Trial of Endovascular Therapy for Acute Ischemic Stroke with Large Infarct.

BACKGROUND: The role of endovascular therapy for acute stroke with a large infarction has not been extensively studied in differing populations. METHODS: We conducted a multicenter, prospective, open-label, randomized trial in China involving patients with acute large-vessel occlusion in the anterior circulation and an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0 to 10, with lower values indicating larger infarction) or an infarct-core volume of 70 to 100 ml. Patients were randomly assigned in a 1:1 ratio within 24 hours from the time they were last known to be well to undergo endovascular therapy and receive medical management or to receive medical management alone. The primary outcome was the score on the modified Rankin scale at 90 days (scores range from 0 to 6, with higher scores indicating greater disability), and the primary objective was to determine whether a shift in the distribution of the scores on the modified Rankin scale at 90 days had occurred between the two groups. Secondary outcomes included scores of 0 to 2 and 0 to 3 on the modified Rankin scale. The primary safety outcome was symptomatic intracranial hemorrhage within 48 hours after randomization. RESULTS: A total of 456 patients were enrolled; 231 were assigned to the endovascular-therapy group and 225 to the medical-management group. Approximately 28% of the patients in both groups received intravenous thrombolysis. The trial was stopped early owing to the efficacy of endovascular therapy after the second interim analysis. At 90 days, a shift in the distribution of scores on the modified Rankin scale toward better outcomes was observed in favor of endovascular therapy over medical management alone (generalized odds ratio, 1.37; 95% confidence interval, 1.11 to 1.69; P = 0.004). Symptomatic intracranial hemorrhage occurred in 14 of 230 patients (6.1%) in the endovascular-therapy group and in 6 of 225 patients (2.7%) in the medical-management group; any intracranial hemorrhage occurred in 113 (49.1%) and 39 (17.3%), respectively. Results for the secondary outcomes generally supported those of the primary analysis. CONCLUSIONS: In a trial conducted in China, patients with large cerebral infarctions had better outcomes with endovascular therapy administered within 24 hours than with medical management alone but had more intracranial hemorrhages. (Funded by Covidien Healthcare International Trading [Shanghai] and others; ANGEL-ASPECT ClinicalTrials.gov number, NCT04551664.).

MiR-106a-5p targets PFKFB3 and improves sepsis through regulating macrophage pyroptosis and inflammatory response.

The enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3 (PFKFB3) is a critical regulator of glycolysis and plays a key role in modulating the inflammatory response, thereby contributing to the development of inflammatory diseases such as sepsis. Despite its importance, the development of strategies to target PFKFB3 in the context of sepsis remains challenging. In this study, we employed a miRNA-based approach to decrease PFKFB3 expression. Through multiple meta-analyses, we observed a downregulation of miR-106a-5p expression and an upregulation of PFKFB3 expression in clinical sepsis samples. These changes were also confirmed in blood monocytes from patients with early sepsis and from a mouse model of lipopolysaccharide (LPS)-induced sepsis. Overexpression of miR-106a-5p significantly decreased the LPS-induced increase in glycolytic capacity, inflammatory response, and pyroptosis in macrophages. Mechanistically, we identified PFKFB3 as a direct target protein of miR-106a-5p and demonstrated its essential role in LPS-induced pyroptosis and inflammatory response in macrophages. Furthermore, treatment with agomir-miR-106a-5p conferred a protective effect in an LPS mouse model of sepsis, but this effect was attenuated in myeloid-specific Pfkfb3 KO mice. These findings indicate that miR-106a-5p inhibits macrophage pyroptosis and inflammatory response in sepsis by regulating PFKFB3-mediated glucose metabolism, representing a potential therapeutic option for the treatment of sepsis.

Celastrol-Induced Nur77 Interaction with TRAF2 Alleviates Inflammation by Promoting Mitochondrial Ubiquitination and Autophagy.

