Sodium oligomannate activates the enteroendocrine-vagal afferent pathways in APP/PS1 mice.

Enteroendocrine cells (EECs) and vagal afferent neurons constitute functional sensory units of the gut, which have been implicated in bottom-up modulation of brain functions. Sodium oligomannate (GV-971) has been shown to improve cognitive functions in murine models of Alzheimer's disease (AD) and recently approved for the treatment of AD patients in China. In this study, we explored whether activation of the EECs-vagal afferent pathways was involved in the therapeutic effects of GV-971. We found that an enteroendocrine cell line RIN-14B displayed spontaneous calcium oscillations due to TRPA1-mediated calcium entry; perfusion of GV-971 (50, 100 mg/L) concentration-dependently enhanced the calcium oscillations in EECs. In ex vivo murine jejunum preparation, intraluminal infusion of GV-971 (500 mg/L) significantly increased the spontaneous and distension-induced discharge rate of the vagal afferent nerves. In wild-type mice, administration of GV-971 (100 mg· kg-1 ·d-1, i.g. for 7 days) significantly elevated serum serotonin and CCK levels and increased jejunal afferent nerve activity. In 7-month-old APP/PS1 mice, administration of GV-971 for 12 weeks significantly increased jejunal afferent nerve activity and improved the cognitive deficits in behavioral tests. Sweet taste receptor inhibitor Lactisole (0.5 mM) and the TRPA1 channel blocker HC-030031 (10 µM) negated the effects of GV-971 on calcium oscillations in RIN-14B cells as well as on jejunal afferent nerve activity. In APP/PS1 mice, co-administration of Lactisole (30 mg ·kg-1 ·d-1, i.g. for 12 weeks) attenuated the effects of GV-971 on serum serotonin and CCK levels, vagal afferent firing, and cognitive behaviors. We conclude that GV-971 activates sweet taste receptors and TRPA1, either directly or indirectly, to enhance calcium entry in enteroendocrine cells, resulting in increased CCK and 5-HT release and consequent increase of vagal afferent activity. GV-971 might activate the EECs-vagal afferent pathways to modulate cognitive functions.

Genome-wide characterization of TCP family and their potential roles in abiotic stress resistance of oat (Avena sativa L.).

The TCP gene family members play multiple functions in plant growth and development and were named after the first three family members found in this family, TB1 (TEOSINTE BRANCHED 1), CYCLOIDEA (CYC), and Proliferating Cell Factor 1/2 (PCF1/2). Nitrogen (N) is a crucial element for forage yield; however, over-application of N fertilizer can increase agricultural production costs and environmental stress. Therefore, the discovery of low N tolerance genes is essential for the genetic improvement of superior oat germplasm and ecological protection. Oat (Avena sativa L.), is one of the world's staple grass forages, but no genome-wide analysis of TCP genes and their roles in low-nitrogen stress has been performed. This study identified the oat TCP gene family members using bioinformatics techniques. It analyzed their phylogeny, gene structure analysis, and expression patterns. The results showed that the AsTCP gene family includes 49 members, and most of the AsTCP-encoded proteins are neutral or acidic proteins; the phylogenetic tree classified the AsTCP gene family members into three subfamilies, and each subfamily has different conserved structural domains and functions. In addition, multiple cis-acting elements were detected in the promoter of the AsTCP genes, which were associated with abiotic stress, light response, and hormone response. The 49 AsTCP genes identified from oat were unevenly distributed on 18 oat chromosomes. The results of real-time quantitative polymerase chain reaction (qRT-PCR) showed that the AsTCP genes had different expression levels in various tissues under low nitrogen stress, which indicated that these genes (such as AsTCP01, AsTCP03, AsTCP22, and AsTCP38) played multiple roles in the growth and development of oat. In conclusion, this study analyzed the AsTCP gene family and their potential functions in low nitrogen stress at the genome-wide level, which lays a foundation for further analysis of the functions of AsTCP genes in oat and provides a theoretical basis for the exploration of excellent stress tolerance genes in oat. This study provides an essential basis for future in-depth studies of the TCP gene family in other oat genera and reveals new research ideas to improve gene utilization.

Associations of cognitive impairment and longitudinal change in cognitive function with the risk of fatal stroke in middle-aged to older Chinese.

