Emerging Roles of Galectin-3 in Pulmonary Diseases.

Galectin-3 is a multifunctional protein that is involved in various physiological and pathological events. Emerging evidence suggests that galectin-3 also plays a critical role in the pathogenesis of pulmonary diseases. Galectin-3 can be produced and secreted by various cell types in the lungs, and the overexpression of galectin-3 has been found in acute lung injury/acute respiratory distress syndrome (ALI/ARDS), pulmonary hypertension (PH), pulmonary fibrosis diseases, lung cancer, lung infection, chronic obstructive pulmonary disease (COPD), and asthma. Galectin-3 exerts diverse effects on the inflammatory response, immune cell activation, fibrosis and tissue remodeling, and tumorigenesis in these pulmonary disorders, and genetic and pharmacologic modulation of galectin-3 has therapeutic effects on the treatment of pulmonary illnesses. In this review, we summarize the structure and function of galectin-3 and the underlying mechanisms of galectin-3 in pulmonary disease pathologies; we also discuss preclinical and clinical evidence regarding the therapeutic potential of galectin-3 inhibitors in these pulmonary disorders. Additionally, targeting galectin-3 may be a very promising therapeutic approach for the treatment of pulmonary diseases.

The effect of body mass index on stroke prognosis: A systematic review and meta-analysis of 32 cohort studies with 330,353 patients.

BACKGROUND: Many studies have explored the impact of body mass index (BMI) on stroke prognosis, yet findings remain inconsistent. AIMS: The aims of this study were to conduct a systematic review and meta-analyses to summarize the existing evidence on BMI and stroke outcomes. METHODS: PubMed, Web of Science, Embase, The Cochrane Library, CNKI, CBM, Wanfang Database, and VIP Database were systematically searched from inception to 1 January 2023. Cohort studies were included if they reported on a population of patients with stroke, evaluated BMI on stroke outcomes (mortality/recurrence/score of modified Rankin scale (mRs)), and reported original data. Data extraction and quality assessment were independently undertaken by two reviewers. Stata 16.0 software was used for meta-analysis. RESULTS: Thirty-two studies involving 330,353 patients (5 Chinese language articles) were included in the analysis. The proportion of underweight, overweight, and obese patients was 1.85%, 18.2%, and 15.6%, respectively. Compared with normal weight, being underweight was associated with an increased risk of mortality (relative risk (RR) = 1.78, 95% confidence interval (CI) = 1.60-1.96), poor functional outcomes defined as modified Rankin scale ⩾ 3 (RR = 1.33, 95% CI = 1.22-1.45), and stroke recurrence (RR = 1.19, 95% CI = 1.04-1.37). Being overweight but not obese was associated with reduced mortality (RR = 0.81, 95% CI = 0.74-0.89) and better functional outcomes (RR = 0.92, 95% CI = 0.89-0.96), but did not alter the risk of stroke recurrence (RR = 1.03, 95% CI = 0.90-1.17). Obesity was associated with lower risk of mortality (RR = 0.76, 95% CI = 0.72-0.81) and better functional outcomes (RR = 0.89, 95% CI = 0.84-0.94). CONCLUSIONS: Our findings indicate that in patients with stroke, being underweight is associated with an increased risk of mortality, poor functional outcomes, and stroke recurrence. In contrast, being overweight but not obese, or being obese, was associated with a decreased risk of mortality and better functional outcomes. This is consistent with the obesity paradox in stroke, whereby obesity increases stroke risk in the general population but is associated with improved outcome in patients suffering stroke.

A Multifunctional CaII-EuIII Heterometallic Organic Framework with Sensing and Selective Adsorption in Water.

