Construction of prognostic markers for pancreatic adenocarcinoma based on mitochondrial fusion-related genes.

Early detection of pancreatic adenocarcinoma (PAAD) remains a pressing clinical problem. Information on the clinical prognostic value of mitochondrial fusion-related genes in PAAD remains limited. In this study, we investigated mitochondrial fusion-related genes of PAAD to establish an optimal signature plate for the early diagnosis and prognosis of PAAD. The cancer genome atlas database was used to integrate the Fragments Per Kilobase Million data and related clinical data for patients with PAAD. Least absolute shrinkage and selection operator regression, cox regression, operating characteristic curves, and cBioPortal database was used to evaluate model performance, assess the prognostic ability and sensitivity. The levels of immune infiltration were compared by CIBERSORT, QUANTISEQ, and EPIC. Chemotherapy sensitivity between the different risk groups was compared by the Genomics of Drug Sensitivity in Cancer database and the "pRRophetic" R package. At last, a total of 4 genes were enrolled in multivariate Cox regression analysis. The risk-predictive signature was constructed as: (0.5438 × BAK1) + (-1.0259 × MIGA2) + (1.1140 × PARL) + (-0.4300 × PLD6). The area under curve of these 4 genes was 0.89. Cox regression analyses indicates the signature was an independent prognostic indicator (P < .001, hazard ratio [HR] = 1.870, 95% CI = 1.568-2.232). Different levels of immune cell infiltration in the 2 risk groups were observed using the 3 algorithms, with tumor mutation load (P = .0063), tumor microenvironment score (P = .01), and Tumor Immune Dysfunction and Exclusion score (P = .0012). The chemotherapeutic sensitivity analysis also revealed that the half-maximal inhibitory concentration of 5-fluorouracil (P = .0127), cisplatin (P = .0099), docetaxel (P < .0001), gemcitabine (P = .0047), and pacilataxel (P < .0001) were lower in the high-risk groups, indicating that the high-risk group patients had a greater sensitivity to chemotherapy. In conclude, we established a gene signature plate comprised of 4 mitochondrial fusion related genes to facilitate early diagnosis and prognostic prediction of PAAD.

Mendelian randomization supports causality between COVID-19 and glaucoma.

To determine whether there is a causal relationship between Corona Virus Disease 2019 (COVID-19) and glaucoma, a 2-sample Mendelian Randomization (MR) design was applied with the main analysis method of inverse-variance-weighted. The reliability of the results was checked using the heterogeneity test, pleiotropy test, and leave-one-out method. Four sets of instrumental variables (IVs) were used to investigate the causality between COVID-19 and glaucoma risk according to data from the IEU Genome Wide Association Study (GWAS). The results showed that 2 sets of COVID-19(RELEASE) were significantly associated with the risk of glaucoma [ID: ebi-a-GCST011071, OR (95% CI) = 1.227 (1.076-1.400), P = .002259; ID: ebi-a-GCST011073: OR (95% CI) = 1.164 (1.022-1.327), P = .022450; 2 sets of COVID-19 hospitalizations were significantly associated with the risk of glaucoma (ID: ebi-a-GCST011081, OR (95% CI) = 1.156 (1.033-1.292), P = .011342; ID: ebi-a-GCST011082: OR (95% CI) = 1.097 (1.007-1.196), P = .034908)]. The sensitivity of the results was acceptable (P > .05) for the 3 test methods. In conclusion, this MR analysis provides preliminary evidence of a potential causal relationship between COVID-19 and glaucoma.

On Difference Pattern Synthesis for Spherical Sensor Arrays.

An innovative method for synthesizing optimum difference patterns of the spherical sensor array is introduced, along with a sidelobe tapering technique. Firstly, we suggest employing the spherical harmonics of degree ±1 to synthesize the spherical array difference pattern; secondly, we study the mapping relationship between the difference pattern of the spherical sensor array and the difference pattern of the uniformly spaced linear array (ULA) with odd-numbered elements; finally, we enhance the Zolotarev difference pattern, which is a counterpart to the Dolph-Chebyshev sum pattern that traditionally allows synthesis only for ULA with even-numbered elements. Our modification extends its applicability to synthesize difference patterns for ULA with odd-numbered elements. Leveraging the optimal difference pattern, a generalized Bayliss difference pattern synthesis method designed for the ULA with odd-numbered elements is further proposed. To illustrate the effectiveness of our approach, we present several design examples through experimental simulation.

