcumin has been shown to improve cognitive impairment and learning ability of AD mice by reducing IL-1β secretion. However, its exact mechanism of action remains unclear. In the present study, we explored the relationship between the neuroprotective effect of curcumin and activation of the NLRP3 inflammasome pathway. Methods BV2 cells were primed with 500 ng/mL lipopolysaccharide (LPS) for 4 h and subsequently treated with 50 μM Aβ 25-35 for 24 h or pretreated with 2.5–10 μM curcumin for 4 h and exposed to 50 μM Aβ 25-35 for 24 h. The effects of curcumin and Aβ 25-35 were assessed by the CCK8 assay. ELISA was used for the detection of IL-1β, IL-6, and tumor necrosis factor (TNF)-α levels in the supernatant of the cell culture medium. The viability of SH-SY5Y cells, which were incubated with conditioned medium (CM) was assessed using the CCK8 assay. The percentage of apoptotic SH-SY5Y cells incubated with CM was assessed using Annexin V-FITC/PI staining flow cytometry analysis. The expression levels of NLRP3, caspase-1 and IL-1β were observed by western blot and immunofluorescence staining analyses; the mRNA levels of nlrp3, caspase-1 and IL-1β were analyzed using qRT-PCR. Results Low (2.5 μM), medium (5 μM), and high (10 μM) concentrations of curcumin and 50 μM Aβ 25-35 were used to perform the experiments in the present study. Curcumin attenuated the IL-1β, IL-6, and TNF-α release and increased SH-SY5Y cell activity, while decreasing the apoptotic percentage of SH-SY5Y cells using Aβ 25-35 for cell stimulation ( p < 0.05). Furthermore, curcumin inhibited the expression of NLRP3, caspase-1 and IL-1β and nlrp3 in BV-2 cells ( p < 0.05), However, curcumin did not affect the expression levels of caspase-1 and IL-1β ( p > 0.05) Conclusion Overall, the data indicated that curcumin is a promising neuroprotective agent for suppressing neuroinflammation by inhibiting the NLRP3 inflammasome pathway.

Background. Hyponatremia is a common complication of liver cirrhosis and aggravates patients’ outcomes. It may be corrected by human albumin (HA) infusion. Herein, we have conducted a systematic review and meta-analysis to evaluate the efficacy of intravenous HA administration for the prevention and treatment of hyponatremia in liver cirrhosis. Methods. Literature was searched in the PubMed, EMBASE, and Cochrane Library databases. If possible, a meta-analysis would be conducted. Incidence of hyponatremia, rate of resolution of hyponatremia, and serum sodium level were compared between cirrhotic patients who received and did not receive HA infusion. Odds ratios (ORs) or mean differences (MDs) with 95% confidence intervals (CIs) were calculated. The quality of evidence was assessed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Results. Initially, 3231 papers were identified. Among them, 30 studies, including 25 randomized controlled trials (RCTs) and 5 cohort studies, were eligible. Among cirrhotic patients without hyponatremia, the HA infusion group had significantly lower incidence of hyponatremia (OR = 0.55, 95%CI = 0.38–0.80, p = 0.001) and higher serum sodium level (MD = 0.95, 95%CI = 0.47–1.43, p = 0.0001) as compared to the control group. Among cirrhotic patients with hyponatremia, the HA infusion group had a significantly higher rate of resolution of hyponatremia (OR = 1.50, 95%CI = 1.17–1.92, p = 0.001) as compared to the control group. Generally, the quality of available evidence is low. Conclusions. Based on the current evidence, HA may be considered for preventing the development of hyponatremia in liver cirrhosis, especially in those undergoing LVP, and treating hyponatremia. Well-designed studies are required to clarify the effects of HA infusion on hyponatremia in liver cirrhosis.

