Chelating Additive Regulating Zn-Ion Solvation Chemistry for Highly Efficient Aqueous Zinc-Metal Battery.

Aqueous zinc-metal batteries (AZMBs) usually suffered from poor reversibility and limited lifespan because of serious water induced side-reactions, hydrogen evolution reactions (HER) and rampant zinc (Zn) dendrite growth. Reducing the content of water molecules within Zn-ion solvation sheaths can effectively suppress those inherent defects of AZMBs. In this work, we originally discovered that the two carbonyl groups of N-Acetyl-ϵ-caprolactam (N-ac) chelating ligand can serve as dual solvation sites to coordinate with Zn2+, thereby minimizing water molecules within Zn-ion solvation sheaths, and greatly inhibit water-induced side-reactions and HER. Moreover, the N-ac chelating additive can form a unique physical barrier interface on Zn surface, preventing the harmful contacting with water. In addition, the preferential adsorption of N-ac on Zn (002) facets can promote highly reversible and dendrite-free Zn2+ deposition. As a result, Zn//Cu half-cell within N-ac added electrolyte delivered ultra-high 99.89 % Coulombic efficiency during 8000 cycles. Zn//Zn symmetric cells also demonstrated unprecedented long life of more than 9800 hours (over one year). Aqueous Zn//ZnV6O16 ⋅ 8H2O (Zn//ZVO) full-cell preserved 78 % capacity even after ultra-long 2000 cycles. A more practical pouch-cell was also obtained (90.2 % capacity after 100 cycles). This method offers a promising strategy for accelerating the development of highly efficient AZMBs.

Lithiophilic Magnetic Host Facilitates Target-Deposited Lithium for Practical Lithium-Metal Batteries.

Lithium-metal shows promising prospects in constructing various high-energy-density lithium-metal batteries (LMBs) while long-lasting tricky issues including the uncontrolled dendritic lithium growth and infinite lithium volume expansion seriously impede the application of LMBs. In this work, it is originally found that a unique lithiophilic magnetic host matrix (Co3 O4 -CCNFs) can simultaneously eliminate the uncontrolled dendritic lithium growth and huge lithium volume expansion that commonly occur in typical LMBs. The magnetic Co3 O4 nanocrystals which inherently embed on the host matrix act as nucleation sites and can also induce micromagnetic field and facilitate a targeted and ordered lithium deposition behavior thus, eliminating the formation of dendritic Li. Meanwhile, the conductive host can effectively homogenize the current distribution and Li-ion flux, thus, further relieving the volume expansion during cycling. Benefiting from this, the featured electrodes demonstrate ultra-high coulombic efficiency of 99.1% under 1 mA cm-2 and 1 mAh cm-2 . Symmetric cell under limited Li (10 mAh cm-2 ) inspiringly delivers ultralong cycle life of 1600 h (under 2 mA cm-2 , 1 mAh cm-2 ). Moreover, LiFePO4 ||Co3 O4 -CCNFs@Li full-cell under practical condition of limited negative/positive capacity ratio (2.3:1) can deliver remarkably improved cycling stability (with 86.6% capacity retention over 440 cycles).

Aligned Dipoles Induced Electric-Field Promoting Zinc-Ion De-Solvation toward Highly Stable Dendrite-Free Zinc-Metal Batteries.

Water-induced parasitic reactions and uncontrolled dendritic Zn growth are long-lasting tricky problems that severely hinder the development of aqueous zinc-metal batteries. Those notorious issues are closely related to electrolyte configuration and zinc-ion transport behavior. Herein, through constructing aligned dipoles induced electric-field on Zn surface, both the solvation structure and transport behavior of zinc-ions are fundamentally changed. The vertically ordered zinc-ion migration trajectory and gradually concentrated zinc-ion achieved inside the polarized electric-field remarkably eliminate water related side-reactions and Zn dendrites. Zn-metal under the polarized electric-field demonstrated significantly improve reversibility and a dendrite-free surface with strong (002) Zn deposition texturing. Zn||Zn symmetric cell delivers greatly prolonged lifespan up to 1400 h (17 times longer than that of the cell based on bare Zn) while the Zn||Cu half-cell demonstrate ultrahigh 99.9% coulombic efficiency. NH4 V4 O10 ||Zn half-cell delivered exceptional-high 132 mAh g-1 capacity after ultralong 2000 cycles (≈100% capacity retention). In addition, MnO2 ||Zn pouch-cell under aligned dipoles induced electric-field maintains 87.9% capacity retention after 150 cycles under practical condition of high MnO2 mass loading (≈10 mg cm-2 ) and limited N/P ratio. It is considered that this new strategy can also be implemented to other metallic batteries and spur the development of batteries with long-lifespan and high-energy-density.

