Global population exposure to landscape fire air pollution from 2000 to 2019.

Wildfires are thought to be increasing in severity and frequency as a result of climate change1-5. Air pollution from landscape fires can negatively affect human health4-6, but human exposure to landscape fire-sourced (LFS) air pollution has not been well characterized at the global scale7-23. Here, we estimate global daily LFS outdoor fine particulate matter (PM2.5) and surface ozone concentrations at 0.25° × 0.25° resolution during the period 2000-2019 with the help of machine learning and chemical transport models. We found that overall population-weighted average LFS PM2.5 and ozone concentrations were 2.5 µg m-3 (6.1% of all-source PM2.5) and 3.2 µg m-3 (3.6% of all-source ozone), respectively, in 2010-2019, with a slight increase for PM2.5, but not for ozone, compared with 2000-2009. Central Africa, Southeast Asia, South America and Siberia experienced the highest LFS PM2.5 and ozone concentrations. The concentrations of LFS PM2.5 and ozone were about four times higher in low-income countries than in high-income countries. During the period 2010-2019, 2.18 billion people were exposed to at least 1 day of substantial LFS air pollution per year, with each person in the world having, on average, 9.9 days of exposure per year. These two metrics increased by 6.8% and 2.1%, respectively, compared with 2000-2009. Overall, we find that the global population is increasingly exposed to LFS air pollution, with socioeconomic disparities.

PB-LKS: a python package for predicting phage-bacteria interaction through local K-mer strategy.

Bacteriophages can help the treatment of bacterial infections yet require in-silico models to deal with the great genetic diversity between phages and bacteria. Despite the tolerable prediction performance, the application scope of current approaches is limited to the prediction at the species level, which cannot accurately predict the relationship of phages across strain mutants. This has hindered the development of phage therapeutics based on the prediction of phage-bacteria relationships. In this paper, we present, PB-LKS, to predict the phage-bacteria interaction based on local K-mer strategy with higher performance and wider applicability. The utility of PB-LKS is rigorously validated through (i) large-scale historical screening, (ii) case study at the class level and (iii) in vitro simulation of bacterial antiphage resistance at the strain mutant level. The PB-LKS approach could outperform the current state-of-the-art methods and illustrate potential clinical utility in pre-optimized phage therapy design.

Correlation between structure and function in phosphatidylinositol lipid-dependent Kir2.2 gating.

SignificancePhosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) levels regulate cell membrane voltage by gluing two halves of a K+ channel together and opening the pore. PI(4)P competes with this process. Because both of these lipids are relatively abundant in the plasma membrane and are directly interconvertible through the action of specific enzymes, they may function together to regulate channel activity.

Hydrophobization of Ribonucleic Acids for Facile Systemic Delivery and Multifaceted Cancer Immunotherapy.

Ribonucleic acids (RNAs) enable disease-related gene inhibition, expression, and editing and represent promising therapeutics in various diseases. The efficacy of RNA relies heavily on the presence of a secure and effective delivery system. Herein, we found that RNA could be hydrophobized by cationic lipid and ionizable lipid and conveniently coassemble with amphiphilic polymer to achieve micelle-like nanoparticles (MNP). The results of the study indicate that MNP exhibits a high level of efficiency in delivering RNA. Besides, the MNP encapsulating siRNA that targets CD47 and PD-L1 remarkably blocked these immune checkpoints in a melanoma tumor model and elicited a robust immune response. Moreover, the MNP encapsulating the mRNA of OVA achieved antigen translation and presentation, leading to an effective antitumor immunoprophylaxis outcome against OVA-expressing melanoma model. Our findings suggest that RNA hydrophobization could serve as a viable approach for delivering RNA, thereby facilitating the exploration of RNA therapy in disease treatment.

Regression of Liver Fibrosis in Patients on Hepatitis B Therapy Is Associated With Decreased Liver-Related Events.

