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Background Advanced glycation end product receptor (RAGE) acts as a receptor of pro-inflammatory ligands and is highly expressed in alveolar epithelial cells (AECs). Autophagy in AECs has received much attention recently. However, the roles of autophagy and RAGE in the pathogenesis of acute lung injury remain unclear. Therefore, this study aimed to explore whether RAGE activation signals take part in the dysfunction of alveolar epithelial barrier through autophagic death. Methods Acute lung injury animal models were established using C57BL/6 and Ager gene knockout ( Ager −/− mice) mice in this study. A549 cells and primary type II alveolar epithelial (ATII) cells were treated with siRNA to reduce Ager gene expression. Autophagy was inhibited by 3-methyladenine (3-MA). Lung injury was assessed by histopathological examination. Cell viability was estimated by cell counting kit-8 (CCK-8) assay. The serum and bronchoalveolar lavage fluid (BALF) levels of interleukin (IL)-6, IL-8 and soluble RAGE (sRAGE) were evaluated by Enzyme-linked immunosorbent assay (ELISA). The involvement of RAGE signals, autophagy and apoptosis was assessed using western blots, immunohistochemistry, immunofluorescence, transmission electron microscopy and TUNEL test. Results The expression of RAGE was promoted by lipopolysaccharide (LPS), which was associated with activation of autophagy both in mice lung tissues and A549 cells as well as primary ATII cells. sRAGE in BALF was positively correlated with IL-6 and IL-8 levels. Compared with the wild-type mice, inflammation and apoptosis in lung tissues were alleviated in Ager −/− mice. Persistently activated autophagy contributed to cell apoptosis, whereas the inhibition of autophagy by 3-MA protected lungs from damage. In addition, Ager knockdown inhibited LPS-induced autophagy activation and attenuated lung injury. In vitro, knockdown of RAGE significantly suppressed the activation of LPS-induced autophagy and apoptosis of A549 and primary ATII cells. Furthermore, RAGE activated the downstream STAT3 signaling pathway. Conclusion RAGE plays an essential role in the pathogenesis of ATII cells injury. Our results suggested that RAGE inhibition alleviated LPS-induced lung injury by directly suppressing autophagic apoptosis of alveolar epithelial cells.

Uncontrollable inflammatory response acts as a driver of sepsis-associated liver injury (SALI). IL-22 plays an important role in regulating inflammatory responses, but its role in SALI remains unknown. The aim of the study was to assess the association of serum IL-22 with SALI in pediatric patients and to enclose the underlying mechanisms of IL-22 involved in lipopolysaccharide (LPS) - induced acute liver injury (ALI) in mice. Serum IL-22 levels in patients with SALI were significantly lower than in septic patients without liver injury, and the area under receiver operating characteristic (ROC) curve of IL-22 for discriminating SALI was 0.765 (95% CI : 0.593–0.937). Pre-administration of recombinant murine IL-22 alleviated LPS-induced ALI in mice, and serum IL-6 levels and the mRNA levels of TNF-α, IL-1β, and IL-6 in livers were decreased in response to IL-22 pre-treatment in mice. More importantly, IL-22 pre-treatment activated hepatic autophagy mediated by activating transcription factor 4 (ATF4)-autophagy-related gene 7 (ATG7) signaling in vivo and in vitro in response to LPS administration. Moreover, knockdown of ATF4 in mice aggravated LPS-induced ALI, which was associated with suppressed ATG7-related autophagy. In addition, the protective effects of IL-22 on LPS-induced ALI was partially blocked by ATF4 knockdown, which was associated with lower expression of LC3II/I in the livers of ATF4 knockdown (HT or Atf4 +/− ) mice compared with wild-type mice (WT or Atf4 +/+ ) mice. In conclusion, low serum IL-22 level is associated with SALI occurrence, and IL-22 pre-administration activates autophagy in hepatocytes and protects mice against LPS-induced ALI partially related to ATF4-ATG7 signaling pathway.

The availability of an ever‐expanding portfolio of 2D materials with rich internal degrees of freedom (spin, excitonic, valley, sublattice, and layer pseudospin) together with the unique ability to tailor heterostructures made layer by layer in a precisely chosen stacking sequence and relative crystallographic alignments, offers an unprecedented platform for realizing materials by design. However, the breadth of multi‐dimensional parameter space and massive data sets involved is emblematic of complex, resource‐intensive experimentation, which not only challenges the current state of the art but also renders exhaustive sampling untenable. To this end, machine learning, a very powerful data‐driven approach and subset of artificial intelligence, is a potential game‐changer, enabling a cheaper – yet more efficient – alternative to traditional computational strategies. It is also a new paradigm for autonomous experimentation for accelerated discovery and machine‐assisted design of functional 2D materials and heterostructures. Here, the study reviews the recent progress and challenges of such endeavors, and highlight various emerging opportunities in this frontier research area. The family of 2D materials is an unprecedented platform for materials by design, thanks to their ever‐expanding material portfolio with rich internal degrees of freedom. The study provides a comprehensive overview of the recent progress, challenges and emerging opportunities in a frontier research area that exploits machine learning—a very powerful data‐driven approach and subset of artificial intelligence—for 2D materials.