Diverse phylogenomic datasets uncover a concordant scenario of laurasiatherian interordinal relationships.

Resolving the interordinal relationships in the mammalian superorder Laurasiatheria has been among the most intractable problems in higher-level mammalian systematics, with many conflicting hypotheses having been proposed. The present study collected three different sources of genome-scale data with comprehensive taxon sampling of laurasiatherian species, including two protein-coding datasets (4,186 protein-coding genes for an amino acid dataset comprising 2,761,247 amino acid residues and a nucleotide dataset comprising 5,516,340 nucleotides from 1st and 2nd codon positions), an intronic dataset (1,210 introns comprising 1,162,723 nucleotides) and an ultraconserved elements (UCEs) dataset (1,246 UCEs comprising 1,946,472 nucleotides) from 40 species representing all six laurasiatherian orders and 7 non-laurasiatherian outgroups. Remarkably, phylogenetic trees reconstructed with the four datasets using different tree-building methods (RAxML, FastTree, ASTRAL and MP-EST) all supported the relationship (Eulipotyphla, (Chiroptera, ((Carnivora, Pholidota), (Cetartiodactyla, Perissodactyla)))). We find a resolution of interordinal relationships of Laurasiatheria among all types of markers used in the present study, and the likelihood ratio tests for tree comparisons confirmed that the present tree topology is the optimal hypothesis compared to other examined hypotheses. Jackknifing subsampling analyses demonstrate that the results of laurasiatherian tree reconstruction varied with the number of loci and ordinal representatives used, which are likely the two main contributors to phylogenetic disagreements of Laurasiatheria seen in previous studies. Our study provides significant insight into laurasiatherian evolution, and moreover, an important methodological strategy and reference for resolving phylogenies of adaptive radiation, which have been a long-standing challenge in the field of phylogenetics.

Association between excessive smartphone use and cervical disc degeneration in young patients suffering from chronic neck pain.

BACKGROUND: With the popularity of smartphones, cervical spondylosis is becoming more and more common among young people. The aim of this study was to investigate the association between excessive smartphone use and cervical disc degeneration in young patients suffering from chronic neck pain. METHODS: A total of 2438 young patients suffering from chronic neck pain were included into this study. All patients underwent the Magnetic Resonance Imaging (MRI) examination of the cervical spine. The degree of cervical disc degeneration, the dependent variable, was evaluated by Cervical Disc Degeneration Scale (CDDS) which was developed from Pfirrmann classification. Smartphone use, the primary independent variable, was assessed by Smartphone Addiction Scale (SAS). RESULTS: In all, 52.9% patients were categorized as smartphone overuse. Patients with overuse of smartphones had higher CDDS scores than those who did not use smartphone excessively. CONCLUSIONS: The results indicate that cervical disc degeneration may be associated with excessive smartphone use, such use may lead to cervical spondylosis.

Controversies on lung cancers manifesting as part-solid nodules.

PURPOSE: Summarise survival of patients with resected lung cancers manifesting as part-solid nodules (PSNs). METHODS: PubMed/MEDLINE and EMBASE databases were searched for all studies/clinical trials on CT-detected lung cancer in English before 21 December 2015 to identify surgically resected lung cancers manifesting as PSNs. Outcome measures were lung cancer-specific survival (LCS), overall survival (OS), or disease-free survival (DFS). All PSNs were classified by the percentage of solid component to the entire nodule diameter into category PSNs <80% or category PSNs ≥80%. RESULTS: Twenty studies reported on PSNs <80%: 7 reported DFS and 2 OS of 100%, 6 DFS 96.3-98.7%, and 11 OS 94.7-98.9% (median DFS 100% and OS 97.5%). Twenty-seven studies reported on PSNs ≥80%: 1 DFS and 2 OS of 100%, 19 DFS 48.0%-98.0% (median 82.6%), and 16 reported OS 43.0%-98.0% (median DFS 82.6%, OS 85.5%). Both DFS and OS were always higher for PSNs <80%. CONCLUSION: A clear definition of the upper limit of solid component of a PSN is needed to avoid misclassification because cell-types and outcomes are different for PSN and solid nodules. The workup should be based on the size of the solid component. KEY POINTS: • Lung cancers manifesting as PSNs are slow growing with high cure rates. • Upper limits of the solid component are important for correct interpretation. • Consensus definition is important for the management of PSNs. • Median disease-free-survival (DFS) increased with decreasing size of the nodule.

