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Background: With the advance in single-cell RNA sequencing (scRNA-seq) technology, deriving inherent biological system information from expression profiles at a single-cell resolution has become possible. It has been known that network modeling by estimating the associations between genes could better reveal dynamic changes in biological systems. However, accurately constructing a single-cell network (SCN) to capture the network architecture of each cell and further explore cell-to-cell heterogeneity remains challenging., Results: We introduce SINUM, a method for constructing the SIngle-cell Network Using Mutual information, which estimates mutual information between any two genes from scRNA-seq data to determine whether they are dependent or independent in a specific cell. Experiments on various scRNA-seq datasets with different cell numbers based on eight performance indexes (e.g., adjusted rand index and F-measure index) validated the accuracy and robustness of SINUM in cell type identification, superior to the state-of-the-art SCN inference method. Additionally, the SINUM SCNs exhibit high overlap with the human interactome and possess the scale-free property., Conclusions: SINUM presents a view of biological systems at the network level to detect cell-type marker genes/gene pairs and investigate time-dependent changes in gene associations during embryo development. Codes for SINUM are freely available at https://github.com/SysMednet/SINUM ., (© 2024. The Author(s).)

Plastic packaging waste, such as polyethylene terephthalate (PET) has increased significantly in recent decades, arousing a considerable and serious public concern regarding the environment, economy, and policy. Plastic recycling is a useful tool to mitigate this issue. Here, a feasible study was performed to investigate the potential of a novel method for identifying virgin and recycled PET. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was combined with various chemometrics, as a simple and reliable method that achieved a high discrimination rate for 105 batches of virgin PET (v-PET) and recycled PET (r-PET) based on 202 non-volatile organic compounds (NVOCs). Making use of orthogonal partial least-squares discrimination analysis (OPLS-DA) together with non-parametric tests, 26 marker compounds (i.e. 12 intentionally added substances (IAS) and 14 non-intentionally added substances (NIAS) as well as 31 marker compounds (i.e. 11 IAS and 20 NIAS) obtained from positive and combination of positive and negative ionization modes of UPLC-Q-TOF-MS, respectively, were successfully identified. Moreover, 100% accuracy was obtained using a decision tree (DT). Cross-discrimination based on misclassified samples using various chemometrics allowed the prediction accuracy to be improved and to identify a large sample set, thus greatly enhancing the application scope of this method. The possible origins of these detected compounds can be the plastic itself, as well as contamination from food, medicine, pesticides, industry-related substances, and degradation and polymerization products. As many of these compounds are toxic, especially those pesticide related, this indicates an urgent requirement for closed loop recycling. Overall, this analytical method provides a quick, accurate, and robust way to distinguish virgin from recycled PET and thus addresses the issue of potential virgin PET adulteration thereby detecting fraud in the area of PET recycling.

Recently, extracting inherent biological system information (e.g. cellular networks) from genome-wide expression profiles for developing personalized diagnostic and therapeutic strategies has become increasingly important. However, accurately constructing single-sample networks (SINs) to capture individual characteristics and heterogeneity in disease remains challenging. Here, we propose a sample-specific-weighted correlation network (SWEET) method to model SINs by integrating the genome-wide sample-to-sample correlation (i.e. sample weights) with the differential network between perturbed and aggregate networks. For a group of samples, the genome-wide sample weights can be assessed without prior knowledge of intrinsic subpopulations to address the network edge number bias caused by sample size differences. Compared with the state-of-the-art SIN inference methods, the SWEET SINs in 16 cancers more likely fit the scale-free property, display higher overlap with the human interactomes and perform better in identifying three types of cancer-related genes. Moreover, integrating SWEET SINs with a network proximity measure facilitates characterizing individual features and therapy in diseases, such as somatic mutation, mut-driver and essential genes. Biological experiments further validated two candidate repurposable drugs, albendazole for head and neck squamous cell carcinoma (HNSCC) and lung adenocarcinoma (LUAD) and encorafenib for HNSCC. By applying SWEET, we also identified two possible LUAD subtypes that exhibit distinct clinical features and molecular mechanisms. Overall, the SWEET method complements current SIN inference and analysis methods and presents a view of biological systems at the network level to offer numerous clues for further investigation and clinical translation in network medicine and precision medicine., (© The Author(s) 2023. Published by Oxford University Press.)

