The Role of Macrophage Efferocytosis in the Pathogenesis of Apical Periodontitis.

Macrophages (Mφs) play a crucial role in the homeostasis of the periapical immune micro-environment caused by bacterial infection. Mφ efferocytosis has been demonstrated to promote the resolution of multiple infected diseases via accelerating Mφ polarization into M2 type. However, the Mφ efferocytosis-apical periodontitis (AP) relationship has not been elucidated yet. This study aimed to explore the role of Mφ efferocytosis in the pathogenesis of AP. Clinical specimens were collected to determine the involvement of Mφ efferocytosis in the periapical region via immunohistochemical and immunofluorescence staining. For a further understanding of the moderator effect of Mφ efferocytosis in the pathogenesis of AP, both an in vitro AP model and in vivo AP model were treated with ARA290, a Mφ efferocytosis agonist. Histological staining, micro-ct, flow cytometry, RT-PCR and Western blot analysis were performed to detect the inflammatory status, alveolar bone loss and related markers in AP models. The data showed that Mφ efferocytosis is observed in the periapical tissues and enhancing the Mφ efferocytosis ability could effectively promote AP resolution via facilitating M2 Mφ polarization. Collectively, our study demonstrates the functional importance of Mφ efferocytosis in AP pathology and highlights that accelerating Mφ efferocytosis via ARA290 could serve as an adjuvant therapeutic strategy for AP.

Effect of the gut microbiota and their metabolites on postoperative intestinal motility and its underlying mechanisms.

Gut microbiota is closely related to human health and disease because, together with their metabolites, gut microbiota maintain normal intestinal peristalsis. The use of antibiotics or opioid anesthetics, or both, during surgical procedures can lead to dysbiosis and affect intestinal motility; however, the underlying mechanisms are not fully known. This review aims to discuss the effect of gut microbiota and their metabolites on postoperative intestinal motility, focusing on regulating the enteric nervous system, 5-hydroxytryptamine neurotransmitter, and aryl hydrocarbon receptor.

Prognostic significance of CircRNAs expression in oral squamous cell carcinoma.

This systematic review was aimed to comprehensively evaluate the clinicopathological and prognostic value of dysregulated expression of circRNAs in OSCC. The research was carried out by searching mainstream electronic databases including PubMed, Embase, Web of Science, Scopus, LILACS, and Cochrane Library to collect relevant studies on prognostic role of circRNAs in OSCC. Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association between circRNAs expression, overall survival (OS), disease/recurrence/progression survival (DFS/RFS/PFS), and clinical parameters. This research included 1813 patients from 26 selected articles. The pooled HR values (95% CIs) in OS were 2.38 (1.92-2.93) for oncogenic circRNAs and 0.43 (0.28-0.66) for tumor-suppressor circRNAs, respectively, in DFS/RFS/PFS were 2.34 (1.73-3.17). The meta-analysis on clinicopathology features showed higher level of oncogenic circRNAs is related to advanced TNM stage, tumor stage, worse histological differentiation, positive lymph node and distant metastasis, while enforced expression of tumor-suppressor circRNAs is related to inferior TNM stage, tumor stage and lymphatic metastasis. In conclusion, our meta-analysis implies that circRNAs may be candidate biomarkers for the prognosis and clinicopathology of OSCC.

Indigenous Saccharomyces cerevisiae Could Better Adapt to the Physicochemical Conditions and Natural Microbial Ecology of Prince Grape Must Compared with Commercial Saccharomyces cerevisiae FX10.

Indigenous Saccharomyces cerevisiae, as a new and useful tool, can be used in fermentation to enhance the aroma characteristic qualities of the wine-production region. In this study, we used indigenous S. cerevisiae L59 and commercial S. cerevisiae FX10 to ferment Prince (a new hybrid variety from Lion Winery) wine, detected the basic physicochemical parameters and the dynamic changes of fungal communities during fermentation, and analyzed the correlations between fungal communities and volatile compounds. The results showed that the indigenous S. cerevisiae L59 could quickly adapt to the specific physicochemical conditions and microbial ecology of the grape must, showing a strong potential for winemaking. Compared with commercial S. cerevisiae FX10, the wine fermented by indigenous S. cerevisiae L59 contained more glycerol and less organic acids, contributing to a rounder taste. The results of volatile compounds indicated that the indigenous S. cerevisiae L59 had a positive effect on adding rosy, honey, pineapple and other sweet aroma characteristics to the wine. Overall, the study we performed showed that selection of indigenous S. cerevisiae from the wine-producing region as a starter for wine fermentation is conducive to improving the aroma profile of wine and preserving the aroma of the grape variety.

