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Background Sepsis is one of the leading causes of death in critically ill patients worldwide due to its complex pathogenesis, poor prognosis, and high mortality rate. The diagnosis and treatment of sepsis are still a severe challenge for clinicians. The immune analysis of Sepsis Cuproptosis-related genes (CRGs) was performed based on the single sample Gene Set Enrichment Analysis. The purpose of clarifying the correlation between CRGs and sepsis immunity is to explore new targets and potential clinical values for the immune mechanism of sepsis and to provide a new perspective for the basic and clinical research of sepsis. Method The data set of the sepsis whole blood gene expression matrix was downloaded from the Gene Expression Omnibus database, from which CRGs expression was extracted. The infiltration matrix of immune cells and functions was obtained by ssGSEA function, and the differences in immune cells and immune function between sepsis and healthy control groups were analyzed. The correlation coefficient was calculated by cor-function. Test function to analyze the correlation between CRGs and immune cells and immune function in sepsis and to screen out target genes. Target genes were used to perform KEGG and go enrichment analysis, predict miRNA regulatory relationships, and predict potential drugs in the Enrichr database. Results There were significant differences in immune cells and immune function between the sepsis group and the healthy control group. Eleven target genes were screened out, which were closely related to immunity in sepsis. The citrate cycle was the most enriched pathway. The biological process was mainly enriched in metabolic processes, copper ion transport, etc. The cell component was significantly enriched in the mitochondrial matrix and the like. The molecular function was mainly concentrated in transition metal ion transmembrane transporter activity, cuprous ion binding, and so on. The Enrichr database was applied to screen six human miRNAs with potential regulatory relationships with sepsis CRGs, and a variety of chemical and natural drug components were screened as potential therapeutic agents. Conclusion CRGs in sepsis are closely related to immune cells and immune functions. As a new form of cell death, cuproptosis may play an important role in the development of sepsis.

Two-dimensional ferromagnetic (FM) half-metals are promising candidates for advanced spintronic devices with small size and high capacity. Motivated by a recent report on controlling the synthesis of FM Cr

Zhishen Ruan,1,* Dan Li,1,* Yuanlong Hu,1 Zhanjun Qiu,1,2 Xianhai Chen1,2 1The First Clinical College, Shandong Chinese Medical University, Ji Nan, People’s Republic of China; 2Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Ji Nan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhanjun Qiu; Xianhai Chen, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Ji Nan, People’s Republic of China, Tel/Fax +86 0531 18660199889, Email qiuzhj227@163.com; chenxianhai18@163.comBackground: Acute respiratory failure (ARF) is a common cause of admission to the intensive care unit (ICU) for patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). There is still a lack of effective interventions and treatments. ACE inhibitors (ACEI)/ angiotensin II receptor blockers (ARB) were effective in COPD patients. We aimed to study the effect of ACEI/ARB use on AECOPD combined with ARF and evaluate the effect of in-hospital continuation of medication.Methods: We included patients with AECOPD and ARF from the Medical Information Bank for Intensive Care (MIMIC-III) database. MIMIC III is a large cohort database from Boston, USA. Patients were divided into two groups according to the use of ACEI/ARB before admission. Propensity score matching (PSM) was used to reduce potential bias between the two groups. Cox regression and Kaplan-Meier curves compared 30-day mortality in ACEI/ARB users and non-users. We also defined and analyzed the use of in-hospital ACEI/ARB. Multiple models were used to ensure the robustness of the findings. Subgroup analysis was used to analyze the variability between groups.Results: A total of 544 patients were included in the original study. After PSM, 256 patients were included in the matched cohort. Multivariate Cox regression showed 30-day mortality was significantly lower in ACEI/ARB users compared with controls (HR = 0.50, 95% CI: 0.29– 0.86, p= 0.013). In PSM and inverse probability-weighted models, the results are stable Continued in-hospital use of ACEI/ARB remains effective (HR 0.40, 95% CI 0.22– 0.74, p = 0.003). Kaplan-Meier showed a significant difference in survival between the two groups.Conclusion: This study found that pre-hospital ACEI/ARB use was associated with reduced mortality in patients with AECOPD and ARF.Keywords: chronic obstructive pulmonary disease, acute respiratory failure, angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, mortality