With increasing global industrialization, it is urgent and challenging to develop multifunctional species for detection and adsorption in the environment. For this purpose, a novel anionic heterometallic organic framework, [(CH3)2NH2][CaEu(CAM)2(H2O)2]·4H2O·4DMF (CaEuCAM), is hydrothermally synthesized based on chelidamic acid (H3CAM). Single crystal analysis shows that CaEuCAM features two different oxygen-rich channels along the c-axis in which one CAM3- bridges two sextuple-coordinated Ca2+ and two octuple-coordinated Eu3+ with a µ4-η1: η1: η1: η1: η1: η1 new chelating and bridging mode. The characteristic bright red emission and superior hydrostability of CaEuCAM under harsh acidic and basic conditions benefit it by acting as a highly sensitive sensor for Fe3+ and 3-nitrophenol (3-NP) with extremely low LODs through remarkable quenching. The combination of experiments and theoretical calculations for sensing mechanisms shows that the competitive absorption and interaction are responsible for Fe3+-induced selective emission quenching, while that for 3-NP is the result of the synergism of host-guest chemistry and the inner filter effect. Meanwhile, the assimilation of negative charge plus channels renders CaEuCAM a highly selective adsorbent for methylene blue (MB) due to a synergy of electrostatic affinity, ion-dipole interaction, and size matching. Of note is the reusability of CaEuCAM toward Fe3+/3-NP sensing and MB adsorption besides its fast response. These findings could be very useful in guiding the development of multifunctional Ln-MOFs for sensing and adsorption applications in water media.

The prevalence and characteristics of alexithymia in stroke patients: a systematic review and meta-analysis.

BACKGROUND: Previous studies have indicated the potential occurrence of alexithymia among stroke patients, yet the prevalence of alexithymia in this population remains disparate across different investigations without a synthesized overview. AIM: To systematically evaluate the prevalence and characteristics of alexithymia in stroke patients. METHODS: A systematic review and meta-analysis was conducted following the PRISMA guidelines. PubMed, Embase, Web of Science, The Cochrane Library, CINAHL, China Knowledge Resource Integrated Database (CNKI), Wanfang Database, Chinese Biomedical Database, and Weipu Database (VIP) were searched from inception to December 31,2022, two independent researchers extracted data and evaluated article quality. RESULTS: Seventeen studies were included, reporting on the prevalence of alexithymia or Toronto Alexithymia Scale-20 (TAS-20) scores among stroke patients. The pooled prevalence was found to be 35.0% (95%CI= 23.0-47.0%; I2 =97.5%), and the total scores (TS) of TAS-20 was 59.90 (95% CI=56.34-63.47; I2 =100.0%). Subgroup analysis revealed significant variation in TAS-20 scores across different geographical regions. Specifically, the total TAS-20 score in Chinese stroke patients (62.95, 95%CI=58.75-67.14; I2=100%) was higher compared to non-Chinese stroke patients (52.58, 95%CI=49.12-56.04; I2 = 99.0%). CONCLUSIONS: The prevalence of alexithymia is high among stroke patients, with TAS-20 scores surpassing those observed in patients with certain other medical conditions. This underscores the importance of addressing alexithymia in stroke patients promptly through assessment and intervention to mitigate negative emotional consequences and enhance overall quality of life. Future research could explore the influence of demographic factors such as age and sex on alexithymia in stroke patients, enabling a more comprehensive understanding of alexithymia.

Design, Synthesis, and Evaluation of Dihydropyrimidine Derivatives as Selective PDE1 Inhibitors for the Treatment of Liver Fibrosis.

Liver fibrosis is a common pathological feature of most chronic liver diseases with no effective drugs available. Phosphodiesterase 1 (PDE1), a subfamily of the PDE super enzyme, might work as a potent target for liver fibrosis by regulating the concentration of cAMP and cGMP. However, there are few PDE1 selective inhibitors, and none has been investigated for liver fibrosis treatment yet. Herein, compound AG-205/1186117 with the dihydropyrimidine scaffold was selected as the hit by virtual screening. A hit-to-lead structural modification led to a series of dihydropyrimidine derivatives. Lead 13h exhibited the IC50 of 10 nM against PDE1, high selectivity over other PDEs, as well as good safety properties. Administration of 13h exerted significant anti-liver fibrotic effects in bile duct ligation-induced fibrosis rats, which also prevented TGF-ß-induced myofibroblast differentiation in vitro, confirming that PDE1 could work as a potential target for liver fibrosis.

