Middle and Late Pleistocene Denisovan subsistence at Baishiya Karst Cave.

Genetic and fragmented palaeoanthropological data suggest that Denisovans were once widely distributed across eastern Eurasia1-3. Despite limited archaeological evidence, this indicates that Denisovans were capable of adapting to a highly diverse range of environments. Here we integrate zooarchaeological and proteomic analyses of the late Middle to Late Pleistocene faunal assemblage from Baishiya Karst Cave on the Tibetan Plateau, where a Denisovan mandible and Denisovan sedimentary mitochondrial DNA were found3,4. Using zooarchaeology by mass spectrometry, we identify a new hominin rib specimen that dates to approximately 48-32 thousand years ago (layer 3). Shotgun proteomic analysis taxonomically assigns this specimen to the Denisovan lineage, extending their presence at Baishiya Karst Cave well into the Late Pleistocene. Throughout the stratigraphic sequence, the faunal assemblage is dominated by Caprinae, together with megaherbivores, carnivores, small mammals and birds. The high proportion of anthropogenic modifications on the bone surfaces suggests that Denisovans were the primary agent of faunal accumulation. The chaîne opératoire of carcass processing indicates that animal taxa were exploited for their meat, marrow and hides, while bone was also used as raw material for the production of tools. Our results shed light on the behaviour of Denisovans and their adaptations to the diverse and fluctuating environments of the late Middle and Late Pleistocene of eastern Eurasia.

Topology-Directed Coassembly of Linear and Cyclic Amphiphilic Diblock Copolymers: A Monte Carlo Study.

The self-assembly behaviors of the mixtures composed of linear and cyclic AB diblock copolymers in A-selective solvents are investigated by means of Monte Carlo simulation. The simulation results indicate that a typical morphological transition of the aggregate from sphere to cylinder, to lamella, and then to vesicle can be achieved via solely adjusting the molar fraction of the cyclic diblock copolymers in the mixture. Furthermore, the simulation results show that under the condition that the pure cyclic and linear diblock copolymers can both form vesicles, the structure characteristics (e.g., the inner radius and hydrophobic membrane thickness of the vesicle) and the formation pathway of the vesicles formed by the mixtures can also be regulated via solely changing the molar fraction of the cyclic diblock copolymers in the mixture. It is worth noting that the inner radius of the vesicle can be considerably increased by increasing the molar fraction of the cyclic diblock copolymers in the mixture, which results in a remarkable increase in the inner capacity of the vesicle. This phenomenon has a unique significance in the field of drug delivery. Our simulation works can provide a new approach to the preparation of polymer materials with novel properties and functions.

Homer1 ameliorates ischemic stroke by inhibiting necroptosis-induced neuronal damage and neuroinflammation.

OBJECTIVE: Proinflammatory necroptosis is the main pathological mechanism of ischemic stroke. Homer scaffolding protein 1 (Homer1) is a postsynaptic scaffolding protein that exerts anti-inflammatory effects in most central nervous system diseases. However, the relationship between Homer1 and proinflammatory necroptosis in ischemic stroke remains unclear. AIM: This study aimed to investigate the role of Homer1 in ischemia-induced necroptosis. METHODS: C57BL/6 mice were used to establish a model of permanent middle cerebral artery occlusion model (pMCAO). Homer1 knockdown mice were generated using adeno-associated virus (AAV) infection to explore the role of Homer1 and its impact on necroptosis in pMCAO. Finally, Homer1 protein was stereotaxically injected into the ischemic cortex of Homer1flox/flox/Nestin-Cre +/- mice, and the efficacy of Homer1 was investigated using behavioral assays and molecular biological assays to explore potential mechanisms. RESULTS: Homer1 expression peaked at 8 h in the ischemic penumbral cortex after pMCAO and colocalized with neurons. Homer1 knockdown promoted neuronal death by enhancing necroptotic signaling pathways and aggravating ischemic brain damage in mice. Furthermore, the knockdown of Homer1 enhanced the expression of proinflammatory cytokines. Moreover, injection of Homer1 protein reduced necroptosis-induced brain injury inhibited the expression of proinflammatory factors, and ameliorated the outcomes in the Homer1flox/flox/Nestin-Cre+/- mice after pMCAO. CONCLUSIONS: Homer1 ameliorates ischemic stroke by inhibiting necroptosis-induced neuronal damage and neuroinflammation. These data suggested that Homer1 is a novel regulator of neuronal death and neuroinflammation.