A Positive Feedback Loop Between Th17 Cells and Dendritic Cells in Patients with Endplate Inflammation.

BACKGROUND: Endplate inflammation remains a difficult disease to treat, in part due to its unclear pathology. Previous experiments showed that patients with idiopathic inflammation presented a systemic upregulation of Th17 cells. Here, we investigated how this change might affect the inflammatory environment in endplate inflammation. METHODS: Peripheral blood was obtained from patients and healthy controls, and Th17 cells were examined. RESULTS: Th17 cells significantly increased the differentiation of CD11c+ and DC-SIGN+ dendritic cells (DCs) from circulating monocytes in the absence of exogenous stimulation as well as in the presence of LPS stimulation. Th17 cells also increased CD80 and CD86 expression by DCs. Importantly, although Th17 cells from both healthy controls and patients with endplate inflammation could induce CD11c, DC-SIGN, CD80, and CD86 expression, Th17 cells from patients with endplate inflammation showed significantly more potent capacity. Both contact-dependent and IL-17-dependent mechanisms were employed by Th17 cells, since blocking cell-to-cell contact significantly inhibited Th17-mediated differentiation of CD11c+ DCs, and neutralization of IL-17 reduced the expression of CD80 and CD86. Strikingly, DCs following incubation with Th17 cells, but not the DCs derived directly from monocytes without Th17 cells, could significantly promote the expression of IL-17 from naive CD4+ T cells. CONCLUSIONS: These results demonstrated that Th17 cells from patients with endplate inflammation could potently induce the differentiation and activation of DCs that preferentially promoted IL-17 response in a positive feedback loop.

Patients with idiopathic endplate inflammation displayed aberrant Th17 responses resulting in proinflammatory monocyte activation.

Endplate inflammation remains a difficult task to diagnose and treat, partly due to the absence of in-depth understanding of the cellular and molecular factors driving this condition. In the current study, we investigated the circulating immune cells in patients with idiopathic endplate inflammation. Compared to healthy controls, the patients with endplate inflammation presented a significant upregulation of Th17 cells, characterized by higher frequencies of circulating IL-17+CD4+ T cells examined directly ex vivo and after PMA and ionomycin (PMA/I) stimulation. The frequency of Th17 cells in patients was not correlated with patient age, sex, or smoking status, but was significantly correlated with patient BMI. The total CD4+ T cells from patients with end plate inflammation also presented significantly higher levels of IL-17 secretion directly ex vivo and after PMA/I stimulation. The IL-17 secretion was primarily mediated by CCR4+CCR6+ CD4+ T cells, followed by CCR4-CCR6+ CD4+ T cells and was nearly absent in CCR4-CCR6- CD4+ T cells. Monocytes incubated with CCR4+CCR6+ CD4+ T cells presented significantly higher MHC class II expression, as well as higher CD80 and CD86 expression. The secretion of IL-6 and TNF was significantly higher in cell cultures containing CCR4+CCR6+ CD4+ T cells than in cell cultures containing CCR4-CCR6- CD4+ T cells. These effects were reduced when the IL-17A cytokine was neutralized. Together, we identified a systemic upregulation of Th17 responses that could contribute to proinflammatory monocyte activation in patients with endplate inflammation.

Bulk Acoustic Wave Characteristics of Pseudo Lateral-Field-Excitation on LGT Single Crystal for Liquid Phase Sensing.