Monoclonal enolase-1 blocking antibody ameliorates pulmonary inflammation and fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic fatal disease with limited therapeutic options. The infiltration of monocytes and fibroblasts into the injured lungs is implicated in IPF. Enolase-1 (ENO1) is a cytosolic glycolytic enzyme which could translocate onto the cell surface and act as a plasminogen receptor to facilitate cell migration via plasmin activation. Our proprietary ENO1 antibody, HL217, was screened for its specific binding to ENO1 and significant inhibition of cell migration and plasmin activation (patent: US9382331B2). METHODS: In this study, effects of HL217 were evaluated in vivo and in vitro for treating lung fibrosis. RESULTS: Elevated ENO1 expression was found in fibrotic lungs in human and in bleomycin-treated mice. In the mouse model, HL217 reduced bleomycin-induced lung fibrosis, inflammation, body weight loss, lung weight gain, TGF-ß upregulation in bronchial alveolar lavage fluid (BALF), and collagen deposition in lung. Moreover, HL217 reduced the migration of peripheral blood mononuclear cells (PBMC) and the recruitment of myeloid cells into the lungs. In vitro, HL217 significantly reduced cell-associated plasmin activation and cytokines secretion from primary human PBMC and endothelial cells. In primary human lung fibroblasts, HL217 also reduced cell migration and collagen secretion. CONCLUSIONS: These findings suggest multi-faceted roles of cell surface ENO1 and a potential therapeutic approach for pulmonary fibrosis.

High-performance van der Waals antiferroelectric CuCrP2S6-based memristors.

Layered thio- and seleno-phosphate ferroelectrics, such as CuInP2S6, are promising building blocks for next-generation nonvolatile memory devices. However, because of the low Curie point, the CuInP2S6-based memory devices suffer from poor thermal stability (<42 °C). Here, exploiting the electric field-driven phase transition in the rarely studied antiferroelectric CuCrP2S6 crystals, we develop a nonvolatile memristor showing a sizable resistive-switching ratio of ~ 1000, high switching endurance up to 20,000 cycles, low cycle-to-cycle variation, and robust thermal stability up to 120 °C. The resistive switching is attributed to the ferroelectric polarization-modulated thermal emission accompanied by the Fowler-Nordheim tunneling across the interfaces. First-principles calculations reveal that the good device performances are associated with the exceptionally strong ferroelectric polarization in CuCrP2S6 crystal. Furthermore, the typical biological synaptic learning rules, such as long-term potentiation/depression and spike amplitude/spike time-dependent plasticity, are also demonstrated. The results highlight the great application potential of van der Waals antiferroelectrics in high-performance synaptic devices for neuromorphic computing.

Unrevealed roles of extracellular enolase­1 (ENO1) in promoting glycolysis and pro­cancer activities in multiple myeloma via hypoxia­inducible factor 1α.