It is unclear whether cognitive impairment and the longitudinal change in cognition are associated with the risk of fatal stroke in aging populations. Based on the Guangzhou Biobank Cohort Study data a sum of 26,064 participants at baseline and all deaths caused by stroke in a mean follow-up of 14.3 years (standard deviation = 3.2) were included, and the Cox proportional hazard regression was used in this prospective cohort study. Cognitive impairment was respectively associated with an increased risk of fatal strokes (the adjusted hazard ratio (aHR) = 1.38, 95% CI1.16-1.64, P < 0.001) and fatal ischaemic stroke (aHR = 1.39, 95% CI1.10-1.77, P = 0.007), compared to median cognition; the Delayed Word Recall Test (DWRT) score was associated with a decreasing trend for the risk of fatal strokes in a restricted cubic spline analysis; the longitudinal DWRT score decline was associated with the increased risks of fatal strokes (aHR = 1.42, 95% CI 1.11-1.82, P = 0.006) and fatal haemorrhagic stroke (aHR = 1.75, 95% CI 1.10-2.78, P = 0.02), compared to the longitudinal DWRT score rise. In summary, cognitive impairment and the longitudinal decline in DWRT scores were associated with the increased risk of fatal strokes; early screening of cognitive function should be conducive to predictive intervention in fatal stroke among relatively healthy middle-aged to older populations.

Benzoic acid inhibits intrinsic ion migration for efficient and stable perovskite solar cells.

An efficient perovskite solar cell (PSC) has the following characteristics: (1) large perovskite grain size; (2) small ion migration; (3) low defect density states. Here, benzoic acid was employed as an additive to a perovskite solution to improve the thin film quality. Surprisingly, 1.0%-BA can implement all of these features. Therefore, the power conversion efficiency (PCE) of the champion PSC is 18.05%, which is superior to that of the control device (15.42%). In addition, BA-doped PSC kept 86% of its primary PCE after 30 days (RH: 35%), but the control device only retained 75% under the same conditions. The improvement of its stability is because of the inhibition of the cation migration of perovskite by the addition of BA and the passivation of perovskite defects. The results can acquire a better understanding of the potential applications of small organic molecules in improving the PCE and stability of PSC devices.

Infarct-related artery only revascularization versus multi-vessel revascularization for patients with Killip I-IV acute myocardial infarction and multivessel disease.

BACKGROUND: The optimal revascularization strategy for non-culprit vessels is still up for debate nowadays, particularly when it comes to individuals with different Killip classes. Therefore, the aim of our study was to investigate whether multivessel revascularization, as compared with infarct-related artery (IRA) alone revascularization, improves long-term prognosis in patients who have experienced an acute myocardial infarction (AMI) and have multivessel coronary artery disease (CAD). METHODS: A retrospective analysis was conducted on clinical data from 646 patients who presented with AMI and multivessel CAD at Beijing Chaoyang hospital between November 2014 and November 2020. Based on various revascularization strategies, patients were categorised into two groups: IRA-only revascularization (n = 416) and multivessel revascularization (n = 230). The primary endpoint was cardiovascular death. RESULTS: In the following 60.6 months (60.6 ± 23.9), the primary endpoint occurred in 3% of the multivessel revascularization group versus 9.6% in the IRA-only revascularization group (HR 0.284, CI 0.120-0.669, p = 0.002). For the Killip I-II patients (n = 533), the primary endpoint occurred in 2.6% of the multivessel revascularization group versus 9.5% in the IRA-only revascularization group (HR 0.236, CI 0.083-0.667, p = 0.003). For Killip III-IV patients (n = 113), there was no significance differences in the primary endpoint. After using the inverse probability weighted method, the benefit of complete revascularization was consistently observed. CONCLUSIONS: Multivessel revascularization significantly reduced the incidence of cardiovascular death for patients presenting with AMI and multivessel CAD, particularly for Killip I-II patients. There were no significant differences in the primary outcome across the groups of patients with Killip III-IV.

A Self-Powered Biochemical Sensor for Intelligent Agriculture Enabled by Signal Enhanced Triboelectric Nanogenerator.

