A positive feedback between PDIA3P1 and OCT4 promotes the cancer stem cell properties of esophageal squamous cell carcinoma.

BACKGROUND: Increasing evidence has indicated that long non-coding RNAs (lncRNAs) have been proven to regulate esophageal cancer progression. The lncRNA protein disulfide isomerase family A member 3 pseudogene 1 (PDIA3P1) has been shown to promote cancer stem cell properties; however, its mechanism of action remains unclear. In this study, we investigated the regulation of esophageal cancer stem cell properties by the interaction of PDIA3P1 with proteins. METHODS: The GEPIA2 and Gene Expression Omnibus databases were used to analyze gene expression. PDIA3P1 expression in human esophageal squamous cell carcinoma (ESCC) tissues and cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Loss-of-function experiments were performed to determine the effects of PDIA3P1 on ESCC cell proliferation, migration, and invasion. The sphere formation assay, number of side population cells, and CD271 + /CD44 + cells were detected by flow cytometry to identify the cancer stem cell properties. RNA immunoprecipitation (RIP), RNA pull-down, co-immunoprecipitation (co-IP), dual luciferase reporter, and cleavage under targets and tagmentation (CUT&Tag) assays were performed to elucidate the underlying molecular mechanisms. RESULTS: PDIA3P1 expression was upregulated in ESCC cell lines and tissues. Functionally, higher PDIA3P1 expression promoted cell proliferation, invasion, and metastasis and inhibited apoptosis in esophageal cancer. Importantly, PDIA3P1 promoted cancer stem cell properties in ESCC. Mechanistically, PDIA3P1 interacted with and stabilized octamer-binding transcription factor 4 (OCT4) by eliminating its ubiquitination by the ubiquitinating enzyme WW domain-containing protein 2 (WWP2). Moreover, as a transcription factor, OCT4 bound to the PDIA3P1 promoter and promoted its transcription. CONCLUSIONS: Our research revealed a novel mechanism by which a positive feedback loop exists between PDIA3P1 and OCT4. It also demonstrated that the PDIA3P1-WWP2-OCT4 loop is beneficial for promoting the cancer stem cell properties of ESCC. Owing to this regulatory relationship, the PDIA3P1-WWP2-OCT4-positive feedback loop might be used in the diagnosis and prognosis, as well as in the development of novel therapeutics for esophageal cancer.

Association Between Atherogenic Index of Plasma and Risk of Incident Major Adverse Cardiovascular Events.

It is unclear whether the atherogenic index of plasma (AIP) is associated with major adverse cardiovascular events (MACEs) in the general population. A total of 361,644 participants (aged 56.19 ± 8.09 years; 44.79% male) free of a history of MACEs at baseline from the UK Biobank data were included in the analysis. The AIP was calculated using log (triglyceride/high-density lipoprotein-cholesterol). Over a mean follow-up of 12.19 ± 1.60 years, 16,683 participants developed MACEs. After adjustment for traditional risk factors, each 1 unit increase in AIP was associated with a 45.3% higher risk of incident MACEs (hazard ratio (HR), 1.453 [95% confidence interval (CI) 1.371-1.540], P < 0.001). Results were similar when individuals were categorized by the AIP quartiles (HR, 1.283 [95% CI 1.217-1.351]; comparing extreme quartiles). The subgroup analyses showed that the association between AIP and risk of incident MACEs was more obvious in female participants who are < 60 years old and free of hypertension or diabetes. Sensitivity analysis included participants without any lipid-lowering medication or excluded incident MACEs in the first 2 years of follow-up confirming the robustness of the findings. Elevated AIP is a risk factor of incident MACEs in the general population, independent of traditional risk factors.Dynamic monitoring of the AIP may help select the population at high risk of cardiovascular events and guide primary prevention.

The validity, reliability and feasibility of four instruments for assessing the consciousness of stroke patients in a neurological intensive care unit compared.