Variation in Screening CT-Detected Nodule Volumetry as a Function of Size.

OBJECTIVE: The objective of this study is to evaluate measurement variability in volumetric assessment of pulmonary nodules on low-dose CT images with a view toward determining how this variability is influenced by nodule size. MATERIALS AND METHODS: A large CT screening database was reviewed to identify solid pulmonary nodules that had remained stable in size on the basis of findings from at least three scans obtained over a 2-year period. Two software packages (Lung VCAR and syngo.via) were used to assess the nodule volume on the two most recent CT scans, which were obtained at a slice thickness of 0.625 mm. The percentage of volume change was calculated for each nodule. The SD of the percentage of volume change was determined for nodules in each of the following nodule diameter size categories: less than 4 mm, 4-5 mm, 6-9 mm, and 10 mm or larger. The diameter was the mean of the length and width in the CT image that represented the largest cross-sectional area of the nodule. RESULTS: The 171 stable nodules that were identified in 117 CT screening participants (median age, 61 years) ranged in size from 2.2 to 18.7 mm. The time between acquisition of the first and last CT images ranged from 3.7 to 17.8 years (median, 11.5 years). For each of the four categories of diameter size (< 4, 4-5, 6-9, and ≥ 10 mm), the SD of the percentage of volume change was 20.4%, 17.7%, 14.6%, and 3.7%, with the use of Lung VCAR, and 59.5%, 24.3%, 9.1%, and 6.2%, with the use of syngo.via, respectively. The SD decreased with increasing nodule diameter, with the use of both software packages. CONCLUSION: Measurement variability decreased with increasing nodule diameter for both software packages and was different between the two software packages.

Study on chemical constituents of Cyclocarya paliurus.

A new dammarane triterpenoid glycoside named cyclocarioside J (1) and other three known triterpenoid glycosides were isolated from the leaves of Cyclocarya paliurus. Based on ESI-MS, HR-ESI-MS, (1)H NMR, (13)C NMR, and 2D NMR techniques including (1)H-(1)H COSY, HMBC, HMQC, and NOESY correlations, the structure of cyclocarioside J was elucidated as (20S,24R)-epoxydammarane 3ß,12ß,25-trihydroxy-12-O-ß-d-quinovopyranosyl-3-O-α-l-arabinopyranoside.

Studies on chemical constituents of Ophiopogon japonicus.

Two new and six known steroidal glucosides were isolated from the tuber of Ophiopogon japonicus. The new steroidal glucosides were established as (20R,25R)-26-O-ß-d-glucopyranosyl-3ß,26-dihydroxycholest-5-en-16,22-dioxo-3-O-α-l-rhamnopyranosyl-(1 â†’ 2)-ß-d-glucopyranoside (1) and 26-O-ß-d-glucopyranosyl-(25R)-furost-5-en-3ß,14α,17α,22α,26-pentaol-3-O-α-l-rhamnopyranosyl-(1 â†’ 2)-ß-d-glucopyranoside (3) on the basis of spectroscopic data as well as chemical evidence.

[The design of plantar pressure distribution monitoring system and preliminary clinical application].

Plantar pressure distribution can reflect the force of several key points on foot while standing and walking. A comprehensive understanding of the plantar pressure distribution makes great sense in the following aspects: the understanding of the normal foot biomechanics and function, clinical diagnosis, measurement of disease extent, postoperative efficacy evaluation, and rehabilitation research. A simple plantar pressure measurement device was designed in this study. This paper uses FlexiForce flexible sensor to pickup plantar pressure signal and USB A/D board to do data acquisition. The data are transferred into a laptop and processed by a VB-based software which can display, remember and replay the data. We chose patients with hallux valgus and normal people to measure the pressure distribution and make contrast analysis of plantar pressure with this device. It can be concluded that people with hallux valgus have higher pressure on the second metatarsophalangeal joint and the distribution move outward. The plantar pressure of patients postoperative could be greatly improved compared to the preoperative. The function of this device has been confirmed.