Precise agriculture based on intelligent agriculture plays a significant role in sustainable development. The agricultural Internet of Things (IoTs) is a crucial foundation for intelligent agriculture. However, the development of agricultural IoTs has led to exponential growth in various sensors, posing a major challenge in achieving long-term stable power supply for these distributed sensors. Introducing a self-powered active biochemical sensor can help, but current sensors have poor sensitivity and specificity making this application challenging. To overcome this limitation, a triboelectric nanogenerator (TENG)-based self-powered active urea sensor which demonstrates high sensitivity and specificity is developed. This device achieves signal enhancement by introducing a volume effect to enhance the utilization of charges through a novel dual-electrode structure, and improves the specificity of urea detection by utilizing an enzyme-catalyzed reaction. The device is successfully used to monitor the variation of urea concentration during crop growth with concentrations as low as 4 µm, without being significantly affected by common fertilizers such as potassium chloride or ammonium dihydrogen phosphate. This is the first self-powered active biochemical sensor capable of highly specific and highly sensitive fertilizer detection, pointing toward a new direction for developing self-powered active biochemical sensor systems within sustainable development-oriented agricultural IoTs.

Biomechanics of the lower limb in patients with mild knee osteoarthritis during the sit-to-stand task.

BACKGROUND: Knee osteoarthritis (KOA) is a prevalent and debilitating condition that markedly affects the sit-to-stand (STS) activity of patients, a prerequisite for daily activities. Biomechanical recognition of movements in patients with mild KOA is currently attracting attention. However, limited studies have been conducted solely on the observed differences in sagittal plane movement and muscle activation. AIM: This study aimed to identify three-dimensional biomechanical and muscle activation characteristics of the STS activity in patients with mild KOA. METHODS: A cross-sectional study was conducted to observe the differences between patients with mild KOA and a control group (CG). It was conducted to observe the differences in muscle activation, including root mean square (RMS%) and integrated electromyography (items), kinematic parameters like range of motion (ROM) and maximum angular velocity, as well as dynamic parameters such as joint moment and vertical ground reaction force (vGRF). RESULTS: Patients with mild KOA had a higher body mass index and longer task duration. In the sagittal plane, patients with KOA showed an increased ROM of the pelvic region, reduced ROM of the hip-knee-ankle joint, and diminished maximum angular velocity of the knee-ankle joint. Furthermore, patients with KOA displayed increased knee-ankle joint ROM in the coronal plane and decreased ankle joint ROM in the horizontal plane. Integrated vGRF was higher in both lower limbs, whereas the vGRF of the affected side was lower. Furthermore, patients showed a decreased peak adduction moment (PADM) and increased peak external rotation moment in the knee joint and smaller PADM and peak internal rotation moment in the ankle joint. The affected side exhibited decreased RMS% and iEMG values of the gluteus medius, vastus medialis, and vastus lateralis muscles, as well as a decreased RMS% of the rectus femoris muscle. Conversely, RMS% and iEMG values of the biceps femoris, lateral gastrocnemius, and medial gastrocnemius muscles were higher. CONCLUSION: The unbalanced activation characteristics of the anterior and posterior muscle groups, combined with changes in joint moment in the three-dimensional plane of the affected joint, may pose a potential risk of injury to the irritated articular cartilage.

Single-cell transcriptomics in MI identify Slc25a4 as a new modulator of mitochondrial malfunction and apoptosis-associated cardiomyocyte subcluster.

Myocardial infarction (MI) is the leading cause of premature death. The death of cardiomyocytes (CMs) and the dysfunction of the remaining viable CMs are the main pathological factors contributing to heart failure (HF) following MI. This study aims to determine the transcriptional profile of CMs and investigate the heterogeneity among CMs under hypoxic conditions. Single-cell atlases of the heart in both the sham and MI groups were developed using single-cell data (GSE214611) downloaded from Gene Expression Omnibus (GEO) database ( https://www.ncbi.nlm.nih.gov/geo/ ). The heterogeneity among CMs was explored through various analyses including enrichment, pseudo time, and intercellular communication analysis. The marker gene of C5 was identified using differential expression analysis (DEA). Real-time polymerase chain reaction (RT-PCR), bulk RNA-sequencing dataset analysis, western blotting, immunohistochemical and immunofluorescence staining, Mito-Tracker staining, TUNEL staining, and flow cytometry analysis were conducted to validate the impact of the marker gene on mitochondrial function and cell apoptosis of CMs under hypoxic conditions. We identified a cell subcluster named C5 that exhibited a close association with mitochondrial malfunction and cellular apoptosis characteristics, and identified Slc25a4 as a significant biomarker of C5. Furthermore, our findings indicated that the expression of Slc25a4 was increased in failing hearts, and the downregulation of Slc25a4 improved mitochondrial function and reduced cell apoptosis. Our study significantly identified a distinct subcluster of CMs that exhibited strong associations with ventricular remodeling following MI. Slc25a4 served as the hub gene for C5, highlighting its significant potential as a novel therapeutic target for MI.