Adverse outcomes of intrinsic capacity in older adults: A scoping review.

Background and Purpose Intrinsic capacity (IC) has been shown to have the greatest impact on an individual's health status and health trajectory and can independently predict adverse outcomes such as mortality and care dependency in older adults. However, the current understanding of adverse outcomes associated with IC is incomplete. Methods A scoping review of the literature from PubMed, Web of Science (WOS), The Cochrane Library, CINAHL, and Embase databases was conducted from January 2015 to March 2023 to identify articles related to the adverse outcomes associated with IC in older adults. Results 711 studies met screening criteria, and 25 studies met inclusion criteria. These studies reported a total of 17 adverse outcomes related to IC across four domains. (1) Adverse outcomes in the physiological function domains included frailty, pneumonia onset, memory impairment, polypharmacy, incontinence, and poor/fair self-rated health. (2) Clinical outcomes domains included IADL disability, ADL disability, mortality, falls, autonomy decline, and incident dependence. (3) The resource utilization domains included hospitalization, nursing home stays, polypharmacy healthcare costs, and emergency department visits. (4) The other domains mainly included poor quality of life. Conclusion It is evident that IC decline in older adults is associated with a broad spectrum of adverse outcomes spanning cognitive function, activity ability, sensory perception, physical and mental health and living standards. Future studies should further deepen the exploration of IC.

Factors associated with the intrinsic capacity in older adults: A scoping review.

INTRODUCTION: In 2015, the term 'intrinsic capacity' (IC) was proposed by the World Health Organisation to promote healthy aging. However, the factors associated with IC are still discrepant and uncertain. AIM: We aim to synthesise the factors connected with IC. METHODS: This scoping review followed the five-stage framework of Arksey and O'Malley and was reported using PRISMA-ScR guidelines. RESULTS: In all, 29 articles were included. IC of older adults is associated with demographic characteristics, socioeconomic factors, disease conditions, behavioural factors, and biomarkers. Age, sex, marital status, occupation status, education, income/wealth, chronic diseases, hypertension, diabetes, disability, smoking status, alcohol consumption, and physical activity were emerged as important factors related to the IC of older adults. CONCLUSIONS: This review shows that IC is related to multiple factors. Understanding these factors can provide the healthcare personnel with the theoretical basis for intervening and managing IC in older adults. RELEVANCE TO CLINICAL PRACTICE: The influencing factors identified in the review help to guide older adults to maintain their own intrinsic capacity, thereby promoting their health and well-being. The modifiable factors also provide evidence for healthcare personnel to develop targeted intervention strategies to delay IC decline. NO PATIENT OR PUBLIC CONTRIBUTION: As this is a scoping review, no patient or public contributions are required.

Discovery of novel selective phosphodiesterase­1 inhibitors for the treatment of acute myelogenous leukemia.

Acute myelogenous leukemia (AML) is the most common form of acute leukemia in adults. PDE1 (Phosphodiesterase 1) is a subfamily of the PDE super-enzyme families that can hydrolyze the second messengers cAMP and cGMP simultaneously. Previous research has shown that suppressing the gene expression of PDE1 can trigger apoptosis of human leukemia cells. However, no selective PDE1 inhibitors have been used to explore whether PDE1 is a potential target for treating AML. Based on our previously reported PDE9/PDE1 dual inhibitor 11a, a series of novel pyrazolopyrimidinone derivatives were designed in this study. The lead compound 6c showed an IC50 of 7.5 nM against PDE1, excellent selectivity over other PDEs and good metabolic stability. In AML cells, compound 6c significantly inhibited the proliferation and induced apoptosis. Further experiments indicated that the apoptosis induced by 6c was through a mitochondria-dependent pathway by decreasing the ratio of Bcl-2/Bax and increasing the cleavage of caspase-3, 7, 9, and PARP. All these results suggested that PDE1 might be a novel target for AML.