The involvement of enolase­1 (ENO1), intracellularly or extracellularly, has been implicated in cancer development. Moreover, anticancer activities of an ENO1­targeting antibody has demonstrated the pathological roles of extracellular ENO1 (surface or secreted forms). However, although ENO1 was first identified as a glycolytic enzyme in the cytosol, to the best of our knowledge, extracellular ENO1 has not been implicated in glycolysis thus far. In the present study, the effects of extracellular ENO1 on glycolysis and other related pro­cancer activities were investigated in multiple myeloma (MM) cells in vitro and in vivo. Knockdown of ENO1 expression reduced lactate production, cell viability, cell migration and surface ENO1 expression in MM cells. Notably, addition of extracellular ENO1 protein in cancer cell culture enhanced glycolytic activity, hypoxia­inducible factor 1­α (HIF­1α) expression, glycolysis­related gene (GRG) expression and pro­cancer activities, such as cell migration, cell viability and tumor­promoting cytokine secretion. Consistently, these extracellular ENO1­induced cellular effects were inhibited by an ENO1­specific monoclonal antibody (mAb). In addition, extracellular ENO1­mediated glycolysis, GRG expression and pro­cancer activities were also reduced by HIF­1α silencing. Lastly, administration of an ENO1 mAb reduced tumor growth and serum lactate levels in an MM xenograft model. These results suggested that extracellular ENO1 (surface or secreted forms) enhanced a HIF­1α­mediated glycolytic pathway, in addition to its already identified roles. Therefore, the results of the present study highlighted the therapeutic potential of ENO1­specific antibodies in treating MM, possibly via glycolysis inhibition, and warrant further studies in other types of cancer.

The associations of gestational weight gain and midpregnancy lipid levels with placental size and placental-to-birth weight ratio: findings from a chinese birth cohort study.

BACKGROUND: The placenta serves as the sole maternal organ responsible for transmitting nutrients to the fetus, playing a crucial role in supporting standard fetal growth and development. To date, only a small number of studies have investigated the impact of maternal gestational weight gain and lipid concentrations on placental development. This study aimed to explore the influence of weight gain during pregnancy and lipid levels in the second trimester on placental weight, volume, and the placental weight ratio. METHODS: This birth cohort study encompassed 1,358 mother-child pairs. Placental data for each participant was gathered immediately post-delivery, and the study incorporated data on gestational weight gain throughout pregnancy and lipid profiles from the mid-trimester. A linear regression model was employed to assess the correlations between gestational weight gain, mid-trimester lipid levels, and metrics such as placental weight, placental volume, and the placental-to-birth weight ratio (PFR). RESULTS: In the study groups of pre-pregnancy underweight, normal weight, and overweight, the placental weight increased by 4.93 g (95% CI: 1.04-8.81), 2.52 g (95% CI: 1.04-3.99), and 3.30 g (95% CI: 0.38-6.22) per 1 kg of gestational weight gain, respectively. Within the pre-pregnancy underweight and normal weight groups, the placental volume increased by 6.79 cm^3 (95% CI: 3.43-10.15) and 2.85 cm^3 (95% CI: 1.31-4.39) per 1 kg of gestational weight gain, respectively. Additionally, placental weight exhibited a positive correlation with triglyceride (TG) levels (ß = 9.81, 95% CI: 3.28-16.34) and a negative correlation with high-density lipoprotein (HDL-C) levels (ß = - 46.30, 95% CI: - 69.49 to - 23.11). Placental volume also showed a positive association with TG levels (ß = 14.54, 95% CI: 7.69-21.39). Conversely, PFR demonstrated a negative correlation with increasing HDL-C levels (ß = - 0.89, 95% CI: - 1.50 to - 0.27). CONCLUSIONS: Gestational weight gain was significantly correlated with both placental weight and volume. This association was especially pronounced in women who, prior to pregnancy, were underweight or of normal weight. Additionally, TG and HDL-C levels during the mid-trimester were linked to placental development.

Anti-Spoofing Method for Improving GNSS Security by Jointly Monitoring Pseudo-Range Difference and Pseudo-Range Sum Sequence Linearity.

Spoofing interference is one of the most emerging threats to the Global Navigation Satellite System (GNSS); therefore, the research on anti-spoofing technology is of great significance to improving the security of GNSS. For single spoofing source interference, all the spoofing signals are broadcast from the same antenna. When the receiver is in motion, the pseudo-range of spoofing signals changes nonlinearly, while the difference between any two pseudo-ranges changes linearly. Authentic signals do not have this characteristic. On this basis, an anti-spoofing method is proposed by jointly monitoring the linearity of the pseudo-range difference (PRD) sequence and pseudo-range sum (PRS) sequence, which transforms the spoofing detection problem into the sequence linearity detection problem. In this paper, the model of PRD and PRS is derived, the hypothesis based on the linearity of PRD sequence and PRS sequence is given, and the detection performance of the method is evaluated. This method uses the sum of squares of errors (SSE) of linear fitting of the PRD sequence and PRS sequence to construct detection statistics, and has low computational complexity. Simulation results show that this method can effectively detect spoofing interference and distinguish spoofing signals from authentic signals.