Background: There is a high incidence of leprosy among house-contacts compared with the general population. We aimed to establish a predictive model using these genetic factors along with epidemiological factors to predict leprosy risk of leprosy household contacts (HHCs). Methods: Weighted genetic risk score (wGRS) encompassing genome wide association studies (GWAS) variants and five non-genetic factors were examined in a case–control design associated with leprosy risk including 589 cases and 647 controls from leprosy HHCs. We constructed a risk prediction nomogram and evaluated its performance by concordance index (C-index) and calibration curve. The results were validated using bootstrap resampling with 1000 resamples and a prospective design including 1100 HHCs of leprosy patients. Finding: The C-index for the risk model was 0·792 (95% confidence interval [CI] 0·768-0·817), and was confirmed to be 0·780 through bootstrapping validation. The calibration curve for the probability of leprosy showed good agreement between the prediction of the nomogram and actual observation. HHCs were then divided into the low-risk group (nomogram score ≤ 81) and the high-risk group (nomogram score > 81). In prospective analysis, 12 of 1100 participants had leprosy during 63 months’ follow-up. We generated the nomogram for leprosy in the validation cohort (C-index 0·773 [95%CI 0·658-0·888], sensitivity75·0%, specificity 66·8%). Interpretation The nomogram achieved an effective prediction of leprosy in HHCs. Using the model, the risk of an individual contact developing leprosy can be determined, which can lead to a rational preventive choice for tracing higher-risk leprosy contacts. Funding: The ministry of health of China, ministry of science and technology of China, Chinese academy of medical sciences, Jiangsu provincial department of science and technology, Nanjing municipal science and technology bureau.

β cell dedifferentiation is a key mechanism for β cell dysfunction in type 2 diabetes mellitus (T2DM). Although it has been indicated in previous studies that β cell dedifferentiation could be induced by inflammation, the cytohistologic analyses of inflammation-induced β cell dedifferentiation in human islets is lacking. The present study aims to cytohistologically characterize the β cell dedifferentiation of human islets treated by proinflammatory cytokines Interleukin-1β/Tuman necrosis factor-α/Interferon-γ (IL-1β/TNF-α/IFN-γ), which is a frequently-used method to mimic the islet inflammation in previous studies. The loss of cytosolic FOXO1 expression, the loss of nucleic NKX6.1 expression, and the gain of ALDH1A3 expression in β cells are proclaimed as marking events for β cell dedifferentiation. Taking advantages of islets from organ donors and the immunofluorescence staining methods, the present study visualized the β cell dedifferentiation events marked by different markers, and quantified the frequency of each event as well. We successfully captured and described the characteristics of the differentiating/differentiated β cells. We found that dedifferentiated β cells were increased in the cytokines treated islets, evidenced by the increase of β cells with FOXO1 translocated to the nucleus (INS + FOXO nuc ), β cells with NKX6.1 exported from the nucleus (INS + NKX6.1 cyt ), and β cells loss of NKX6.1 expression (INS + NKX6.1 - ), and β cells with dual expression of insulin and progenitor marker ALDH1A3. Consistently, we found that proinflammatory cytokines IL-1β/TNF-α/IFN-γ treatment reduced the mRNA expression of key β cell markers, but elevated the expression of progenitor marker genes. This study gives the most direct evidence for inflammation-induced β cell dedifferentiation in human islets, and supports the concept that anti-inflammation treatments may facilitate alleviating the β cell dedifferentiation in human T2DM islets.