Mitochondria play an integral role in cell death, autophagy, immunity, and inflammation. We previously showed that Nur77, an orphan nuclear receptor, induces apoptosis by targeting mitochondria. Here, we report that celastrol, a potent anti-inflammatory pentacyclic triterpene, binds Nur77 to inhibit inflammation and induce autophagy in a Nur77-dependent manner. Celastrol promotes Nur77 translocation from the nucleus to mitochondria, where it interacts with tumor necrosis factor receptor-associated factor 2 (TRAF2), a scaffold protein and E3 ubiquitin ligase important for inflammatory signaling. The interaction is mediated by an LxxLL motif in TRAF2 and results not only in the inhibition of TRAF2 ubiquitination but also in Lys63-linked Nur77 ubiquitination. Under inflammatory conditions, ubiquitinated Nur77 resides at mitochondria, rendering them sensitive to autophagy, an event involving Nur77 interaction with p62/SQSTM1. Together, our results identify Nur77 as a critical intracellular target for celastrol and unravel a mechanism of Nur77-dependent clearance of inflamed mitochondria to alleviate inflammation.

A novel 193-plex MPS panel integrating STRs and SNPs highlights the application value of forensic genetics in individual identification and paternity testing.

Massively parallel sequencing (MPS) has emerged as a promising technology for targeting multiple genetic loci simultaneously in forensic genetics. Here, a novel 193-plex panel was designed to target 28 A-STRs, 41 Y-STRs, 21 X-STRs, 3 sex-identified loci, and 100 A-SNPs by employing a single-end 400 bp sequencing strategy on the MGISEQ-2000™ platform. In the present study, a series of validations and sequencing of 1642 population samples were performed to evaluate the overall performance of the MPS-based panel and its practicality in forensic application according to the SWGDAM guidelines. In general, the 193-plex markers in our panel showed good performance in terms of species specificity, stability, and repeatability. Compared to commercial kits, this panel achieved 100% concordance for standard gDNA and 99.87% concordance for 14,560 population genotypes. Moreover, this panel detected 100% of the loci from 0.5 ng of DNA template and all unique alleles at a 1:4 DNA mixture ratio (0.2 ng minor contributor), and the applicability of the proposed approach for tracing and degrading DNA was further supported by case samples. In addition, several forensic parameters of STRs and SNPs were calculated in a population study. High CPE and CPD values greater than 0.9999999 were clearly demonstrated and these results could be useful references for the application of this panel in individual identification and paternity testing. Overall, this 193-plex MPS panel has been shown to be a reliable, repeatable, robust, inexpensive, and powerful tool sufficient for forensic practice.

High-Fidelity Sensitive Tracing Circulating Tumor Cell Telomerase Activity.

Dynamic tracing of intracellular telomerase activity plays a crucial role in cancer cell recognition and correspondingly in earlier cancer diagnosis and personalized precision therapy. However, due to the complexity of the required reaction system and insufficient loading of reaction components into cells, achieving a high-fidelity determination of telomerase activity is still a challenge. Herein, an Aptamer-Liposome mediated Telomerase activated poly-Molecular beacon Arborescent Nanoassembly(ALTMAN) approach was described for direct high-fidelity visualization of telomerase activity. Briefly, intracellular telomerase activates molecular beacons, causing their hairpin structures to unfold and produce fluorescent signals. Furthermore, multiple molecular beacons can self-assemble, forming arborescent nanostructures and leading to exponential amplification of fluorescent signals. Integrating the enzyme-free isothermal signal amplification successfully increased the sensitivity and reduced interference by leveraging the skillful design of the molecular beacon and the extension of the telomerase-activated TTAGGG repeat sequence. The proposed approach enabled ultrasensitive visualization of activated telomerase exclusively with a prominent detection limit of 2 cells·µL-1 and realized real-time imaging of telomerase activity in living cancer cells including blood samples from breast cancer patients and urine samples from bladder cancer patients. This approach opens an avenue for establishing a telomerase activity determination and in situ monitoring technique that can facilitate both telomerase fundamental biological studies and cancer diagnostics.

Riboflavin mediates m6A modification targeted by miR408, promoting early somatic embryogenesis in longan.