Osteopontin: A Novel Therapeutic Target for Respiratory Diseases.

Osteopontin (OPN) is a multifunctional phosphorylated protein that is involved in physiological and pathological events. Emerging evidence suggests that OPN also plays a critical role in the pathogenesis of respiratory diseases. OPN can be produced and secreted by various cell types in lungs and overexpression of OPN has been found in acute lung injury/acute respiratory distress syndrome (ALI/ARDS), pulmonary hypertension (PH), pulmonary fibrosis diseases, lung cancer, lung infection, chronic obstructive pulmonary disease (COPD), and asthma. OPN exerts diverse effects on the inflammatory response, immune cell activation, fibrosis and tissue remodeling, and tumorigenesis of these respiratory diseases, and genetic and pharmacological moudulation of OPN exerts therapeutic effects in the treatment of respiratory diseases. In this review, we summarize the recent evidence of multifaceted roles and underlying mechanisms of OPN in these respiratory diseases, and targeting OPN appears to be a potential therapeutic intervention for these diseases.

Blood pressure variability predicts poor outcomes in acute stroke patients without thrombolysis: a systematic review and meta-analysis.

BACKGROUND: Stroke is a significant medical condition, and blood pressure stands out as the most prevalent treatable risk factor associated with it. Researches link blood pressure variability (BPV) with stroke; however, the specific relationship between with the outcomes of stroke patients remains unclear. As blood pressure variability and mean blood pressure are interrelated, it remains uncertain whether BPV adds additional information to understanding the outcome of acute stroke patients. OBJECTIVE: To systematically review studies investigating the association between blood pressure variability and prognosis in acute stroke patients. METHODS: Embase, PubMed, Web of Science, and the Cochrane Library were searched for English language full-text articles from the inception to 1 January 2023. Stroke patients aged ≥ 18 years were included in this analysis. Stroke types were not restricted. RESULTS: This meta-analysis shows that higher systolic blood pressure variability is linked to a higher risk of poor outcome, including function disability, mortality, early neurological deterioration, and stroke recurrence, among acute stroke patients without thrombolysis. A higher diastolic blood pressure variability is linked with to a higher risk of mortality and functional disability. CONCLUSIONS: This review reveals that blood pressure variability is a novel and clinically relevant risk factor for stroke patients' outcome. Future studies should investigate how best to measure and define BPV in acute stroke. Larger studies are warranted to provide more robust evidence in this area.

Adipokines in pulmonary hypertension: angels or demons?

Pulmonary hypertension (PH) is a devastating cardiopulmonary disorder with poor prognosis and limited curative options. Recent studies revealed a strong association between adipose tissue dysfunction (e.g., obesity) and PH. Adipokines are bioactive polypeptides with pleiotropic effects mainly produced by adipose tissue, and it is suggested that imbalanced production of adipokines in obesity may play a key role in the pathogenesis of PH. Alternations in the production and secretion of adipokines have been observed in PH patients and rodents PH models. In this review, we summarize the expressions and functions of several well-recognized adipokines, the roles of adipokines in the pathogenesis of PH and recent advances in the pharmacological and molecular modulation of adipokines in the treatment of PH. We found that several adipokines (e.g., leptin, resistin, and chemerin) have been demonstrated to display pro-proliferation, pro-inflammatory, and pro-oxidative properties and exacerbate PH. Other adipokines (e.g., adiponectin, apelin, and omentin-1) have anti-proliferation, anti-inflammatory, anti-fibrotic and anti-oxidative impacts on the pulmonary vascular remodeling of PH and are suggested as protective factors against PH, and targeting imbalanced adipokines appears to be a potential novel therapeutic strategy for the treatment of PH.

Intrinsically Stretchable, Self-Healing, and Large-Scale Epidermal Bioelectrode Arrays for Electrophysiology and Gesture Recognition.