The association between weight-adjusted-waist index and psoriasis: A cross-sectional study.

INTRODUCTION: This study explored the association between psoriasis and the weight-adjusted waist index (WWI), a newly developed measure of adiposity. The research was conducted among adults in the United States. METHODS: Utilizing survey data from the National Health and Nutrition Examination Survey (NHANES) spanning the years 2009 to 2014, the present study aimed to investigate the potential correlation between psoriasis and WWI within a sample of 15,920 adult participants. Employing multivariable logistic regression and nonlinear curve fitting techniques, we analyzed this plausible association. Additionally, a subgroup analysis was conducted to ascertain the consistency across diverse populations. RESULTS: A significant positive association was discovered between psoriasis and WWI in the investigated sample of 15,920 adults. After conducting a comprehensive adjustment of the model, it was observed that each incremental unit of WWI was significantly associated with an 14% elevated likelihood of developing psoriasis (OR = 1.16, 95% CI 1.01-1.36). Moreover, individuals belonging to the highest quartile of WWI exhibited a 47% higher risk of psoriasis compared to those in the lowest quartile (OR = 1.44, 95% CI 1.01-2.06). This positive correlation remained consistent across various subgroups. The study also compared WWI with BMI and waist circumference, finding that WWI is a more stable metric of obesity. CONCLUSIONS: Our study suggested that in US adults, there is a positive association between WWI and psoriasis. It also indicated that WWI showed potential as a valuable index of psoriasis among the general population.

The association between triglyceride-glucose index and its combination with systemic inflammation indicators and all-cause and cardiovascular mortality in the general US population: NHANES 1999-2018.

BACKGROUND: The correlation between the triglyceride-glucose (TyG) index and mortality in the general population remains controversial, with inconsistent conclusions emerging from different studies. OBJECTIVE: This study aims to investigate whether there is an association between the TyG index and mortality in the general population in the United States, and to explore whether a new index combining the TyG index with systemic inflammation indicators can better predict all-cause and cardiovascular mortality risks in the general population than using the TyG index alone. METHODS: Calculate the systemic inflammation indicators and TyG index for each participant based on their complete blood count, as well as their triglyceride and glucose levels in a fasting state. TyG-inflammation indices were obtained by multiplying the TyG index with systemic inflammation indicators (TyG-NLR, TyG-MLR, TyG-lgPLR, TyG-lgSII, and TyG-SIRI). Based on the weighted Cox proportional hazards model, assess whether the TyG and TyG-Inflammation indices are associated with mortality risk in the general population. Restricted cubic splines (RCS) are used to clarify the dose-response relationship between the TyG and TyG-Inflammation indices and mortality, and to visualize the results. Time-dependent receiver operating characteristic (ROC) curves are used to evaluate the accuracy of the TyG and TyG-Inflammation indices in predicting adverse outcomes. RESULTS: This study included 17,118 participants. Over a median follow-up period of 125 months, 2595 patients died. The TyG index was not found to be related to mortality after adjusting for potentially confounding factors. However, the TyG-inflammation indices in the highest quartile (Q4), except for TyG-lgPLR, were significantly associated with both all-cause and cardiovascular mortality, compared to those in the lowest quartile (Q1). Among them, TyG-MLR and TyG-lgSII showed the strongest correlations with all-cause mortality and cardiovascular mortality. Specifically, compared to their respective lowest quartiles (Q1), participants in the highest quartile (Q4) of TyG-MLR had a 48% increased risk of all-cause mortality (95% CI: 1.23-1.77, P for trend < 0.0001), while participants in the highest quartile (Q4) of TyG-lgSII had a 92% increased risk of cardiovascular mortality (95% CI: 1.31-2.81, P for trend < 0.001). Time-dependent ROC curve analysis showed that the TyG-MLR had the highest accuracy in predicting long-term mortality outcomes. CONCLUSIONS: The TyG-Inflammation indices constructed based on TyG and systemic inflammation indicators are closely related to mortality in the general population and can better predict the risk of adverse outcomes. However, no association between TyG and mortality in the general population was found.

