Structural Modification and Optimisation of Hyperoside Oriented to Inhibit TGF-ß-Induced EMT Activity in Alveolar Epithelial Cells.

Pulmonary fibrosis (PF) is a disease characterised by diffuse nonspecific alveolar inflammation with interstitial fibrosis, which clinically manifests as dyspnoea and a significant decline in lung function. Many studies have shown that the epithelial-mesenchymal transition (EMT) plays a pivotal role in the pathogenesis of pulmonary fibrosis. Based on our previous findings, hypericin (Hyp) can effectively inhibit the process of the EMT to attenuate lung fibrosis. Therefore, a series of hyperoside derivatives were synthesised via modifying the structure of hyperoside, and subsequently evaluated for A549 cytotoxicity. Among these, the pre-screening of eight derivatives inhibits the EMT. In this study, we evaluated the efficacy of Z6, the most promising hyperoside derivative, in reversing TGF-ß1-induced EMTs and inhibiting the EMT-associated migration of A549 cells. After the treatment of A549 cells with Z6 for 48 h, RT-qPCR and Western blot results showed that Z6 inhibited TGF-ß1-induced EMTs in epithelial cells by supressing morphological changes in A549 cells, up-regulating E-cadherin (p < 0.01, p < 0.001), and down-regulating Vimentin (p < 0.01, p < 0.001). This treatment significantly reduced the mobility of transforming growth factor ß1 (TGF-ß1)-stimulated cells (p < 0.001) as assessed by wound closure, while increasing the adhesion rate of A549 cells (p < 0.001). In conclusion, our results suggest that hyperoside derivatives, especially compound Z6, are promising as potential lead compounds for treating pulmonary fibrosis, and therefore deserve further investigation.

Testing of Anti-EMT, Anti-Inflammatory and Antibacterial Activities of 2',4'-Dimethoxychalcone.

Chalcone (1,3-diaryl-2-propen-1-one) is an α, ß-unsaturated ketone that serves as an active constituent or precursor of numerous natural substances, exhibiting a broad spectrum of pharmacological effects. In this study, the classical Claisen-Schmidt condensation method was used to synthesize the chalcone derivative 2',4'-dimethoxychalcone (DTC) and evaluate its pharmacological activity. By upregulating the expression of the epithelial cell marker E-cadherin and downregulating the expression of the mesenchymal cell marker vimentin, DTC was found to inhibit transforming growth factor-ß1 (TGF-ß1)-induced epithelial-mesenchymal transition (EMT) process in A549 cells, maintaining the cells' epithelial-like morphology and reducing the ability of the cells to migrate. Additionally, DTC demonstrated the ability to decrease the expression levels of nitric oxide (NO), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) in RAW264.7 cells, suggesting a possible anti-inflammatory effect. Furthermore, DTC was found to exhibit bacteriostatic activity against Staphylococcus aureus (S. aureus), Proteus vulgaris (P. vulgaris), methicillin-resistant Staphylococcus aureus (MRSA), and Candida albicans (C. albicans), indicating that this chemical may possess broad-spectrum antibacterial activity.

Investigation of morphology and structure of drug-loaded PLA-b-PEO-b-PLA polymeric micelle: A dissipative particle dynamics simulations study.