BACKGROUND & AIMS: Liver fibrosis in patients with chronic hepatitis B can regress with successful antiviral therapy. However, the long-term clinical benefits of fibrosis regression have not been fully elucidated. This study investigated the association between biopsy-proven fibrosis regression by predominantly progressive, indeterminate, and predominantly regressive (P-I-R) score and liver-related events (LREs) in chronic hepatitis B patients. METHODS: Patients with on-treatment liver biopsy and significant fibrosis/cirrhosis (Ishak stage ≥3) were included in this analysis. Fibrosis regression was evaluated according to the P-I-R score of the Beijing Classification. LREs were defined as decompensations, hepatocellular carcinoma, liver transplantation, or death. The Cox proportional hazards model was used to determine associations of fibrosis regression with LREs. RESULTS: A total of 733 patients with Ishak stages 3/4 (n = 456; 62.2%) and cirrhosis (Ishak stages 5/6; n = 277; 37.8%) by on-treatment liver biopsy were enrolled. According to the P-I-R score, fibrosis regression, indeterminate, and progression were observed in 314 (42.8%), 230 (31.4%), and 189 (25.8%) patients, respectively. The 7-year cumulative incidence of LREs was 4.1%, 8.7%, and 18.1% in regression, indeterminate, and progression, respectively (log-rank, P < .001). Compared with patients with fibrosis progression, those with fibrosis regression had a lower risk of LREs (adjusted hazard ratio, 0.40; 95% CI, 0.16-0.99; P = .047), followed by the indeterminate group (adjusted hazard ratio, 0.86; 95% CI, 0.40-1.85; P = .691). Notably, this favorable association also was observed in patients with cirrhosis or low platelet counts (<150 × 109/L). CONCLUSIONS: Antiviral therapy-induced liver fibrosis regression assessed by P-I-R score is associated with reduced LREs. This shows the utility of histologic fibrosis regression assessed by on-treatment P-I-R score as a surrogate endpoint for clinical events in patients with hepatitis B virus-related fibrosis or early cirrhosis.

Intelligent Cell Profiling and Precision Release: Multimolecular Marker-Activated Transmembrane DNA Computing Nanosystem.

Accurate classification of tumor cells is of importance for cancer diagnosis and further therapy. In this study, we develop multimolecular marker-activated transmembrane DNA computing systems (MTD). Employing the cell membrane as a native gate, the MTD system enables direct signal output following simple spatial events of "transmembrane" and "in-cell target encounter", bypassing the need of multistep signal conversion. The MTD system comprises two intelligent nanorobots capable of independently sensing three molecular markers (MUC1, EpCAM, and miR-21), resulting in comprehensive analysis. Our AND-AND logic-gated system (MTDAND-AND) demonstrates exceptional specificity, allowing targeted release of drug-DNA specifically in MCF-7 cells. Furthermore, the transformed OR-AND logic-gated system (MTDOR-AND) exhibits broader adaptability, facilitating the release of drug-DNA in three positive cancer cell lines (MCF-7, HeLa, and HepG2). Importantly, MTDAND-AND and MTDOR-AND, while possessing distinct personalized therapeutic potential, share the ability of outputting three imaging signals without any intermediate conversion steps. This feature ensures precise classification cross diverse cells (MCF-7, HeLa, HepG2, and MCF-10A), even in mixed populations. This study provides a straightforward yet effective solution to augment the versatility and precision of DNA computing systems, advancing their potential applications in biomedical diagnostic and therapeutic research.

PsSOC1 is involved in the gibberellin pathway to trigger cell proliferation and budburst during endodormancy release in tree peony.