Long Non-Coding RNA H19 Leads to Upregulation of γ-Globin Gene Expression during Erythroid Differentiation.

Long noncoding RNAs (lncRNAs) are important because they are involved in a variety of life activities and have many downstream targets. Moreover, there is also increasing evidence that some lncRNAs play important roles in the expression and regulation of γ-globin genes. In our previous study, we analyzed genetic material from nucleated red blood cells (NRBCs) extracted from premature and full-term umbilical cord blood samples. Through RNA sequencing (RNA-Seq) analysis, lncRNA H19 emerged as a differentially expressed transcript between the two blood types. While this discovery provided insight into H19, previous studies had not investigated its effect on the γ-globin gene. Therefore, the focus of our study was to explore the impact of H19 on the γ-globin gene. In this study, we discovered that overexpressing H19 led to a decrease in HBG mRNA levels during erythroid differentiation in K562 cells. Conversely, in CD34+ hematopoietic stem cells and human umbilical cord blood-derived erythroid progenitor (HUDEP-2) cells, HBG expression increased. Additionally, we observed that H19 was primarily located in the nucleus of K562 cells, while in HUDEP-2 cells, H19 was present predominantly in the cytoplasm. These findings suggest a significant upregulation of HBG due to H19 overexpression. Notably, cytoplasmic localization in HUDEP-2 cells hints at its potential role as a competing endogenous RNA (ceRNA), regulating γ-globin expression by targeting microRNA/mRNA interactions.

Advances in Electrospun Nanofiber Membranes for Dermatological Applications: A Review.

In recent years, a wide variety of high-performance and versatile nanofiber membranes have been successfully created using different electrospinning methods. As vehicles for medication, they have been receiving more attention because of their exceptional antibacterial characteristics and ability to heal wounds, resulting in improved drug delivery and release. This quality makes them an appealing choice for treating various skin conditions like wounds, fungal infections, skin discoloration disorders, dermatitis, and skin cancer. This article offers comprehensive information on the electrospinning procedure, the categorization of nanofiber membranes, and their use in dermatology. Additionally, it delves into successful case studies, showcasing the utilization of nanofiber membranes in the field of skin diseases to promote their substantial advancement.

Establishment and application of the BRP prognosis model for idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial lung disease. Clinical models to accurately evaluate the prognosis of IPF are currently lacking. This study aimed to construct an easy-to-use and robust prediction model for transplant-free survival (TFS) of IPF based on clinical and radiological information. METHODS: A multicenter prognostic study was conducted involving 166 IPF patients who were followed up for 3 years. The end point of follow-up was death or lung transplantation. Clinical information, lung function tests, and chest computed tomography (CT) scans were collected. Body composition quantification on CT was performed using 3D Slicer software. Risk factors in blood routine examination-radiology-pulmonary function (BRP) were identified by Cox regression and utilized to construct the "BRP Prognosis Model". The performance of the BRP model and the gender-age-physiology variables (GAP) model was compared using time-ROC curves, calibration curves, and decision curve analysis (DCA). Furthermore, histopathology fibrosis scores in clinical specimens were compared between the different risk stratifications identified by the BRP model. The correlations among body composition, lung function, serum inflammatory factors, and profibrotic factors were analyzed. RESULTS: Neutrophil percentage > 68.3%, pericardial adipose tissue (PAT) > 94.91 cm3, pectoralis muscle radiodensity (PMD) ≤ 36.24 HU, diffusing capacity of the lung for carbon monoxide/alveolar ventilation (DLCO/VA) ≤ 56.03%, and maximum vital capacity (VCmax) < 90.5% were identified as independent risk factors for poor TFS among patients with IPF. We constructed a BRP model, which showed superior accuracy, discrimination, and clinical practicability to the GAP model. Median TFS differed significantly among patients at different risk levels identified by the BRP model (low risk: TFS > 3 years; intermediate risk: TFS = 2-3 years; high risk: TFS ≈ 1 year). Patients with a high-risk stratification according to the BRP model had a higher fibrosis score on histopathology. Additionally, serum proinflammatory markers were positively correlated with visceral fat volume and infiltration. CONCLUSIONS: In this study, the BRP prognostic model of IPF was successfully constructed and validated. Compared with the commonly used GAP model, the BRP model had better performance and generalization with easily obtainable indicators. The BRP model is suitable for clinical promotion.