Water Catchers within Sub-Nano Channels Promote Step-by-Step Zinc-Ion Dehydration Enable Highly Efficient Aqueous Zinc-Metal Batteries.

Zinc metal suffers from violent and long-lasting water-induced side reactions and uncontrollable dendritic Zn growth, which seriously reduce the coulombic efficiency (CE) and lifespan of aqueous zinc-metal batteries (AZMBs). To suppress the corresponding harmful effects of the highly active water, a stable zirconium-based metal-organic framework with water catchers decorated inside its sub-nano channels is used to protect Zn-metal. Water catchers within narrow channels can constantly trap water molecules from the solvated Zn-ions and facilitate step-by-step desolvation/dehydration, thereby promoting the formation of an aggregative electrolyte configuration, which consequently eliminates water-induced corrosion and side reactions. More importantly, the functionalized sub-nano channels also act as ion rectifiers and promote fast but even Zn-ions transport, thereby leading to a dendrite-free Zn metal. As a result, the protected Zn metal demonstrates an unprecedented cycling stability of more than 10 000 h and an ultra-high average CE of 99.92% during 4000 cycles. More inspiringly, a practical NH4V4O10//Zn pouch-cell is fabricated and delivers a capacity of 98 mAh (under high cathode mass loading of 25.7 mg cm-2) and preserves 86.2% capacity retention after 150 cycles. This new strategy in promoting highly reversible Zn metal anodes would spur the practical utilization of AZMBs.

Postoperative CT surveillance in the evaluation of local recurrence after sub-lobar resection of neoplastic lesions of the lung.

OBJECTIVE: As indications for sub-lobar resections increase, it will become more important to identify risk factors for postsurgical recurrence. We investigated retrospectively the association between local recurrence after sub-lobar resection of neoplastic lung lesions and pre- and post-operative CT imaging and pathologic features. MATERIALS AND METHODS: We reviewed retrospectively neoplastic lung lesions with postoperative chest CT surveillance of sub-lobar resections in 2006-2016. We defined "suspicious" findings as nodularity ≥3 mm or soft tissue thickening ≥4 mm along the suture line and/or progression and explored their association with local recurrence. Primary lung cancer stage, tumoral invasion of lymphatics, visceral pleura or large vessels, bronchial and vascular margin distance were also assessed. RESULTS: Our study group included 45 cases of sub-lobar resection took for either primary (n = 37) or metastatic (n = 8) lung tumors. Local recurrence was observed in 16 of those patients. New nodularity ≥3 mm or soft tissue thickening ≥4 mm along the suture line on surveillance CT was significantly associated with local recurrence (p = 0.037). Additionally, solid nodule (p = 0.005), age at surgery ≤60 years (p = 0.006), two or more sites of invasion (p < 0.0001) and poor histologic differentiation (p = 0.0001) were also significantly associated with local tumor recurrence. Of 16 patients with surveillance post-surgical PET-CT, 15 had elevated FDG uptake. CONCLUSION: The postoperative changes along the suture line should follow a predictable time course demonstrating a pattern of stability, thinning or resolution on CT surveillance. New or increasing postoperative nodularity ≥3 mm or soft tissue thickening ≥4 mm along the suture line requires close diagnostic work-up. Surgical pathology characteristics added prognostic value on postoperative recurrence surveillance.

Role of toll-like receptor 4 on lupus lung injury and atherosclerosis in LPS-challenge ApoE⁻/⁻ mice.

To investigate the pathologic mechanisms of toll-like receptor 4 (TLR4) in lung injury and atherosclerosis, ApoE⁻/⁻ or wild-type mice were intraperitoneally administered saline, lipopolysaccharides (LPS), or LPS plus TAK-242 (TLR4 inhibitor), respectively, twice a week for 4 weeks. Serum autoantibody of antinuclear antibody (ANA), anti-double-stranded DNA (anti-dsDNA), and cytokines of interferon-gamma (IFN-γ), tumor necrosis factor (TNF-α ), and interleukin-1 (IL-1ß) were assessed by ELISA. Hematoxylin and eosin (HE) and Perl's stains for lung pathomorphology as well as HE staining for atherosclerosis were employed. TLR4 in macrophages was detected by double immunofluorescent staining. While protein expressions of TLR4, nuclear factor-kappa B p65 (NF-κB p65), and B cell activating factor belonging to the TNF family (BAFF) were examined by immunohistochemistry. We found that serum autoantibody (ANA and anti-dsDNA), cytokines (IFN-γ, TNF-α, IL-1ß), lung inflammation, and intima-media thickness in brachiocephalic artery were obviously increased after LPS challenge in both genotypes, but to a lesser extent in wild-type strains. And those alterations were alleviated by coadministration of LPS and TAK-242. Mechanistically, upregulation of TLR4, NF-κb, and BAFF was involved. We concluded that TLR4/NF-κb/BAFF in macrophages might be a possible common autoimmune pathway that caused lung injury and atherosclerosis. TLR4 signal will be a therapeutic target in atherosclerosis and immune-mediated lung injury.