In the present study, pseudo lateral-field-excitation (LFE) bulk acoustic wave characteristics on LGT crystals are investigated to increase the sensitivity of LFE devices on the liquid characteristic variations. The cut orientation of LGT crystals for pseudo-LFE is investigated and verified experimentally. For an LFE device in the pseudo-LFE mode, the thickness shear mode wave is excited by the thickness field rather than the lateral field. The present work shows that when the (yxl) 13.8° LGT plate is excited by the electric field parallel to the crystallographic axis x, it operates in the pseudo-LFE mode. Moreover, characteristics of devices including the sensitivity and impedance are investigated. The present work shows that sensitivity of LFE devices to variation of the conductivity and permittivity of the aqueous solution are 9 and 3.2 times higher than those for AT-cut quartz crystal based devices, respectively. Furthermore, it has been found that the sensitivity of the LGT LFE sensor to liquid acoustic viscosity variations is 1.4 times higher than the one for the AT-cut quartz sensor. The results are a critical basis of designing high-performance liquid phase sensors by using pseudo-LFE devices.

Administration of SB203580, a p38 MAPK Inhibitor, Reduced the Expression of MMP9, and Relieved Neurologic Severity in the Experimental Autoimmune Neuritis (EAN) in Rats.

Dysfunctional expression of matrix metalloproteinase-9 (MMP-9) has been found to be closely associated with the experimental autoimmune neuritis (EAN). In this study, we explored the role of p38 mitogen-activated protein kinases (p38 MAPK) in the regulation of MMP-9 in sciatic nerves of EAN rats. We analyzed the expression changes of MMP-2, MMP-3, MMP-9, and mitogen-activated protein kinases (MAP kinases) in sciatic nerves of EAN rats and investigated the effect of p38 MAPK inhibitor (SB203580) on MMP-9 expression and pathological changes in EAN. Real-time PCR and western blot analyses showed that the expression of MMP-2 exhibited no significant changes throughout the course of EAN, while MMP-3 and MMP-9 presented the relatively increased expression compared with that in control group. MAP kinases, including p38 MAPK, ERK1/2, and JNK1/2, were activated in the sciatic nerve of EAN rats, and phosphorylated p38 MAPK showed similar patterns of expression to MMP-9. The expression of MMP-9 and phosphorylated p38 MAPK in sciatic nerves were in positive correlation with disease severity. In addition, SB203580 treatment significantly reduced the mRNA and protein level of MMP-9 in sciatic nerves on the peak phase of EAN. Inhibition of p38 MAPK also relieved neurologic severity and ameliorated pathological changes in EAN. In conclusion, SB203580 may ameliorate clinical deficit and pathological changes in EAN by reducing the MMP-9 expression in sciatic nerves, which suggest that p38 MAPK inhibitor such as SB203580 could be considered as a therapeutic candidate in autoimmune neuropathies.

Severe inflammation in C57/BL6 mice leads to prolonged cognitive impairment by initiating the IL-1ß/TRPM2 pathway.

BACKGROUND: Sepsis could lead to chronic cognitive impairment by unclear molecular mechanisms. Transient receptor potential melastatin-2 (TRPM2) is essential against immunity-related activities and inflammation. Our study attempted to decipher the relationship between cognitive impairment caused by severe inflammation and TRPM2 expression levels. METHODS: Severe inflammation was induced by intraperitoneally injecting C57/BL6 mice with a high dosage (5 mg kg-1) of Lipopolysaccharide (LPS). Fear conditioning and a Morris water maze test were performed to examine the cognitive abilities of the mice. Moreover, the signaling and expression of pro-inflammatory cytokines and TRPM2 were measured using Western blotting and Reverse transcription-polymerase chain reaction (RT-PCR). Flow cytometry and immunofluorescence staining helped to determine the astrocyte apoptosis rate. RESULTS: Severe inflammation can lead to long-term cognitive impairment in C57/BL6 mice. The interleukin-1 beta (IL-1ß) levels intra-hippocampus were significantly elevated until P14 post-LPS introduction. At both P7 and P14, there is an up-regulation of TRPM2 expression within hippocampus. Administration of recombinant IL-1ß to astrocytes results in a significant up-regulation of TRPM2 expression. IL-1ß or TRPM2 level knockdown helped counter the cognitive impairment caused by significant inflammation. CONCLUSIONS: A continuous increase in IL-1ß levels within the hippocampus can lead to cognitive impairment by enhancing TRPM2 levels caused by severe inflammation.

The development and nutritional quality of Lyophyllum decastes affected by monochromatic or mixed light provided by light-emitting diode.