Joint effects of prenatal exposure to air pollution and pregnancy-related anxiety on birth weight: A prospective birth cohort study in Ma'anshan, China.

BACKGROUND: A growing number of studies have shown that prenatal exposure to chemical and non-chemical stressors has effects on fetal growth. The co-exposure of both better reflects real-life exposure patterns. However, no studies have included air pollutants and pregnancy-related anxiety (PrA) as mixtures in the analysis. METHOD: Using the birth cohort study method, 576 mother-child pairs were included in the Ma'anshan Maternal and Child Health Hospital. Evaluate the exposure levels of six air pollutants during pregnancy using inverse distance weighting (IDW) based on the pregnant woman's residential address and air pollution data from monitoring stations. Prenatal anxiety levels were assessed using the PrA Questionnaire. Generalized linear regression (GLR), quantile g-computation (QgC) and bayesian kernel machine regression (BKMR) were used to assess the independent or combined effects of air pollutants and PrA on birth weight for gestational age z-score (BWz). RESULT: The results of GLR indicate that the correlation between the six air pollutants and PrA with BWz varies depending on the different stages of pregnancy and pollutants. The QgC shows that during trimester 1, when air pollutants and PrA are considered as a whole exposure, an increase of one quartile is significantly negatively correlated with BWz. The BKMR similarly indicates that during trimester 1, the combined exposure of air pollutants and PrA is moderately correlated with a decrease in BWz. CONCLUSION: Using the method of analyzing mixed exposures, we found that during pregnancy, the combined exposure of air pollutants and PrA, particularly during trimester 1, is associated with BWz decrease. This supports the view that prenatal exposure to chemical and non-chemical stressors has an impact on fetal growth.

The effects of gestational diabetes mellitus on fetal growth: is it different for low-risk and medium-high-risk pregnant women?

BACKGROUND: It has been suggested that gestational diabetes mellitus (GDM) alters the growth trajectory of a fetus and increases the risk of abnormal birth weight. In spite of this, there is still a significant debate regarding the mode and optimal timing of diagnosing this condition. Our aim was to determine fetal growth velocity and birth biometry in pregnant women with GDM at varying risk levels. METHODS: We conducted a cohort study involving 1023 pregnant women at a maternity hospital in Ma'anshan, China. All women completed an oral glucose tolerance test at 24-28 weeks' gestation. We measured fetal head circumference (HC), femoral length (FL), abdominal circumference (AC), biparietal diameter (BPD), and estimate fetal weight (EFW) by ultrasound at 17, 24, 31, and 35 weeks' gestation, respectively. RESULTS: Overall, 5115 ultrasound scans were performed. Among both low-risk and medium-high-risk pregnant women at 17-24 weeks' gestation, GDM exposure was associated with an increase in fetal growth velocity. Neonates born to women with GDM at medium-high risk had significantly larger birth weights than those born to women without GDM, while this was not observed in women at low risk. CONCLUSION: In medium-high-risk pregnant women, exposure to GDM has a greater effect on the fetus, leading to abnormal fetal growth velocity that lasts beyond week 24. It is evident from our results that the effects of GDM on fetal growth differ between medium-high-risk pregnant women and low-risk pregnant women, and therefore a different screening program based on the risk factor for GDM is warranted.

The impact of household fuel usage on adverse pregnancy outcomes in rural Ma'anshan City, Anhui Province: a birth cohort study.