Background: We have revealed that neuropilin-1 (NRP-1) promoted hepatic stellate cell activation and liver fibrosis through its profibrogenic signalling pathways. However, the role of NRP-1 in angiogenesis in hepatic sinusoidal endothelial cells (HSECs) during liver cirrhosis remains unclear. Methods: The correlation between NRP-1 expression and angiogenesis was evaluated in both human and murine cirrhotic liver tissues by immunohistochemical staining, quantitative real-time PCR, and western blotting. In addition, the role and mechanism of NRP-1 in regulating VEGFR2-dependent angiogenesis was identified in endothelial cells (ECs) in vitro. Moreover, liver histocultures were used to test the therapeutic effect of NRP-1 blocking in liver fibrosis. Findings: Higher expression of NRP-1 in HSECs was detected, which was positively correlated with angiogenesis in liver cirrhosis. In vitro, NRP-1 knockdown suppressed the expression and activation of VEGFR2, accompanied by reduced ability of the vascular tube formation and the migration of ECs. Conversely, NRP-1 overexpression upregulated VEGFR2, promoted tube formation, and the migration of ECs. Mechanistically, NRP-1 modulated the expression of VEGFR2 by regulating FAK and its kinase activity. Furthermore, NRP-1 promoted VEGFR2-dependent angiogenesis via the PI3K/Akt pathway in HSECs. Blocking NRP-1 function reduced intrahepatic angiogenesis and fibrosis-associated factors in the in vitro liver histocultures. Interpretation: NRP-1 promotes angiogenesis by upregulating the expression and activation of VEGFR2 through the PI3K/Akt signalling pathway in liver cirrhosis. This study highlights the possibility of therapeutically targeting NRP-1 for the treatment of cirrhosis. Fund: National Natural Science Foundation of China (No. 81570551; 81770607; 81600469; 81401868), Key Research project of Shandong Province (No. 2016GSF201008; 2017GSF218053), Natural Science Foundation of Shandong Province (No. ZR2017MH102), National Science and Technology Major Project of China (No. 2018ZX10302206-001-006). Keywords: Neuropilin-1, Vascular growth factor receptor 2, Hepatic sinusoidal endothelial cells, Intrahepatic angiogenesis, Cirrhosis

In recent years, high utility itemsets (HUIs) mining has been an active research topic in data mining. In this study, we propose two efficient pattern-growth based HUI mining algorithms, called High Utility Itemset based on Length and Tail-Node tree (HUIL-TN) and High Utility Itemset based on Tail-Node tree (HUI-TN). These two algorithms avoid the time-consuming candidate generation stage and the need of scanning the original dataset multiple times for exact utility values. A novel tree structure, named tail-node tree (TN-tree) is proposed as a key element of our algorithms to maintain complete utililty-information of existing itemsets of a dataset. The performance of HUIL-TN and HUI-TN was evaluated against state-of-the-art reference methods on various datasets. Experimental results showed that our algorithms exceed or close to the best performance on all datasets in terms of running time, while other algorithms can only excel in certain types of dataset. Scalability tests were also performed and our algorithms obtained the flattest curves among all competitors.

In water scenes, where hazy images are subject to multiple scattering and where ideal data sets are difficult to collect, many dehazing methods are not as effective as they could be. Therefore, an unsupervised water scene dehazing network using atmospheric multiple scattering model is proposed. Unlike previous image dehazing methods, our method uses the unsupervised neural network and the atmospheric multiple scattering model and solves the problem of difficult acquisition of ideal datasets and the effect of multiple scattering on the image. In our method, in order to embed the atmospheric multiple scattering model into the unsupervised dehazing network, the unsupervised dehazing network uses four branches to estimate the scene radiation layer, transmission map layer, blur kernel layer and atmospheric light layer, the hazy image is then synthesized from the four output layers, minimizing the input hazy image and the output hazy image, where the output scene radiation layer is the final dehazing image. In addition, we constructed unsupervised loss functions which applicable to image dehazing by prior knowledge, i.e., color attenuation energy loss and dark channel loss. The method has a wide range of applications, with haze being thick and variable in marine, river and lake scenes, the method can be used to assist ship vision for target detection or forward road recognition in hazy conditions. Through extensive experiments on synthetic and real-world images, the proposed method is able to recover the details, structure and texture of the water image better than five advanced dehazing methods.