BACKGROUND: Early rehabilitation is the foundation for recovery for those admitted to an intensive care unit. Appropriate assessment of consciousness is needed before any rehabilitative intervention begins. METHODS: This prospective study compared the validity, reliability and applicability of the sedation-agitation scale, the Richmond Agitation-Sedation Scale, the motor activity assessment scale and the Glasgow Coma Scale in a working neurological intensive care unit. Eighty-three stroke patients were assessed with the four scales by the same 3 raters acting independently: a senior physician, a senior therapist and a trainee. That generated 996 assessment records for comparison. RESULTS: Good agreement (r=0.98-0.99) was found among the sedation-agitation scale, the Richmond Agitation-Sedation Scale, the motor activity assessment scale scores, but the Glasgow Coma Scale ratings correlated less well (r=0.72-0.76) with the others. Consistent results were also found among the three raters. After stratification of the ratings by age, gender, level of consciousness and Acute Physiology and Chronic Health Evaluation score, the scales reported significant differences among the levels of consciousness and among those with different Acute Physiology and Chronic Health Evaluation results, but not with different age or gender strata. CONCLUSIONS: The four instruments tested are all reliable enough and feasible for use as a tool for consciousness screening in a neurological intensive care unit.

Identification of differentially expressed genes, transcription factors, microRNAs and pathways in neutrophils of sepsis patients through bioinformatics analysis.

Sepsis has been recognized to be a life-threatening organ dysfunction caused by the dysregulation of the host response to infections. Our work aims to screen key biomarkers related to neutrophils in sepsis using bioinformatics analysis. For this purpose, the microarray datasets related to neutrophils in sepsis patients were downloaded from the Gene Expression Omnibus (GEO) database. According to the Bayesian test, the Limma package in R was used to screen differentially expressed genes (DEGs). Then, DEGs were uploaded to the DAVID online diagnostic tool for subsequent Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment on the selected DEGs. Next, protein-protein interaction (PPI) network was established based on the selected DEGs using the STRING website and the Cytoscape software. Furthermore, according to the function of the iRegulon plug-in in Cytoscape, our study further predicts and established regulatory networks related to transcription factors and regulatory genes. In addition, the miRWalk2.0 database was used to search for miRNA-DEG pairs, associated with the conduction of intersections of miRNAs predicted by TargetScan, Miranda, miRDB and RNA22 databases. Then, these miRNA-DEG pairs were also displayed in the form of a regulatory network through Cytoscape. Finally, two datasets were selected to verify the screened genes, regulatory factors, and miRNAs, to plot receiver operating characteristics (ROC) curves and compute the area under the curve (AUC) values. The results showed that AKT1, MMP9, ARG1, ETS1 targeting AKT1, and has-miR-124-3p targeting RPS6KA5 may have diagnostic value for patients with sepsis and septic shock. While further experimental studies are required to confirm their role in septic neutrophils.

Protective effects of P2X7R antagonist in sepsis-induced acute lung injury in mice via regulation of circ_0001679 and circ_0001212 and downstream Pln, Cdh2, and Nprl3 expression.

BACKGROUND: Sepsis induces pulmonary P2X7 receptor (P2X7 R) expression and P2X7 R-knockout reduced lung inflammation in mice. The present study investigated the expression of circular RNA (circRNA) and mRNA in sepsis-induced acute lung injury (ALI) treated with a P2X7 R antagonist. METHODS: Sepsis was induced by tracheal administration of lipopolysaccharide (LPS), and the mice were then divided into two groups: without [sepsis + dimethyl sulfoxide (DMSO)] or with P2X7 R antagonist treatment (sepsis + P2X7 A). Sham mice were administrated sterile normal saline. Serum levels of interleukin (IL)-1ß and tumor necrosis factor (TNF)-α, pathological changes, cell apoptosis and P2X7 R expression in lung were assessed, followed by RNA sequencing (RNA-seq) and bioinformatics analyses. A quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR) was used to validate circRNAs and mRNAs. RESULTS: Compared to the sham group, LPS-induced sepsis produced obvious pathological changes in lung tissue, as well as increased apoptotic lung cells, serum TNF-α and IL-1ß levels, and P2X7 R expression; P2X7 R antagonism significantly ameliorated these changes. RNA-seq identified many dysregulated circRNAs and mRNAs during sepsis, whereas this changed with P2X7 R antagonism. RT-qPCR confirmed that Mus musculus (mmu)_circ_0001679, mmu_circ_0001212, phospholamban (Pln), cadherin-2 (Cdh2) and nitrogen permease regulator 3-like (Nprl3) expression were significantly increased in the sepsis + DMSO group compared to that in the sham group but were decreased in the sepsis + P2X7 A group compared to that in the sepsis + DMSO group. The circRNA-microRNA-mRNA coexpression network indicated that mmu_circ_0001679 may regulate Nprl3 and that mmu_circ_0001212 may similarly regulate Pln, Cdh2 and Nprl3 as a competing endogenous RNA. CONCLUSIONS: P2X7 R antagonism attenuates sepsis-induced ALI by inhibiting dysregulated expression of circRNA (circ_0001679, circ_0001212) and mRNA (Pln, Cdh2 and Nprl3).