Plant somatic embryogenesis (SE) is an in vitro biological process wherein bipolar structures are induced to form somatic cells and regenerate into whole plants. MicroRNA (miRNA) is an essential player in plant SE. However, the mechanism of microRNA408 (miR408) in SE remains elusive. Here, we used stable transgenic technology in longan (Dimocarpus longan) embryogenic calli to verify the mechanism by which miR408 promotes cell division and differentiation of longan early SE. dlo-miR408-3p regulated riboflavin biosynthesis by targeting nudix hydrolase 23 (DlNUDT23), a previously unidentified gene mediating N6-methyladenosine (m6A) modification and influencing RNA homeostasis and cell cycle gene expression during longan early SE. We showed that DlMIR408 overexpression (DlMIR408-OE) promoted 21-nt miRNA biosynthesis. In DlMIR408-OE cell lines, dlo-miR408-3p targeted and downregulated DlNUDT23, promoted riboflavin biosynthesis, decreased flavin mononucleotide (FMN) accumulation, promoted m6A level, and influenced miRNA homeostasis. DNA replication, glycosylphosphatidylinositol (GPI)-anchor biosynthesis, the pentose phosphate pathway, and taurine and hypotaurine metabolism were also closely associated with riboflavin metabolism. In a riboflavin feeding assay, dlo-miR408-3p and pre-miR408 were upregulated and DlNUDT23 was downregulated, increasing the m6A level and cell division and differentiation in longan globular embryos. When riboflavin biosynthesis was inhibited, dlo-miR408-3p was downregulated and DlNUDT23 was upregulated, which decreased m6A modification and inhibited cell division but did not inhibit cell differentiation. FMN artificial demethylated m6A modification affected the homeostasis of precursor miRNA and miRNA. Our results revealed a mechanism underlying dlo-miR408-3p-activated riboflavin biosynthesis in which DlNUDT23 is targeted, m6A modification is dynamically mediated, and cell division is affected, promoting early SE in plants.

Genome-wide high-throughput chromosome conformation capture analysis reveals hierarchical chromatin interactions during early somatic embryogenesis.

Somatic embryogenesis (SE), like zygotic embryo development, is a progressive process. Early SE is the beginning of a switch from a somatic to an embryogenic state and is an important stage for initiating chromatin reprogramming of SE. Previous studies suggest that changes in chromatin accessibility occur during early SE, although information on the 3D structure of chromatin is not yet available. Here, we present a chromosome-level genome assembly of longan (Dimocarpus longan) using PacBio combined with high-through chromosome conformation capture scaffolding, which resulted in a 446 Mb genome assembly anchored onto 15 scaffolds. During early SE, chromatin was concentrated and then decondensed, and a large number of long terminal repeat retrotransposons (LTR-RTs) were enriched in the local chromatin interaction region, suggesting LTR-RTs were involved in chromatin reorganization. Early SE was accompanied by the transformation from A to B compartments, and the interactions between B compartments were enhanced. Results from chromatin accessibility, monomethylation of histone H3 at lysine 4 (H3K4me1) modification, and transcription analyses further revealed a gene regulatory network for cell wall thickening during SE. Particularly, we found that the H3K4me1 differential peak binding motif showed abnormal activation of ethylene response factor transcription factors and participation in SE. The chromosome-level genomic and multiomics analyses revealed the 3D conformation of chromatin during early SE, providing insight into the molecular mechanisms underlying cell wall thickening and the potential regulatory networks of TFs during early SE in D. longan. These results provide additional clues for revealing the molecular mechanisms of plant SE.

Generative Quantum Machine Learning via Denoising Diffusion Probabilistic Models.

Deep generative models are key-enabling technology to computer vision, text generation, and large language models. Denoising diffusion probabilistic models (DDPMs) have recently gained much attention due to their ability to generate diverse and high-quality samples in many computer vision tasks, as well as to incorporate flexible model architectures and a relatively simple training scheme. Quantum generative models, empowered by entanglement and superposition, have brought new insight to learning classical and quantum data. Inspired by the classical counterpart, we propose the quantum denoising diffusion probabilistic model (QuDDPM) to enable efficiently trainable generative learning of quantum data. QuDDPM adopts sufficient layers of circuits to guarantee expressivity, while it introduces multiple intermediate training tasks as interpolation between the target distribution and noise to avoid barren plateau and guarantee efficient training. We provide bounds on the learning error and demonstrate QuDDPM's capability in learning correlated quantum noise model, quantum many-body phases, and topological structure of quantum data. The results provide a paradigm for versatile and efficient quantum generative learning.