Endothelial cell (EC) injury is a critical factor in sepsis-induced organ failure. Continuous renal replacement therapy (CRRT) is used to improve hemodynamically unstable sepsis. We conducted a single-center, prospective, observational cohort study to assess whether CRRT attenuates sepsis-associated with EC injury. Based on whether CRRT was implemented within 24 h after admission, patients were divided into non-CRRT and CRRT groups. Demographic data, clinical features, and laboratory indexes were collected, and blood samples were collected at admission, 24 h and 7 days after PICU admission. The levels of vascular endothelial growth factor [VEGF], serum intercellular adhesion molecule-1 [sICAM-1], serum vascular cell adhesion molecule-1 [sVCAM-1], vimentin [VIM]), tissue plasminogen activator-plasminogen activator inhibitor-1 complex [t-PAIC], and thrombomodulin [TM] were not different between the CRRT and non-CRRT groups at PICU admission. The mixed-effects models revealed a significant decreasing trend in EC injury biomarkers (sICAM-1, sVCAM-1, VEGF, and VIM). Nevertheless, there were no obvious changes in these indicators in the non-CRRT group. In the CRRT group, EC injury indicators correlated with albumin and lactic acid at sepsis diagnosis. Serum VEGF, VIM, TM, and t-PAIC levels, but not sVCAM-1 or sICAM-1, were significantly lower in survivors than in non-survivors. Patients with higher serum VEGF, VIM, TM, and t-PAIC levels were at risk of worsening pediatric sepsis outcomes. CRRT downregulated the serum levels of EC injury indicators. This is the first prospective pediatric study linking CRRT to endothelial recovery, and EC biomarkers may serve as surrogate markers for endothelial recovery during CRRT.

Neurodegenerative diseases are primarily characterized by the selective loss of neurons in the brain, leading to a significant and widespread global public health burden. Although numerous mechanisms underlying neurodegenerative diseases have been elucidated, effective therapeutic strategies are still being explored. Several drugs have been proposed to halt disease progression; however, they often come with severe side effects. Recently, polysaccharides have garnered considerable attention due to their antioxidant, anti-neuroinflammatory, anticholinesterase, and anti-amyloidogenic properties. The ocean contains a large number of animals, plants, algae and fungal species. Its rich sources and wide availability make the research on marine drugs become a hot topic. Recently, polysaccharides dominated by fucoidan and chitosan have been reported to inhibit the progression of neurodegenerative diseases in a variety of ways. In this review article, we provide a comprehensive summary of reported polysaccharides that intervene in neurodegenerative diseases with the aim of exploring their potential as therapeutic agents.

The design and optimization of a sinter mixture moisture controlling system usually require complex process mechanisms and time-consuming field experimental simulations. Based on BP neural networks, a new KPCA-GA optimization method is proposed to predict the mixture moisture content sequential values with time more accurately so as to derive the optimal water addition to meet industrial requirements. Firstly, the normalized input variables affecting the output were dimensionalized using kernel principal component analysis (KPCA), and the contribution rates of the factors affecting the water content were analyzed. Then, a BP neural network model was established. In order to get rid of the randomness of the initial threshold and weights on the prediction accuracy of the model, a genetic algorithm is proposed to preferentially find the optimal initial threshold and weights for the model. Then, statistical indicators, such as the root mean square error, were used to evaluate the fit and prediction accuracy of the training and test data sets, respectively. The available experimental data show that the KPCA-GA model has high fitting and prediction accuracy, and the method has significant advantages over traditional neural network modeling methods when dealing with data sets with complex nonlinear characteristics, such as those from the sintering process.

Background Higher dietary quality, including increased vegetable consumption, was associated with a reduced risk of metabolic syndrome (MetS). However, specific vegetable consumption in the development of MetS remains obscure. Our study aimed to investigate the correlation between starchy and non-starchy vegetables and MetS. Methods Secondary data analysis from the National Health and Nutrition Examination Survey (NHANES 1999–2018). MetS was defined by National Cholesterol Education Program-Adult treatment Panel III (NCEP ATPIII) and dietary consumption was assessed by trained staff using two 24-h diet recall methods. Weighted logistic regression analysis was carried out to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses and restricted cubic spline (RCS) regression were performed to further investigate specific vegetable subtypes and MetS. Results This research enrolled 24,646 individuals (11,725 females and 12,921 males), with an average age of 45.84 ± 0.23 years. Approximately 15,828(64.22%) participants were defined to be with non-MetS and 8818(35.78%) were with MetS. Both total starchy vegetables and potatoes were associated with increased MetS risk, with the corresponding OR per standard deviation (SD) (95%CI, p -trend) being 1.06(1.02–1.11, p -trend = 0.028) and 1.08(1.04–1.13, p -trend = 0.011), respectively. However, an inverse correlation was found between dark-green vegetables and MetS, and the OR per SD (95%CI, p -trend) was 0.93(0.90–0.97, p -trend = 0.010). Subgroup analyses showed that the positive associations of starchy vegetables and potatoes on MetS risk were stronger in non-Hispanic White participants ( p for interaction < 0.050). Conclusion Total starchy vegetables and white potatoes were both associated with an increased risk of MetS, while consumption of dark-green vegetables was negatively associated with MetS risk. These findings might provide a promising and healthy dietary strategy for preventing MetS.