Edible fungi has certain photo-sensitivity during the mushroom emergence stage, but there has been few relevant studies on the responses of Lyophyllum decastes to different light quality. L. decastes were planted in growth chambers with different light qualities that were, respectively, white light (CK), monochromatic red light (R), monochromatic blue light (B), mixed red and blue light (RB), and the mixture of far-red and blue light (FrB). The photo-sensitivity of L. decastes was investigated by analyzing the growth characteristics, nutritional quality, extracellular enzymes as well as the light photoreceptor genes in mushroom exposed to different light treatments. The results showed that R led to mycelium degeneration, fungal skin inactivation and failure of primordial formation in L. decastes. The stipe length, stipe diameter, pileus diameter and the weight of fruiting bodies exposed to RB significantly increased by 8.0, 28.7, 18.3, and 58.2% respectively, compared to the control (p < 0.05). B significantly decreased the stipe length and the weight of fruiting body, with a decrease of 8.5 and 20.2% respectively, compared to the control (p < 0.05). Increased color indicators and deepened simulated color were detected in L. decastes pileus treated with B and FrB in relative to the control. Meanwhile, the expression levels of blue photoreceptor genes such as WC-1, WC-2 and Cry-DASH were significantly up-regulated in mushroom exposed to B and FrB (p < 0.05). Additionally, the contents of crude protein and crude polysaccharide in pileus treated with RB were, respectively, increased by 26.5 and 9.4% compared to the control, while those in stipes increased by 5.3 and 58.8%, respectively. Meanwhile, the activities of extracellular enzyme such as cellulase, hemicellulase, laccase, manganese peroxidase, lignin peroxidase and amylase were significant up-regulated in mushroom subjected to RB (p < 0.05), which may promote the degradation of the culture materials. On the whole, the largest volume and weight as well as the highest contents of nutrients were all detected in L. decastes treated with RB. The study provided a theoretical basis for the regulation of light environment in the industrial production of high quality L. decastes.

Ginsenoside RB1 Influences Macrophage-DPSC Interactions in Inflammatory Conditions.

INTRODUCTION AND AIMS: Unresolved inflammation and tissue destruction are supposed to underlie the failure of dental pulp repair. As crucial regulators of the injury response, dental pulp stem cells (DPSCs) play a key role in pulp tissue repair and regeneration. M2 macrophages have been demonstrated to induce osteogenic/odontogenic differentiation of DPSCs. Ginsenoside Rb1 (GRb1) is the major component of ginseng and manifested an anti-inflammatory role by promoting M1 macrophage polarised into M2 macrophage in inflammatory disease. However, whether GRb1 facilitates odontogenic differentiation of DPSCs via promoting M2 macrophage polarisation under inflammatory conditions has yet to be established. METHODS: Human monocyte leukemic cells (THP-1) differentiated macrophages were induced into M1 subsets and then treated with GRb1. After that, the conditioned medium was added to DPSCs. The cell co-cultured system was then subjected to odontogenic differentiation in osteogenic media. Effects of GRb1 on human dental pulp stem cells' (hDPSCs') osteogenic/odontogenic differentiation under inflammatory conditions were assessed by alkaline phosphatase (ALP) staining, Alizarin Red S (ARS) staining, and quantitative polymerase chain reaction testing. RESULTS: Results demonstrated that GRb1 could facilitate the polarisation of macrophages from the M1 subtype to the M2 subtype. Conditioned medium from GRb1 + M1 macrophages, in comparison with M1 macrophages, may markedly increase the gene expression of ALP, DSPP, and DMP1. Moreover, ALP and ARS staining uncovered that the osteogenic/odontogenic differentiation ability of hDPSCs was strengthened in the M1 + GRb1 co-culture group. CONCLUSIONS: GRb1 plays a crucial role in the inflammatory response and reparative dentine formation after dental pulp injury. Findings show that GRb1 modulates the interaction between macrophages and DPSCs during inflammation. The current study discusses modifications of deep caries therapy.

Molecular characterization and clinical relevance of metabolic signature subtypes in gastric cancer.