Brown Adipocyte ADRB3 Mediates Cardioprotection via Suppressing Exosomal iNOS.

BACKGROUND: The ADRB3 (ß3-adrenergic receptors), which is predominantly expressed in brown adipose tissue (BAT), can activate BAT and improve metabolic health. Previous studies indicate that the endocrine function of BAT is associated with cardiac homeostasis and diseases. Here, we investigate the role of ADRB3 activation-mediated BAT function in cardiac remodeling. METHODS: BKO (brown adipocyte-specific ADRB3 knockout) and littermate control mice were subjected to Ang II (angiotensin II) for 28 days. Exosomes from ADRB3 antagonist SR59230A (SR-exo) or agonist mirabegron (MR-exo) treated brown adipocytes were intravenously injected to Ang II-infused mice. RESULTS: BKO markedly accelerated cardiac hypertrophy and fibrosis compared with control mice after Ang II infusion. In vitro, ADRB3 KO rather than control brown adipocytes aggravated expression of fibrotic genes in cardiac fibroblasts, and this difference was not detected after exosome inhibitor treatment. Consistently, BKO brown adipocyte-derived exosomes accelerated Ang II-induced cardiac fibroblast dysfunction compared with control exosomes. Furthermore, SR-exo significantly aggravated Ang II-induced cardiac remodeling, whereas MR-exo attenuated cardiac dysfunction. Mechanistically, ADRB3 KO or SR59230A treatment in brown adipocytes resulted an increase of iNOS (inducible nitric oxide synthase) in exosomes. Knockdown of iNOS in brown adipocytes reversed SR-exo-aggravated cardiac remodeling. CONCLUSIONS: Our data illustrated a new endocrine pattern of BAT in regulating cardiac remodeling, suggesting that activation of ADRB3 in brown adipocytes offers cardiac protection through suppressing exosomal iNOS.

Supersensitive detection of lincomycin with an ECL aptasensor based on the synergistic integration of gold-functionalized upconversion nanoparticles and thiolated 3,4,9,10-perylene tetracarboxylic acid.

In this work, the supersensitive and selective determination of lincomycin (Lin) was achieved using a novel electroluminescent (ECL) aptasensor based on the synergistic integration of gold functionalized upconversion nanoparticles (UCNPs) and thiolated 3,4,9,10-perylene tetracarboxylic acid (PTCA). The integration of two luminophores of UCNPs and PTCA combined the merits of the cathodoluminescence stability of UCNPs and the high quantum yield of PTCA, which significantly promoted the ECL signal and analytical performance of the proposed sensor. The introduction of gold nanoparticles in UCNPs can not only improve the conductivity and ECL performance of UCNPs but also cause them to easily integrate with thiolated PTCA (t-PTCA) via an Au-S bond. The ECL signal of UCNPs@Au/t-PTCA/GCE was almost twice as strong as that of t-PTCA/GCE and tenfold higher than that of UCNPs@Au/GCE. Because of the non-conductive protein of the Lin aptamer, the ECL intensity of apt/UCNPs@Au/t-PTCA/GCE noticeably decreased. In the presence of Lin, the aptamer was pulled down from the sensing interface, resulting in the recovery of the ECL intensity of the sensor. Under optimal conditions, our proposed sensor can quantify the concentration of Lin in the range from 1.0 × 10-15 to 1.0 × 10-7 M with a low detection limit of 2.4 × 10-16 M (S/N = 3), exhibiting high sensitivity and specificity for the determination of Lin.

A national survey on current state and development needs of clinical and academic emergency medicine in China.