Electrophysiological (EP) signals, referred to as low-level biopotentials driven by active or passive human movements, are of great importance for kinesiology, rehabilitation, and human-machine interaction. To capture high-fidelity EP signals, bioelectrodes should possess high conductivity, high stretchability, and high conformability to skin. While traditional metal bioelectrodes are endowed with stretchability via complex structural designs, they are vulnerable to external or internal inference due to their low fracture strain and large modulus. Here, we report a self-healing elastic composite of silver nanowire (AgNW), graphite nanosheet, and styrene-block-poly(ethylene-ran-butylene)-block-polystyrene, which exhibits high stretchability of ε = 500%, high conductivity of σ = ∼1923 S·cm-1, and low resistance change (ΔR/R0) of 0.14 at ε = 40% while its resistance increases ∼0.8% after a 24 h stretching operation at ε = 50%. We employed the elastic composites for accurate and stable monitoring of electrocardiograph and surface electromyography (sEMG) signals. Further, we demonstrate an all-solution and printable process to obtain a large-scale sEMG bioelectrode array, enabling highly conformal adhesion on skin and high-fidelity gesture recognition.

Predicting the Pressure Behavior and Sensing Property of Elastic Pressure Exerting and Sensing Fabrics for Compression Textiles.

Using compression textiles to exert an appropriate and steady pressure on human limbs is a primary treatment method in the medical area. Compression pressure is a crucial parameter that determines the treatment efficacy. However, there is a lack of pressure-sensing fabrics that can both apply and measure the pressure of compression textiles, particularly the theoretical study of the prediction of the pressure and sensing performance of such a sensing fabric. In this study, based on the developed elastic pressure-exerting and -sensing fabrics and a setup test protocol simulating the pressure-exerting process, the relationships between the displacement of the press head, resultant fabric extension, and pressure were theoretically explored. Two finite element (FE) models, continuum and discontinuous models, were first established to predict the pressure behavior of elastic pressure-exerting and -sensing fabrics. The simulation results present good agreement with the experimental results wherein the pressure generated increases with the increase of the fabric strain in a nonlinear form. Furthermore, with the above FE models for the relationship between fabric extension and pressure generated, as well as the measured electrical resistance of the sensing fabric, a model for the electrical resistance of the sensing fabric can thus be established. Among pressure-sensing fabrics in three different structures, the sensing fabric in sateen exhibits better pressure prediction accuracy and a faster response to the pressure change. Finally, a series of numerical simulations were conducted to investigate the effects of the press head diameter, the unit cell crimp factor of fabric and the fabric pretension on the fabric extension, the resultant pressure, and electrical resistance change. The simulation results show that the pressure decreases with the increase of the press head diameter. The crimp factor and pretension of the sensing fabric also have a significant effect on the pressure and electrical resistance change generated. This simulation approach provides a new theoretical understanding of the pressure behavior and mechanism of pressure-sensing fabrics for future smart compression textiles.

Identification of Novel Quinolin-2(1H)-ones as Phosphodiesterase 1 Inhibitors for the Treatment of Inflammatory Bowel Disease.

Phosphodiesterase 1 (PDE1) is a subfamily of PDE super enzyme families that can hydrolyze cyclic adenosine monophosphate and cyclic guanosine monophosphate simultaneously. Currently, the number of PDE1 inhibitors is relatively few, significantly limiting their application. Herein, a novel series of quinolin-2(1H)-ones were designed rationally, leading to compound 10c with an IC50 of 15 nM against PDE1C, high selectivity across other PDEs, and remarkable safety properties. Furthermore, we used the lead compound 10c as a chemical tool to explore whether PDE1 could work as a novel potential target for the treatment of inflammatory bowel disease (IBD), a disease which is a chronic, relapsing disorder of the gastrointestinal tract inflammation lacking effective treatment. Our results showed that administration of 10c exerted significant anti-IBD effects in the dextran sodium sulfate-induced mice model and alleviated the inflammatory response, indicating that PDE1 could work as a potent target for IBD.

LPS priming before plaque deposition impedes microglial activation and restrains Aß pathology in the 5xFAD mouse model of Alzheimer's disease.