Metabolic reprogramming dictates tumor molecular attributes and therapeutic potentials. However, the comprehensive metabolic characteristics in gastric cancer (GC) remain obscure. Here, metabolic signature-based clustering analysis identifies three subtypes with distinct molecular and clinical features: MSC1 showed better prognosis and upregulation of the tricarboxylic acid (TCA) cycle and lipid metabolism, combined with frequent TP53 and RHOA mutation; MSC2 had moderate prognosis and elevated nucleotide and amino acid metabolism, enriched by intestinal histology and mismatch repair deficient (dMMR); and MSC3 exhibited poor prognosis and enhanced glycan and energy metabolism, accompanied by diffuse histology and frequent CDH1 mutation. The Shandong Provincial Hospital (SDPH) in-house dataset with matched transcriptomic, metabolomic, and spatial-metabolomic analysis also validated these findings. Further, we constructed the metabolic subtype-related prognosis gene (MSPG) scoring model to quantify the activity of individual tumors and found a positive correlation with cuproptosis signaling. In conclusion, comprehensive recognition of the metabolite signature can enhance the understanding of diversity and heterogeneity in GC.

[Pretreatment method of near-infrared diffuse reflection spectra used for sugar content prediction of pears].

The content of sugar is an important quality index for pears. However, the traditional sugar measurement methods are time-consuming and destructive. In the present study, the authors measured the sugar content of pears using visible and near infrared diffuse reflection spectroscopy. The pretreatment methods of multiplicative scatter correction (MSC), baseline correction, standard normal variate (SNV) transformation, and moving average algorithms were used on the original absorbance spectrum. Results indicate that the absorbance spectra after pretreatment are better than the original absorbance spectra for prediction. Partial least squares (PLS) regression was also used on the original absorbance spectrum and the absorbance spectrum after moving average and baseline correction. It follows that the forecast accuracy of the absorbance spectra after moving average is higher than that of the original absorbance spectra. The models gave good predictions of the sugar content of pears, with corresponding r values of 0.990 8, and standard errors of predictions of 0.019 0.

Low MHR Is Associated with Hemorrhagic Transformation in Acute Large Artery Atherosclerosis Ischemic Stroke Patients with Intravenous Thrombolysis.

Background: Hemorrhagic transformation (HT) is a common complication of intravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS) and may lead to neurological deterioration. This article discusses whether monocyte count to high-density lipoprotein ratio (MHR) level is associated with HT in AIS patients. Materials and methods: The clinical data of AIS patients who underwent rt-PA IVT treatment were continuously collected. According to whether HT occurred, patients were divided into HT group and non-HT group. Potential association between MHR and HT in different subtypes AIS was explored by using logistic regression. Results: A total of 444 AIS patients were retrospective analyzed. The MHR level was lower in HT group compared with the non-HT group in all AIS patients (0.28 vs 0.36, P = .031) and in large-artery atherosclerosis (LAA) type AIS patients (0.31 vs 0.37, P = .032). Low MHR was independently related to HT (OR:0.035, 95%CI:0.003-0.390, P = .006). Among all TOAST subtypes, low MHR was only independently associated with HT in patients of LAA-type AIS after adjusting for confounding factors (OR:0.01, 95%CI:0.00-0.62, P = .031), with an optimal cut-off value of 0.41, sensitivity of 85.7%, and specificity of 43.1%. MHR was not correlated with SVO, VE, and CE subtype AIS. Conclusion: Low MHR may be an independent predictor of HT in patients with AIS and this conclusion only existed in LAA-type AIS.

Effects of La Addition on Microstructure Evolution and Thermal Stability of Cu-2.35Ni-0.59Si Sheet.

A Cu-2.35Ni-0.69Si alloy with low La content was designed in order to study the role of La addition on microstructure evolution and comprehensive properties. The results indicate that the La element demonstrates a superior ability to combine with Ni and Si elements, via the formation of La-rich primary phases. Owing to existing La-rich primary phases, restricted grain growth was observed, due to the pinning effect during solid solution treatment. It was found that the activation energy of the Ni2Si phase precipitation decreased with the addition of La. Interestingly, the aggregation and distribution of the Ni2Si phase, around the La-rich phase, was observed during the aging process, owing to the attraction of Ni and Si atoms by the La-rich phase during the solid solution. Moreover, the mechanical and conductivity properties of aged alloy sheets suggest that the addition of the La element showed a slight reducing effect on the hardness and electrical conductivity. The decrease in hardness was due to the weakened dispersion and strengthening effect of the Ni2Si phase, while the decrease in electrical conductivity was due to the enhanced scattering of electrons by grain boundaries, caused by grain refinement. More notably, excellent thermal stabilities, including better softening resistance ability and microstructural stability, were detected for the low-La-alloyed Cu-Ni-Si sheet, owing to the delayed recrystallization and restricted grain growth caused by the La-rich phases.