During the process of human islet isolation a cascade of stressful events are triggered and negatively influence islet yield, viability, and function, including the production of proinflammatory cytokines and activation of apoptosis. Carbon monoxide-releasing molecule 2 (CORM-2) is a donor of carbon monoxide (CO) and can release CO spontaneously. Accumulating studies suggest that CORM-2 exerts cytoprotective and anti-inflammatory properties. However, the effect of CORM-2 on islet isolation is still unclear. In this study, we found that CORM-2 pretreatment significantly decreased the expression of critical inflammatory genes, including tissue factor , intercellular adhesion molecule-1 , chemokine ( C-C motif ) ligand 2 , C-X-C motif chemokine 10 , Toll-like receptor 4 , interleukin-1β , interleukin-6 , and tumor necrosis factor-α ( TNF-α ). The isolated islets of the CORM-2 pretreatment group showed reduced apoptotic rate, improved viability, and higher glucose-stimulated insulin secretion, and functional gene expression in comparison to control group. Importantly, CORM-2 pretreatment prevented the impairment caused by TNF-α, evidenced by the improved glucose-stimulated index and transplantation outcomes. The present study demonstrated the anti-inflammatory property of CORM-2 during human islet isolation, and we suggest that CORM-2 pretreatment is an appealing treatment to mitigate inflammation-mediated islet dysfunction during isolation and culture ex vivo and to preserve long-term islet survival and function.

BACKGROUND:The expression of the L-type amino acid transporter 1 (LAT1) plays a significant role in tumor progression. However, it remains unclear whether high LAT1 expression correlates with poor prognosis of solid tumor patients. Here, we conducted a meta-analysis to assess the potential of LAT1 in predicting the prognosis of tumor patients. METHODS AND FINDINGS:A total of 4,579 cases were analyzed from 35 qualified studies. In patients with solid tumors, elevated expression of LAT1 is associated with poor prognosis (overall survival [OS]: pooled hazard ratio (HR) = 1.848, 95% confidence interval (CI) = 1.620-2.108, P < 0.001; disease free survival [DFS]: pooled HR = 1.923, 95% CI = 1.585-2.333, P < 0.001; progression free survival [PFS]: pooled HR = 1.345, 95% CI = 1.133-1.597, P = 0.001). Furthermore, in subgroup analysis, we found an association between high LAT1 expression and poor OS in non-small cell lung cancer (HR = 1.554, 95% CI = 1.345-1.794, P < 0.001), pancreatic cancer (HR = 2.052, 95% CI = 1.613-2.724, P < 0.001) and biliary tract cancer (HR = 2.253, 95% CI = 1.562-3.227, P < 0.001). CONCLUSION:The results of this meta-analysis indicate the reliability and potential of using LAT1 expression as a predictive biomarker in solid cancers prior to treatment. However, further studies with larger sample sizes would be beneficial for fully evaluating the predictive value of LAT1 expression for clinical applications.

Background: A physiological hallmark of patients with type 2 diabetes mellitus (T2DM) is β cell dysfunction. Despite adequate treatment, it is an irreversible process that follows disease progression. Therefore, the development of novel therapies that restore β cell function is of utmost importance. Methods: This study aims to unveil the mechanistic action of mesenchymal stem cells (MSCs) by investigating its impact on isolated human T2DM islets ex vivo and in vivo. Findings: We propose that MSCs can attenuate β cell dysfunction by reversing β cell dedifferentiation in an IL-1Ra-mediated manner. In response to the elevated expression of proinflammatory cytokines in human T2DM islet cells, we observed that MSCs was activated to secret IL-1R antagonist (IL-1Ra) which acted on the inflammed islets and reversed β cell dedifferentiation, suggesting a crosstalk between MSCs and human T2DM islets. The co-transplantation of MSCs with human T2DM islets in diabetic SCID mice and intravenous infusion of MSCs in db/db mice revealed the reversal of β cell dedifferentiation and improved glycaemic control in the latter. Interpretation: This evidence highlights the potential of MSCs in future cell-based therapies regarding the amelioration of β cell dysfunction. Keywords: Mesenchymal stem cells, Type 2 diabetes mellitus, β cell dysfunction, Inflammation, β cell dedifferentiation