Moniezia benedeni infection increases IgE+ cells in sheep (Ovis aries) small intestine.

The concentration of immunoglobulin (Ig) E is the lowest among serum Igs, but it can induces type I hypersensitivity and plays an important role in anti-parasitic infection. The present study aimed to explore the residence characteristics of IgE+ cells in the sheep small intestine and the impact of Moniezia benedeni infection on them. The recombinant plasmids pET-28a-IgE were constructed and induced and expressed in Escherichia coli. BL21 (DE3). The rabbit anti-sheep IgE polyclonal antibody was prepared using the obtained recombinant protein as antigen. Finally, the levels of IgE+ cells in the small intestine of healthy (Control group) and naturally M. benedeni-infected (Infected group) sheep were detected analyzed. The results showed that the rabbit anti-sheep IgE polyclonal antibody with good immunogenicity (titer = 1: 128000) could specifically bind to the heavy chain of natural sheep IgE. In the Control group, the IgE+ cells were mainly distributed in lamina propria of the small intestine, and the densities were significantly decreased from duodenum to ileum (P<0.05), with respective values of (4.28 cells / 104 µm2, 1.80 cells / 104 µm2, and 1.44 cells / 104 µm2 in duodenum, jejunum, and ileum. In the Infected group, IgE+ cells density were 6.26 cells / 104 µm2, 3.01 cells / 104 µm2, and 2.09 cells / 104 µm2 in duodenum, jejunum and ileum respectively, which were significantly higher in all segments compared to the Control group (P<0.05), increasing by 46.26%, 67.22% and 45.14%, respectively. In addition, compared with the Control group, the IgE protein levels were significantly increased in all intestinal segments of the Infected group (P<0.01), however, there was no significant differences among the different intestinal segments within the same group (P>0.05). The results demonstrated that M. benedeni infection could significantly increase the content of IgE and the distribution density of its secreting cells in sheep small intestine. The intestinal mucosal immune system of sheep presented obvious specificity against M. benedeni infection. This lays a good foundation for further exploring molecular mechanisms of the intestinal mucosal immune system monitoring and responding to M. benedeni infection.

Dental and skeletal maturation of Chinese male children with unilateral cleft lip and palate.

The aim of this study was to determine whether the relationship between dental age (DA), cervical stage (CS) and chronological age (CA) in Chinese male children with unilateral cleft lip and palate (UCLP) is similar to that of children without clefts. Panoramic and cephalometric radiographs of 105 male UCLP patients, aged from 8 to 16 years, were collected and compared to 210 age-matched healthy control males. The Demirjian and cervical vertebral maturation (CVM) methods were used to visually examine the radiographs and Spearman's correlation analysis was used to identify differences between the two groups with regards to CS, DA and CA. There was a significant positive correlation between DA and CA in both groups and the mean CA-DA difference was significantly higher in children with UCLP when compared to controls (0.319 vs. 0.003, p < 0.05). A significant delay in tooth development was detected in UCLP children from 10 to 12 years-of-age. Both the UCLP and control groups showed high correlations between CS and DA. Calcification stage D appeared only before CS3; however, from CS5 to 6, all teeth have almost completed their maturation phase. Chinese male UCLP patients are likely to experience delayed tooth development compared to healthy controls, especially during the fast-growing period. Evaluating the stages of tooth mineralization could represent a rapid method to assess growth potential.

Optimizing mycelial protein yield in Pleurotus djamor via ARTP mutagenesis and hybridization strategies.