The combustion of cooking fuels generates detrimental gases significantly impacting human health, particularly for vulnerable populations like expectant mothers. Prenatal exposure of such hazardous emissions raises the probability of adverse pregnancy outcomes, including preterm birth (PTB) and low birth weight (LBW). Our research aims to explore the association between cooking fuel utilization and adverse birth outcomes in rural Ma'anshan, Anhui Province. A prospective cohort study was executed, employing the Maternal and Infant Health Assessment questionnaire to classify fuels into clean (natural gas, electricity) and polluting energy sources (coal, coal gas, firewood). Multivariate logistic regression models were conducted to evaluate the association between fuel consumption and postpartum maternal and infant outcomes. Among the 442 surveyed pregnant women, 38.2% (N=169) utilized polluting fuels. After adjusting for covariates such as age and BMI, the relative risks of preterm birth, low birth weight, and postpartum hemorrhage in the polluting fuel group compared to the clean fuel group were OR: 3.27, 95% CI: 1.34, 8.00; OR: 3.50, 95% CI: 1.12, 10.90; and OR: 3.18, 95% CI: 1.06, 9.46, respectively. These results indicate that the usage of polluting fuels during pregnancy may heighten the risk of adverse birth outcomes. Consequently, additional research is advised to mitigate the harmful emissions generated by cooking fuels and advocate for clean energy adoption, enhancing maternal and infant well-being.

Feasibility and safety of expandable mediastinoscopic and laparoscopic radical esophagectomy.

Background: At present, minimally invasive radical esophagectomy is the main surgical method for esophageal cancer treatment, but it has inherent limitations. We have developed a novel method of radical esophagectomy without thoracotomy to improve this situation, namely, by using EMLE. We evaluated the feasibility and safety of expandable mediastinoscopic and laparoscopic radical esophagectomy (EMLE) through a retrospective analysis. Methods: From January 2019 to June 2022, we successfully performed 106 cases of radical resection of esophageal cancer with this new surgical technique, gradually improved the surgical path, and recorded the perioperative data and postoperative complications of all patients. Results: The operation was successfully performed in all patients except for two patients who required a switch to open surgery. The mean operation time was 171.11 ± 33.29 min and the mean intraoperative blood loss was 93.53 ± 56.32 ml. The mean number of removed lymph nodes was 23.59 ± 5.42. The postoperative complications included pneumonia (3.77%), recurrent laryngeal nerve palsy (1.89%), anastomotic leak (14.15%), pleural effusion (5.66%), chylothorax (2.83%), and reoperation (4.72%). All complications were graded I-III per the Clavien-Dindo classification. No perioperative death was recorded. Conclusion: Expandable mediastinoscopic and laparoscopic radical esophagectomy is feasible for radical resection of esophageal cancer, with good therapeutic effect and safety. Because of its minimal impact on patients and convenient operation, it is a novel surgical option for patients with esophageal cancer and is expected to become a standard surgical method for radical esophagectomy in the future.

Screening and identification of the core immune-related genes and immune cell infiltration in severe burns and sepsis.

Severe burns often have a high mortality rate due to sepsis, but the genetic and immune crosstalk between them remains unclear. In the present study, the GSE77791 and GSE95233 datasets were analysed to identify immune-related differentially expressed genes (DEGs) involved in disease progression in both burns and sepsis. Subsequently, weighted gene coexpression network analysis (WGCNA), gene enrichment analysis, protein-protein interaction (PPI) network construction, immune cell infiltration analysis, core gene identification, coexpression network analysis and clinical correlation analysis were performed. A total of 282 common DEGs associated with burns and sepsis were identified. Kyoto Encyclopedia of Genes and Genomes pathway analysis identified the following enriched pathways in burns and sepsis: metabolic pathways; complement and coagulation cascades; legionellosis; starch and sucrose metabolism; and ferroptosis. Finally, six core DEGs were identified, namely, IL10, RETN, THBS1, FGF13, LCN2 and MMP9. Correlation analysis showed that some core DEGs were significantly associated with simultaneous dysregulation of immune cells. Of these, RETN upregulation was associated with a worse prognosis. The immune-related genes and dysregulated immune cells in severe burns and sepsis provide potential research directions for diagnosis and treatment.

circPLOD2 knockdown suppresses endometriosis progression via the miR-216a-5p/ZEB1 axis.