BACKGROUND: To characterize the current state of emergency medicine (EM) and the requirements for advancing EM clinical practice, education and research in China. METHODS: An anonymous electronic survey was conducted by Chinese Society of Emergency Medicine during September to October 2021. The survey contained 30 questions divided into 2 sections: the current state of EM development and the requirements for EM growth. RESULTS: 722 hospitals were included, of 487 were Level III and 235 were Level II hospitals. We found that after 40 years of development, EM had established a mature disciplinary system and refined sub-specialties including critical care, cardiopulmonary resuscitation, toxicology, disaster and emergency rescue. In Level III hospitals, 70.8% of EDs were standardized training centers for EM residents, but master's degree program, Doctor Degree program and post-doctoral degree program was approved in only 37.8%, 8.4% and 2.9% of EDs respectively and postgraduate curriculum was available in 1/4 of EDs. Only 8% have national or provincial key laboratories. In addition to advance clinical practice, there was also a high demand to improve teaching and research capacities, mainly focusing on literature review, research design and delivery, paper writing, residency training. CONCLUSIONS: EM has built a mature discipline system and refined sub-specialties in China. Teaching and research developed parallel with clinical practice. However, there was still a lack of EM master's and doctoral programs and research capacities need to be improved. More outstanding clinical and academic training should be provided to promote the rapid growth of EM in China.

Hydrous Molybdenum Oxide Coating of Zinc Metal Anode via the Facile Electrodeposition Strategy and Its Performance Improvement Mechanisms for Aqueous Zinc-Ion Batteries.

Aqueous zinc-ion batteries (ZIBs) are widely recognized as highly promising energy storage devices because of their inherent characteristics, including superior safety, affordability, eco-friendliness, and various other benefits. However, the significant corrosion of the zinc metal anode, side reactions occurring between the anode and electrolyte, and the formation of zinc dendrites significantly hinder the practical utilization of ZIBs. Herein, we utilized an electrodeposition method to apply a unique hydrous molybdenum oxide (HMoOx) layer onto the surface of the zinc metal anode, aiming to mitigate its corrosion and side reactions during the process of zinc deposition and stripping. In addition, the HMoOx layer not only improved the hydrophilicity of the zinc anode, but also adjusted the migration of Zn2+, thus facilitating the uniform deposition of Zn2+ to reduce dendrite formation. A symmetrical cell with the HMoOx-Zn anode displayed reduced-voltage hysteresis (80 mV at 2.5 mA/cm2) and outstanding cycle stability after 3000 cycles, surpassing the performance of the uncoated Zn anode. Moreover, the HMoOx-Zn anode coupled with a γ-MnO2 cathode created a considerably more stable rechargeable full battery compared to the bare Zn anode. The HMoOx-Zn||γ-MnO2 full cell also displayed excellent cycling stability with a charge/discharge-specific capacity of 129/133 mAh g-1 after 300 cycles. In summary, this research offers a straightforward and advantageous approach that can significantly contribute to the future advancements in rechargeable ZIBs.

An All-Rounder for NIR-II Phototheranostics: Well-Tailored 1064 nm-Excitable Molecule for Photothermal Combating of Orthotopic Breast Cancer.

The second near-infrared (NIR-II, 1000-1700 nm) light-activated organic photothermal agent that synchronously enables satisfying NIR-II fluorescence imaging is highly warranted yet rather challenging on the basis of the overwhelming nonradiative decay. Herein, such an agent, namely TPABT-TD, was tactfully designed and constructed via employing benzo[c]thiophene moiety as bulky electron donor/π-bridge and tailoring the peripheral molecular rotors. Benefitting from its high electron donor-acceptor strength and finely modulated intramolecular motion, TPABT-TD simultaneously exhibits ultralong absorption in NIR-II region, intense fluorescence emission in the NIR-IIa (1300-1500 nm) region as nanoaggregates, and high photothermal conversion upon 1064 nm laser irradiation. Those intrinsic advantages endow TPABT-TD nanoparticles with prominent fluorescence/photoacoustic/photothermal trimodal imaging-guided NIR-II photothermal therapy against orthotopic 4T1 breast tumor with negligible adverse effect.

Screening of candidate genes related to differences in growth and development between Chinese indigenous and Western pig breeds.