Objective: This study was undertaken to evaluate functional and safety outcomes for endovascular thrombectomy (EVT) versus medical management (MM) in patients with large vessel occlusion (LVO) and mild neurological deficits, stratified by perfusion imaging mismatch., Methods: The pooled cohort consisted of patients with National Institutes of Health Stroke Scale (NIHSS) < 6 and internal carotid artery (ICA), M1, or M2 occlusions from the Extending the Time for Thrombolysis in Emergecy Neurological Deficits - Intra-Arterial (EXTEND-IA) Trial,  Tenecteplase vs Alteplase before Endovascular Thrombectomy in Ischemic Stroke (EXTEND-IA TNK) trials Part I/II and prospective data from 15 EVT centers from October 2010 to April 2020. RAPID software estimated ischemic core and mismatch. Patients receiving primary EVT (EVT pri ) were compared to those who received primary MM (MM pri ), including those who deteriorated and received rescue EVT, in overall and propensity score (PS)-matched cohorts. Patients were stratified by target mismatch (mismatch ratio ≥ 1.8 and mismatch volume ≥ 15ml). Primary outcome was functional independence (90-day modified Rankin Scale = 0-2). Secondary outcomes included safety (symptomatic intracerebral hemorrhage [sICH], neurological worsening, and mortality)., Results: Of 540 patients, 286 (53%) received EVT pri and demonstrated larger critically hypoperfused tissue (Tmax > 6 seconds) volumes (median [IQR]: 64 [26-96] ml vs MM pri : 40 [14-76] ml, p < 0.001) and higher presentation NIHSS (median [IQR]: 4 [2-5] vs MM pri : 3 [2-4], p < 0.001). Functional independence was similar (EVT pri : 77.4% vs MM pri : 75.6%, adjusted odds ratio [aOR] = 1.29, 95% confidence interval [CI] = 0.82-2.03, p = 0.27). EVT had worse safety regarding sICH (EVT pri : 16.3% vs MM pri : 1.3%, p < 0.001) and neurological worsening (EVT pri : 19.6% vs MM pri : 6.7%, p < 0.001). In 414 subjects (76.7%) with target mismatch, EVT was associated with improved functional independence (EVT pri : 77.4% vs MM pri : 72.7%, aOR = 1.68, 95% CI = 1.01-2.81, p = 0.048), whereas there was a trend toward less favorable outcomes with primary EVT (EVT pri : 77.4% vs MM pri : 83.3%, aOR = 0.39, 95% CI = 0.12-1.34, p = 0.13) without target mismatch (p interaction  = 0.06). Similar findings were observed in a propensity score-matched subpopulation., Interpretation: Overall, EVT was not associated with improved clinical outcomes in mild strokes due to LVO, and sICH was increased. However, in patients with target mismatch profile, EVT was associated with increased functional independence. Perfusion imaging may be helpful to select mild stroke patients for EVT. ANN NEUROL 2022;92:364-378., (© 2022 American Neurological Association.)