With the world's population rapidly increasing, the demand for high-quality protein is on the rise. Edible fungi breeding technology stands as a crucial avenue to obtain strains with high yield, high-quality protein, and robust stress resistance. To address the protein supply gap, Atmospheric and Room Temperature Plasma (ARTP) mutagenesis, and spore hybridization techniques were employed to enhance Pleurotus djamor mycelium protein production. Beginning with the original strain Pleurotus djamor JD-1, ARTP was utilized to mutate spore suspension. The optimal treatment time for Pleurotus djamor spores, determined to achieve optimal mortality, was 240 s. Through primary and secondary screenings, 6 mutant strains out of 39 were selected, exhibiting improved protein yield and growth rates compared to the original strain. Among these mutagenic strains, 240S-4 showcased the highest performance, with a mycelial growth rate of 9.5±0.71 mm/d, a biomass of 21.45±0.54 g/L, a protein content of 28.75±0.92%, and a remarkable protein promotion rate of 128.03±7.29%. Additionally, employing spore hybridization and breeding, 7 single-nuclei strains were selected for pin-two hybridization, resulting in 21 hybrid strains. The biomass and protein content of 9 hybrid strains surpassed those of the original strains. One hybrid strain, H-5, exhibited remarkable mycelial protein production, boasting a mycelial growth rate of 26.5±0.7 mm/d, a biomass of 21.70±0.46 g/L, a protein content of 28.44±0.22%, and a protein promotion rate of 128.02±1.73%. Notably, both strains demonstrated about a 28% higher mycelial protein yield than the original strains, indicating comparable effectiveness between hybrid breeding and mutagenesis breeding. Finally, we analyzed the original and selected strains by molecular biological identification, which further proved the effectiveness of the breeding method. These findings present novel insights and serve as a reference for enhancing edible fungi breeding, offering promising avenues to meet the escalating protein demand.

Combined detection of serum IL-6 and CEA contributes to the diagnosis of lung adenocarcinoma in situ.

Background: Effective discrimination of lung adenocarcinoma (LUAD) in situ (AIS) from benign pulmonary nodules (BPN) is critical for the early diagnosis of AIS. Our pilot study in a small cohort of 90 serum samples has shown that serum interleukin 6 (IL-6) detection can distinguish AIS from BPN and health controls (HC). In this study, we intend to comprehensively define the diagnostic value of individual and combined detection of serum IL-6 related to the traditional tumor markers carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1) for AIS. Methods: The diagnostic performance of serum IL-6 along with CEA and CYFRA21-1 were evaluated in a large cohort of 300 serum samples by a chemiluminescence immunoassay and an electrochemiluminescence immunoassay. A training set comprised of 65 AIS, 65 BPN, and 65 HC samples was used to develop the predictive model for AIS. Data obtained from an independent validation set was applied to evaluate and validate the predictive model. Results: In the training set, the levels of serum IL-6 and CEA in the AIS group were significantly higher than those in the BPN/HC group (P < 0.05). There was no significant difference in serum CYFRA21-1 levels between the AIS group and the BPN/HC group (P> 0.05). Serum IL-6 and CEA levels for AIS patients showed an area under the curve (AUC) of 0.622 with 23.1% sensitivity at 90.7% specificity, and an AUC of 0.672 with 24.6% sensitivity at 97.6% specificity, respectively. The combination of serum IL-6 and CEA presented an AUC of 0.739, with 60.0% sensitivity at 95.4% specificity. The combination of serum IL-6 and CEA showed an AUC of 0.767 for AIS patients, with 57.1% sensitivity at 91.4% specificity in the validation set. Conclusions: IL-6 shows potential as a prospective serum biomarker for the diagnosis of AIS, and the combination of serum IL-6 with CEA may contribute to increased accuracy in AIS diagnosis. However, it is worth noting that further research is still necessary to validate and optimize the diagnostic efficacy of these biomarkers and to address potential sensitivity limitations.

Comparative Analysis of Plant Growth-Promoting Rhizobacteria's Effects on Alfalfa Growth at the Seedling and Flowering Stages under Salt Stress.

Alfalfa (Medicago sativa L.), a forage legume known for its moderate salt-alkali tolerance, offers notable economic and ecological benefits and aids in soil amelioration when cultivated in saline-alkaline soils. Nonetheless, the limited stress resistance of alfalfa could curtail its productivity. This study investigated the salt tolerance and growth-promoting characteristics (in vitro) of four strains of plant growth-promoting rhizobacteria (PGPR) that were pre-selected, as well as their effects on alfalfa at different growth stages (a pot experiment). The results showed that the selected strains belonged to the genera Priestia (HL3), Bacillus (HL6 and HG12), and Paenibacillus (HG24). All four strains exhibited the ability to solubilize phosphate and produce indole-3-acetic acid (IAA) and 1-aminocyclopropane-1-carboxylate (ACC) deaminase. Among them, except for strain HG24, the other strains could tolerate 9% NaCl stress. Treatment with 100 mM NaCl consistently decreased the IAA production levels of the selected strains, but inconsistent changes (either enhanced or reduced) in terms of phosphate solubilization, ACC deaminase, and exopolysaccharides (EPS) production were observed among the strains. During the various growth stages of alfalfa, PGPR exhibited different growth-promoting effects: at the seedling stage, they enhanced salt tolerance through the induction of physiological changes; at the flowering stage, they promoted growth through nutrient acquisition. The current findings suggest that strains HL3, HL6, and HG12 are effective microbial inoculants for alleviating salt stress in alfalfa plants in arid and semi-arid regions. This study not only reveals the potential of indigenous salt-tolerant PGPR in enhancing the salt tolerance of alfalfa but also provides new insights into the mechanisms of action of PGPR.