The dissipative particle dynamics (DPD) simulation was used to study the morphologies and structures of the paclitaxel-loaded PLA-b-PEO-b-PLA polymeric micelle. We focused on the influences of PLA block length, PLA-b-PEO-b-PLA copolymer concentration, paclitaxel drug content on morphologies and structures of the micelle. Our simulations show that: (i) with the PLA block length increase, the self-assemble structure of PLA-b-PEO-b-PLA copolymers with paclitaxel vary between onion-like structure (core-middle layer-shell) to spherical core-shell structure. The PEO shell thins and the size of the PLA core increases. The onionlike structures are comprised of the PEO hydrophilic core, the PLA hydrophobic middle layer, and the PEO hydrophilic shell, the distribution of the paclitaxel drug predominantly occurs within the hydrophobic intermediate layer; (ii) The system forms a spherical core-shell structure when a small amount of the drug is added, and within a certain range, the size of the spherical structure increases as the drug amount increases. When the drug contents (volume fraction) cdrug = 10%, it can be observed that the PLA4-b-PEO19-b-PLA4 spherical structures connect to form rod-shaped structures. With the length of PLA block NPLA = 8, as the paclitaxel drug concentrations cdrug = 4%, PEO has been insufficient to completely encapsulate the PLA and paclitaxel drug beads. To enhance drug loading capacity while maintaining stability of the system in aqueous solution, the optimal composition for loading paclitaxel is PLA4-b-PEO19-b-PLA4; the drug content is not higher than 4%; (iii) The paclitaxel-loaded PLA4-b-PEO19-b-PLA4 micelle undergo the transition from onionlike (core-middle layer-shell) to spherical (core-shell) to rod-shaped and lamellar structure as the PLA4-b-PEO19-b-PLA4 copolymer concentration increases from ccp = 10% to 40%.

The burden and predictors of 30-day unplanned readmission in patients with acute liver failure: a national representative database study.

BACKGROUND: Liver diseases were significant source of early readmission burden. This study aimed to evaluate the 30-day unplanned readmission rates, causes of readmissions, readmission costs, and predictors of readmission in patients with acute liver failure (ALF). METHODS: Patients admitted for ALF from 2019 National Readmission Database were enrolled. Weighted multivariable logistic regression models were applied and based on Directed Acyclic Graphs. Incidence, causes, cost, and predictors of 30-day unplanned readmissions were identified. RESULTS: A total of 3,281 patients with ALF were enrolled, of whom 600 (18.3%) were readmitted within 30 days. The mean time from discharge to early readmission was 12.6 days. The average hospital cost and charge of readmission were $19,629 and $86,228, respectively. The readmissions were mainly due to liver-related events (26.6%), followed by infection (20.9%). The predictive factors independently associated with readmissions were age, male sex (OR 1.227, 95% CI 1.023-1.472; P = 0.028), renal failure (OR 1.401, 95% CI 1.139-1.723; P = 0.001), diabetes with chronic complications (OR 1.327, 95% CI 1.053-1.672; P = 0.017), complicated hypertension (OR 1.436, 95% CI 1.111-1.857; P = 0.006), peritoneal drainage (OR 1.600, 95% CI 1.092-2.345; P = 0.016), etc. CONCLUSIONS: Patients with ALF are at relatively high risk of early readmission, which imposes a heavy medical and economic burden on society. We need to increase the emphasis placed on early readmission of patients with ALF and establish clinical strategies for their management.

Neuroendoscopic Surgery Versus Stereotactic Aspiration in the Treatment of Supratentorial Intracerebral Hemorrhage: A Meta-Analysis.

BACKGROUND: Debate persists over the relative merits of neuroendoscopic surgery (NS) compared to stereotactic aspiration (SA) for treating supratentorial intracerebral hemorrhage (ICH). Consequently, we undertook this meta-analysis to assess the efficacy and safety of NS versus SA. METHODS: We searched for the all-relevant studies systematically from English databases including PubMed, Embase, Web of Science, and the Cochrane Library. Three independent researchers identified and selected these literatures that met the inclusion criteria. Then we evaluated the quality of these studies according to the Cochrane Collaboration's risk of bias tool and the Newcastle-Ottawa Scale. RevMan 5.4 statistical software was used to conduct this meta-analysis. RESULTS: Sixteen studies, including 2722 supratentorial ICH patients, were included in our meta-analysis. The pooled results showed that NS could effectively improve the functional prognosis (P = 0.002), reduce the postoperative mortality (P < 0.00001), and increase the hematoma evacuation rate (P < 0.00001). In addition, SA had more advantages in shortening operation time (P < 0.00001) and reducing intraoperative blood loss (P < 0.0001). However, there was no obvious statistical difference in intensive care unit stays (P = 0.23) between NS and SA. Besides, no sufficient evidence could support a significant difference in hospital stays. In the aspect of complications, NS was discovered to have a positive effect on preventing rebleeding (P = 0.005) and intracranial infection (P = 0.003). However, no significant differences between the 2 groups in digestive tract ulcer (P = 0.34), epilepsy (P = 0.99), and pneumonia (P = 0.58) were discovered. In the subgroup analysis, factors including publication time, Glasgow Coma Scale score, age, and follow-up, all significantly influenced the good functional outcome and mortality. Meanwhile, NS behaved more advantageous in improving functional prognosis for patients with hematoma located in the basal ganglia. CONCLUSIONS: NS may hold more advantages over SA in the treatment of supratentorial ICH. However, SA is also an effective and suitable alternative for elderly patients, especially those with multiple comorbidities intolerant to extended surgical procedures. Further high-quality studies are warranted to substantiate our findings in the future.