Resource Allocation in the Cognitive Radio Network-Aided Internet of Things for the Cyber-Physical-Social System: An Efficient Jaya Algorithm.

Currently, there is a growing demand for the use of communication network bandwidth for the Internet of Things (IoT) within the cyber-physical-social system (CPSS), while needing progressively more powerful technologies for using scarce spectrum resources. Then, cognitive radio networks (CRNs) as one of those important solutions mentioned above, are used to achieve IoT effectively. Generally, dynamic resource allocation plays a crucial role in the design of CRN-aided IoT systems. Aiming at this issue, orthogonal frequency division multiplexing (OFDM) has been identified as one of the successful technologies, which works with a multi-carrier parallel radio transmission strategy. In this article, through the use of swarm intelligence paradigm, a solution approach is accordingly proposed by employing an efficient Jaya algorithm, called PA-Jaya, to deal with the power allocation problem in cognitive OFDM radio networks for IoT. Because of the algorithm-specific parameter-free feature in the proposed PA-Jaya algorithm, a satisfactory computational performance could be achieved in the handling of this problem. For this optimization problem with some constraints, the simulation results show that compared with some popular algorithms, the efficiency of spectrum utilization could be further improved by using PA-Jaya algorithm with faster convergence speed, while maximizing the total transmission rate.

Transplantation with hypoxia-preconditioned mesenchymal stem cells suppresses brain injury caused by cardiac arrest-induced global cerebral ischemia in rats.

Cardiac arrest-induced global cerebral ischemia is a main cause of neurological dysfunction in emergency medicine. Transplantation with bone marrow mesenchymal stem cells (MSCs) has been used in stroke models to repair the ischemic brain injury, but it is little studied in models with global cerebral ischemia. In the present study, a hypoxia precondition was used to improve the efficacy of MSC transplantation, given the low survival and migration rates and limited differentiation capacities of MSCs. We found that hypoxia can increase the expansion and migration of MSCs by activating the PI3K/AKT and hypoxia-inducible factor-1α/CXC chemokine receptor-4 pathways. By using a cardiac arrest-induced global cerebral ischemic model in rats, we found that transplantation of hypoxia-preconditioned MSCs promoted the migration and integration of MSCs and decreased neuronal death and inflammation in the ischemic cortex. © 2017 Wiley Periodicals, Inc.

Reduced Severity of Outcome of Recurrent Ipsilateral Transient Cerebral Ischemia Compared with Contralateral Transient Cerebral Ischemia in Rats.

BACKGROUND: To investigate whether prior transient ischemic attack (TIA) had a preconditioning effect on subsequent cerebral infarction in a rat model using middle cerebral artery occlusion (MCAO). METHODS: Thirty-six adult male Sprague-Dawley rats were divided into 3 groups: those with transient (5 minutes) left MCAO (left TIA) (n = 15), those with transient right MCAO (right TIA) (n = 15), and a sham operation group (n = 6). Seven days after the initial transient MCAO, rats in all groups underwent permanent left MCAO. After 24 hours, all rats underwent motor function measurement (the Garcia score and tilting plane test), magnetic resonance imaging, postmortem brain examination, and biomarkers of stroke. RESULTS: Following permanent MCAO, the Garcia score, the brain edema area of T2-weighted images, brain infarction volume, and the level of tumor necrosis factor α mRNA of the ipsilateral and contralateral TIA groups showed no significant difference. The angle of sliding off in the tilting plane test, the mean intensity of the brain edema area of T2-weighted images, levels of matrix metalloproteinase 9, interleukin-1ß, inducible nitric oxide synthase mRNA, and apoptosis-related proteins, BAX, and phosphorylated-p38, were lower in the ipsilateral TIA group compared with the contralateral TIA group. CONCLUSION: The main finding of this study was that a transient, mild, unilateral focus of cerebral ischemia (or TIA) in either the left or right hemisphere, which is then followed by a second unilateral severe and focal ischemic event, results in brain injury. The severity of the brain injury following this second ischemic event will be alleviated when the second insult is ipsilateral to the first TIA.

A fast method based on NESTA to accurately reconstruct CT image from highly undersampled projection measurements.