Microglia have an innate immunity memory (IIM) with divergent functions in different animal models of neurodegenerative diseases, including Alzheimer's disease (AD). AD is characterized by chronic neuroinflammation, neurodegeneration, tau tangles and ß-amyloid (Aß) deposition. Systemic inflammation has been implicated in contributing to the progression of AD. Multiple reports have demonstrated unique microglial signatures in AD mouse models and patients. However, the proteomic profiles of microglia modified by IIM have not been well-documented in an AD model. Therefore, in the present study, we investigate whether lipopolysaccharide (LPS)-induced IIM in the pre-clinical stage of AD alters the microglial responses and shapes the neuropathology. We accomplished this by priming 5xFAD and wild-type (WT) mice with an LPS injection at 6 weeks (before the robust development of plaques). 140 days later, we evaluated microglial morphology, activation, the microglial barrier around Aß, and Aß deposition in both 5xFAD primed and unprimed mice. Priming induced decreased soma size of microglia and reduced colocalization of PSD95 and Synaptophysin in the retrosplenial cortex. Priming appeared to increase phagocytosis of Aß, resulting in fewer Thioflavin S+ Aß fibrils in the dentate gyrus. RIPA-soluble Aß 40 and 42 were significantly reduced in Primed-5xFAD mice leading to a smaller size of MOAB2+ Aß plaques in the prefrontal cortex. We also found that Aß-associated microglia in the Primed-5xFAD mice were less activated and fewer in number. After priming, we also observed improved memory performance in 5xFAD. To further elucidate the molecular mechanism underlying these changes, we performed quantitative proteomic analysis of microglia and bone marrow monocytes. A specific pattern in the microglial proteome was revealed in primed 5xFAD mice. These results suggest that the imprint signatures of primed microglia display a distinctive phenotype and highlight the potential for a beneficial adaption of microglia when intervention occurs in the pre-clinical stage of AD.

[Effect and mechanism of amphiregulin on acute respiratory distress syndrome in mice].

OBJECTIVE: To explore the protective effect of amphiregulin (Areg) on acute respiratory distress syndrome (ARDS) in mice and its underlying mechanism. METHODS: (1) Male C57BL/6 mice aged 6-8 weeks were selected for animal experiments and divided into 3 groups (n = 10) according to the random number table method, which includes sham-operated group (Sham group), ARDS model group [ARDS model in mice was established by intratracheal instillation of lipopolysaccharide (LPS) 3 mg/kg] and ARDS+Areg intervention group [recombinant mice Areg (rmAreg) 5 µg was injected intraperitoneally 1 hour after LPS modeling]. The mice were sacrificed at 24 h after LPS injection lung histopathological changes were observed under hematoxylin-eosin (HE) staining and scored for lung injury; oxygenation index and wet/dry ratio of lung tissue were measured; the content of protein in bronchoalveolar lavage fluid (BALF) was detected by bicinchoninic acid (BCA) method, the level of inflammatory factors interleukins (IL-1ß, IL-6) and tumor necrosis factor-α (TNF-α) in BALF were measured by enzyme-linked immunosorbent assay (ELISA). (2) Mice alveolar epithelial cell line MLE12 cells were obtained and cultured for experiment in vitro. Blank control group (Control group), LPS group (LPS 1 mg/L) and LPS+Areg group (rmAreg 50 µg/L was added 1 hour after LPS stimulation) were set. The cells and culture fluid were collected at 24 hours after LPS stimulation, and the apoptosis level of MLE12 cells was detected by flow cytometry; the activation level of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) and the expressions of apoptosis-related proteins Bcl-2 and Bax in MLE12 cells were detected by Western blotting. RESULTS: (1) Animal experiments: compared with the Sham group, the lung tissue structure of ARDS model group was destroyed, the lung injury score was significantly increased, the oxygenation index was significantly decreased, the wet/dry weight ratio of lung was significantly increased, and the levels of protein and inflammatory factors in BALF were significantly increased. Compared with ARDS model group, lung tissue structure damage was reduced, pulmonary interstitial congestion, edema and inflammatory cell infiltration were significantly reduced, and lung injury score was significantly decreased (scores: 0.467±0.031 vs. 0.690±0.034) in ARDS+Areg intervention group. In addition, oxygenation index in ARDS+Areg intervention group was significantly increased [mmHg (1 mmHg ≈ 0.133 kPa): 380.00±22.36 vs. 154.00±20.74]. Lung wet/dry weight ratio (5.40±0.26 vs. 6.63±0.25), protein and inflammatory factors levels in BALF [protein (g/L): 0.42±0.04 vs. 0.86±0.05, IL-1ß (ng/L): 30.00±2.00 vs. 40.00±3.65, IL-6 (ng/L): 190.00±20.30 vs. 581.30±45.76, TNF-α (ng/L): 30.00±3.65 vs. 77.00±4.16], and the differences were statistically significant (all P < 0.01). (2) Cell experiments: compared with the Control group, the number of apoptotic MLE12 cells was significantly increased in the LPS group, and the levels of PI3K phosphorylation, anti-apoptotic gene Bcl-2 level and pro-apoptotic gene Bax level were increased in MLE12 cells. Compared with the LPS group, the number of apoptosis in MLE12 cells was significantly reduced in the LPS+Areg group after administration of rmAreg treatment [(17.51±2.12)% vs. (36.35±2.84)%], and the levels of PI3K/AKT phosphorylation and Bcl-2 expression in MLE12 cells were significantly increased (p-PI3K/PI3K: 2.400±0.200 vs. 0.550±0.066, p-AKT/AKT: 1.647±0.103 vs. 0.573±0.101, Bcl-2/GAPDH: 0.773±0.061 vs. 0.343±0.071), and Bax expression was significantly suppressed (Bax/GAPDH: 0.810±0.095 vs. 2.400±0.200). The differences were statistically significant (all P < 0.01). CONCLUSIONS: Areg could alleviate ARDS in mice by inhibiting the apoptosis of alveolar epithelial cells through activating PI3K/AKT pathway.