Babesiosis concurrent with multiple abscesses from Staphylococcus aureus infection: A case report.

Background: Babesiosis is a tick-borne illness. These patients may have signs of a systemic inflammatory response, but abscess formation is unusual. Multiple abscesses in a patient with confirmed babesiosis is very rare, so concurrent infection by another pathogen should be considered. Case presentation: We report a 42-year-old male patient who had fever, chills, joint pain, abdominal pain, and altered mental status after a possible tick bite on his right foot while fishing in a river. The laboratory tests, including a blood smear, suggested babesiosis. Imaging studies showed multiple brain and spleen abscesses due to Staphylococcus aureus based on the results of a blood culture and next-generation sequencing. The patient eventually recovered after treatment with azithromycin, fosfomycin, and vancomycin. Conclusion: Concurrent bacterial infection can occur in a patient with babesiosis. Additional tests should be performed when a babesiosis patient presents with signs inconsistent with Babesia infection. Prompt and appropriate treatment is necessary and may be life-saving for these patients.

Management strategy of a carotid-esophageal fistula with a right common carotid artery pseudoaneurysm due to chicken bone ingestion: A case report and literature review.

Common carotid artery (CCA) pseudoaneurysm is a rare clinical disorder. CCA pseudoaneurysm that occurs with a carotid-esophageal fistula and causes massive upper gastrointestinal bleeding is especially uncommon but can be life-threatening. Accurate diagnosis and prompt managements are essential to save lives. Here, we report a case of a 58-year-old female who presented with dysphagia and throat pain after accidental ingestion of a chicken bone. The patient presented with active upper gastrointestinal bleeding which quickly developed into hemorrhage shock. Imaging studies confirmed a diagnosis of right CCA pseudoaneurysm and carotid-esophageal fistula. The patient had a satisfactory recovery after a right CCA balloon occlusion, right CCA pseudoaneurysm excision, and right CCA and esophageal repairs. We present and discuss this case here to remind physicians to rule out rare causes of upper gastrointestinal bleeding. A multidisciplinary approach is commonly required to achieve satisfactory outcomes in these cases.

Highly Stable Aqueous Zinc Metal Batteries Enabled by an Ultrathin Crack-Free Hydrophobic Layer with Rigid Sub-Nanochannels.

Aqueous zinc-metal batteries (AZMBs) have received tremendous attentions due to their high safety, low cost, environmental friendliness, and simple process. However, zinc-metal still suffer from uncontrollable dendrite growth and surface parasitic reactions that reduce the Coulombic efficiency (CE) and lifetime of AZMBs. These problems which are closely related to the active water are not well-solved. Here, an ultrathin crack-free metal-organic framework (ZIF-7x -8) with rigid sub-nanopore (0.3 nm) is constructed on Zn-metal to promote the de-solvation of zinc-ions before approaching Zn-metal surface, reduce the contacting opportunity between water and Zn, and consequently eliminate water-induced corrosion and side-reactions. Due to the presence of rigid and ordered sub-nanochannels, Zn-ions deposits on Zn-metal follow a highly ordered manner, resulting in a dendrite-free Zn-metal with negligible by-products, which significantly improve the reversibility and lifespan of Zn-metals. As a result, Zn-metal protected by ultrathin crack-free ZIF-7x -8 layer exhibits excellent cycling stability (over 2200 h) and extremely-high 99.96% CE during 6000 cycles. The aqueous PANI-V2 O5 //ZIF-7x -8@Zn full-cell preserves 86% high-capacity retention even after ultra-long 2000 cycles. The practical pouch-cell can also be cycled for more than 120 cycles. It is believed that the simple strategy demonstrated in this work can accelerate the practical utilizations of AZMBs.