Tree peony (Paeonia suffruticosa) undergoes bud endodormancy, and gibberellin (GA) pathway plays a crucial role in dormancy regulation. Recently, a key DELLA protein PsRGL1 has been identified as a negative regulator of bud dormancy release. However, the mechanism of GA signal to break bud dormancy remains unknown. In this study, yeast two-hybrid screened PsSOC1 interacting with PsRGL1 through its MADS domain, and interaction was identified using pull-down and luciferase complementation imaging assays Transformation in tree peony and hybrid poplar confirmed that PsSOC1 facilitated bud dormancy release. Transcriptome analysis of PsSOC1-overexpressed buds indicated PsCYCD3.3 and PsEBB3 were its potential downstream targets combining with promoter survey, and they also accelerated bud dormancy release verified by genetic analysis. Yeast one-hybrid, electrophoretic mobility shifts assays, chromatin immunoprecipitation quantitative PCR, and dual luciferase assays confirmed that PsSOC1 could directly bind to the CArG motif of PsCYCD3.3 and PsEBB3 promoters via its MADS domain. PsRGL1-PsSOC1 interaction inhibited the DNA-binding activity of PsSOC1. Additionally, PsCYCD3.3 promoted bud dormancy release by rebooting cell proliferation. These findings elucidated a novel GA pathway, GA-PsRGL1-PsSOC1-PsCYCDs, which expanded our understanding of the GA pathway in bud dormancy release.

Hidden Role of Organic Matter in the Immobilization and Transformation of Iodine on Fe-OM Associations.

The biogeochemical processes of iodine are typically coupled with organic matter (OM) and the dynamic transformation of iron (Fe) minerals in aquifer systems, which are further regulated by the association of OM with Fe minerals. However, the roles of OM in the mobility of iodine on Fe-OM associations remain poorly understood. Based on batch adsorption experiments and subsequent solid-phase characterization, we delved into the immobilization and transformation of iodate and iodide on Fe-OM associations with different C/Fe ratios under anaerobic conditions. The results indicated that the Fe-OM associations with a higher C/Fe ratio (=1) exhibited greater capacity for immobilizing iodine (∼60-80% for iodate), which was attributed to the higher affinity of iodine to OM and the significantly decreased extent of Fe(II)-catalyzed transformation caused by associated OM. The organic compounds abundant in oxygen with high unsaturation were more preferentially associated with ferrihydrite than those with poor oxygen and low unsaturation; thus, the associated OM was capable of binding with 28.1-45.4% of reactive iodine. At comparable C/Fe ratios, the mobilization of iodine and aromatic organic compounds was more susceptible in the adsorption complexes compared to the coprecipitates. These new findings contribute to a deeper understanding of iodine cycling that is controlled by Fe-OM associations in anaerobic environments.

miR-455-3p regulates lymphangiogenesis in silicosis by regulating VEGF-C/VEGFR3.

Silicosis is a disease characterized by lung inflammation and fibrosis caused by long-term inhalation of free silicon dioxide (SiO2). Recent studies have found that a large number of lymphatic hyperplasia occurs during the occurrence and development of silicosis. miRNAs play an important role in lymphangiogenesis. However, the regulation and mechanism of miRNAs on lymphangiogenesis in silicosis remain unclear. In this study, lymphangiogenesis was observed in silicosis rats, and VEGF-C-targeted miRNAs were screened, and the effect of miRNAs on the formation of human lymphatic endothelial cells (HLECs) tubular structure was investigated in vitro. The results showed that SiO2 promoted the expressions of Collagen Ι and α-SMA, TNF-α, IL-6 and VEGF-C increased first and then decreased, and promoted the formation of lymphatic vessels. Bioinformatics methods screened miR-455-3p for targeted binding to VEGF-C, and dual luciferase reporter genes confirmed VEGF-C as the target gene of miR-455-3p, and miR-455-3p was down-regulated in the lung tissue of silicosis rats. Transfection of miR-455-3p Inhibitors down-regulated the expression level of miR-455-3p and up-regulated the expression levels of VEGF-C and VEGFR-3 in HLECs, enhanced migration ability and increased tube formation. Transfection of miR-455-3p Mimics showed an opposite trend. These results suggest that miR-455-3p further regulates the tubular structure formation of HLECs by regulating VEGF-C/VEGFR3. Therefore, targeting miR-455-3p may provide a new therapeutic strategy for SiO2-induced silicosis injury.