Dual-functional ionic liquids additive enables dendrite-free Zn anode with ultra-long cycle life over one year.

Zn anodes suffer from the formation of uncontrolled dendrites aggravated by the uneven electric field and the insulating by-product accumulation in aqueous zinc-ion batteries (AZIBs). Here, an effective strategy implemented by 1-butyl-3-methylimidazolium hydrogen sulfate (BMIHSO4) additive is proposed to synergistically tune the crystallographic orientation of zinc deposition and suppress the formation of zinc hydroxide sulfate for enhancing the reversibility on Zn anode surface. As a competing cation, BMI+ is proved to preferably adsorb on Zn-electrode compared with H2O molecules, which shields the "tip effect" and inhibits the Zn-deposition agglomerations to inducing the horizontal growth along Zn (002) crystallographic texture. Simultaneously, the protonated BMIHSO4 additives could remove the detrimental OH- in real-time to fundamentally eliminate the accumulation of 6Zn(OH)2·ZnSO4·4H2O and Zn4SO4(OH)6·H2O on Zn anode surface. Consequently, Zn anode exhibits an ultra-long cycling stability of one year (8762 h) at 0.2 mA cm-2/0.2 mAh cm-2, 3600 h at 2 mA cm-2/2 mAh cm-2 with a high plating cumulative capacity of 3.6 Ah cm-2, and a high average Coulombic efficiency of 99.6 % throughout 1000 cycles. This work of regulating Zn deposition texture combined with eliminating notorious by-products could offer a desirable way for stabilizing the Zn-anode/electrolyte interface in AZIBs.

Provincial Maternal and Child Information System in Inner Mongolia, China: Descriptive Implementation Study.

BACKGROUND: After the implementation of 2- and 3-child policies, the rising proportion of high-age and high-risk pregnancies put enormous pressure on maternal and child health (MCH) services for China. This populous nation with an increasing population flow imperatively required the support of large-scale information systems for management. Municipal MCH information systems were commonly applied in developed cities of eastern provinces in China. However, implementation of provincial MCH information systems in relatively low-income areas is lacking. In 2020, the implementation of a regional maternal and child information system (RMCIS) in Inner Mongolia filled this gap. OBJECTIVE: This paper aimed to demonstrate the construction process and evaluate the implementation effect of an RMCIS in improving the regional MCH in Inner Mongolia. METHODS: We conducted a descriptive study for the implementation of an RMCIS in Inner Mongolia. Based on the role analysis and information reporting process, the system architecture design had 10 modules, supporting basic health care services, special case management, health support, and administration and supervision. Five-color management was applied for pregnancy risk stratification. We collected data on the construction cost, key characteristics of patients, and use count of the main services from January 1, 2020, to October 31, 2022, in Inner Mongolia. Descriptive analysis was used to demonstrate the implementation effects of the RMCIS. RESULTS: The construction and implementation of the RMCIS cost CNY 8 million (US $1.1 million), with a duration of 13 months. Between 2020 and 2022, the system recorded 221,772 registered pregnant women, with a 44.75% early pregnancy registry rate and 147,264 newborns, covering 278 hospitals and 225 community health care centers in 12 cities. Five-color management of high-risk pregnancies resulted in 76,975 (45.45%) pregnancies stratified as yellow (general risk), 36,627 (21.63%) as orange (relatively high risk), 156 (0.09%) as red (high risk), and 3888 (2.30%) as purple (infectious disease). A scarred uterus (n=28,159, 36.58%), BMI≥28 (n=14,164, 38.67%), aggressive placenta praevia (n=32, 20.51%), and viral hepatitis (n=1787, 45.96%) were the top factors of high-risk pregnancies (yellow, orange, red, and purple). In addition, 132,079 pregnancies, including 65,018 (49.23%) high-risk pregnancies, were registered in 2022 compared to 32,466 pregnancies, including 21,849 (67.30%) high-risk pregnancies, registered in 2020. CONCLUSIONS: The implementation of an RMCIS in Inner Mongolia achieved the provincial MCH data interconnection for basic services and obtained both social and economic benefits, which could provide valuable experience to medical administration departments, practitioners, and medical informatics constructors worldwide.