The present study aimed to identify the role of circPLOD2 in endometriosis and its underlying mechanisms. We determined circPLOD2 and miR-216a-5p expression in ectopic endometrial (EC) and eutopic endometrial (EU) samples as well as in endometrial samples from uterine fibroids of ectopic patients (EN) and embryonic stem cells (ESCs) using qRT-PCR. The association between circPLOD2 and miR-216a-5p or miR-216a-5p and zinc finger E-box binding homeobox 1 (ZEB1) expression was analyzed using Starbase, TargetScan, and dual-luciferase reporter gene assays. Cell viability, apoptosis, and migration and invasion were assessed using MTT, flow cytometry, and transwell assays, respectively. In addition, qRT-PCR and western blotting was used to measure circPLOD2, miR-216a-5p, E-cadherin, N-cadherin, and ZEB1 expression. circPLOD2 was upregulated and miR-216a-5p was downregulated in EC samples compared with that in EU samples. Similar trends were observed in ESCs. circPLOD2 interacted and negatively regulated miR-216a-5p expression in EC-ESCs. circPLOD2-siRNA significantly inhibited EC-ESC growth; promoted cellular apoptosis; and inhibited EC-ESC migration, invasion, and epithelial-mesenchymal transition; these effects could be reversed following miR-216a-5p inhibitor transfection. miR-216a-5p directly targeted and negatively regulated ZEB1 expression in EC-ESCs. In conclusion, circPLOD2 promotes the proliferation, migration, and invasion of EC-ESCs and inhibits their apoptosis by targeting miR-216a-5p. These findings indicate potential therapeutic targets for endometriosis.

Pollution level mapping of heavy metal in soil for ground-airborne hyperspectral data with support vector machine and deep neural network: A case study of Southwestern Xiong'an, China.

Heavy metal in soil is a significant issue with the urban development in China, and traditional ground spectra are difficult to satisfy the demands for heavy metal monitoring and assessment in large-scale areas. In the paper, ground-airborne hyperspectral data is utilized to analyze the pollution level of heavy metal, 423 soil samples and corresponding ground spectra are collected synchronously with airborne hyperspectral image acquisition in Southwestern Xiong'an, China. Among them, support vector machine (SVM) is utilized to predict the concentration of independent samples, deep neural network (DNN) is aimed to estimate the spatial distribution of concentration with airborne image scenes. Finally, the pollution level is generated by the Softmax function, and it is defined by the risk control standard of heavy metals. The ground spectra and airborne image are closely integrated by the proposed method, the pollution situation is directly evaluated by ground-airborne hyperspectral data and indirectly evaluated by the concentration of local space, and the mapping results are believed to provide constructive advices about environmental protection.

The association between early pregnancy exposure to green space and maternal glucolipid metabolism disorders: evaluation of the mediating role of serum 25-hydroxyvitamin D.

Green space and 25-hydroxyvitamin D (25(OH)D) can affect maternal and infant health, but limited studies have examined their effects on disorders of maternal glucolipid metabolism. We aimed to explore the interaction between green space, maternal serum 25(OH)D, and disorders of glucolipid metabolism in early pregnancy. A total of 2551 pregnant women were recruited from the Maanshan Maternal and Child Health Hospital birth cohort in China between 2020 and 2022. We calculated average residential greenness during early pregnancy using 250 m normalized difference vegetation index (NDVI) from satellites. Serum biomarkers (25(OH)D, total cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol(HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1(ApoA1), and apolipoprotein B(ApoB)) were measured. Associations between the factors were analyzed using multiple linear regression, mediation analysis, and stratified analysis. After adjusting for potential confounders, green space exposure associated with decreased TG (- 7.8%; 95% confidence interval (CI): - 12.8, - 2.9), TC (- 7.0%; 95% CI: - 11.4, - 2.7), and LDL-C (- 8.4%; 95% CI: - 12.9, - 3.9), ApoB (- 2.0%; 95% CI: - 3.0, - 1.0) and increased HDL-C (2.7%; 95% CI: 1.5, 3.8) and ApoA1 (5.1%; 95% CI: 3.9, 6.3) for each IQR increase in NDVI. A comparable link was found between maternal serum 25(OH)D and indicators of glucolipid metabolism (P < 0.05). In addition, mediation analysis showed that the association between green space exposure and maternal glucolipid metabolic index was mediated by serum 25(OH)D at 6.37%. In stratified analyses, a considerable association between 25(OH)D and glucolipid metabolic index (except TG) was observed only at higher green space exposures. This study confirms that high levels of green space exposure in early pregnancy and vitamin D are associated with a reduced risk of glucolipid metabolism disorders and suggests that green space may favor glucolipid metabolism by increasing vitamin D levels, particularly at high NDVI values.