Application of oncolytic virus in tumor therapy.

Oncolytic viruses (OVs) can selectively kill tumor cells without affecting normal cells, as well as activate the innate and adaptive immune systems in patients. Thus, they have been considered as a promising measure for safe and effective cancer treatment. Recently, a few genetically engineered OVs have been developed to further improve the effect of tumor elimination by expressing specific immune regulatory factors and thus enhance the body's antitumor immunity. In addition, the combined therapies of OVs and other immunotherapies have been applied in clinical. Although there are many studies on this hot topic, a comprehensive review is missing on illustrating the mechanisms of tumor clearance by OVs and how to modify engineered OVs to further enhance their antitumor effects. In this study, we provided a review on the mechanisms of immune regulatory factors in OVs. In addition, we reviewed the combined therapies of OVs with other therapies including radiotherapy and CAR-T or TCR-T cell therapy. The review is useful in further generalize the usage of OV in cancer treatment.

Highly sensitive magnetic field sensors based on Fe2O3 nanorods grown on the surface of a tapered few mode fiber.

A magnetic field (MF) sensor with a stable structure and high sensitivity has been proposed and experimentally verified. We used the water bath method to produce a layer of Fe2O3 nanorods on a tapered few mode fiber (FMF) surface to form a Mach-Zehnder interferometer (MZI). The experiment found that the nanostructure produced on the surface of FMF were particularly stable and firm. Under the action of an external MF, the magnetic permeability of a Fe2O3 nanorod will change, leading to a change in its refractive index, resulting in a linear shift in the resonance wavelength of MZI. The experimental results showed that the MF sensitivity of MZI reached -0.5348 nm/mT in 10 mT∼80 mT. In addition, MZI has a certain sensitivity to environmental humidity and temperature. A long-period fiber grating and a fiber Bragg grating are cascaded with MZI to achieve a simultaneous measurement of three quantities and eliminate their cross-sensitivity.

Multiple brain regions are involved in reaction to acute restraint stress in CYLD-knockout mice.

The lysine 63 deubiquitinase cylindromatosis (CYLD) is expressed at high levels in the brain and is considered to be involved in anxious and depressive behavior, cognitive inflexibility, and autism disorders. Previous research was limited in some brain regions, including the hippocampus, striatum, and amygdala. To better understand whether CYLD plays a role in adaptation to stress and which brain regions are involved, we analyzed the behavior of CYLD-knockout mice in the elevated plus maze (EPM) and light-dark box test (LDT) after acute restraint stress (ARS) and mapped their c-Fos immunoreactivity in brain sections. Here we report that CYLD deficiency leads to an unexpected reaction to ARS in mice, and is accompanied by significant neuronal activation of brain regions including the medial prefrontal cortex (mPFC), dorsal striatum (DS), nucleus accumbens (NAc), and basal lateral amygdala (BLA), but not ventral hippocampus (vHPC). Our findings show that CYLD participates in ARS-induced anxious behavior and that this involves multiple brain regions.

Solution Self-Assembly of Amphiphilic Tadpole-like Giant Molecules Constructed by Monotethering Diblock Copolymer Chain onto a Nanoparticle.

The self-assembly behavior of a tadpole-like giant molecule (TGM) constructed from a hydrophobic nanoparticle (NP) monotethered by a single amphiphilic AB diblock copolymer chain was investigated by combining self-consistent field theory and density functional theory in solution. The effects of the hydrophobicities of the B blocks and NPs (i.e., solvent properties) on the self-assembly behavior of the TGMs were investigated in the cases of weak and strong intramolecular interactions (i.e., incompatibilities) between the components of giant molecules, respectively. Besides conventional ordered aggregates (such as spheres, rings, and vesicles) with hydrophobic B-cores covered by NP shells, several aggregates with novel hierarchical structures, including vesicles with NP-inserted hydrophobic walls, bead-string-like micelles, and long cylindrical micelles with NP bumps, were obtained by tuning the solvent properties under different intramolecular interactions. Noteworthy that the simulation results show that the arrangement of the NP bumps on the long cylindrical micelles may have a certain degree of helicity, which means that these micelles may have some unique electromagnetic features such as circular dichroism. Phase diagrams as a function of the hydrophobicities of the B blocks and NPs were constructed to show the formation conditions of these novel structures. These findings can not only offer new insights into understanding of the self-assembly behavior of the TGM in solution but also provide useful guidance for simple and efficient regulation of the morphology, as well as the NP distribution and arrangement of the ordered aggregates in experiments.