Prognostic value of neutrophil count to albumin ratio in patients with decompensated cirrhosis.

Our study aimed to investigate the prognostic value of neutrophil count to albumin ratio (NAR) in predicting short-term mortality of patients with decompensated cirrhosis (DC). A total of 623 DC patients were recruited from a retrospective observational cohort study. They were admitted to our hospital from January 2014 to December 2015. NAR of each patient was calculated and analyzed for the association with 90-day liver transplantation-free (LT-free) outcome. The performance of NAR and the integrated model were tested by a receiver-operator curve (ROC) and C-index. The 90-day LT-free mortality of patients with DC was 10.6%. NAR was significantly higher in 90-day non-survivors than in survivors (The median: 1.73 vs 0.76, P < 0.001). A threshold of 1.40 of NAR differentiated patients with a high risk of death (27.45%) from those with a low risk (5.11%). By multivariate analysis, high NAR was independently associated with poor short-term prognosis (high group: 5.07 (2.78, 9.22)). NAR alone had an area under the ROC curve of 0.794 and C-index of 0.7789 (0.7287, 0.8291) in predicting 90-day mortality. The integrated MELD-NAR (iMELD) model had a higher area under the ROC (0.872) and C-index (0.8558 (0.8122, 0.8994)) than the original MELD in predicting 90-day mortality. NAR can be used as an independent predictor of poor outcomes for patients with DC during short-term follow-up.

Innovative Use of Waste PET-Derived Additive to Enhance Application Potentials of Recycled Concrete Aggregates in Asphalt Rubber.

Polyethylene terephthalate (PET) drinking bottles, rubber tires, and concrete are the very common municipal solid wastes, which are usually disposed of at landfills and stockpiles and cause continuous damage to the environment. Some studies have indicated that waste PET can be chemically converted into an additive for improving the overall properties of asphalt pavement incorporating natural aggregates, especially the moisture-induced damage resistance. However, it is not clear whether this PET additive still works for asphalt rubber containing recycled concrete aggregates (RCA). To well reveal this issue, this study first adopted a similar way to chemically recycle waste PET into the additive for modifying crumb rubber modified asphalt (CRMA) binder and then mixed the binder with the 13 mm maximum aggregate stone matrix asphalt containing 100% coarse RCA for preparing the mixtures. After a series of physicochemical characterizations of the PET additive, the moisture resistance, rutting resistance, low-temperature cracking resistance, and fatigue resistance of the mixture were systematically evaluated. The results showed that the PET additive is capable of improving the resistance to moisture and high-temperature deformation of asphalt rubber and helps greatly reduce the moisture-induced damage to the interfacial bonding layer. To be more detailed, the residual Marshall stability (RMS) value of RCA-CRMAM/1PET after 72 h of immersion is higher than 85% by contrast to that of RCA-CRMAM (77.1%), while the tensile strength ratio (TSR) value of RCA-CRMAM/1PET shows more than 80% compared to that of 65.2%. In addition, only 1% PET additive can enhance the high-temperature resistance of asphalt rubber containing RCA to rut and allow it to maintain higher resistance to rut after moisture-induced damage. 1% PET additive can help improve the bearing capacity of RCA-CRMAM under a low-temperature environment and delay its fatigue life at small stresses. Generally, with the successful introduction of PET additives to asphalt rubber containing RCA, more durable and sustainable highway pavement can be produced and applied in practice to alleviate the negative impacts caused by waste PET, waste tire rubber, and waste concrete.