Two-dimensional ferromagnetic (FM) half-metals are promising candidates for advanced spintronic devices with small-size and high-capacity. Motivated by recent report on controlling synthesis of FM Cr$_3$Te$_4$ nanosheet, herein, to explore the potential application in spintronics, we designed spintronic devices based on Cr$_3$X$_4$ (X=Se, Te) monolayers and investigated their spin transport properties. We found that Cr$_3$Te$_4$ monolayer based device shows spin filtering and dual spin diode effect when applying bias voltage, while Cr$_3$S$_4$ monolayer is an excellent platform to realize a spin valve. The different transport properties are primarily ascribed to the semiconducting spin channel, which is close to and away from the Fermi level in Cr$_3$Te$_4$ and Cr$_3$Se$_4$ monolayers, respectively. Interestingly, the current in monolayer Cr$_3$Se$_4$ based device also displays a negative differential resistance effect (NDRE) and a high magnetoresistance ratio (up to 2*10$^3$). Moreover, we found thermally induced spin filtering effect and NDRE in Cr$_3$Se$_4$ junction when applying temperature gradient instead of bias voltage. These theoretical findings highlight the potential of Cr$_3$X$_4$ (X=Se, Te) monolayers in spintronic applications and put forward realistic materials to realize nanosale spintronic device.

The investigation of thermal transport is crucial to the thermal management of modern electronic devices. To obtain the thermal conductivity through solution of the Boltzmann transport equation, calculation of the anharmonic interatomic force constants has a high computational cost based on the current method of single-point density functional theory force calculation. The recent suggested machine learning interatomic potentials (MLIPs) method can avoid these huge computational demands. In this work, we study the thermal conductivity of two-dimensional MoS2-like hexagonal boron dichalcogenides (H-B2 VI 2; VI = S, Se, Te) with a combination of MLIPs and the phonon Boltzmann transport equation. The room-temperature thermal conductivity of H-B2S2 can reach up to 336 W⋅m−1⋅K−1, obviously larger than that of H-B2Se2 and H-B2Te2. This is mainly due to the difference in phonon group velocity. By substituting the different chalcogen elements in the second sublayer, H-B2 VIVI′ have lower thermal conductivity than H-B2 VI 2. The room-temperature thermal conductivity of B2STe is only 11% of that of H-B2S2. This can be explained by comparing phonon group velocity and phonon relaxation time. The MLIP method is proved to be an efficient method for studying the thermal conductivity of materials, and H-B2S2-based nanodevices have excellent thermal conduction.

Total serum bilirubin (TBIL) levels are a risk factor in critically ill patients. However, the relationship between the dynamics of TBIL and the prognosis of acute respiratory failure (ARF) patients is unclear.This study aimed to investigate the impact of different levels of TBIL during hospitalization on mortality in ARF patients.This study used a retrospective cohort study. We extracted information on ARF patients from the Medical Information Bank for Intensive Care (MIMIC)-III (version 1.4). We used propensity score matching (PSM) to adjust for the level of potential baseline-level differences between groups. Cox regression was used to analyze mortality risk factors in patients with ARF. Subgroup analysis was used to explore special populations.2673 patients were included in the study, and 19.7% developed hyperbilirubinemia (TBIL ≥ 2 mg/dL) during their hospitalization. After PSM, multivariate Cox regression showed a 50% and 135% increased risk of death for a maximum value of TBIL ≥ 5 mg/dL and minimum value of TBIL ≥ 2 mg/dL during hospitalization, respectively, compared to the control population. In addition, age ≥ 65 years, previous comorbid malignancies, respiratory rate ≥ 22 beats/min, SpO2 ≥ 95, BUN ≥ 20 mg/dL, lactate ≥ 5 mmol/L, platelet100 * 10 ^ 9/L were independent risk factors for 1-year mortality in ARF patients. Subgroup analysis showed that high bilirubin had a greater effect on patients aged less than 65 years (P for interaction0.05).Hyper TBIL (TBIL max ≥ 5 mg/dL or TBIL min ≥ 2 mg/dL) was an independent risk factor for 1-year mortality in patients with ARF. This study suggests that clinicians should be aware of TBIL levels and intervene early in these patients.

Applying tensile strain on an intrinsic lattice always results in the reduction in thermal conductivity due to the red-shift of phonon frequency and enhanced phonon anharmonicity. However, in this work, we explored an unexpected strain-enhanced thermal conductivity of a planar biphenylene network (BPN) in the frame of a Boltzmann transport equation combined with the machine learning interatomic potential. Under 5% biaxial tensile strain, the room temperature thermal conductivity of BPN reaches to about 4–5 times of that in an intrinsic sample. This phenomenon can be understood by considering a mirror symmetry induced phonon selection rule. This work highlights the significant effect of the selection rule on thermal transport and enriches the understanding of the thermal conductivity regulation in strained two-dimensional materials.