Neijiang (NJ) and Yacha (YC) are two indigenous pig breeds in the Sichuan basin of China, displaying higher resistance to diseases, lower lean ratio, and slower growth rate than the commercial Western pig breed Yorkshire (YS). The molecular mechanisms underlying the differences in growth and development between these pig breeds are still unknown. In the present study, five pigs from NJ, YC, and YS breeds were subjected to the whole genome resequencing, and then the differential single-nucleotide polymorphisms (SNPs) were screened using a 10-kb window sliding in 1-kb step using the Fst method. Finally, 48,924, 48,543, and 46,228 nonsynonymous single-nucleotide polymorphism loci (nsSNPs) were identified between NJ and YS, NJ and YC, and YC and YS, which highly or moderately affected 2,490, 800, and 444 genes, respectively. Moreover, three nsSNPs were detected in the genes of acetyl-CoA acetyltransferase 1 (ACAT1) insulin-like growth factor 2 receptor (IGF2R), insulin-like growth factor 2 and mRNA-binding protein 3 (IGF2BP3), which potentially affected the transformation of acetyl-CoA to acetoacetyl-CoA and the normal functions of the insulin signaling pathways. Moreover, serous determinations revealed significantly lower acetyl-CoA content in YC than in YS, supporting that ACAT1 might be a reason explaining the differences in growth and development between YC and YS breeds. Contents of phosphatidylcholine (PC) and phosphatidic acid (PA) significantly differed between the pig breeds, suggesting that glycerophospholipid metabolism might be another reason for the differences between Chinese and Western pig breeds. Overall, these results might contribute basic information to understand the genetic differences determining the phenotypical traits in pigs.

Diallyl trisulfide alleviates chemotherapy sensitivity of ovarian cancer via the AMPK/SIRT1/PGC1α pathway.

Platinum-based chemotherapy promotes drug resistance in ovarian cancer. We investigated the antichemoresistance characteristics of diallyl trisulfide (DATS) in cisplatin-resistant ovarian cancer cells, in vitro and in vivo. Previous preclinical studies have revealed that DATS regulates distinct hallmark cancer-signaling pathways. The cell cycle pathway is the most investigated signaling pathway in DATS. Additionally, post-DATS treatment has been found to promote proapoptotic capacity through the regulation of intrinsic and extrinsic apoptotic pathway components. In the present study, we found that treating cisplatin-sensitive and cisplatin-resistant ovarian cell lines with DATS inhibited their proliferation and reduced their IC50. It induced cell apoptosis and promoted oxidative phosphorylation through the regulation of the AMPK/SIRT1/PGC1α pathway, OXPHOS, and enhanced chemotherapy sensitivity. DATS treatment alleviated glutamine consumption in cisplatin-resistant cells. Our findings highlight the role of DATS in overcoming drug resistance in ovarian cancer in vitro and in vivo. In addition, we elucidated the role of the AMPK/SIRT1/PGC1α signaling pathway as a potential target for the treatment of drug-resistant ovarian cancer.

LPLUNC1 reduces glycolysis in nasopharyngeal carcinoma cells through the PHB1-p53/c-Myc axis.

Cancer cells prefer glycolysis to support their proliferation. Our previous studies have shown that the long palate, lung, and nasal epithelial cell clone 1 (LPLUNC1) can upregulate prohibitin 1 (PHB1) expression to inhibit the proliferation of nasopharyngeal carcinoma (NPC) cells. Given that PHB1 is an important regulator of cell energy metabolism, we explored whether and how LPLUNC1 regulated glucose glycolysis in NPC cells. LPLUNC1 or PHB1 overexpression decreased glycolysis and increased oxidative phosphorylation (OXPHOS)-related protein expression in NPC cells, promoting phosphorylated PHB1 nuclear translocation through 14-3-3σ. LPLUNC1 overexpression also increased p53 but decreased c-Myc expression in NPC cells, which were crucial for the decrease in glycolysis and increase in OXPHOS-related protein expression induced by LPLUNC1 overexpression. Finally, we found that treatment with all-trans retinoic acid (ATRA) reduced the viability and clonogenicity of NPC cells, decreased glycolysis, and increased OXPHOS-related protein expression by enhancing LPLUNC1 expression in NPC cells. Therefore, the LPLUNC1-PHB1-p53/c-Myc axis decreased glycolysis in NPC cells, and ATRA upregulated LPLUNC1 expression, ATRA maybe a promising drug for the treatment of NPC.