Comprehensive analysis of 33 human cancers reveals clinical implications and immunotherapeutic value of the solute carrier family 35 member A2.

Background: Solute carrier family 35 member A2 (SLC35A2), which belongs to the SLC35 solute carrier family of human nucleoside sugar transporters, has shown regulatory roles in various tumors and neoplasms. However, the function of SLC35A2 across human cancers remains to be systematically assessed. Insights into the prediction ability of SLC35A2 in clinical practice and immunotherapy response remains limited. Materials and methods: We obtained the gene expression and protein levels of SLC35A2 in a variety of tumors from Molecular Taxonomy of Breast Cancer International Consortium, The Cancer Genome Atlas, Gene Expression Omnibus, Chinese Glioma Genome Atlas, and Human Protein Atlas databases. The SLC35A2 level was validated by immunohistochemistry. The predictive value for prognosis was evaluated by Kaplan-Meier survival and Cox regression analyses. Correlations between SLC35A2 expression and DNA methylation, genetic alterations, tumor mutation burden (TMB), microsatellite instability (MSI), and tumor microenvironment were performed using Spearman's correlation analysis. The possible downstream pathways of SLC35A2 in different human cancers were explored using gene set variation analysis. The potential role of SLC35A2 in the tumor immune microenvironment was evaluated via EPIC, CIBERSORT, MCP-counter, CIBERSORT-ABS, quanTIseq, TIMER, and xCell algorithms. The difference in the immunotherapeutic response of SLC35A2 under different expression conditions was evaluated by the tumor immune dysfunction and exclusion (TIDE) score as well as four independent immunotherapy cohorts, which includes patients with bladder urothelial carcinoma (BLCA, N = 299), non-small cell lung cancer (NSCLC, N = 72 and N = 36) and skin cutaneous melanoma (SKCM, N = 25). Potential drugs were identified using the CellMiner database and molecular docking. Results: SLC35A2 exhibited abnormally high or low expression in 23 cancers and was significantly associated with the prognosis. In various cancers, SLC35A2 expression and mammalian target of rapamycin complex 1 signaling were positively correlated. Multiple algorithmic immune infiltration analyses suggested an inverse relation between SLC35A2 expression and infiltrating immune cells, which includes CD4+T cells, CD8+T cells, B cells, and natural killer cells (NK) in various tumors. Furthermore, SLC35A2 expression was significantly correlated with pan-cancer immune checkpoints, TMB, MSI, and TIDE genes. SLC35A2 showed significant predictive value for the immunotherapy response of patients with diverse cancers. Two drugs, vismodegib and abiraterone, were identified, and the free binding energy of cytochrome P17 with abiraterone was higher than that of SLC35A2 with abiraterone. Conclusion: Our study revealed that SLC35A2 is upregulated in 20 types of cancer, including lung adenocarcinoma (LUAD), breast invasive carcinoma (BRCA), colon adenocarcinoma (COAD), and lung squamous cell carcinoma (LUSC). The upregulated SLC35A2 in five cancer types indicates a poor prognosis. Furthermore, there was a positive correlation between the overexpression of SLC35A2 and reduced lymphocyte infiltration in 13 cancer types, including BRCA and COAD. Based on data from several clinical trials, patients with LUAD, LUSC, SKCM, and BLCA who exhibited high SLC35A2 expression may experience improved immunotherapy response. Therefore, SLC35A2 could be considered a potential predictive biomarker for the prognosis and immunotherapy efficacy of various tumors. Our study provides a theoretical basis for further investigating its prognostic and therapeutic potentials.

EPAS1 prevents telomeric damage-induced senescence by enhancing transcription of TRF1, TRF2, and RAD50.