BACKGROUND: The CT image reconstruction algorithm based compressed sensing (CS) can be formulated as an optimization problem that minimizes the total-variation (TV) term constrained by the data fidelity and image nonnegativity. There are a lot of solutions to this problem, but the computational efficiency and reconstructed image quality of these methods still need to be improved. OBJECTIVE: To investigate a faster and more accurate mathematical algorithm to settle TV term minimization problem of CT image reconstruction. METHOD: A Nesterov's algorithm (NESTA) is a fast and accurate algorithm for solving TV minimization problem, which can be ascribed to the use of most notably Nesterov's smoothing technique and a subtle averaging of sequences of iterates, which has been shown to improve the convergence properties of standard gradient-descent algorithms. In order to demonstrate the superior performance of NESTA on computational efficiency and image quality, a comparison with Simultaneous Algebraic Reconstruction Technique-TV (SART-TV) and Split-Bregman (SpBr) algorithm is made using a digital phantom study and two physical phantom studies from highly undersampled projection measurements. RESULTS: With only 25% of conventional full-scan dose and, NESTA method reduces the average CT number error from 51.76HU to 9.98HU on Shepp-Logan phantom and reduces the average CT number error from 50.13HU to 0.32HU on Catphan 600 phantom. On an anthropomorphic head phantom, the average CT number error is reduced from 84.21HU to 1.01HU in the central uniform area. CONCLUSIONS: To the best of our knowledge this is the first work that apply the NESTA method into CT reconstruction based CS. Research shows that this method is of great potential, further studies and optimization are necessary.

Pyruvate oral rehydration solution improved visceral function and survival in shock rats.

BACKGROUND: Recent findings showed advantages of a novel pyruvate-enriched oral rehydration solution (Pyr-ORS) in resuscitation of burns. This study focused on effects of Pyr-ORS on the visceral blood perfusion (VBP), gastrointestinal function, and survival rate, compared with the bicarbonate-based World Health Organization-guided oral rehydration solution (WHO-ORS), during intragastric rehydration of lethal hemorrhagic shock in rats. METHODS: Sixty adult rats were subjected to 45% total blood volume loss and were randomly allocated to the following three groups (n = 20): group NR (no fluid resuscitation), group PORS (oral Pyr-ORS rehydration), and group BORS (oral WHO-ORS rehydration), respectively. Other 10 rats were served as group NH (the sham group). Enteral rehydration lasted for 4 h after hemorrhage. The mean arterial pressure (MAP), VBP, and plasma enzymes activities of heart, liver, and kidney, and intestinal fatty acid binding protein were measured. Liver, kidney, and ileum were harvested for the evaluation of activities of oxidative enzymes and intestinal barrier protein (ZO-1). Other 84 rats with identical procedures without sampling were observed for their 24-h survival rates. RESULTS: Pyr-ORS was more effective in enhancing the MAP and VBP, inhibiting tissue oxidative damage, and improving organ function, compared with WHO-ORS. Hypoxic lactic acidosis was fully corrected in group PORS in 4 h, whereas it worsened in group BORS, and the 24-h survival rate was twice higher in group PORS than in group BORS (45.8 versus 20.8%, P < 0.05). CONCLUSIONS: A small amount of pyruvate in Pyr-ORS was more therapeutically beneficial than equivalent bicarbonate in WHO-ORS and greatly raised survival in enteral rehydration of lethal hemorrhagic shock. The Pyr-ORS may be an ideal oral fluid in resuscitation of hypovolemic shock, especially in prehospital and resource-poor settings.

The role of glutamate transporter-1 in the acquisition of brain ischaemic tolerance in rats induced by electro-acupuncture pre-treatment.

OBJECTIVE: To investigate whether electro-acupuncture can serve as a method of inducing brain ischaemic tolerance (BIT) by encouraging the expression of glutamate transporter-1 (GLT-1) and suppressing the release of glutamate (Glu). METHODS: Sprague-Dawley (SD) rats were divided into sham, ischaemia and EA groups. EA was performed on dazhui and baihui acupoints and the rat cerebral ischaemia model was achieved by occluding the middle cerebral artery (MCA) for 2 hours, followed by reperfusion. Dialysate was collected from the striatum in vivo to detect the concentration of Glu and the expression of Glutamate Transporter-1 (GLT-1) was examined. The changes of neurological deficit scores were evaluated at 24 hours after reperfusion, while the infarct volumes of brains were then measured with 2,3,5-triphenyltetrazolium chloride (TTC) staining. RESULTS: Compared with the ischaemia group, the concentration of Glu decreased and the expression of GLT-1 increased at most of the detective time points in the EA group; the neurological deficit scores were lower and the infarct volumes were smaller in the EA group. CONCLUSION: EA can up-regulate the expression of GLT-1 and inhibit the excessive release of Glu in the striatum in the process of subsequent ischaemic-reperfusion brain injury, which may be one of the mechanisms of inducing BIT and, thus, be neuroprotective for early ischaemic brain injury.