Establishment and evaluation of a modified mouse model of renal subcapsular transplantation of microvolume cells.

The renal subcapsular space provides an easily accessible, nutrition-rich pocket that supports engraftment, and as such, is often used as a site for stem and cancer cell transplantation. Renal capsule transplantation requires high technical requirements, the recipient mice have greater surgical damage, the mouse kidney is small and the kidney capsule is fragile, and the operation is easy to fail. The conventional method is not suitable for microvolume cell transplantation to this site in animals with a small kidney, such as mice, due to high risks of cell loss or dislocation or injury to the capsule. In this study, we developed and validated a modified approach for the mouse model of renal subcapsular transplantation of microvolume mouse skeletal stem cells (SSCs). We used a pipette with a refined tip to separate the capsule from the parenchyma. Moreover, we used cells suspended in Matrigel rather than a liquid carrier for transplantation. Using the modified method, we were able to transplant microvolume mouse SSCs as low as 0.2 µL beneath the mouse renal capsule with excellent reproducibility. After 4 weeks of in vivo culture, the implanted mouse SSCs formed grafts on the surface of the parenchyma at the target site of transplantation. Histological staining of the grafts indicated osteogenic, fibrogenic, and lipogenic differentiation. Micro-CT imaging of the grafts revealed bone formation. This modified model could be used to effectively transplant different types of microvolume cells to the renal subcapsular space when the donor cells are difficult to acquire or the recipient mice have a very small size kidney.

Value of Non-Contrast-Enhanced Vessel Wall MR Imaging in Assessing Vascular Invasion of Retroperitoneal Tumors.

BACKGROUND: Due to their location and growth patterns, retroperitoneal tumors often involve the surrounding blood vessels. Clinical decisions on a proper treatment depend on the information on this condition. Evaluation of blood vessels using non-contrast-enhanced vessel wall MRI may provide noninvasive assessment of the extent of tumor invasion to assist clinical decision-making. PURPOSE: To investigate the performance and potential of non-contrast-enhanced vessel wall MRI in evaluating the degree of vessel wall invasion of retroperitoneal tumors. STUDY TYPE: Prospective. POPULATION: Thirty-seven participants (mean age: 60.59 ± 11.77 years, 59% male) with retroperitoneal tumors close to vessels based on their diagnostic computer tomography. FIELD STRENGTH/SEQUENCES: 3 T; vessel wall MRI sequences: two-dimensional T2-weighted MultiVane XD turbo spin-echo (2D-T2-MVXD-TSE) and three-dimensional T1-weighted motion sensitized driven equilibrium fat suppression turbo spin-echo (3D-T1-MSDE-TSE) sequences; conventional MRI sequences: T2-weighted fat suppression turbo spin-echo (T2-FS-TSE), T2-weighted turbo spin-echo (T2-TSE), modified Dixon T1-weighted fast field echo (T1-mDixon-FFE), and diffusion-weighted echo planar imaging (DWI-EPI) sequences. ASSESSMENT: All patients underwent preoperative imaging using both non-contrast conventional and vessel wall MRI sequences. Images obtained from conventional and vessel wall MRI sequences were evaluated independently by three junior radiologists (3 and 2 years of experience in reading MRI) and reviewed by one senior radiologist (25 years of experience in reading MRI) to assess the degree of vessel wall invasion. MRI were validated results from the clinical standard diagnosis based on surgical confirmation or histopathological reports. Interobserver agreement was determined based on the reports from three readers with similar years of experiences. Intraobserver variability was assessed based on categorizing and recategorizing the vessels of 37 patients 1 month apart. STATISTICAL TESTS: Intra-class correlation efficient (ICC), Chi-square test, McNemar test, area under the receiver-operating characteristic curve (AUC), Delong test, P < 0.05 was considered significant. RESULTS: The accuracy of vessel wall MRI (91.96%, 95% CI: 85.43-95.71; 103 of 112) in detecting the degree of vessel wall invasion was significantly higher than that of conventional MRI (75%, 95% CI: 66.24-82.10; 84 of 112). The interobserver variability or reproducibility in categorization of the degree of vascular wall invasion was good in evaluating images from conventional and vessel wall MRI sequences (ICC = 0.821, 95% CI: 0.765-0.867 and ICC = 0.881, 95% CI: 0.842-0.913, respectively). DATA CONCLUSION: Diagnosis of vessel wall invasion of retroperitoneal tumors and assessment of its severity can be improved by using non-contrast-enhanced vessel wall MRI. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 3.