Intravenous dexamethasone administration during anesthesia induction can improve postoperative nutritional tolerance of patients following elective gastrointestinal surgery: A post-hoc analysis.

Aim: To investigate the effect of intravenous dexamethasone administration on postoperative enteral nutrition tolerance in patients following gastrointestinal surgery. Methods: Based on the previous results of a randomized controlled study to explore whether intravenous administration of dexamethasone recovered gastrointestinal function after gastrointestinal surgery, we used the existing research data from 1 to 5 days post operation in patients with enteral nutrition tolerance and nutrition-related analyses of the changes in serum indices, and further analyzed the factors affecting resistance to enteral nutrition. Result: The average daily enteral caloric intake was significantly higher in patients receiving intravenous administration of dexamethasone during anesthesia induction than in controls (8.80 ± 0.92 kcal/kg/d vs. 8.23 ± 1.13 kcal/kg/d, P = 0.002). Additionally, intravenous administration of 8 mg dexamethasone during anesthesia induction can reduce the changes in postoperative day (POD) 3, POD5, and preoperative values of serological indices, including ΔPA, ΔALB, and ΔRBP (P < 0.05). In the subgroup analysis, dexamethasone significantly increased the average daily enteral nutrition caloric intake in patients undergoing enterotomy (8.98 ± 0.87 vs. 8.37 ± 1.17 kcal/kg/d, P = 0.010) or in female patients (8.94 ± 0.98 vs. 8.10 ± 1.24 kcal/kg/d, P = 0.019). The changes of serological indexes (ΔPA, ΔALB, and ΔRBP) in the dexamethasone group were also significantly different on POD3 and POD5 (P < 0.05). In addition, multivariate analysis showed that dexamethasone use, surgical site, and age might influence enteral nutrition caloric tolerance. Conclusion: Postoperative enteral nutrition tolerance was significantly improved in patients receiving intravenous administration of dexamethasone during anesthesia induction, especially in patients following enterotomy surgery, with significant improvements in average daily enteral caloric intake, PA levels, ALB levels, and RBP levels. Clinical trial registration: http://www.chictr.org.cn, identifier: ChiCTR1900024000.

Using OPLS-DA to Fingerprint Key Free Amino and Fatty Acids in Understanding the Influence of High Pressure Processing in New Zealand Clams.

This study investigated the effect of high pressure processing (HPP) on the fatty acids and amino acids content in New Zealand Diamond Shell (Spisula aequilatera), Storm Shell (Mactra murchisoni), and Tua Tua (Paphies donacina) clams. The clam samples were subjected to HPP with varying levels of pressure (100, 200, 300, 400, 500, and 600 MPa) and holding times (5 and 600 s) at 20 °C. Partial Least Squares Discriminant Analysis (PLS-DA) and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) were deployed to fingerprint the discriminating amino and fatty acids post-HPP processing while considering their inherent biological variation. Aspartic acid (ASP), isoleucine (ILE), leucine (LEU), lysine (LYS), methionine (MET), serine (SER), threonine (THR), and valine (VAL) were identified as discriminating amino acids, while C18:0, C22:1n9, C24:0, and C25:5n3 were identified as discriminating fatty acids. These amino and fatty acids were then subjected to mixed model ANOVA. Mixed model ANOVA was employed to investigate the influence of HPP pressure and holding times on amino acids and fatty acids in New Zealand clams. A significant effect of pressure levels was reported for all three clam species for both amino and fatty acids composition. Additionally, holding time was a significant factor that mainly influenced amino acid content. butnot fatty acids, suggesting that hydrostatic pressure hardly causes hydrolysis of triglycerides. This study demonstrates the applicability of OPLS-DA in identifying the key discriminating chemical components prior to traditional ANOVA analysis. Results from this research indicate that lower pressure and shorter holding time (100 MPa and 5 s) resulted in the least changes in amino and fatty acids content of clams.