Exercise pretreatment promotes mitochondrial dynamic protein OPA1 expression after cerebral ischemia in rats.

Exercise training is a neuroprotective strategy in cerebral ischemic injury, but the underlying mechanisms are not yet clear. In the present study, we investigated the effects of treadmill exercise pretreatment on the expression of mitochondrial dynamic proteins. We examined the expression of OPA1/DLP1/MFF/Mfn1/Mfn2, which regulates mitochondrial fusion and fission, and cytochrome C oxidase subunits (COX subunits), which regulate mitochondrial functions, after middle cerebral artery occlusion (MCAO) in rats. T2-weighted magnetic resonance imaging (MRI) was evaluated as indices of brain edema after ischemia as well. Treadmill training pretreatment increased the expression levels of OPA1 and COXII/III/IV and alleviated brain edema, indicating that exercise pretreatment provided neuroprotection in cerebral ischemic injury via the regulation of mitochondrial dynamics and functions.

PLANNER: a multi-scale deep language model for the origins of replication site prediction.

Origins of replication sites (ORIs) are crucial genomic regions where DNA replication initiation takes place, playing pivotal roles in fundamental biological processes like cell division, gene expression regulation, and DNA integrity. Accurate identification of ORIs is essential for comprehending cell replication, gene expression, and mutation-related diseases. However, experimental approaches for ORI identification are often expensive and time-consuming, leading to the growing popularity of computational methods. In this study, we present PLANNER (DeeP LeArNiNg prEdictor for ORI), a novel approach for species-specific and cell-specific prediction of eukaryotic ORIs. PLANNER uses the multi-scale ktuple sequences as input and employs the DNABERT pre-training model with transfer learning and ensemble learning strategies to train accurate predictive models. Extensive empirical test results demonstrate that PLANNER achieved superior predictive performance compared to state-of-the-art approaches, including iOri-Euk, Stack-ORI, and ORI-Deep, within specific cell types and across different cell types. Furthermore, by incorporating an interpretable analysis mechanism, we provide insights into the learned patterns, facilitating the mapping from discovering important sequential determinants to comprehensively analysing their biological functions. To facilitate the widespread utilisation of PLANNER, we developed an online webserver and local stand-alone software, available at http://planner.unimelb-biotools.cloud.edu.au/ and https://github.com/CongWang3/PLANNER, respectively.

Disorder of consciousness related pattern could distinguish minimally conscious state from unresponsive wakefulness syndrome: A F-18-FDG-PET study.

BACKGROUND: Accurate evaluation of level of disorder of consciousness (DOC) is clinically challenging. OBJECTIVE: This study aimed to establish a distinctive DOC-related pattern (DOCRP) for assessing disease severity and distinguishing unresponsive wakefulness syndrome (UWS) from minimally conscious state (MCS). METHODS: Fifteen patients with DOC and eighteen health subjects with F-18-fluorodeoxyglucose (F-18-FDG) positron emission tomography (PET) were enrolled in this study. All patients were assessed by Coma Recovery Scale-Revised (CRS-R) and all individuals were randomly divided into two cohorts (Cohort A and B). DOCRP was identified in Cohort A and subsequently validated in Cohort B and A+B. We also assessed the discriminatory power of DOCRP between MCS and UWS. RESULTS: The DOCRP was characterized bilaterally by relatively decreased metabolism in the medial and lateral frontal lobes, parieto-temporal lobes, cingulate gyrus and caudate, associated with relatively increased metabolism in the cerebellum and brainstem. DOCRP expression exhibited high accuracy in differentiating DOC patients from controls (P<0.0001, AUC=1.000), and furthermore could effectively distinguish MCS from UWS (P=0.037, AUC=0.821, sensitivity: 85.7 %, specificity: 75.0 %). Particularly in the subgroup of DOC patients survived global hypoxic-ischemic brain injury, DOCRP expression exhibited even better discriminatory power between MCS and UWS (P=0.046, AUC=1.000). CONCLUSIONS: DOCRP might serve as an objective biomarker in distinguishing between UWS and MCS, especially in patients survived global hypoxic-ischemic brain injury. TRIAL REGISTRATION NUMBER: ChiCTR2300073717 (Chinese clinical trial registry site, http://www.chictr.org).