Identification of PDK4 as Hub Gene for Diabetic Nephropathy Using Co-Expression Network Analysis.

INTRODUCTION: Diabetic nephropathy (DN) is related to type 1 and type 2 diabetes. They are the leading cause of end-stage renal disease, but the underling specific pathogenesis of DN is not yet clear. Our study was conducted to explore how DN changed the transcriptome profiles in the kidney. METHODS: The gene expression profile of microdissected glomeruli of 41 type 2 DN patients and 20 healthy controls were included. The sample dataset GSE96804 was obtained from the GEO database. Differentially expressed genes (DEGs) were analyzed in R with the limma package and the important modules were found by weighted gene co-expression network analysis (WGCNA) clustering. The modules were then analyzed based on Gene Ontology (GO) gene set enrichment analysis, and the hub genes were found out. We next validated the hub gene, PDK4, in a cell model of DN. We also constructed the PDK4-related PPI network to investigate the correlation between PDK4 expression and other genes. RESULTS: Heatmap and volcano map were drawn to illustrate the mRNA expression profile of 1,204 DEGs in both samples of DN patients and the control group. Using WGCNA, we selected the blue module in which genes showed the strongest correlation with the phenotype and the smallest p value. We also identified PDK4 as a hub gene. PDK4 expression was upregulated in human diabetic kidney tissue. Moreover, PDK4 was speculated to play a role in glomerular basement membrane development and kidney development according to the enrichment of functions and signaling pathways. Furthermore, PDK4 and two key genes GSTA2 and G6PC protein expression were verified highly expressed in the cell model of DN. CONCLUSION: During the pathogenesis of DN, many genes may change expression in a coordinated manner. The discovery of PDK4 as key gene using WGCNA is of great significance for the development of new treatment strategies to block the development of DN.

Metagenomics reveals the effects of glyphosate on soil microbial communities and functional profiles of C and P cycling in the competitive vegetation control process of Chinese fir plantation.

Although considerable efforts have been devoted to investigate the behavior of glyphosate on microbiome in various environment, knowledge about the soil microbial community and functional profile in weeds control process of the Chinese fir plantation are limited. In this study, shotgun metagenomic sequencing was used to determine the abundance and diversity of microbial communities and functional genes after foliar application of glyphosate for 1, 2, 3 and 4 months in a Chinese fir plantation. The results showed that glyphosate increased the copy numbers (qPCR) of 16S rRNA gene for 16.9%, improved the bacterial diversity (Shannon index) and complexity of bacterial co-occurrence network, and changed the abundances of some bacterial and fungal taxa, but had no effects on ITS gene copy numbers, fungal Shannon index, and bacterial and fungal communities (PCoA). Glyphosate application significantly decreased the amount of microbial function potentials involved in organic P mineralization for 10.7%, chitin degradation for 13.1%, and CAZy gene families with an exception of PL for 11.5% at the first month, while did not affect the profile of microbial genes response to P and C cycling in longer term. In addition, glyphosate reduced the contents of soil TOC, DOC and NH4+-H for 17.6%, 52.3% and 44.6% respectively, and decreased the starch, soluble sugar, Zn and Fe of Chinese fir leaves for 20.6%, 19.8%, 32.8% and 48.4% respectively. Mantle test, Spearman's correlation, and PLS-PM model revealed the connections among soil properties, tree nutrients, bacterial and fungal communities, and microbial function potentials were influenced by glyphosate. While our findings need to be validated in other filed and mechanistic studies, they may indicate that the foliar application of glyphosate has a potential effect on Chinese fir seedlings, and this effect may contribute to the changes of the bacterial community and soil properties including AN, DON and NH4+-H.

Correlation between white matter hyperintensity and delusional symptoms in Alzheimer's disease.