Vascular dementia (VaD), one of the brain injuries, is difficult to be cured, so it is important to take active neuroprotective treatment after its occurrence. Many studies have shown that apoptosis serves an important role in VaD occurrence; therefore, inhibition of apoptosis may contribute to the recovery of neurological function after VaD occurrence. Cerebroprotein hydrolysate-I (CH-I), a neuropeptide preparation which consists of several amino acids and small molecular peptides as the main active constituent, is extracted using a method similar to cerebrolysin (CBL) which has neuroprotective and neurotrophic effects. In the present study, a VaD model which was constructed using bilateral common carotid artery occlusion (BCCAO) in Kunming mice was applied to examine the neuroprotective effects of CH-I. The results show that CH-I treatment could attenuate the decrease of learning and memory ability, cell apoptosis in the hippocampal CA1 region and inhibit the activation of caspase-3 and caspase-9 in VaD mice. Furthermore, CH-I treatment could also upregulate Bcl-2 protein levels and activate PI3K and Akt. We speculate that CH-I may induce a neuroprotective effect activating PI3K/Akt signaling pathway in VaD mice.

To investigate the neuroprotective effect and mechanism of cerebroprotein hydrolysate-I (CH-I) on cerebral ischemia/reperfusion injury in rats. A total of 100 adult healthy male rats were randomly divided into a sham group, model group, CH-I treated group, and cerebrolysin (CBL) positive group, consisting of 20 rats in each group. The middle cerebral artery occlusion/reperfusion (MCAO/R) model of rats was built by inserting a suture into the left external carotid artery (ECA) through the internal carotid artery (ICA). Treatment was performed by intraperitoneal injection of CH-I (20 mg/kg). The neurobehavioral function of rats was evaluated by modified neurological severity scores (mNSS). TTC staining was used to detect the cerebral infarction volume (CIV) of rats. The morphological and structural changes of nerve cells were observed by HE staining and the neuronal apoptosis was counted by TUNEL assay. Immunohistochemical (IHC) analysis was used to detect BDNF and pMEK1/2 expressions. The expressions of BDNF, pMEK1/2, pERK1/2, and pCREB were determined with Western blotting. After treatment with CH-I, the mNSS and CIV of rats were improved ( <0.05). And the CH-I can reduce the degeneration and apoptosis of nerve cells in rats ( <0.01). Western blotting showed that the expressions of pMEK1/2, pERK1/2, and pCREB in rats were increased, while the expression of BDNF was decreased after modeling ( <0.05). After treatment, the expressions of pMEK1/2, pERK1/2, and pCREB in the CH-I group were decreased ( <0.05), while the expression of BDNF was significantly increased ( <0.05) compared with the model group. IHC showed that the expression of BDNF and pMEK1/2 was consistent with Western blotting. It is suggested that the CH-I might play a neuroprotective role by inhibiting the expression of MEK-ERK-CREB and enhancing the expression of BDNF after cerebral ischemia/reperfusion injury, thus improving the neurobehavioral function of MCAO/R rats.

Background Liver dysfunction is an independent risk factor for poor prognosis of patients with sepsis. The aim of this study is to evaluate the effects of continuous hemofiltration in patients with bacterial sepsis complicated by liver dysfunction. Methods We retrospectively analyzed the medical records of 27 cases of bacterial sepsis with liver dysfunction admitted to pediatric intensive care unit (PICU) of Shanghai Children’s Hospital between January 2013 and December 2016. Results 28-day mortality and length of PICU stay were significantly reduced in the continuous hemofiltration group ( n  = 16) compared with the conventional management group ( n  = 11) (31.3% vs. 72.7%, 9 [4–23] vs. 14 [4–36], respectively, both P  < 0.05). The interval time between PICU admission and continuous hemofiltration initiation was (22.06 ± 17.68) h, and the median time of continuous hemofiltration duration was 48 h (31–70 h). After 72 h hemofiltration, the levels of total bilirubin (TBIL), direct bilirubin (DBIL), total bile acids (TBA), ammonia, lactate (Lac), TNF-α and IL-6 were significantly decreased in the continuous hemofiltration group. Moreover, multivariate logistic regression analysis indicated that continuous hemofiltration treatment and the TBIL level were independently associated with 28-day mortality of patients with bacterial sepsis complicated by liver dysfunction. Conclusions Continuous hemofiltration significantly decreases the serum levels of TBIL, DBIL, TBA, Lac, ammonia, TNF-α, IL-6, and improves 28-day mortality of patients with bacterial sepsis complicated by liver dysfunction.