Crude Tieguanyin oolong tea polysaccharides regulate intestinal immune and gut microflora in dextran sulfate sodium-induced mice colitis.

BACKGROUND: The global incidence and prevalence of inflammatory bowel diseases (IBDs) have been increasing. Epidemiological studies, clinical trials, and animal experiments have indicated a negative association between the consumption of tea and IBD. This study aims to investigate the protective effects of crude Tieguanyin oolong tea polysaccharides (CTPS) on experimental colitis, while also exploring the underlying mechanisms. RESULTS: The administration of CTPS significantly alleviated IBD in the mouse model, and was found to regulate T-cell mediated immune responses in the colon by modulating cytokine production associated with T cells. Furthermore, CTPS demonstrated a positive impact on the gut microbiota, reversing the increase in pathogenic Helicobacter and enhancing the relative abundances of beneficial bacteria such as Akkermansia, Lachnospiraceae, and Odoribacter. Oral administration of CTPS also led to an improvement in intestinal metabolism, specifically by increasing the levels of short-chain fatty acids. CONCLUSION: This study provides the first in vivo evidence of the protective effects of CTPS on colitis in mice. The effects are likely facilitated through the regulation of T cell-mediated responses and modulation of the gut microbiota, suggesting that CTPS may be a potential preventive and therapeutic approach for IBD. © 2023 Society of Chemical Industry.

[A multicenter study of neonatal stroke in Shenzhen, China]. / 深圳市新生儿脑卒中多中心现况调查.

OBJECTIVES: To investigate the incidence rate, clinical characteristics, and prognosis of neonatal stroke in Shenzhen, China. METHODS: Led by Shenzhen Children's Hospital, the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022. The incidence, clinical characteristics, treatment, and prognosis of neonatal stroke in Shenzhen were analyzed. RESULTS: The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137, 1/6 060, and 1/7 704, respectively. Ischemic stroke accounted for 75% (27/36); boys accounted for 64% (23/36). Among the 36 neonates, 31 (86%) had disease onset within 3 days after birth, and 19 (53%) had convulsion as the initial presentation. Cerebral MRI showed that 22 neonates (61%) had left cerebral infarction and 13 (36%) had basal ganglia infarction. Magnetic resonance angiography was performed for 12 neonates, among whom 9 (75%) had involvement of the middle cerebral artery. Electroencephalography was performed for 29 neonates, with sharp waves in 21 neonates (72%) and seizures in 10 neonates (34%). Symptomatic/supportive treatment varied across different hospitals. Neonatal Behavioral Neurological Assessment was performed for 12 neonates (33%, 12/36), with a mean score of (32±4) points. The prognosis of 27 neonates was followed up to around 12 months of age, with 44% (12/27) of the neonates having a good prognosis. CONCLUSIONS: Ischemic stroke is the main type of neonatal stroke, often with convulsions as the initial presentation, involvement of the middle cerebral artery, sharp waves on electroencephalography, and a relatively low neurodevelopment score. Symptomatic/supportive treatment is the main treatment method, and some neonates tend to have a poor prognosis.

Synergistic Incorporation of Two ssDNA Activators Enhances the Trans-Cleavage of CRISPR/Cas12a.

CRISPR/Cas12a has been believed to be powerful in molecular detection and diagnostics due to its amplified trans-cleavage feature. However, the activating specificity and multiple activation mechanisms of the Cas12a system are yet to be elucidated fully. Herein, a "synergistic activator effect" is discovered, which supports an activation mechanism that a synergistic incorporation of two short ssDNA activators can promote the trans-cleavage of CRISPR/Cas12a, while either of them is too short to work independently. As a proof-of-concept example, the synergistic activator-triggered CRISPR/Cas12a system has been successfully harnessed in the AND logic operation and the discrimination of single-nucleotide variants, requiring no signal conversion elements or other amplified enzymes. Moreover, a single-nucleotide specificity has been achieved for the detection of single-nucleotide variants by pre-introducing a synthetic mismatch between crRNA and the "helper" activator. The finding of "synergistic activator effect" not only provides deeper insight into CRISPR/Cas12a but also may facilitate its expanded application and power the exploration of the undiscovered properties of other CRISPR/Cas systems.