Modeling the power system resilience in China under different natural disasters.

A good understanding of the power system resilience is necessary for optimizing the investment strategies and supporting the emergency rescue, but the existing quantitative estimation results based on real outage events are still lacked due to the data limitations. Therefore, this study first establishes a unified framework to measure the power system resilience under different natural disasters, by integrating the electricity performance curve with the dynamic inoperability input-output model. Then, a database of 285 Chinese historical big power outage events caused by natural disasters is established, and the city-level power system resilience values are estimated. Finally, a benefit analysis is conducted for improving the power system resilience. Our major findings are that: (1) Electricity system recoveries quickest from hail (23.05 h), while restores slowest from snowstorm (117.31 h). (2) China's city electricity system is the most resilient to the thunderstorm, while is the least resilient to the earthquake. (3) Enhancing the power system resilience will significantly reduce the requirements for rescue resources, and the saved emergency rescue cost ranges from 0.57 million yuan to 12.08 million yuan with 1% reduction of initial inoperability.

Pan-cancer analysis of kinesin family members with potential implications in prognosis and immunological role in human cancer.

Background: Kinesin is a molecular motor for transporting "goods" within cells and plays a key role in many types of tumors. The multi-angle study of kinesin at the pan-cancer level is conducive to understanding its role in tumorigenesis and development and clinical treatment potential. Methods: We evaluated the expression of KIF genes, performed differential analysis by using the R package limma, and explored the pan-cancer prognosis of KIF genes by univariate Cox regression analysis. To evaluate the pan-cancer role of KIF genes as a whole, we defined the KIFscore with the help of gene set variation analysis (GSVA) and explored the KIFscores across normal tissues, tumor cell lines, and 33 tumor types in TCGA. Next, we used spearman correlation analysis to extensively study the correlation between the KIFscore and tumor prognosis and be-tween the KIFscore and clinical indicators. We also identified the relationship between the KIFscore and genomic variation and immune molecular signatures by multiplatform analysis. Finally, we identified the key genes in clear cell renal cell carcinoma (ccRCC) through machine learning algorithms and verified the candidate genes by CCK8, wound healing assay, Transwell assay, and flow cytometry. Results: In most cancers, KIFscores are high and they act as a risk factor for cancer. The KIFscore was significantly associated with copy number variation (CNV), tumor mutation burden (TMB), immune subtypes, DNA repair deficiency, and tumor stemness indexes. Moreover, in almost all cancer species, the KIFscore was positively correlated with T cell CD4+ TH2, the common lymphoid pro-genitor, and the T cell follicular helper. In addition, it was negatively correlated with CXCL16, CCL14, TNFSF13, and TNFRSF14 and positively correlated with ULBP1, MICB, and CD276. Machine learning helped us to identify four hub-genes in ccRCC. The suitable gene, KIF14, is highly expressed in ccRCC and promotes tumor cell proliferation, migration, and invasion. Conclusion: Our study shows that the KIF genes play an important pan-cancer role and may become a potential new target for a variety of tumor treatments in the future. Furthermore, KIF14, a key molecule in the KIF genes, can provide a new idea for the ccRCC treatment.

Akkermansia muciniphila-Nlrp3 is involved in the neuroprotection of phosphoglycerate mutase 5 deficiency in traumatic brain injury mice.