Diagnosis of benign and malignant nodules with a radiomics model integrating features from nodules and mammary regions on DCE-MRI.

Objectives: To establish a radiomics model for distinguishing between the benign and malignant mammary gland nodules via combining the features from nodule and mammary regions on DCE-MRI. Methods: In this retrospective study, a total of 103 cases with mammary gland nodules (malignant/benign = 80/23) underwent DCE-MRI, and was confirmed by biopsy pathology. Features were extracted from both nodule region and mammary region on DCE-MRI. Three SVM classifiers were built for diagnosis of benign and malignant nodules as follows: the model with the features only from nodule region (N model), with the features only from mammary region (M model) and the model combining the features from nodule region and mammary region (NM model). The performance of models was evaluated with the area under the curve of receiver operating characteristic (AUC). Results: One radiomic features is selected from nodule region and 3 radiomic features is selected from mammary region. Compared with N or M model, NM model exhibited the best performance with an AUC of 0.756. Conclusions: Compared with the model only using the features from nodule or mammary region, the radiomics-based model combining the features from nodule and mammary region outperformed in the diagnosis of benign and malignant nodules.

Emerging therapeutic strategies for metastatic uveal melanoma: Targeting driver mutations.

Uveal melanoma (UM) is the most common primary malignant intraocular tumor in adults. Although primary UM can be effectively controlled, a significant proportion of cases (40% or more) eventually develop distant metastases, commonly in the liver. Metastatic UM remains a lethal disease with limited treatment options. The initiation of UM is typically attributed to activating mutations in GNAQ or GNA11. The elucidation of the downstream pathways such as PKC/MAPK, PI3K/AKT/mTOR, and Hippo-YAP have provided potential therapeutic targets. Concurrent mutations in BRCA1 associated protein 1 (BAP1) or splicing factor 3b subunit 1 (SF3B1) are considered crucial for the acquisition of malignant potential. Furthermore, in preclinical studies, actionable targets associated with BAP1 loss or oncogenic mutant SF3B1 have been identified, offering promising avenues for UM treatment. This review aims to summarize the emerging targeted and epigenetic therapeutic strategies for metastatic UM carrying specific driver mutations and the potential of combining these approaches with immunotherapy, with particular focus on those in upcoming or ongoing clinical trials.

Molecular Interactions Required for Activation of Complement Component C2 Include Exosites Located on the Serine Protease Domain of C1s and Mannose-Binding Lectin Associated Protease-2.

The activation of the CP/LP C3 proconvertase complex is a key event in complement activation and involves cleavage of C4 and C2 by the C1s protease (classical pathway) or the mannose-binding lectin-associated serine protease (MASP)-2 (lectin pathway). Efficient cleavage of C4 by C1s and MASP-2 involves exosites on the complement control protein and serine protease (SP) domains of the proteases. The complement control protein domain exosite is not involved in cleavage of C2 by the proteases, but the role of an anion-binding exosite (ABE) on the SP domains of the proteases has (to our knowledge) never been investigated. In this study, we have shown that the ABE on the SP of both C1s and MASP-2 is crucial for efficient cleavage of C2, with mutant forms of the proteases greatly impaired in their rate of cleavage of C2. We have additionally shown that the site of binding for the ABE of the proteases is very likely to be located on the von Willebrand factor domain of C2, with the precise area differing between the enzymes: whereas C1s requires two anionic clusters on the von Willebrand factor domain to enact efficient cleavage of C2, MASP-2 apparently only requires one. These data provide (to our knowledge) new information about the molecular determinants for efficient activation of C2 by C1s and MASP-2. The enhanced view of the molecular events underlying the early stages of complement activation provides further possible intervention points for control of this activation that is involved in a number of inflammatory diseases.