Background: Shensong Yangxin Capsule (SSYX), traditional Chinese medicine, has been used to treat arrhythmias, angina, cardiac remodeling, cardiac fibrosis, and so on, but its effect on cardiac energy metabolism is still not clear. The objective of this study was to investigate the effects of SSYX on myocardium energy metabolism in angiotensin (Ang) II-induced cardiac hypertrophy. Methods: We used 2 μl (10−6 mol/L) AngII to treat neonatal rat cardiomyocytes (NRCMs) for 48 h. Myocardial α-actinin staining showed that the myocardial cell volume increased. Expression of the cardiac hypertrophic marker-brain natriuretic peptide (BNP) messenger RNA (mRNA) also increased by real-time polymerase chain reaction (PCR). Therefore, it can be assumed that the model of hypertrophic cardiomyocytes was successfully constructed. Then, NRCMs were treated with 1 μl of different concentrations of SSYX (0.25, 0.5, and 1.0 μg/ml) for another 24 h. To explore the time-depend effect of SSYX on energy metabolism, 0.5 μg/ml SSYX was added into cells for 0, 6, 12, 24, and 48 h. Mitochondria was assessed by MitoTracker staining and confocal microscopy. mRNA and protein expression of mitochondrial biogenesis-related genes – Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), energy balance key factor – adenosine monophosphate-activated protein kinase (AMPK), fatty acids oxidation factor – carnitine palmitoyltransferase-1 (CPT-1), and glucose oxidation factor – glucose transporter- 4 (GLUT-4) were measured by PCR and Western blotting analysis. Results: With the increase in the concentration of SSYX (from 0.25 to 1.0 μg/ml), an increased mitochondrial density in AngII-induced cardiomyocytes was found compared to that of those treated with AngII only (0.25 μg/ml, 18.3300 ± 0.8895 vs. 24.4900 ± 0.9041, t = 10.240, P < 0.0001; 0.5 μg/ml, 18.3300 ± 0.8895 vs. 25.9800 ± 0.8187, t = 12.710, P < 0.0001; and 1.0 μg/ml, 18.3300 ± 0.8895 vs. 24.2900 ± 1.3120, t = 9.902, P < 0.0001; n = 5 per dosage group). SSYX also increased the mRNA and protein expression of PGC-1α (0.25 μg/ml, 0.8892 ± 0.0848 vs. 1.0970 ± 0.0994, t = 4.319, P = 0.0013; 0.5 μg/ml, 0.8892 ± 0.0848 vs. 1.2330 ± 0.0564, t = 7.150, P < 0.0001; and 1.0 μg/ml, 0.8892 ± 0.0848 vs. 1.1640 ± 0.0755, t = 5.720, P < 0.0001; n = 5 per dosage group), AMPK (0.25 μg/ml, 0.8872 ± 0.0779 vs. 1.1500 ± 0.0507, t = 7.239, P < 0.0001; 0.5 μg/ml, 0.8872 ± 0.0779 vs. 1.2280 ± 0.0623, t = 9.379, P < 0.0001; and 1.0 μg/ml, 0.8872 ± 0.0779 vs. 1.3020 ± 0.0450, t = 11.400, P < 0.0001; n = 5 per dosage group), CPT-1 (1.0 μg/ml, 0.7348 ± 0.0594 vs. 0.9880 ± 0.0851, t = 4.994, P = 0.0007, n = 5), and GLUT-4 (0.5 μg/ml, 1.5640 ± 0.0599 vs. 1.7720 ± 0.0660, t = 3.783, P = 0.0117; 1.0 μg/ml, 1.5640 ± 0.0599 vs. 2.0490 ± 0.1280, t = 8.808, P < 0.0001; n = 5 per dosage group). The effect became more obvious with the increasing concentration of SSYX. When 0.5 μg/ml SSYX was added into cells for 0, 6, 12, 24, and 48 h, the expression of AMPK (6 h, 14.6100 ± 0.6205 vs. 16.5200 ± 0.7450, t = 3.456, P = 0.0250; 12 h, 14.6100 ± 0.6205 vs. 18.3200 ± 0.9965, t = 6.720, P < 0.0001; 24 h, 14.6100 ± 0.6205 vs. 21.8800 ± 0.8208, t = 13.160, P < 0.0001; and 48 h, 14.6100 ± 0.6205 vs. 23.7400 ± 1.0970, t = 16.530, P < 0.0001; n = 5 per dosage group), PGC-1α (12 h, 11.4700 ± 0.7252 vs. 16.9000 ± 1.0150, t = 7.910, P < 0.0001; 24 h, 11.4700 ± 0.7252 vs. 20.8800 ± 1.2340, t = 13.710, P < 0.0001; and 48 h, 11.4700 ± 0.7252 vs. 22.0300 ± 1.4180, t = 15.390; n = 5 per dosage group), CPT-1 (24 h, 15.1600 ± 1.0960 vs. 18.5800 ± 0.9049, t = 6.048, P < 0.0001, n = 5), and GLUT-4 (6 h, 10.2100 ± 0.9485 vs. 12.9700 ± 0.8221, t = 4.763, P = 0.0012; 12 h, 10.2100 ± 0.9485 vs. 16.9100 ± 0.8481, t = 11.590, P < 0.0001; 24 h, 10.2100 ± 0.9485 vs. 19.0900 ± 0.9797, t = 15.360, P < 0.0001; and 48 h, 10.2100 ± 0.9485 vs. 14.1900 ± 0.9611, t = 6.877, P < 0.0001; n = 5 per dosage group) mRNA and protein increased gradually with the prolongation of drug action time. Conclusions: SSYX could increase myocardial energy metabolism in AngII-induced cardiac hypertrophy. Therefore, SSYX might be considered to be an alternative therapeutic remedy for myocardial hypertrophy.