Vibrio alginolyticus is a Gram-negative bacillus that causes vibriosis to human and aquatic products, including fish, shrimp and shellfish. It poses a threat to public health and causes enormous economic losses to the aquaculture industry. However, research on genetic diversity and pathogenicity-related genetic elements based on whole genome is still lacking. In this study, sixty-eight strains of V. alginolyticus were collected from four provinces of China and the whole genome sequences were obtained. Combined with 113 publicly available genome sequences downloaded from NCBI, we inferred the population structure of V. alginolyticus by using fineSTRUCTURE software, and identified the virulence and antibiotic resistance factors using the VFDB, CARD and ResFinder database. The results indicated that V. alginolyticus included two main lineages, named Lineage 1 and Lineage 2. Both lineages distributed in America and Asia, but all the European genomes were classified into Lineage 1. A single cross-ocean transmission event was inferred from one of the 12 identified clonal groups in our dataset. V. alginolyticus genome contains a variety of virulence factors, such as tlh, OmpU, and IlpA, etc. The distribution of virulence factors revealed no lineage-specificity, but some of which revealed differences in their geographical distribution. A lower frequency of VP1611, vcrD, vopD, fleR/flrC and a higher frequency of IlpA were observed in genomes of Europe than other continents. In China, a lower frequency of fleR/flrC, and no IlpA were observed in genomes from Guangxi province. Among the identified antibiotic resistance genes, TxR and fos are significantly enriched in Lineage 2. In addition, TxR is more common in genomes from Asia, compared with the American and European genomes. But in China, the frequency of TxR in Sichuan genomes is much lower than in other provinces. We also found that large fragments of plasmids or ICEs that carried multiple drug resistance genes were present in five V. alginolyticus genomes (VA24, VA28, 2014V-1011, ZJ-T and Vb1833). Based on population genomics analysis, our study delineated the population structure, distribution of virulence and antibiotic resistance related factors of V. alginolyticus, which lays a foundation for future study of genetic characters and pathogenesis mechanism of this pathogen and will improve the works on monitoring, prevention and control of this pathogen.

Aims: This study aims to determine whether door-to-needle times (DNT) for reversal of anticoagulant-associated intracerebral haemorrhage (ICH) (1) have improved over time, (2) differ between warfarin and dabigatran and (3) are comparable to ischaemic stroke (IS) thrombolysis DNT, and (4) whether reversal is monitored., Methods: Retrospective review of all warfarin- and dabigatran-associated ICH presenting to Christchurch Hospital over a 15-year period. DNT data from 2013-2018 were compared between warfarin-related ICH (WRICH), dabigatran-related ICH (DRICH) and IS thrombolysis., Results: 172 WRICH were identified. Over time there were significant reductions in door-to-first-reversal-agent (r=-0.21, p=0.01), scan-to-first-reversal-agent (r=-0.27, p=0.001) and scan-to-prothrombin-complex-concentrate (PCC) (r=-0.33, p=0.001) times. In the 2013-2018 cohort, WRICH had significantly slower DNT, door-to-scan time and scan-to-needle time compared to DRICH and IS thrombolysis (all p<0.001). There was no statistical difference between DRICH and IS. Median DNT was 183 minutes for WRICH, 72 minutes for DRICH and 52 minutes for IS. Median time to repeat international normalised ratio was 231 minutes, and the median time to repeat thrombin clotting time was 825 minutes., Conclusion: Door-to-any-reversal-agent and scan-to-PCC times have improved over time, but they remain significantly longer than IS thrombolysis times. Monitoring of reversal is inadequate, particularly for WRICH receiving PCC., Competing Interests: Nil.