Which cutoff value of the Montreal Cognitive Assessment should be used for post-stroke cognitive impairment? A systematic review and meta-analysis on diagnostic test accuracy.

BACKGROUND: Post-stroke cognitive impairment (PSCI) is one of the serious complications of stroke. The Montreal Cognitive Assessment (MoCA), as a brief cognitive impairment screening tool, is widely used in stroke survivors. However, some studies have suggested that the use of the universal cutoff value of 26 may be inappropriate for detecting cognitive impairments in stroke settings. AIM: We conducted this study to identify the optimal cutoff value of the MoCA in screening for PSCI. METHODS: PubMed, CINAHL, Embase, the Cochrane Library, and Web of Science were searched for eligible studies until March 23, 2023. All studies were screened by two independent researchers. The quality of each article was evaluated by the Quality Assessment of Diagnostic Accuracy Studies-2 tool. A bivariate mixed-effects model was used to pool sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and the summary receiver operating characteristic curve. RESULTS: Twenty-four studies with a total of 4231 patients were included in this review. Despite the lack of evidence of publication bias, a high degree of heterogeneity was observed. A meta-analysis revealed that a cutoff value of 21/22 yielded the best diagnostic accuracy. The optimal cutoff varied in different regions, stroke types, and stroke phases as well. CONCLUSION: The optimal cutoff of MoCA was 21/22 for stroke populations rather than the initially recommended cutoff of 26. A revised (lower) cutoff should be considered for stroke survivors.

Experimental Study on the Influence of Transverse Crack on Chloride Ingress in Concrete Slab Track of High-Speed Railway.