FIB-4 index is associated with mortality in critically ill patients with alcohol use disorder: Analysis from the MIMIC-IV database.

BACKGROUND: The relationship between fibrosis-4 (FIB-4) index and all-cause mortality in critically ill patients with alcohol use disorder (AUD) is unclear. The present study aimed to investigate the predictive ability of FIB-4 for all-cause mortality in critically ill AUD patients and the association between them. METHODS: A total of 2528 AUD patients were included using the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. FIB-4 was calculated for each patient using the existing formula. The patients were equally divided into four groups based on the quartiles of FIB-4. Multivariate logistic regression and Cox proportional hazard model were used to evaluate the association of FIB-4 with in-hospital mortality, 28-day mortality and 1-year mortality. Kaplan-Meier curves were used to analyse the incidence of 28-day mortality among four groups. RESULTS: FIB-4 was positively associated with 28-day mortality of AUD patients with hazard ratio (HR) of 1.354 [95% confidence interval (CI) 1.192-1.538]. There were similar trends in the in-hospital mortality [odds ratio (OR): 1.440, 95% CI (1.239-1.674)] and 1-year mortality [HR: 1.325, 95% CI (1.178-1.490)]. CONCLUSION: Increased FIB-4 is associated with greater in-hospital mortality, 28-day mortality and 1-year mortality in critically ill AUD patients.

Effectiveness of opportunistic osteoporosis screening on chest CT using the DCNN model.

OBJECTIVE: To develop and evaluate a deep learning model based on chest CT that achieves favorable performance on opportunistic osteoporosis screening using the lumbar 1 + lumbar 2 vertebral bodies fusion feature images, and explore the feasibility and effectiveness of the model based on the lumbar 1 vertebral body alone. MATERIALS AND METHODS: The chest CT images of 1048 health check subjects from January 2021 to June were retrospectively collected as the internal dataset (the segmentation model: 548 for training, 100 for tuning and 400 for test. The classification model: 530 for training, 100 for validation and 418 for test set). The subjects were divided into three categories according to the quantitative CT measurements, namely, normal, osteopenia and osteoporosis. First, a deep learning-based segmentation model was constructed, and the dice similarity coefficient(DSC) was used to compare the consistency between the model and manual labelling. Then, two classification models were established, namely, (i) model 1 (fusion feature construction of lumbar vertebral bodies 1 and 2) and (ii) model 2 (feature construction of lumbar 1 alone). Receiver operating characteristic curves were used to evaluate the diagnostic efficacy of the models, and the Delong test was used to compare the areas under the curve. RESULTS: When the number of images in the training set was 300, the DSC value was 0.951 ± 0.030 in the test set. The results showed that the model 1 diagnosing normal, osteopenia and osteoporosis achieved an AUC of 0.990, 0.952 and 0.980; the model 2 diagnosing normal, osteopenia and osteoporosis achieved an AUC of 0.983, 0.940 and 0.978. The Delong test showed that there was no significant difference in area under the curve (AUC) values between the osteopenia group and osteoporosis group (P = 0.210, 0.546), while the AUC value of normal model 2 was higher than that of model 1 (0.990 vs. 0.983, P = 0.033). CONCLUSION: This study proposed a chest CT deep learning model that achieves favorable performance on opportunistic osteoporosis screening using the lumbar 1 + lumbar 2 vertebral bodies fusion feature images. We further constructed the comparable model based on the lumbar 1 vertebra alone which can shorten the scan length, reduce the radiation dose received by patients, and reduce the training cost of technologists.

Descriptor for C2N-Supported Single-Cluster Catalysts in Bifunctional Oxygen Evolution and Reduction Reactions.

Developing highly active cluster catalysts for the bifunctional oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) is significant for future renewable energy technology. Here, we employ first-principles calculations combined with a genetic algorithm to explore the activity trends of transition metal clusters supported on C2N. Our results indicate that the supported clusters, as bifunctional catalysts for the OER and the ORR, may outperform single-atom catalysts. In particular, the C2N-supported Ag6 cluster exhibits outstanding bifunctional activity with low overpotentials. Mechanistic analysis indicates that the activity of the cluster is related to the number of atoms in the active site as well as the interaction between the intermediate and the cluster. Accordingly, we identify a descriptor that links the intrinsic properties of the clusters with the activity of both the OER and the ORR. This work provides guidelines and strategies for the rational design of highly efficient bifunctional cluster catalysts.