A research on urban disaster resilience assessment system for rainstorm and flood disasters: A case study of Beijing.

Under the background of global climate change, rainstorm and flood disasters have become the most serious cataclysm. Under the circumstances of an increasingly severe risk situation, it is necessary to enhance urban disaster resilience. Based on the disaster resilience process of prevention, absorption, and enhancement, and considering the safety factors such as personnel, facility, environment and management, this paper forms a dual dimension of the urban disaster resilience assessment model covering the key elements of urban disaster response and the core capacity of urban disaster recovery. Furthermore, if taking into account the characteristics of rainstorm and flood disasters, the paper screens the key indicators to build up an assessment index system of an urban rainstorm and flood disaster. The practical application was implemented in Beijing to have an assessment of the ability to recover from rainstorm and flood disasters in all districts of Beijing. And then, some pertinent suggestions for enhancing the resilience of Beijing to rainstorm and flood disasters were proposed.

ITGB1-mediated molecular landscape and cuproptosis phenotype induced the worse prognosis in diffuse gastric cancer.

Diffuse type gastric cancer was identified with relatively worse prognosis than other Lauren's histological classification. Integrin ß1 (ITGB1) was a member of integrin family which played a markedly important role in tumorigenesis and progression. However, the influence of ITGB1 in diffuse gastric cancer (DGC) remains uncertain. Here, we leveraged the transcriptomic and proteomic data to explore the association between ITGB1 expression and clinicopathologic information and biological process in DGC. Cell phenotype experiments combined with quantitative-PCR (q-PCR) and western blotting were utilized to identify the potential molecular mechanism underling ITGB1.Transcriptomics and proteomics both revealed that the higher ITGB1 expression was significantly associated with worse prognosis in DGC, but not in intestinal GC. Genomic analysis indicated that the mutation frequency of significantly mutated genes of ARID1A and COL11A1, and mutational signatures of SBS6 and SBS15 were markedly increased in the ITGB1 low expression subgroup. The enrichment analysis revealed diverse pathways related to dysregulation of ITGB1 in DGC, especially in cell adhesion, proliferation, metabolism reprogramming, and immune regulation alterations. Elevated activities of kinase-ROCK1, PKACA/PRKACA and AKT1 were observed in the ITGB1 high-expression subgroup. The ssGSEA analysis also found that ITGB1 low-expression had a higher cuproptosis score and was negatively correlated with key regulators of cuproptosis, including FDX1, DLAT, and DLST. We further observed that the upregulated expression of mitochondrial tricarboxylic acid (TCA) cycle in the ITGB1 low-expression group. Reduced expression of ITGB1 inhibited the ability of cell proliferation and motility and also potentiated the cell sensitive to copper ionophores via western blotting assay. Overall, this study revealed that ITGB1 was a protumorigenic gene and regulated tumor metabolism and cuproptosis in DGC.

Suppression of tumorigenesis in LUAD by LRP1B through regulation of the IL-6-JAK-STAT3 pathway.

Lung adenocarcinoma (LUAD) is the most common type of lung cancer. LRP1B was initially identified as a cancer suppressor in several cancers. However, the potential biological phenotypes and molecular mechanisms of LRP1B in LUAD have not been fully investigated. In our study, we showed that the expression of LRP1B in LUAD tissues was lower than that in normal tissues. Knockdown of LRP1B markedly enhanced malignancy of LUAD cells. Genomic analysis indicated that the population expressing low-levels of LRP1B had higher genomic instability, which accounted for a larger proportion of aneuploidy and inflammation subtyping. Enrichment analysis of bulk and cell-line transcriptomic data both showed that the low expression of LRP1B could induce the activation of IL-6-JAK-STAT3, chemokine, cytokine, and other inflammation signaling pathways. Moreover, our findings revealed that knockdown LRP1B enhanced the secretion of IL-6 and IL-8, as confirmed by ELISA assays. Further validation using PCR and WB confirmed that downregulation of LRP1B mRNA significantly upregulated the activity of the IL-6-JAK-STAT3 pathway. Collectively, this study highlights LRP1B as a tumor suppressor gene and reveals that LRP1B knockdown promotes malignant progression in LUAD by inducing inflammation through the IL-6-JAK-STAT3 pathway.