Yuanlong Hu,1,* Xiaomeng Cheng,1,* Zhanjun Qiu,2 Xianhai Chen2 1Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 2The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhanjun Qiu; Xianhai Chen Email qiuzhj227@163.com; chenxianhai18@163.comPurpose: This study aimed to identify the COPD molecular subtypes reflecting pulmonary function damage on the basis of metabolism-related gene expression, which provided the opportunity to study the metabolic heterogeneity and the association of metabolic pathways with pulmonary function damage.Methods: Univariate linear regression and the Boruta algorithm were used to select metabolism-related genes associated with forced expiratory volume in the first second (FEV1) and FEV1/forced vital capacity (FVC) in the Evaluation of COPD to Longitudinally Identify Predictive Surrogate Endpoints (ECLIPSE) cohort. COPD subtypes were further identified by consensus clustering with best-fit. Then, we analyzed the differences in the clinical characteristics, metabolic pathways, immune cell characteristics, and transcription features among the subtypes.Results: This study identified two subtypes (C1 and C2). C1 exhibited higher levels of lower pulmonary function and innate immunity than C2. Ten metabolic pathways were confirmed as key metabolic pathways. The pathways related to N-glycan, hexosamine, purine, alanine, aspartate and glutamate tended to be positively associated with the abundance of adaptive immune cells and negatively associated with the abundance of innate immune cells. In addition, other pathways had opposite trends. All results were verified in Genetic Epidemiology of COPD (COPDGene) datasets.Conclusion: The two subtypes reflect the pulmonary function damage and help to further understand the metabolic mechanism of pulmonary function in COPD. Further studies are needed to prove the prognostic and therapeutic value of the subtypes.Keywords: chronic obstructive pulmonary disease, molecular subtype, metabolic pathway, pulmonary function

BACKGROUND Chronic obstructive pulmonary disease (COPD) is a disease with high heterogeneity, which is a major challenge in clinical individualized treatment. A mucus phenotype is one of the main characteristics of COPD. MATERIAL AND METHODS Gene expression profiles of lung tissue samples were from the Lung Genomics Research Consortium. MUC5B-associated gene signatures were obtained based on a nonlinear feature screening algorithm. These signatures were used to fit a latent profile analysis (LPA) model to identify COPD molecular subtypes and build a subtype classifier to verify the subtypes. Then, we explored the characteristics of cilium assembly and beating signatures, transcriptome features, immune infiltration among the 3 subtypes by xCell, single-sample gene set enrichment analysis, network perturbation amplitude, and weighted gene co-expression network analysis algorithms. An external dataset was used to verify the above COPD subtypes. RESULTS Three subtypes associated with mucus were identified by LPA and verified in an external dataset. Subtype 1 displayed higher T helper type 1 (Th1) and basophil infiltration, higher Th17/regulatory T cells (Tregs) ratio, a higher level of cilium assembly and beating, and lower mast cell and Treg infiltration. The subtypes 2 and 3 demonstrated higher macrophage M2 infiltration in lung tissue, while subtype 3 had higher neutrophil and eosinophil infiltration than subtype 2. CONCLUSIONS Overall, this work identified 3 mucus-associated molecular subtypes related to MUC5B expression, which deepens the understanding of airway mucus secretion in COPD and potentially provides valuable information for precision therapy.

Background: Up to now, there is still no specific drug against COVID-19. However, Ribavirin may bring clinical benefits to COVID-19 patients.Methods: This study was designed as a real-world retrospective cohort study based on electronic medical record (EMR), and linear regression model was used to evaluate the effect of Ribavirin on recovery time.Results: 342 patients were enrolled in this study. Both unadjusted and unadjusted models showed that interferon or Lopinavir-Ritonavir combined with Ribavirin could shorten the recovery time of patients, which was evident in all subgroups considered except the severe subgroup and after fine adjustments.Conclusion: This study shows that interferon or Lopinavir-Ritonavir combined with Ribavirin can shorten the recovery time of patients with non-severe COVID-19.