BACKGROUND: Patients with Alzheimer's disease (AD) often exhibit neuropsychiatric symptoms (NPS), particularly delusions. Previous studies have shown an association between white matter hyperintensities (WMH) and specific NPS. This study aims to explore the relationship between WMH volume and delusions in AD patients by comparing the WMH volumes of delusional and non-delusional subgroups. METHODS: 80 AD patients were divided into a delusion group (n = 36) and a non-delusion group (n = 44) based on the Neuropsychiatric Inventory (NPI). The brain cortical volume and WMH volume were quantitatively calculated for all 80 patients, including total WMH volume, periventricular WMH (PVWMH) volume, deep WMH volume, as well as bilateral frontal lobe, temporal lobe, parietal lobe, and occipital lobe WMH volumes. Firstly, we compared the differences in WMH volumes between the delusion group and non-delusion group. Then, within the delusion group, we further categorized patients based on severity scores of their delusional symptoms into mild (1 point), moderate (2 points), or severe groups (3 points). We compared the WMH volumes among these three groups to investigate the role of WMH volume in delusional symptoms. RESULTS: There was a significant difference in left occipital lobe WMH volume between the delusion group and non-delusion group(P < 0.05). Within the delusion group itself, there were significant differences in overall WMH volume as well as PVWMH volume among patients with mild or severe levels of delusions(P < 0.05). CONCLUSION: Left occipital lobe WMH volume may be associated with the occurrence of delusional AD patients, and the total volume of whole-brain WMH and PVWMH volume may affect the degree of severity of delusional symptoms.

Correlations between Multiple SNPs and HbF Levels in ß-Thalassemia Carriers.

BACKGROUND: Increased hemoglobin F (HbF) expression in individuals with ß-thalassemia contributes to the alleviation of pathological phenomena and the reduction of mortality. We have investigated the correlation between six single nucleotide polymorphisms (SNPs) in BCL11A, XmnI-HBG2, HBS1L-MYB, and ANTXR1 and the levels of HbF in ß-thalassemia carriers. METHODS: Samples were collected from 330 cases of ß-thalassemia carriers. The genotypes of the rs4671393, rs-7482144, rs28384513, rs4895441, rs9399137, and rs4527238 were determined using Sanger sequencing. RESULTS: The results both of quantitative and qualitative analysis showed that rs4671393 (BCL11A), rs7482144 (Xmn1-HBG2), and rs9399137 (HBS1L-MYB) in ß-thalassemia carriers correlated with the levels of HbF (p < 0.05), only rs28384513 (HBS1L-MYB) and rs4527238 (ANTXR1) were associated with HbF expression in ß-thalassemia minor (p < 0.05). CONCLUSIONS: These results indicate that the SNP rs4527238 in the ANTXR1 gene was found likely to play a role as a modulator of HbF levels in ß-thalassemia carriers for the first time.

[Risk Factors of Rapidly Progressive Interstitial Lung Disease in Patients With Anti-Melanoma Differentiation-Associated Gene 5 Antibody-Positive Dermatomyositis].

Objective: To investigate the conditions of patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis combined with rapidly progressive interstitial lung disease (RPILD), and to analyze the risk factors. Methods: A total of 145 patients diagnosed with anti-MDA5 antibody-positive dermatomyositis at West China Hospital, Sichuan University between January 2018 and September 2021 were selected, and their general and clinical data were collected. The patients were divided into two groups, a RPILD group of patients with comorbid RPILD and a non-RPILD group of those who did not have comorbid RPILD. Factors that might affect whether patients with anti-MDA5 antibody-positive dermatomyositis also had comorbid RPILD were screened out and binary logistic regression analysis was performed. Results: Among the 145 patients with anti-MDA5 antibody-positive dermatomyositis, 32 (22.07%) patients had comorbid RPILD, while the remaining 113 (77.93%) did not have comorbid RPILD. Binary logistic regression analysis showed that lactate dehydrogenase≥370 IU/L (compared with <370 IU/L, OR=4.066, 95% CI: 1.616-10.230) and carcinoembryo antigen≥5 ng/mL (compared with <5 ng/mL, OR=6.070, 95% CI: 2.013-18.303) were risk factors for comorbid RPILD in patients with anti-MDA5 antibody-positive dermatomyositis ( ß>0, OR>1, P<0.05). Conclusion: It is recommended that close attention be given to changes in high-resolution chest CT and pulmonary functions in patients with lactate dehydrogenase≥370 IU/L and carcinoembryo antigen≥5 ng/mL. If rapid progression of lung disease is detected, it is necessary to strengthen the treatment of the lung disease, thereby improving the prognosis of patients.