Mechanisms underlying the therapeutic effects of 4-octyl itaconate in treating sepsis based on network pharmacology and molecular docking.

Objective: Through network pharmacology and molecular docking technology, the hub genes, biological functions, and signaling pathways of 4-Octyl itaconate (4-OI) against sepsis were revealed. Methods: Pathological targets of sepsis were screened using GeneCards and GEO databases. Similarly, the pharmacological targets of 4-OI were obtained through Swiss TargetPrediction (STP), Similarity ensemble approach (SEA), and TargetNet databases. Then, all the potential targets of 4-OI anti-sepsis were screened by the online platform Draw Venn diagram, and the hub genes were screened by Cytoscape software. The identified hub genes were analyzed by GO and KEGG enrichment analysis, protein interaction (PPI) network, and molecular and docking technology to verify the reliability of hub gene prediction, further confirming the target and mechanism of 4-OI in the treatment of sepsis. Results: After the target screening of 4-OI and sepsis, 264 pharmacological targets, 1953 pathological targets, and 72 genes related to 4-OI anti-sepsis were obtained, and eight hub genes were screened, namely MMP9, MMP2, SIRT1, PPARA, PTPRC, NOS3, TLR2, and HSP90AA1. The enrichment analysis results indicated that 4-OI might be involved in regulating inflammatory imbalance, immunosuppression, and oxidative stress in developing sepsis. 4-OI protects multiple organ dysfunction in sepsis by acting on hub genes, and MMP9 is a reliable gene for the prognosis and diagnosis of sepsis. The molecular docking results showed that 4-OI binds well to the hub target of sepsis. Conclusion: 4-OI plays an antiseptic role by regulating MMP9, MMP2, SIRT1, PPARA, PTPRC, NOS3, TLR2 and HSP90AA1. These Hub genes may provide new insights into follow-up research on the target of sepsis treatment.

Diagnostic and Prognostic Value of Interleukin-6 in Emergency Department Sepsis Patients.

Purpose: The objective of this study was to explore the diagnostic and prognostic value of interleukin-6 (IL-6) in sepsis patients presenting to the emergency department. Patients and Methods: A total of 128 patients who visited the emergency department of West Hospital of Beijing Chaoyang Hospital, affiliated to Capital Medical University, from November 2021 to February 2022 were subjected to this study. According to Sepsis-3.0 diagnostic criteria for sepsis, patients were divided into non-sepsis group (65 cases) and sepsis group (63 cases). Demographic data and clinical characteristics of the two patient groups were compared. Serum levels of biomarkers including IL-6, blood urea nitrogen (BUN), and lactic acid (Lac) were compared with Sequential Organ Failure Assessment (SOFA) and Glasgow Coma Scale (GCS) scores. Logistic regression was used to analyze independent risk factors and Receiver Operating Characteristic Curve (ROC) method was used to analyze the Area Under the Curve (AUC) to determine the diagnostic and prognostic value of markers. Results: Compared with non-sepsis patients, levels of IL-6, PCT, CRP and BUN were significantly higher in sepsis patients (10.84 (4.41-27.01): 92.22 (21.53-201.12), 0.03 (0.01-0.1):0.49 (0.08-3.1), 8.3 (0.5-31.8):39.8(10.3-98.6), 7.01 (4.90-11.74):13.03 (6.93-25.99), all p = 0.001). IL-6, BUN and mean arterial pressure (MAP) were independent risk factors for sepsis diagnosis. AUC values of IL-6, BUN, MAP and IL-6+BUN+MAP were 0.764, 0.696, 0.685, and 0.848, respectively. Lactate, age and SOFA score were independent risk factors for 28-day mortality in sepsis patients. The AUC of Lac, age, SOFA score and Lac+age+SOFA score to predict 28-day death in sepsis patients was 0.679, 0.626, 0.747, and 0.819, respectively. Conclusion: IL-6 is an independent predictor of sepsis diagnosis, and the combination of blood BUN and MAP has superior diagnostic performance. Lac, age, and SOFA score could effectively predict clinical outcomes in patients with sepsis.