Telomeres are nucleoprotein structures located at the end of each chromosome, which function in terminal protection and genomic stability. Telomeric damage is closely related to replicative senescence in vitro and physical aging in vivo. As relatively long-lived mammals based on body size, bats display unique telomeric patterns, including the up-regulation of genes involved in alternative lengthening of telomeres (ALT), DNA repair, and DNA replication. At present, however, the relevant molecular mechanisms remain unclear. In this study, we performed cross-species comparison and identified EPAS1, a well-defined oxygen response gene, as a key telomeric protector in bat fibroblasts. Bat fibroblasts showed high expression of EPAS1, which enhanced the transcription of shelterin components TRF1 and TRF2, as well as DNA repair factor RAD50, conferring bat fibroblasts with resistance to senescence during long-term consecutive expansion. Based on a human single-cell transcriptome atlas, we found that EPAS1 was predominantly expressed in the human pulmonary endothelial cell subpopulation. Using in vitro-cultured human pulmonary endothelial cells, we confirmed the functional and mechanistic conservation of EPAS1 in telomeric protection between bats and humans. In addition, the EPAS1 agonist M1001 was shown to be a protective compound against bleomycin-induced pulmonary telomeric damage and senescence. In conclusion, we identified a potential mechanism for regulating telomere stability in human pulmonary diseases associated with aging, drawing insights from the longevity of bats.

Photon-counting detector CT allows significant reduction in radiation dose while maintaining image quality and noise on non-contrast chest CT.

Purpose: To investigate if clinical non-contrast chest CT studies obtained with PCD CT using much lower radiation exposure can achieve the same image quality as with the currently established EID protocol. Materials/methods: A total of seventy-one patients were identified who had a non-contrast chest computed tomography (CT) done on PCD CT and EID CT scanners within a 4-month interval. Five fellowship trained chest radiologists, blinded to the scanner details were asked to review the cases side-by-side and record their preference for images from either the photon-counting-detector (PCD) CT or the energy-integrating detector (EID) CT scanner. Results: The median CTDIvol for PCD-CT system was 4.710 mGy and EID system was 7.80 mGy (p < 0.001). The median DLP with the PCD-CT was 182.0 mGy.cm and EID system was 262.60 mGy.cm (p < 0.001). The contrast to noise ratio (CNR) was superior on the PCD-CT system 59.2 compared to the EID-CT 53.3; (p < 0.001). Kappa-statistic showed that there was poor agreement between the readers over the image quality from the PCD and EID scanners (κ = 0.19; 95 % CI: 0.12 - 0.27; p < 0.001). Chi-square analysis revealed that 3 out of 5 readers showed a significant preference for images from the PCDCT (p ≤ 0.012). There was no significant difference in the preferences of two readers between EID-CT and PCD-CT images. Conclusion: The first clinical PCD-CT system allows a significant reduction in radiation exposure while maintaining image quality and image noise using a standardized non-contrast chest CT protocol.

Apolipoprotein E-knockout mice show increased titers of serum anti-nuclear and anti-dsDNA antibodies.

Apolipoprotein E-knockout (ApoE(-/-)) mice, atherosclerosis-prone mice, show an autoimmune response, but the pathogenesis is not fully understood. We investigated the pathogenesis in female and male ApoE(-/-) mice. The spleens of all ApoE(-/-) and C57BL/6 (B6) mice were weighed. The serum IgG level and titers of anti-nuclear antibody (ANA) and anti-double-stranded DNA (anti-dsDNA) antibody were assayed by ELISA. Apoptosis of spleen tissue was evaluated by TUNEL. TLR4 level in spleen tissue was tested by immunohistochemistry and Western blot analysis. Levels of MyD88, p38, phosphorylated p38 (pp38), interferon regulatory factor 3 (IRF3) and Bcl-2-associated X protein (Bax) in spleen tissue were detected by Western blot analysis. We also survey the changes of serum autoantibodies, spleen weight, splenocyte apoptosis and the expressions of TLR4, MyD88, pp38, IRF3 and Bax in spleen tissue in male ApoE(-/-) mice after 4weeks of lipopolysaccharide (LPS), Toll-like receptor 4 ligand, administration. ApoE(-/-) mice showed splenomegaly and significantly increased serum level of IgG and titers of ANA and anti-dsDNA antibody as compared with B6 mice. Splenocyte apoptosis and the expression of TLR4, MyD88, pp38, IRF3 and Bax in spleen tissue were significantly lower in ApoE(-/-) than B6 mice. The expression of TLR4, MyD88, IRF3, pp38, and Bax differed by sex in ApoE(-/-) spleen tissue. The down-regulation of TLR4 signal molecules induced by LPS led to decreased expression of Bax and increased serum titers of ANA and anti-dsDNA antibody. Therefore, the TLR4 signal pathway may participate in maintaining the balance of splenocyte apoptosis and autoantibody production in ApoE(-/-) mice.