MERITS: a web-based integrated Mycobacterial PE/PPE protein database.

Motivation: PE/PPE proteins, highly abundant in the Mycobacterium genome, play a vital role in virulence and immune modulation. Understanding their functions is key to comprehending the internal mechanisms of Mycobacterium. However, a lack of dedicated resources has limited research into PE/PPE proteins. Results: Addressing this gap, we introduce MycobactERIal PE/PPE proTeinS (MERITS), a comprehensive 3D structure database specifically designed for PE/PPE proteins. MERITS hosts 22 353 non-redundant PE/PPE proteins, encompassing details like physicochemical properties, subcellular localization, post-translational modification sites, protein functions, and measures of antigenicity, toxicity, and allergenicity. MERITS also includes data on their secondary and tertiary structure, along with other relevant biological information. MERITS is designed to be user-friendly, offering interactive search and data browsing features to aid researchers in exploring the potential functions of PE/PPE proteins. MERITS is expected to become a crucial resource in the field, aiding in developing new diagnostics and vaccines by elucidating the sequence-structure-functional relationships of PE/PPE proteins. Availability and implementation: MERITS is freely accessible at http://merits.unimelb-biotools.cloud.edu.au/.

The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial.

INTRODUCTION: Severe sepsis is associated with a high mortality rate despite implementation of guideline recommendations. Adjunctive treatment may be efficient and require further investigation. In light of the crucial role of immunologic derangement in severe sepsis, thymosin alpha 1 (Tα1) is considered as a promising beneficial immunomodulatory drug. The trial is to evaluate whether Tα1 improves 28-day all-cause mortality rates and immunofunction in patients with severe sepsis. METHODS: We performed a multicenter randomized controlled trial in six tertiary, teaching hospitals in China between May 12, 2008 and Dec 22, 2010. Eligible patients admitted in ICU with severe sepsis were randomly allocated by a central randomization center to the control group or Tα1 group (1:1 ratio). The primary outcome was death from any cause and was assessed 28 days after enrollment. Secondary outcomes included dynamic changes of Sequential Organ Failure Assessment (SOFA) and monocyte human leukocyte antigen-DR (mHLA-DR) on day 0, 3, 7 in both groups. All analyses were done on an intention-to-treat basis. RESULTS: A total of 361 patients were allocated to either the control group (n = 180) or Tα1 (n = 181) group. The mortalities from any cause within 28 days in the Tα1 group and control group were 26.0% and 35.0% respectively with a marginal P value (nonstratified analysis, P = 0.062; log rank, P = 0.049); the relative risk of death in the Tα1 group as compared to the control group was 0.74 (95% CI 0.54 to 1.02). Greater improvement of mHLA-DR was observed in the Tα1 group on day 3 (mean difference in mHLA-DR changes between the two groups was 3.9%, 95% CI 0.2 to 7.6%, P = 0.037) and day 7 (mean difference in mHLA-DR changes between the two groups was 5.8%, 95% CI 1.0 to 10.5%, P = 0.017) than in the control group. No serious drug-related adverse event was recorded. CONCLUSIONS: The use of Tα1 therapy in combination with conventional medical therapies may be effective in improving clinical outcomes in a targeted population of severe sepsis. TRIAL REGISTRATION: ClinicalTrials.gov NCT00711620.

Diagnostic and prognostic value of autophagy-related key genes in sepsis and potential correlation with immune cell signatures.