Compute-and-Release Logic-Gated DNA Cascade Circuit for Accurate Cancer Cell Imaging.

Accurate identification of cancer cells is an essential prerequisite for cancer diagnosis and subsequent effective curative interventions. The logic-gate-assisted cancer imaging system that allows a comparison of expression levels between biomarkers, rather than just reading biomarkers as inputs, returns a more comprehensive logical output, improving its accuracy for cell identification. To fulfill this key criterion, we develop a compute-and-release logic-gated double-amplified DNA cascade circuit. This novel system, CAR-CHA-HCR, consists of a compute-and-release (CAR) logic gate, a double-amplified DNA cascade circuit (termed CHA-HCR), and a MnO2 nanocarrier. CAR-CHA-HCR, a novel adaptive logic system, is designed to logically output the fluorescence signals after computing the expression levels of intracellular miR-21 and miR-892b. Only when miR-21 is present and its expression level is above the threshold CmiR-21 > CmiR-892b, the CAR-CHA-HCR circuit performs a compute-and-release operation on free miR-21, thereby outputting enhanced fluorescence signals to accurately image positive cells. It is capable of comparing the relative concentrations of two biomarkers while sensing them, thus allowing accurate identification of positive cancer cells, even in mixed cell populations. Such an intelligent system provides an avenue for highly accurate cancer imaging and is potentially envisioned to perform more complex tasks in biomedical studies.

A Forceful "Dendrite-Killer" of Polyoxomolybdate with Reusability Effectively Dominating Dendrite-Free Lithium Metal Anode.

In this work, a series of Mo-containing polyoxometalates (POMs) modified separators to inhibit the growth of lithium dendrites, and thus improving the lifespan and safety of the cells is proposed. When the deposited lithium forms dendrites and touches the separator, the optimized Dawson-type POM of (NH4 )6 [P2 Mo18 O62 ]·11H2 O (P2 Mo18 ) with the stronger oxidizability, acts like a "killer", is more inclined to oxidize Li0 into Li+ , thus weakening the lethality of lithium dendrites. The above process is accompanied by the formation of Lix [P2 Mo18 O62 ] (x = 6-10) in its reduced state. Converting to the stripping process, the reduced state Lix [P2 Mo18 O62 ] (x = 6-10) can be reoxidized to P2 Mo18 , which achieves the reusability of P2 Mo18 functional material. Meanwhile, lithium ions are released into the cell system to participate in the subsequent electrochemical cycles, thus the undesired lithium dendrites are converted into usable lithium ions to prevent the generation of "dead lithium". As a result, the Li//Li symmetrical cell with P2 Mo18 modified separator delivers exceptional cyclic stability for over 1000 h at 3 mA cm-2 and 5 mAh cm-2 , and the assembled Li-S full cell maintains superior reversible capacity of 600 mAh g-1 after 200 cycles at 2 C.

Reproductive Toxicity Evaluation of Graphene-Based Tumor Cell Nucleus-Targeting Fluorescent Nanoprobes on Reproduction and Offspring Health.