The concrete track slab and the base slab of the high-speed railway CRTS II track structure are prone to transverse cracks in the initial service period, which are subjected to environmental action and train load. In order to investigate the influence of transverse cracks on chloride ingress of concrete track slab and base slab in a coastal environment, drying-wetting cycle chloride erosion tests were carried out on reinforced concrete track slab and base slab specimens with cracks ranging from 0 mm to 0.6 mm, subjected to continuous bending moment. The chloride ion concentration of concrete along the depth direction was collected during the test process. The experimental results show that the chloride ion concentration of concrete at the crack section is much higher than that at the intact section, and it increases with the increase of crack width in the range of 0.2 mm to 0.6 mm. A chloride diffusion coefficient model of cracked concrete is proposed for slab track based on the experimental results, which can comprehensively consider the effects of surface chloride ion concentration, chloride binding effect, time-varying effect, temperature, relative humidity, and transverse crack width.

A comparison of machine learning approaches for the quantification of microglial cells in the brain of mice, rats and non-human primates.

Microglial cells are brain-specific macrophages that swiftly react to disruptive events in the brain. Microglial activation leads to specific modifications, including proliferation, morphological changes, migration to the site of insult, and changes in gene expression profiles. A change in inflammatory status has been linked to many neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. For this reason, the investigation and quantification of microglial cells is essential for better understanding their role in disease progression as well as for evaluating the cytocompatibility of novel therapeutic approaches for such conditions. In the following study we implemented a machine learning-based approach for the fast and automatized quantification of microglial cells; this tool was compared with manual quantification (ground truth), and with alternative free-ware such as the threshold-based ImageJ and the machine learning-based Ilastik. We first trained the algorithms on brain tissue obtained from rats and non-human primate immunohistochemically labelled for microglia. Subsequently we validated the accuracy of the trained algorithms in a preclinical rodent model of Parkinson's disease and demonstrated the robustness of the algorithms on tissue obtained from mice, as well as from images provided by three collaborating laboratories. Our results indicate that machine learning algorithms can detect and quantify microglial cells in all the three mammalian species in a precise manner, equipotent to the one observed following manual counting. Using this tool, we were able to detect and quantify small changes between the hemispheres, suggesting the power and reliability of the algorithm. Such a tool will be very useful for investigation of microglial response in disease development, as well as in the investigation of compatible novel therapeutics targeting the brain. As all network weights and labelled training data are made available, together with our step-by-step user guide, we anticipate that many laboratories will implement machine learning-based quantification of microglial cells in their research.

Enhanced virulence of genetically engineered Autographa californica nucleopolyhedrovirus owing to accelerated viral DNA replication aided by inserted ascovirus genes.

Genetic engineering technology is an ideal method to improve insecticidal efficiency by combining the advantages of different pathogenic microorganisms. Thus, six ascovirus genes were introduced into the genomic DNA of Autographa californica nucleopolyhedrovirus (AcMNPV) to possibly transfer the intrinsically valuable insecticidal properties from ascovirus to baculovirus. The viral budded virus (BV) production and viral DNA replication ability of AcMNPV-111 and AcMNPV-165 were significantly stronger than that of AcMNPV-Egfp (used as the wild-type virus in this study), whereas AcMNPV-33 had reduced ones. AcMNPV-111 and AcMNPV-165 also exhibited excellent insecticidal efficiency in the in vivo bioassays: AcMNPV-111 showed a 24.1% decrease in the LT50 value and AcMNPV-165 exhibited a 56.3% decrease in the LD50 value compared with AcMNPV-Egfp against the 3rd instar of Spodoptera exigua larvae, respectively. Furthermore, the size of the occlusion bodies (OBs) of AcMNPV-33, AcMNPV-111, and AcMNPV-165 were significantly increased compared to that of AcMNPV-Egfp. AcMNPV-111 and AcMNPV-165 had stable virulence against the 2nd to 4th instars tested larvae and higher OB yield than AcMNPV-Egfp in the 3rd and 4th instar larvae. Correlation and regression analyses indicated that it is better to use 5 OBs/larva virus to infect the 2nd instar larvae to produce AcMNPV-111 and 50 OBs/larva virus to infect the 3rd instar larvae to produce AcMNPV-165. The results of this study obtained recombinant viruses with enhanced virulence and exhibited a diversity of ascovirus gene function based on the baculovirus platform, which provided a novel strategy for the improvement of baculovirus as a biological insecticide.