Introduction: Gut-microbiota-brain axis is a potential treatment to decrease the risk of chronic traumatic encephalopathy following traumatic brain injury (TBI). Phosphoglycerate mutase 5 (PGAM5), a mitochondrial serine/threonine protein phosphatase, resides in mitochondrial membrane and regulates mitochondrial homeostasis and metabolism. Mitochondria mediates intestinal barrier and gut microbiome. Objectives: This study investigated the association between PGAM5 and gut microbiota in mice with TBI. Methods: The controlled cortical impact injury was established in mice with genetically-ablated Pgam5 (Pgam5-/-) or wild type, and WT male mice were treated with fecal microbiota transplantation (FMT) from male Pgam5-/- mice or Akkermansia muciniphila (A. muciniphila). Then the gut microbiota abundance, blood metabolites, neurological function, and nerve injury were detected. Results: Treated with antibiotics for suppressing gut microbiota in Pgam5-/- mice partially relieved the role of Pgam5 deficiency in the improvement of initial inflammatory factors and motor dysfunction post-TBI. Pgam5 knockout exhibited an increased abundance of A. muciniphila in mice. FMT from male Pgam5-/- mice enabled better maintenance of amino acid metabolism and peripherial environment than that in TBI-vehicle mice, which suppressed neuroinflammation and improved neurological deficits, and A. muciniphila was negatively associated with intestinal mucosal injury and neuroinflammation post-TBI. Moreover, A. muciniphila treatment ameliorated neuroinflammation and nerve injury by regulating Nlrp3 inflammasome activation in cerebral cortex with TBI. Conclusion: Thus, the present study provides evidence that Pgam5 is involved in gut microbiota-mediated neuroinflammation and nerve injury, with A. muciniphila-Nlrp3 contributing to peripheral effects.

Multi-Omics Analysis and Verification of the Oncogenic Value of CCT8 in Pan-Cancers.

Background: Chaperonin-containing TCP1 subunit 8 (CCT8) has been proved to be involved in the occurrence and development of some cancers. However, no study has reported the potential role of CCT8 in a pan-cancer manner. Methods: TIMER2.0, GEPIA2, UALCAN and Sangerbox were used to explore the expression, prognosis and methylation of CCT8. We used cBioPortal, TISIDB, SangerBox, TIMER2.0 and TISMO to investigate the genetic alteration of CCT8 and the relationship of CCT8 with molecular subtype, immune subtype, immune infiltration and immunotherapy response. CCT8-related genes were screened out through GEPIA and STRING for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. CCK-8, the colony formation assay, the wound healing assay and the Transwell assay were performed to explore the influence of CCT8 on proliferation and migration. Results: CCT8 was highly expressed in most cancers with a poor prognosis. The expression level of CCT8, which was affected by the promoter region methylation and genetic alteration, was related to the molecular and immune subtype of cancers. Interestingly, CCT8 was positively associated with the activated CD4 T cells and type 2 T-helper cells. CCT8 played a vital role in the cell cycle and RNA transport of cancers, and it significantly inhibited the proliferation and migration of lung adenocarcinoma cells when it was knocked down. Conclusion: CCT8 plays an indispensable role in promoting the proliferation and migration of many cancers. CCT8 might be a biomarker of T-helper type 2 (Th2) cell infiltration and a promising therapeutic target for T-helper type 1(Th1)/Th2 imbalance.

E-cadherin expression in the tumor microenvironment of advanced epidermal growth factor receptor-mutant lung adenocarcinoma and the association with prognosis.

BACKGROUND: The expression of programmed death-ligand 1 (PD-L1), tumor-infiltrating lymphocytes (TILs), E-cadherin, and vimentin in lung cancer tumor microenvironment is known to impact patient survival or response to therapy. The expression of these biomarkers may also differ between primary lung tumors and brain metastatic tumors. In this study, we investigated the interaction between these biomarkers in lung tumors with or without concomitant brain metastasis and the interaction with paired brain metastatic tumors. METHODS: The study included 48 patients with stage IV epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma. Sixteen of the forty-eight patients were diagnosed with brain metastasis, while the remaining thirty-two were not. All sixteen patients with brain metastasis had brain tumors. The expression of PD-L1, TILs (CD8+ T lymphocytes and FOXP3+ regulatory T lymphocytes), E-cadherin, and vimentin were evaluated using immunohistochemical (IHC) staining. RESULTS: Patients with brain metastasis exhibited a higher frequency of exon 19 deletion and uncommon EGFR mutations, a higher lung tumor vimentin score, worse progression-free survival (PFS), and overall survival (OS) than patients without brain metastasis. IHC staining showed no difference between paired lung and brain tumors. Patients with low PD-L1 expression had better PFS and OS. After multivariate analysis, higher body mass index, the presence of brain metastasis, bone metastasis, and uncommon EGFR mutations were correlated with worse PFS, while the presence of brain metastasis and high lung tumor E-cadherin score was associated with worse OS. CONCLUSIONS: In patients with stage IV EGFR-mutant lung adenocarcinoma, high E-cadherin expression in the lung tumor might be associated with worse OS. Vimentin expression in the lung tumor was positively related to the risk of brain metastasis.