A new graphene-based fluorescent nanoprobe for tumor cell nucleus (GTTNs) was synthesized in our laboratory that penetrates the cell membrane and particularly targets cancer cell nucleus and displays tremendous potential for clinical applications. Although acute and subacute toxicity studies have been conducted on GTTNs, a primary result could be drawn that GTTNs appear to have almost no acute and subacute toxicity. However, as an important part of safety evaluation, the influences on reproductive and offspring developmental toxicity are still absent. In this study, male mice were injected intravenously with GTTNs, and the survival status, histopathology of the testes and epididymides, proliferation and apoptosis of testicular tissue, and sperm motility of mice were measured. To evaluate the short- and long-term fertility in male mice, different male mice resided with untreated female mice on days 1 and 30 after the end of the last treatment, and the offspring health parameters were assessed by measuring pup numbers, body weight, and organ indexes of the pups. The results indicated that GTTNs-exposed male mice retained good fertility, healthy structure of testes and epididymides, and production of healthy sperm. Meanwhile, there were no significant differences between the offspring and the control group. In consideration of GTTNs with broad prospects for biomedical applications, our results contribute a basis for further understanding of its biosafety.

Changes of Plasma Blood Ammonia Levels of Chinese Healthy People and the Establishment of Reference Intervals.

BACKGROUND: Blood ammonia detection is used for the diagnosis or differential diagnosis of various hepatitis virus infections, severe liver cirrhosis, and hepatic encephalopathy. It is also one of the important indexes reflecting liver coma, Reyes syndrome, and other diseases. However, blood ammonia changes rapidly with time. If samples are not sent and detected in time, the results will be wrong, resulting in clinical misdiagnosis and life danger to patients. The purpose of this paper is to explore the change of blood ammonia with time and establish its reference interval. METHODS: For this study, 228 healthy patients (111 males and 117 females) were selected who underwent physical examination at the Health Management Center of the Second Xiangya Hospital of Central South University from April to May 2021. The blood ammonia detection kit (colorimetric method) produced by Roche Diagnostics GmbH of Germany was used for detection on the Roche cobas c702 automatic biochemical analyzer. After eliminating outliers from the obtained test results, they were grouped according to gender and age, and SPSS 26.0 software was employed to statistically analyze the blood ammonia test results. RESULTS: The differences in blood ammonia levels at each detection time were statistically significant (p < 0.05). The differences in blood ammonia levels between male and female subjects at 1 hour, 2 hours, and 3 hours were statistically significant (p < 0.05), but all ages saw no statistically significant difference in blood ammonia levels between segments (p > 0.05). The blood ammonia levels of each detection time and different genders showed a normal distribution. Therefore, it is necessary to take the 95% (X ± 1.96S) results of both sides as the reference interval according to the detection time and gender, and establish the reference intervals. The 1-hour blood ammonia reference interval for healthy men in Changsha is 15.8 - 47.5 µmol/L, for healthy women it is 12.4 - 39.6 µmol/L; the 2-hour blood ammonia reference interval for healthy men is 22.3 - 56.5 µmol/L, and for healthy women it is 19.1 - 48.0 µmol/L; the reference interval of 3-hours blood ammonia for healthy men is 27.9 - 65.7 µmol/L, and for healthy women it is 24.6 - 56.7 µmol/L. CONCLUSIONS: There are differences in blood ammonia levels between men and women at different detection times in Changsha. A reference interval suitable for blood ammonia in healthy individuals in the region should be established according to the detection time and gender, so as to provide better relevant evidence for clinical diagnosis.

A Bearing Fault Diagnosis Method Based on a Residual Network and a Gated Recurrent Unit under Time-Varying Working Conditions.

The diagnosis of bearing faults is an important guarantee for the healthy operation of mechanical equipment. Due to the time-varying working conditions of mechanical equipment, it is necessary to achieve bearing fault diagnosis under time-varying working conditions. However, the superposition of the two-dimensional working conditions of speed and acceleration brings great difficulties to diagnosis via data-driven models. The long short-term memory (LSTM) model based on the infinitesimal method is an effective method to solve this problem, but its performance still has certain limitations. On this basis, this article proposes a model for fault diagnosis under time-varying operating conditions that combines a residual network model (ResNet) and a gate recurrent unit (model) (GRU). Firstly, the samples were segmented, and feature extraction was performed using ResNet. We then used GRU to process the information. Finally, the classification results were output through the output network. This model could ignore the influence of acceleration and achieve high fault diagnosis accuracy under time-varying working conditions. In addition, we used t-SNE to reduce the dimensionality of the features and analyzed the role of each layer in the model. Experiments showed that this method had a better performance compared with existing bearing fault diagnosis methods.