Bacillus sp. H16v8 and Bacillus sp. HGD9229 were identified as Aflatoxin B1 (AFB1) degrader in nutrient broth after a 12 h incubation at 37 °C. The degradation efficiency of the two-strain supernatant on 100 μg/L AFB1 was higher than the bacterial cells and cell lysate. Moreover, degradations of AFB1 were strongly affected by the metal ions in which Cu2+ stimulated the degradation and Zn2+ inhibited the degradation. The extracellular detoxifying enzymes produced by co-cultivation of two strains were isolated and purified by ultrafiltration. The molecular weight range of the detoxifying enzymes was 20–25 kDa by SDS-PAGE. The co-culture of two strains improved the total cell growth with the enhancement of the total protein content and detoxifying enzyme production. The degradation efficiency of the supernatant from mixed cultures increased by 87.7% and 55.3% compared to Bacillus sp. H16v8 and HGD9229, individually. Moreover, after the degradation of AFB1, the four products of the lower toxicity were identified by LC-Triple TOF-MS with the two proposed hypothetical degradation pathways.

Abstract 3-Phosphoinositide-dependent protein kinase 1 (PDK1) is a pivotal regulator in the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway that have been shown to play key roles in the functional development of B and T cells via activation of AGC protein kinases during hematopoiesis. However, the role of PDK1 in HSCs has not been fully defined. Here we specifically deleted the PDK1 gene in the hematopoietic system and found that PDK1-deficient HSCs exhibited impaired function and defective lineage commitment abilities. Lack of PDK1 caused HSCs to be less quiescent and to produce a higher number of phenotypic HSCs and fewer progenitors. PDK1-deficient HSCs were also unable to reconstitute the hematopoietic system. Notably, HSC function was more dependent on PDK1 than on mTORC2, which indicates that PDK1 plays a dominant role in the Akt-mediated regulation of HSC function. PDK1-deficient HSCs also exhibited reduced ROS levels, and treatment of PDK1-deficient HSCs with L-butathioninesulfoximine in vitro elevated the low ROS level and promoted colony formation. Therefore, PDK1 appears to contribute to HSC function partially via regulating ROS levels.

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