To clarify the rapid formation and evolutionary mechanisms of an extremely severe and persistent haze and fog (HF) episode that occurred in central-eastern China from Dec 20 to 25, 2015, a novel campaign was conducted and vertical profiles of wind, temperature, light extinction coefficient (LEC) and PM 2.5 concentration were used to analyze the rapid formation and evolutionary mechanisms of this HF episode. The substantial downward transportation of regional pollution from high layers and stagnant weather conditions favorable for the local pollution accumulation were the two main causes of the rapid increase in pollutant concentration. Southwest wind speeds of 4m/s between 300 and 600m and obvious downward flows were observed, whereas the southwest wind speeds were low below 300m, and strong temperature inversion with intensity of 4.5°C/100m expanded vertically to a height of 600m. Two peaks of PM 2.5 concentration were observed at 200 and 700m, corresponding to 235 and 215μg/m 3 , respectively. The frequent change in wind direction and wind speeds resulted in the fluctuation of PM 2.5 concentration. The turbulence within lower layers of the troposphere was enhanced by easterly and northerly winds which decreased the pollution level; however, the strength and stretching height of the winds were insufficient to fully clear the air of pollutants. The PM 2.5 concentration revealed 2-high concentration layers in the vertical direction. The maximum concentration layer was below 100m, while the second high-concentration layer was at 400m., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Diazotrophic (nitrogen-fixing) Gram-positive and endospore-formed Paenibacillus spp. have potential uses as a bacterial fertilizer in agriculture. The transcriptional analysis of nitrogen fixation in Paenibacillus is lacking, although regulation mechanisms of nitrogen fixation have been well studied in Gram-negative diazotrophs., Results: Here we report a global transcriptional profiling analysis of nitrogen fixation in Paenibacillus sp. WLY78 cultured under N2-fixing condition (without O2 and NH4(+)) and non-N2-fixing condition (air and 100 mM NH4(+)). The nif (nitrogen fixation) gene operon composed of 9 genes (nifBHDKENXhesAnifV) in this bacterium was significantly up-regulated in N2-fixing condition compared to non-N2-fixing condition, indicating that nif gene transcription is strictly controlled by NH4(+) and O2. qRT-PCR confirmed that these nif genes were differently expressed. Non-nif genes specifically required in nitrogen fixation, such as mod, feoAB and cys encoding transporters of Mo, Fe and S atoms, were coordinately transcribed with nif genes in N2-fixing condition. The transcript abundance of suf operon specific for synthesis of Fe-S cluster was up-regulated in N2-fixing condition, suggesting that Sul system, which takes place of nifS and nifU, plays important role in the synthesis of nitrogenase. We discover potential specific electron transporters which might provide electron from Fe protein to MoFe protein of nitrogenase. The glnR whose predicted protein might mediate nif transcription regulation by NH4(+) is significantly up-regulated in N2-fixing condition. The transcription levels of nitrogen metabolism and anaerobic respiration were also analyzed., Conclusions: The nif gene operon (nifBHDKENXhesAnifV) in Paenibacillus sp. WLY78 is significantly up-regulated in N2-fixing condition compared to non-N2-fixing condition. Non-nif genes specifically required in nitrogen fixation were also significantly up-regulated in N2-fixing condition. Fur and Fnr which are involved in anaerobic regulation and GlnR which might mediate nif gene transcription regulation by NH4(+) were significantly up-regulated in N2-fixing condition. This study provides valuable insights into nitrogen fixation process and regulation in Gram-positive firmicutes.

Introduction: This study aimed to evaluate the diagnostic value of Bub1 and Mad2 together in endometrial cancer., Materials and Methods: Sixty-three patients with endometrial cancer, including EECs and NEECs, were examined statistically. Bub1 and Mad2 in patient tissues were detected by indirect streptavidin-biotin-peroxidase complex method., Results: 39 cases (61.9 %) were in clinical stage I, 17 cases (27 %) in stage II, 5 (7.9 %) in stage III and 2 cases (3.2 %) in stage IV. Bub1 positive and Mad2 positive rate were identified in 18 and 54 patients. The lower positive of Bub1 and higher positive rate of Mad2 were related to clinical stage and histological grade of endometrial cancer (P = 0.009, 0.002, respectively), especially in NEECs. The expression of Bub1 was negatively correlated with Mad2 and Mtp53 (both P < 0.05). The expression of Mad2 with Mtp53 was positively correlated (P < 0.05). Statistically significant difference between Bub1/Mad2 expression and survival was discovered in endometrial cancer. Specificity and sensitivity of combination between Bub1 negative and Mad2 positive cases were higher than those alone in NEEC subtype. Bub1 and Mad2 are associated with histological differentiation, clinical stage and decreased postoperative survival in endometrial cancer., Conclusions: The combination analysis of Bub1 and Mad2 might be the valuable prognostic, even diagnostic clinicopathologic factor which can be applicable in routine examination.