A dynamic recursive feature elimination framework (dRFE) to further refine a set of OMIC biomarkers.

MOTIVATION: A feature selection algorithm may select the subset of features with the best associations with the class labels. The recursive feature elimination (RFE) is a heuristic feature screening framework and has been widely used to select the biological OMIC biomarkers. This study proposed a dynamic recursive feature elimination (dRFE) framework with more flexible feature elimination operations. The proposed dRFE was comprehensively compared with 11 existing feature selection algorithms and five classifiers on the eight difficult transcriptome datasets from a previous study, the ten newly collected transcriptome datasets and the five methylome datasets. RESULTS: The experimental data suggested that the regular RFE framework did not perform well, and dRFE outperformed the existing feature selection algorithms in most cases. The dRFE-detected features achieved Acc = 1.0000 for the two methylome datasets GSE53045 and GSE66695. The best prediction accuracies of the dRFE-detected features were 0.9259, 0.9424 and 0.8601 for the other three methylome datasets GSE74845, GSE103186 and GSE80970, respectively. Four transcriptome datasets received Acc = 1.0000 using the dRFE-detected features, and the prediction accuracies for the other six newly collected transcriptome datasets were between 0.6301 and 0.9917. AVAILABILITY AND IMPLEMENTATION: The experiments in this study are implemented and tested using the programming language Python version 3.7.6. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Systemic LPS-induced microglial activation results in increased GABAergic tone: A mechanism of protection against neuroinflammation in the medial prefrontal cortex in mice.

Neuroinflammation with excess microglial activation and synaptic dysfunction are early symptoms of most neurological diseases. However, how microglia-associated neuroinflammation regulates synaptic activity remains obscure. We report here that acute neuroinflammation induced by intraperitoneal injection of lipopolysaccharide (LPS) results in cell-type-specific increases in inhibitory postsynaptic currents in the glutamatergic, but not the GABAergic, neurons of medial prefrontal cortex (mPFC), coinciding with excessive microglial activation. LPS causes upregulation in levels of GABAAR subunits, glutamine synthetase and vesicular GABA transporter, and downregulation in brain-derived neurotrophic factor (BDNF) and its receptor, pTrkB. Blockage of microglial activation by minocycline ameliorates LPS-induced abnormal expression of GABA signaling-related proteins and activity of synaptic and network. Moreover, minocycline prevents the mice from LPS-induced aberrant behavior, such as a reduction in total distance and time spent in the centre in the open field test; decreases in entries into the open arm of elevated-plus maze and in consumption of sucrose; increased immobility in the tail suspension test. Furthermore, upregulation of GABA signaling by tiagabine also prevents LPS-induced microglial activation and aberrant behavior. This study illustrates a mode of bidirectional constitutive signaling between the neural and immune compartments of the brain, and suggests that the mPFC is an important area for brain-immune system communication. Moreover, the present study highlights GABAergic signaling as a key therapeutic target for mitigating neuroinflammation-induced abnormal synaptic activity in the mPFC, together with the associated behavioral abnormalities.

Analysis of molecular ligand functionalization process in nano-molecular electronic devices containing densely packed nano-particle functionalization shells.

Molecular electronic devices based on few and single-molecules have the advantage that the electronic signature of the device is directly dependent on the electronic structure of the molecules as well as of the electrode-molecule junction. In this work, we use a two-step approach to synthesise functionalized nanomolecular electronic devices (nanoMoED). In first step we apply an organic solvent-based gold nanoparticle (AuNP) synthesis method to form either a 1-dodecanethiol or a mixed 1-dodecanethiol/ω-tetraphenyl ether substituted 1-dodecanethiol ligand shell. The functionalization of these AuNPs is tuned in a second step by a ligand functionalization process where biphenyldithiol (BPDT) molecules are introduced as bridging ligands into the shell of the AuNPs. From subsequent structural analysis and electrical measurements, we could observe a successful molecular functionalization in nanoMoED devices as well as we could deduce that differences in electrical properties between two different device types are related to the differences in the molecular functionalization process for the two different AuNPs synthesized in first step. The same devices yielded successful NO2gas sensing. This opens the pathway for a simplified synthesis/fabrication of molecular electronic devices with application potential.