Objectives: The purpose of this study was to determine the relationship of health beliefs interpersonal loneliness among front-line healthcare workers working in 2019 novel coronavirus epidemic areas. Methods: We conducted a cross-sectional study of 205 clinical medical staff from epidemic areas to examine the associations of self-efficacy with interpersonal loneliness in Hubei. We use the Internet questionnaire survey platform "questionnaire Star" to make an online questionnaire system to collect the basic socio-demographic characteristics of the participants, loneliness score, self-efficacy score, and locus of control. The linear regression model was used to examine the relationship between self-efficacy score and loneliness score, adjusted for sex and education. Results: Self-efficacy score was a positive correlation with loneliness score in the in both the unadjusted (β=0.30, 95%CI=0.12 to 0.48, p

Emerging evidence indicates that the lncRNAs/microRNA/mRNA axis plays important roles in a variety of diseases. This study was aimed to investigate the potential roles and underlying molecular mechanisms of lncRNA H19 and H19-derived miR-675 in regulating hepatitis B virus (HBV)-associated liver injury. mRNA and miR-675 levels were determined by quantitative real-time PCR (qRT-PCR), protein levels were determined by western blot, cell viability was measured by the MTT assay, cell apoptosis was measured by flow cytometry, inflammatory cytokine production was determined by ELISA, oxidative stress and energy metabolism were assessed by commercial kits, and the target relationship between PPARα and miR-675 was confirmed by the dual-luciferase reporter assay. The results showed that the expression of lncRNA H19 and miR-675 was up-regulated in patients with chronic hepatitis B (n = 20). Inhibition of lncRNA H19 or miR-675 in L02 cells increased cell viability, suppressed hepatitis B X protein (HBx)-induced cell apoptosis, inflammatory cytokine production, and oxidative stress, and remodelled energy metabolism. Furthermore, PPARα was found to be a target gene of miR-675. The expression of PPARα was down-regulated in patients with chronic hepatitis B, and there was a negative correlation between the expression of lncRNA H19 and PPARα, or between miR-675 and PPARα. Moreover, by knocking down the expression of PPARα, the actions (apoptosis, inflammatory factors, oxidative stress, and energy metabolism) of lncRNA H19 or miR-675 inhibition in HBx-induced L02 cells were at least partially reversed. In addition, HBx-induced elevated levels of p-AktSer473, p-AktThr308 and p-mTORSer2448 were down-regulated by lncRNA H19 or miR-675 inhibition. Furthermore, PPARα knockdown partly reversed the down-regulated effects of H19 or miR-675 inhibition. Taken together, these data indicate that the lncRNA H19/miR-675/PPARα axis regulates liver cell injury and energy metabolism remodelling induced by HBx, which may be related to the modulation of Akt/mTOR signalling.

Myocardial infarction, one of the main factors that threatens human health, leads to cardiac cell death. Myocardial cells suffer ischemia and hypoxia for a long period of time, which can lead to irreversible cell death or apoptosis and cardiac dysfunction. MicroRNAs (miRs) have been reported to play an important role in a wide range of biological processes in cardiac myocytes, which respond to inflammation and oxidative stress. The aim of the present study was to investigate the effect of miR-370 on oxidative stress and apoptosis of cardiac myocytes in ischemic H9C2 cells induced by hydrogen peroxide (H2O2). H9C2 cells were cultured and treated with different concentrations of H2O2 solution. Then, cells were transfected with miR-370 mimic or negative control (NC) mimic, small interfering (si)-RNA-Forkhead box O1 (FOXO1) and NC siRNA. A Cell Counting Kit-8 and flow cytometry assay were conducted to detect cell viability and cell apoptosis. The expression of oxidative stress associated factors were detected by ELISA. The levels of miR-370 and FOXO1 were examined using western blotting and reverse transcription-quantitative PCR. A luciferase reporter gene assay was performed to verify whether FOXO1 was a target gene of miR-370. The results revealed that miR-370 expression was downregulated and FOXO1 expression was increased in H9C2 cells induced by H2O2. Additionally, FOXO1 was proven to be a target of miR-370. The ELISA and flow cytometry assay revealed that miR-370 overexpression and FOXO1 silencing reversed H2O2-induced oxidative stress and apoptosis. The results indicated that miR-370 could inhibit the oxidative stress and apoptosis of H9C2 cells induced by H2O2 by targeting FOXO1. Therefore, miR-370 may be a new therapeutic target for ischemic heart disease.