Identification of diagnostic markers related to oxidative stress and inflammatory response in diabetic kidney disease by machine learning algorithms: Evidence from human transcriptomic data and mouse experiments.

Introduction: Diabetic kidney disease (DKD) is a long-term complication of diabetes and causes renal microvascular disease. It is also one of the main causes of end-stage renal disease (ESRD), which has a complex pathophysiological process. Timely prevention and treatment are of great significance for delaying DKD. This study aimed to use bioinformatics analysis to find key diagnostic markers that could be possible therapeutic targets for DKD. Methods: We downloaded DKD datasets from the Gene Expression Omnibus (GEO) database. Overexpression enrichment analysis (ORA) was used to explore the underlying biological processes in DKD. Algorithms such as WGCNA, LASSO, RF, and SVM_RFE were used to screen DKD diagnostic markers. The reliability and practicability of the the diagnostic model were evaluated by the calibration curve, ROC curve, and DCA curve. GSEA analysis and correlation analysis were used to explore the biological processes and significance of candidate markers. Finally, we constructed a mouse model of DKD and diabetes mellitus (DM), and we further verified the reliability of the markers through experiments such as PCR, immunohistochemistry, renal pathological staining, and ELISA. Results: Biological processes, such as immune activation, T-cell activation, and cell adhesion were found to be enriched in DKD. Based on differentially expressed oxidative stress and inflammatory response-related genes (DEOIGs), we divided DKD patients into C1 and C2 subtypes. Four potential diagnostic markers for DKD, including tenascin C, peroxidasin, tissue inhibitor metalloproteinases 1, and tropomyosin (TNC, PXDN, TIMP1, and TPM1, respectively) were identified using multiple bioinformatics analyses. Further enrichment analysis found that four diagnostic markers were closely related to various immune cells and played an important role in the immune microenvironment of DKD. In addition, the results of the mouse experiment were consistent with the bioinformatics analysis, further confirming the reliability of the four markers. Conclusion: In conclusion, we identified four reliable and potential diagnostic markers through a comprehensive and systematic bioinformatics analysis and experimental validation, which could serve as potential therapeutic targets for DKD. We performed a preliminary examination of the biological processes involved in DKD pathogenesis and provide a novel idea for DKD diagnosis and treatment.

Enlargement of the Middle Meningeal Artery may be an Initiating Factor of Chronic Subdural Hematoma: Three Rase reports and a Literature Review.

Middle Meningeal Artery (MMA) embolization for the treatment of refractory Chronic Subdural Hematoma (CSDH) was first described by Mandai et al. in 2000. Since then, more surgeons have begun to pay attention to such surgery to treat CSDH and explore the changes in the middle meningeal artery in the formation of hematomas. We have presented three cases of chronic subdural hematoma after head trauma and compared the diameter of the middle meningeal artery in MRA images before and after chronic subdural hematoma to discuss our new understanding of CSDH.

Combined Use of Polyurethane Prepolymer and Aromatic Oil in Physicochemical Rejuvenation of Aged SBS Modified Bitumen for Performance Recovery.