Defect-suppressed submillimeter-scale WS2 single crystals with high photoluminescence quantum yields by alternate-growth-etching CVD.

Defects, such as uncontrollable vacancies, will intensively degrade the material properties and device performance of CVD-grown transition metal dichalcogenides (TMDs). Although vacancies can be repaired by some post-processing measures, these treatments are usually time-consuming, complicated and may introduce uncontrollable chemical contaminants into TMDs. How to efficiently suppress the uncontrollable defects during CVD growth and acquire intrinsic high-quality CVD-grown TMDs without any after-treatment remains a critical challenge, and has not yet been well resolved. Here, an alternate-growth-etching (AGE) CVD method was demonstrated to fabricate defect-suppressed submillimeter-scale monolayer WS2 single crystals. Compared with normal CVD, the grain size of the as-grown WS2 can be enlarged by 4-5 times (∼520 µm) and the growth rate of ∼14.4 µm min-1 is also at a high level compared to reported results. Moreover, AGE-CVD can efficiently suppress atomic vacancies in WS2. In every growth-etching cycle, the etching of WS2 occurs preferentially at the defective sites, which will be healed at the following growth stage. As a result, WS2 monolayers obtained by AGE-CVD possess higher crystal quality, carrier mobility (8.3 cm2 V-1 s-1) and PL quantum yield (QY, 52.6%) than those by normal CVD. In particular, such a PL QY is the highest value ever reported for in situ CVD-grown TMDs without any after-treatment, and is even comparable to the values of mechanically exfoliated samples. This AGE-CVD method is also appropriate for the synthesis of other high-quality TMD single crystals on a large-scale.

Engineering Graphene Grain Boundaries for Plasmonic Multi-Excitation and Hotspots.

Surface plasmons, merging photonics and electronics in nanoscale dimensions, have been the cornerstones in integrated informatics, precision detection, high-resolution imaging, and energy conversion. Arising from the exceptional Fermi-Dirac tunability, ultrafast carrier mobility, and high-field confinement, graphene offers excellent advantages for plasmon technologies and enables a variety of state-of-the-art optoelectronic applications ranging from tight-field-enhanced light sources, modulators, and photodetectors to biochemical sensors. However, it is challenging to co-excite multiple graphene plasmons on one single graphene sheet with high density, a key step toward plasmonic wavelength-division multiplexing and next-generation dynamical optoelectronics. Here, we report the heteroepitaxial growth of a polycrystalline graphene monolayer with patterned gradient grain boundary density, which is synthesized by creating diverse nanosized local growth environments on a centimeter-scale substrate with a polycrystalline graphene ring seed in chemical vapor deposition. Such geometry enables plasmonic co-excitation with varied wavelength diversification in the nanoscale. Via using high-resolution scanning near-field optical microscopy, we demonstrate rich plasmon standing waves, even bright plasmonic hotspots with a size up to 3 µm. Moreover, by changing the grain boundary density and annealing, we find the local plasmonic wavelengths are widely tunable, from 70 to 300 nm. Theoretical modeling supports that such plasmonic versatility is due to the grain boundary-induced plasmon-phonon interactions through random phase approximation. The seed-induced heteroepitaxial growth provides a promising way for the grain boundary engineering of two-dimensional materials, and the controllable grain boundary-based plasmon co-generation and manipulation in one single graphene monolayer will facilitate the applications of graphene for plasmonics and nanophotonics.