The aim of this study was to establish a system for high expression of Aspergillus niger glucose oxidase (GOD) with glyceraldehyde-3-phosphate dehydrogenase gene promoter (pGAP) in Pichia SMD1168. The GOD gene from A. niger accc30161 was inserted into pGAPZαA plasmid carrying a pGAP promoter and was expressed in yeast Pichia pastoris. The expression vector, pGAPZαA-GOD, was validated by colony polymerase chain reaction (PCR), agarose gel electrophoresis, restriction enzyme analysis and sequencing methods. The pGAPZαA-GOD vector was transformed into yeast P. pastoris SMD1168 by electroporation and the positive strain was validated by PCR. The expression and enzyme activity of the recombinant GOD were analysed by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and enzymatic detection. The recombinant GOD in yeast was purified by ion exchange chromatography, and its biochemical properties (dynamics, thermal and pH stability) were analysed. The obtained results showed that the expression vector, pGAPZαA-GOD, was successfully constructed to express A. niger accc30161 GOD protein. After transformation, the pGAPZαA-GOD DNA fragment had been integrated into the P. pastoris SMD1168-GOD genome. High expression of GOD was achieved in SMD1168-GOD, and the enzyme activity of GOD reached 107.18 U/mL in the supernatant of the culture medium at 30 °C and pH 6. The activity of recombinant GOD protein in yeast was 1.35-fold higher than the commercial A. niger GOD, and its affinity to glucose, thermal stability and pH stability are similar to commercial GOD. Using pGAP promoter, A. niger GOD protein is efficiently expressed in recombinant P. pastoris SMD1168-GOD with defective protease.

This study was performed to characterize the bone metabolism in ten 6-month-old male Goto-Kakizaki (GK) rats, a spontaneous type 2 diabetic model, with ten age- and sex-matched non-diabetic Wistar rats as controls. The femora and the fifth lumbar vertebrae were analyzed by a dual energy X-ray absorptiometry for bone mineral density. Histomorphometrical analyses were performed on the sections from the tibia embedded in methylmethacrylate. Biomechanical characterizations were made by a three-point bending test and a compressive test on the femur and the fifth vertebral body respectively. Compared to the control rats, the bone mineral density was significantly deceased and the histomorphometrical studies showed significantly decreased trabecular bone volume, trabecular thickness and number, osteoid surface and thickness, mineralizing surface, mineral apposition rate and bone formation rate, and also a significant increase in mineralization lag time in the diabetic rats. Strength in both bones and elastic modulus of vertebral body significantly decreased in the diabetic rats as well. In addition, the serum osteocalcin levels were significantly decreased and the serum tartrate-resistant acid phosphatase activity was significantly increased. In conclusion, the 6-month-old GK diabetic rats developed osteopenia with an increased risk of fracture owing to the decreased bone formation, and might be a useful model for unraveling the effects of diabetes on bones independent of obesity frequently seen in the type 2 diabetic patients.

Objective To study the changes on bone metabolic characteristics, bone mineral density (BMD) and bone biomechanics in type 2 diabetic model of female rats, and investigate the relationships between these indexes. Methods Type 2 diabetic model of rats was set up by feeding high-glucose-high-fat diet and by injecting intraperitoneally with a low-dose streptozotocin (STZ).All rats were sacrificed after 20 weeks. The BMD of femora and lumbar vertebra, the ratio of ash weight to dry weight, the biomechanical parameters and the bone metabolic related indexes, such as serum Ca, BGP, TRAP, urinary calcium/creatinine(Ca/Cr),urinary hydroxyproline/creatinine(HYP/Cr), and fasting blood glucose, GHbA1c, TG, TC, HDL-C,LDL-C,fasting serum insulin, IGF-Ⅰwere measured. Results Compared with normal control group, the BMD of femora and lumbar vertebra, the ratio of ash weight to dry weight and the bone biomechanical indexes of type 2 diabetic rats decreased rapidly. Insulin resistance was induced in rats of type 2 diabetes mellitus as the level of FPG, FINS, HOMA-IR markedly increased. Serum concentrations of TRAP, TG, TC, LDL-C, GHbA1c markedly increased, and BGP,IGF-Ⅰ,HDL-C decreased. There were even significant differences. BMD of femora showed a positive correlation with BGP strongly.Conclusions The rat model of type 2 diabetes mellitus which is similar to human type 2 diabetes mellitus is induced by feeding high-glucose-high-fat diet and by intraperitoneal injection with a low-dose STZ. This rat model is characterized by moderate hyperglycemia, lipid disorder and insulin resistance. The Bone resorption was accelerated and the formation decreased in this type 2 diabetic model rats, which consequently resulted in the descending bone mass and the changes of the bone biomechanical properties.