Comprehensive analysis of ncRNA involvement in brain microglia immunology.

Microglia is a major class of brain-resident myeloid cells and non-coding RNAs (ncRNAs) serves as key regulators in microglia homeostasis and inflammatory process. Here, we constructed the systematical association between microglia and ncRNAs including miRNAs, lncRNAs and circRNAs from two aspects, manual retrieval and computational detection. A total of 648 experimental verified ncRNA-microglia associations were obtained from published studies, including ncRNA regulatory patterns within different experimental models. Furthermore, we extracted 9 miRNA and 1 lncRNA expression profiles from the GEO database. Also, we obtained 31 sample-match miRNA and mRNA expression profiles, containing a total of 2335 normal or disordered brain samples. Finally, we developed a platform named MG-ncRexplorer (http://bio-bigdata.hrbmu.edu.cn/MG-ncRexplorer/), exploring the associations between ncRNAs and microglia among experimental validated and computational detection. To demonstrate the usage of MG-ncRexplorer, we constructed regulatory target networks based on manual retrieval associations and identified risk glioma miRNAs among multiple high-throughput expression profiles.

Fast and efficient generation of a full-length balancer chromosome by a single Cre/loxP recombination event.

Balancer chromosomes, primarily discovered and used in Drosophila melanogaster, are valuable tools to maintain lethal mutations in a particular genomic segment. Full-length balancer chromosomes would be particularly useful because of the capacity to maintain whole genomic traits. However, murine full-length balancer chromosomes generated via a single Cre/loxP recombination are still not demonstrated. In this study, we developed a novel mouse strain with full-length inverted chromosome 17 (Ch17Inv balancer) via a single Cre/loxP recombination event in mES cells. The Ch17Inv balancer mice are viable and phenotypically normal. When bred with other strains, the haplotype of chromosome 17 can be stably maintained as determined by the high throughput SNPs assay. Interestingly, we found that the recombination events were efficiently reduced within the inverted region but not eliminated. The method established in this study can be applied to generate other full-length balancer chromosomes. Moreover, the Ch17Inv balancer strain would be a valuable resource to maintain the entire chromosome 17 from different donor strains.

Comprehensive analysis of microglia gene and subpathway signatures for glioma prognosis and drug screening: linking microglia to glioma.

Glioma is the most common malignant tumors in the brain. Previous studies have revealed that, as the innate immune cells in nervous system, microglia cells were involved in glioma pathology. And, the resident microglia displayed its specific biological roles which distinguished with peripheral macrophages. In this study, an integrated analysis was performed based on public resource database to explore specific biological of microglia within glioma. Through comprehensive analysis, the biological characterization underlying two conditions, glioma microglia compared to glioma macrophage (MicT/MacT) as well as glioma microglia compared to normal microglia (MicT/MicN), were revealed. Notably, nine core MicT/MicN genes displayed closely associations with glioma recurrence and prognosis, such as P2RY2, which was analyzed in more than 2800 glioma samples from 25 studies. Furthermore, we applied a random walk based strategy to identify microglia specific subpathways and developed SubP28 signature for glioma prognostic analysis. Multiple validation data sets confirmed the predictive performance of SubP28 and involvement in molecular subtypes. The associations between SuP28 score and microglia M1/M2 polarization were also explored for both GBM and LGG types. Finally, a comprehensive drug-subpathway network was established for screening candidate medicable molecules (drugs) and identifying therapeutic subpathway targets. In conclusions, the comprehensive analysis of microglia related gene and functional signatures in glioma pathobiologic events by large-scale data sets displayed a framework to dissect inner connection between microglia and glioma, and identify robust signature for glioma clinical implications.