Advanced Glycation End Products' Receptor DNA Methylation Associated with Immune Infiltration and Prognosis of Lung Adenocarcinoma and Lung Squamous Cell Carcinoma.

Background: Advanced glycation end products' receptor (AGER) is a multiligand receptor that interacts with a wide range of ligands. Previous studies have shown that abnormal AGER expression is closely related to immune infiltration and tumorigenesis. However, the AGER DNA methylation relationship between prognosis and infiltrating immune cells in LUAD and LUSC is still unclear. Methods: AGER expression in pan-cancer was obtained by using the UALCAN databases. Kaplan-Meier plotter showed the correlation of AGER mRNA expression levels and clinicopathological parameters. The protein expression levels for AGER were derived from Human Protein Atlas Database Analysis. The copy number, somatic mutation, and DNA methylation of AGER were presented with UCSC Xena database. TIMER platform and TISIDB website were used to show the correlation between AGER expression and tumor immune cell infiltration level. Results: The expression level of AGER was significantly reduced in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Low expression of AGER was significantly correlated with histology, stage, lymph node metastasis, and tumor protein 53 (TP53) mutation and could be used as a potential indicator of poor prognosis of LUAD and LUSC. Moreover, AGER expression was positively correlated with the infiltrating immune cells. Further analysis showed that copy number variation (CNV), mutation, and DNA methylation were involved in AGER downregulation. In addition, we also found that hypermethylated AGER was significantly correlated with tumor-infiltrating lymphocytes. Conclusion: AGER may be a candidate for the prognostic biomarker of LUAD and LUSC related to tumor immune microenvironment.

Paenibacillus mangrovi sp. nov., a novel endophytic bacterium isolated from bark of Kandelia candel.

A endospore-forming bacterium, designated strain KQZ6P-2T, was isolated from surface-sterilized bark of the mangrove plant Kandelia candel, collected from Maowei Sea Mangrove Nature Reserve in Guangxi Zhuang Autonomous Region, China. Strain KQZ6P-2T was able to grow at NaCl concentrations in the range of 0-3 % (w/v) with optimum growth at 0-1 % (w/v) NaCl. Growth occurred at 20-42 °C (optimal growth at 30-37 °C) and pH 5.5-6.5 (optimal growth at pH 6.5). The 16S rRNA gene sequence similarity between strain KQZ6P-2T and its closest phylogenetic neighbour Paenibacillus chibensis JCM 9905T was 98.2 %. Phylogenetic analyses using 16S rRNA gene sequences showed that strain KQZ6P-2T formed a distinct lineage with Paenibacillus chibensis JCM 9905T. The draft genome of strain KQZ6P-2T was 5 937 633 bp in size and its DNA G+C content was 47.2mol%. Comparative genome analysis revealed that the average nucleotide identity, digital DNA-DNA hybridization and average amino acid identity values among strain KQZ6P-2T and its related species were below the cut-off levels of 95, 70 and 95.5%, respec-tively. The cell-wall peptidoglycan of strain KQZ6P-2T contained meso-diaminopimelic acid as the diagnostic diamino acid. Major cellular fatty acids were anteiso-C15:0 and C16:0. The polar lipids comprised diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, two unidentified aminophospholipids, four unidentified phospholipids, an unidentified aminolipid and five unidentified lipids. Based on phylogenetic, phenotypic and chemotaxonomic data, strain KQZ6P-2T represents a novel species of the genus Paenibacillus, for which the name Paenibacillus mangrovi sp. nov. is proposed. The type strain is KQZ6P-2T (=MCCC 1K07172T =JCM 34931T).