Background: Autophagy is involved in the pathophysiological process of sepsis. This study was designed to identify autophagy-related key genes in sepsis, analyze their correlation with immune cell signatures, and search for new diagnostic and prognostic biomarkers. Methods: Whole blood RNA datasets GSE65682, GSE134347, and GSE134358 were downloaded and processed. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were used to identify autophagy-related key genes in sepsis. Then, key genes were analyzed by functional enrichment, protein-protein interaction (PPI), transcription factor (TF)-gene and competing endogenous RNA (ceRNA) network analysis. Subsequently, key genes with diagnostic efficiency and prognostic value were identified by receiver operating characteristic (ROC) curves and survival analysis respectively. The signatures of immune cells were estimated using CIBERSORT algorithm. The correlation between significantly different immune cell signatures and key genes was assessed by correlation analysis. Finally, key genes with both diagnostic and prognostic value were verified by RT-qPCR. Results: 14 autophagy-related key genes were identified and their TF-gene and ceRNA regulatory networks were constructed. Among the key genes, 11 genes (ATIC, BCL2, EEF2, EIF2AK3, HSPA8, IKBKB, NLRC4, PARP1, PRKCQ, SH3GLB1, and WIPI1) had diagnostic efficiency (AUC > 0.90) and 5 genes (CAPN2, IKBKB, PRKCQ, SH3GLB1 and WIPI1) were associated with survival prognosis (p-value < 0.05). IKBKB, PRKCQ, SH3GLB1 and WIPI1 had both diagnostic and prognostic value, and their expression were verified by RT-qPCR. Analysis of immune cell signatures showed that the abundance of neutrophil, monocyte, M0 macrophage, gamma delta T cell, activated mast cell and M1 macrophage subtypes increased in the sepsis group, while the abundance of resting NK cell, resting memory CD4+ T cell, CD8+ T cell, naive B cell and resting dendritic cell subtypes decreased. Most of the key genes correlated with the predicted frequencies of CD8+ T cells, resting memory CD4+ T cells, M1 macrophages and naive B cells. Conclusion: We identified autophagy-related key genes with diagnostic and prognostic value in sepsis and discovered associations between key genes and immune cell signatures. This work may provide new directions for the discovery of promising biomarkers for sepsis.

An advanced remote sensing retrieval method for urban non-optically active water quality parameters: An example from Shanghai.

The optical insensitivity of non-optically active water quality parameters (NAWQPs) presents a significant challenge for remote sensing-based quantitative monitoring, which is an important tool for water quality assessment and management. Based on the analysis of the samples from Shanghai, China, it was found that the spectral morphological characteristics of the water body were obviously different under the combined effect of multiple NAWQPs. In view of this, in this paper, a machine learning method was proposed for the retrieval of urban NAWQPs by using multi-spectral scale morphological combined feature (MSMCF). The proposed method integrates both local and global spectral morphological features, and employs a multi-scale approach to enhance its applicability and stability, providing a more accurate and robust solution. To explore the applicability of the MSMCF method in retrieving urban NAWQPs, different methods were tested in terms of the retrieval accuracy and stability on the measured data and three different hyperspectral data. As can be seen from the results, the proposed method has good retrieval performance, which can be applied to hyperspectral data with different spectral resolutions with certain ability to suppress noise. Further analysis indicates that the sensitivity of each NAWQP to spectral morphological features varies. The research methods and findings in this paper can promote the development of hyperspectral and remote sensing technology in the prevention and treatment of urban water quality deterioration, and provide reference for related research.

Optimized Cingulate Island Sign in Discriminating Dementia With Lewy Bodies From Alzheimer Disease.

PURPOSE: This study aimed to optimize the analysis of cingulate island sign (CIS) to improve its diagnostic accuracy in discriminating dementia with Lewy bodies (DLB) from Alzheimer disease (AD). PATIENTS AND METHODS: Patients with DLB (n = 80), AD (n = 75), and normal controls (n = 22) with 18 F-FDG PET imaging were enrolled in this study. Sixty-two DLB patients also underwent dopaminergic PET scans. The optimized/conventional CIS ratios and metabolism in associated brain regions were evaluated by diagnostic accuracy among groups and correlation with cognitive/dopaminergic dysfunction. RESULTS: In discriminating DLB from AD, the optimized CIS ratio calculated by dorsal posterior cingulate cortex (PCC)/lateral occipital lobe metabolism achieved the highest specificity, sensitivity, and accuracy at 0.907, 0.750, and 0.825, respectively. The metabolism of dorsal-PCC positively correlated with cognitive impairment in DLB patients cross-sectionally and longitudinally ( P < 0.001, r = 0.601; P = 0.044, r = 0.645), and also correlated with dopaminergic impairment in the caudate ( P = 0.048, r = 0.315). CONCLUSIONS: Optimized CIS ratios of incorporated metabolic activity of dorsal-PCC and occipital subregions are clinically useful for differentiating DLB from AD, in which dorsal-PCC metabolism may provide an objective biomarker to reflect the severity of cognitive impairment in DLB.