The high-quality reutilization of waste styrene-butadiene-styrene copolymer (SBS) modified asphalt mixtures is a difficult issue in the field of highways today, and the main reason is that conventional rejuvenation technology fails to achieve the effective rejuvenation of aged SBS in binder, causing significant deterioration in the high-temperature performance of the rejuvenated mixture. In view of this, this study proposed a physicochemical rejuvenation process using a reactive single-component polyurethane (PU) prepolymer as the repairing substance for structural reconstruction and aromatic oil (AO) as a common rejuvenator used to supplement the lost light fractions of asphalt molecules in aged SBSmB, according to the characteristics of oxidative degradation products of SBS. The joint rejuvenation of aged SBS modified bitumen (aSBSmB) by PU and AO was investigated based on Fourier transform infrared Spectroscopy, Brookfield rotational viscosity, linear amplitude sweep, and dynamic shear rheometer tests. The results show that 3 wt% PU can completely react with the oxidation degradation products of SBS and rebuild its structure, while AO mainly acted as an inert component to increase the content of aromatic components, thereby reasonably adjusting the compatibility of chemical components of aSBSmB. Compared with the PU reaction-rejuvenated binder, the 3 wt% PU/10 wt% AO rejuvenated binder had a lower high-temperature viscosity for better workability. The chemical reaction between PU and SBS degradation products dominated in the high-temperature stability of rejuvenated SBSmB and had a negative impact on its fatigue resistance, while the joint rejuvenation of 3 wt% PU and 10 wt% AO not only gave a better high-temperature property to aged SBSmB but could also have the capacity to improve its fatigue resistance. Compared to virgin SBSmB, PU/AO rejuvenated SBSmB has comparative low-temperature viscoelastic behavior characteristics and a much better resistance to medium-high-temperature elastic deformation.

Unified ICH quantification and prognosis prediction in NCCT images using a multi-task interpretable network.

With the recent development of deep learning, the regression, classification, and segmentation tasks of Computer-Aided Diagnosis (CAD) using Non-Contrast head Computed Tomography (NCCT) for spontaneous IntraCerebral Hematoma (ICH) have become popular in the field of emergency medicine. However, a few challenges such as time-consuming of ICH volume manual evaluation, excessive cost demanding patient-level predictions, and the requirement for high performance in both accuracy and interpretability remain. This paper proposes a multi-task framework consisting of upstream and downstream components to overcome these challenges. In the upstream, a weight-shared module is trained as a robust feature extractor that captures global features by performing multi-tasks (regression and classification). In the downstream, two heads are used for two different tasks (regression and classification). The final experimental results show that the multi-task framework has better performance than single-task framework. And it also reflects its good interpretability in the heatmap generated by Gradient-weighted Class Activation Mapping (Grad-CAM), which is a widely used model interpretation method, and will be presented in subsequent sections.

The burden of liver cirrhosis and underlying etiologies: results from the Global Burden of Disease Study 2019.

BACKGROUND: Liver cirrhosis is a major health concern. Herein, we aimed to estimate the incidence, prevalence, and mortality of liver cirrhosis caused by specific etiologies for 204 countries and territories. MATERIALS AND METHODS: The data were retrieved from the Global Burden of Disease Study 2019. The age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized death rate, and estimated annual percentage changes were used to estimate the trends in incidence, prevalence, and mortality of liver cirrhosis by sex, region, country, and etiology between 2009 and 2019. RESULTS: From 2009 to 2019, the incident cases of liver cirrhosis increased by 16.7%, from 1.8 million (95% uncertainty interval: 1.5-2.1) to 2.1 million (1.7-2.5), and the prevalent cases increased from 1378.3 million (1275.1-1498.8) to 1691.0 million (1560.9-1845.5). Liver cirrhosis contributed to nearly 1.5 million (1.4-1.6) deaths in 2019, nearly 0.2 million more than in 2009. However, the age-standardized death rate fell from 20.71 (19.79-21.65) per 100,000 population in 2009 to 18.00 (16.80-19.31) per 100,000 population in 2019. In terms of sex, males showed higher ASIR, ASPR, and age-standardized death rate than females. Among the etiologies, the ASIR and ASPR of NAFLD increased markedly, and there was also a modest increase in ASIR and ASPR for HCV and alcohol use. In contrast, the ASIR and ASPR of HBV decreased considerably. CONCLUSIONS: Our finding suggests an increasing burden of liver cirrhosis worldwide but a declining attributed death. A high prevalence and still rising trend of NAFLD and alcohol use-etiology were found in patients with cirrhosis globally, although variation was found between regions/countries. These data indicate that efforts to reduce the associated burden need to be improved.