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2.
Cancer Cell ; 42(5): 815-832.e12, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38640932

ABSTRACT

Monocyte-derived tumor-associated macrophages (Mo-TAMs) intensively infiltrate diffuse gliomas with remarkable heterogeneity. Using single-cell transcriptomics, we chart a spatially resolved transcriptional landscape of Mo-TAMs across 51 patients with isocitrate dehydrogenase (IDH)-wild-type glioblastomas or IDH-mutant gliomas. We characterize a Mo-TAM subset that is localized to the peri-necrotic niche and skewed by hypoxic niche cues to acquire a hypoxia response signature. Hypoxia-TAM destabilizes endothelial adherens junctions by activating adrenomedullin paracrine signaling, thereby stimulating a hyperpermeable neovasculature that hampers drug delivery in glioblastoma xenografts. Accordingly, genetic ablation or pharmacological blockade of adrenomedullin produced by Hypoxia-TAM restores vascular integrity, improves intratumoral concentration of the anti-tumor agent dabrafenib, and achieves combinatorial therapeutic benefits. Increased proportion of Hypoxia-TAM or adrenomedullin expression is predictive of tumor vessel hyperpermeability and a worse prognosis of glioblastoma. Our findings highlight Mo-TAM diversity and spatial niche-steered Mo-TAM reprogramming in diffuse gliomas and indicate potential therapeutics targeting Hypoxia-TAM to normalize tumor vasculature.


Subject(s)
Adrenomedullin , Brain Neoplasms , Glioblastoma , Tumor-Associated Macrophages , Humans , Glioblastoma/pathology , Glioblastoma/drug therapy , Glioblastoma/blood supply , Glioblastoma/genetics , Glioblastoma/metabolism , Animals , Adrenomedullin/genetics , Adrenomedullin/metabolism , Mice , Brain Neoplasms/drug therapy , Brain Neoplasms/pathology , Brain Neoplasms/blood supply , Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Tumor-Associated Macrophages/metabolism , Neovascularization, Pathologic/genetics , Tumor Microenvironment , Isocitrate Dehydrogenase/genetics , Xenograft Model Antitumor Assays , Cell Line, Tumor , Macrophages/metabolism , Cell Hypoxia
3.
Environ Sci Pollut Res Int ; 31(18): 27273-27285, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38507167

ABSTRACT

Excessive fluoride emissions threaten ecological stability and human health. Previous studies have noted that industrial sources could be significant. However, quantifying industrial fluoride emissions has not been yet reported. In this study, both bottom-up and top-down approaches were used to estimate the fluoride emissions in the Nansi Lake Basin. Global and local spatial autocorrelation were adopted to reveal the spatial agglomeration effects. The fluoride emissions calculated by the bottom-up approach were larger than those calculated by the top-down method. The highest fluoride input mainly occurred in Zoucheng and Mudan. The highest fluoride emissions mainly occurred in Zoucheng and Rencheng using the bottom-up approach. The highest fluoride emissions mainly occurred in Zoucheng and Yanzhou using the top-down approach. Mining and washing of bituminous coal and anthracite (BAW) was the most significant source of fluoride input and emissions. A significant spatial agglomeration effect of fluoride emissions was found. These findings could provide a method for accurate industrial fluoride emission estimation, complement the critical data on the fluoride emissions of main industrial sectors, and provide a scientific basis for tracing fluoride sources.


Subject(s)
Environmental Monitoring , Fluorides , Lakes , China , Fluorides/analysis , Lakes/chemistry , Industry
4.
Pathol Res Pract ; 256: 155251, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38490097

ABSTRACT

Aberrant adrenal function has been frequently reported in COVID-19 patients, but histopathological evidence remains limited. This retrospective autopsy study aims to scrutinize the impact of COVID-19 duration on adrenocortical zonational architecture and peripheral corticosteroid reactivity. The adrenal glands procured from 15 long intensive care unit (ICU)-stay COVID-19 patients, 9 short ICU-stay COVID-19 patients, and 20 matched controls. Subjects who had received glucocorticoid treatment prior to sampling were excluded. Applying hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining, we disclosed that the adrenocortical zonational structure was substantially disorganized in COVID-19 patients, which long ICU-stay patients manifested a higher prevalence of severe disorganization (67%) than short ICU-stay patients (11%; P = 0.0058). The adrenal cortex of COVID-19 patients exhibited a 40% decrease in the zona glomerulosa (ZG) area and a 74% increase in the zona fasciculata (ZF) area (both P < 0.0001) relative to controls. Furthermore, among long ICU-stay COVID-19 patients, the ZG area diminished by 31% (P = 0.0004), and the ZF area expanded by 27% (P = 0.0004) in comparison to short ICU-stay patients. The zona reticularis (ZR) area remained unaltered. Nuclear translocation of corticosteroid receptors in the liver and kidney of long ICU-stay COVID-19 patients was at least 43% lower than in short ICU-stay patients (both P < 0.05). These findings underscore the necessity for clinicians to monitor adrenal function in long-stay COVID-19 patients.


Subject(s)
Adrenal Cortex , COVID-19 , Humans , Critical Illness , Retrospective Studies , Adrenal Glands , Adrenal Cortex Hormones
5.
Nurs Crit Care ; 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38358027

ABSTRACT

BACKGROUND: Although the circuit condensate, an ideal bacterial reservoir during mechanical ventilation, may flow into the humidifier reservoir, no studies have investigated if humidifier reservoir colonized bacteria colonize other circuit locations with airflow. AIMS: We aimed to prove whether the humidifier reservoir colonized bacteria colonize other circuit locations with airflow and provide some advice on the disposal of condensate in the clinical setting. STUDY DESIGN: An in vitro experiment was conducted. Mechanical ventilation simulators (n = 90) were divided into sterile water group (n = 30) and broth group (n = 60). In the sterile water group, sterile water was used for humidification, either Acinetobacter baumannii or Pseudomonas aeruginosa were inoculated to humidifier water in the humidifier reservoir, each accounted for 50% of the simulators. The broth group was performed the same as the sterile water group except for the addition of broth into the humidified water. After 24, 72, and 168 h of continuous ventilation, the humidifier water and different locations of the circuits were sampled for bacterial culture. RESULTS: All bacterial culture results of the sterile water group were negative. Bacteria in the humidifier water continued to proliferate in the broth group. With prolonged ventilation, the bacteria at the humidifier reservoir outlet increased. The bacteria at the humidifier reservoir outlet were much more in the Pseudomonas aeruginosa subgroup than in the Acinetobacter baumannii subgroup and the difference was statistically significant (p < .05). During continuous ventilation, no bacterial growth occurred at 10 cm from the humidifier reservoir outlet and the Y-piece of the ventilator circuits. CONCLUSIONS: Sterile water in the humidifier reservoir was not conducive to bacterial growth. Even if bacteria grew in the humidifier reservoir and could reach the humidifier reservoir outlet, colonization of further circuit locations with the airflow was unlikely. During a certain mechanical ventilation time, the amount of bacteria reaching the outlet of the humidifier reservoir varied due to different mobility of bacteria. RELEVANCE TO CLINICAL PRACTICE: In a clinical setting, nurses should not worry about a small amount of condensate backflow into the humidifier reservoir. Draining condensate into the humidifier reservoir can be used as a low risk and convenient method in clinical practice.

7.
Insect Biochem Mol Biol ; 157: 103959, 2023 06.
Article in English | MEDLINE | ID: mdl-37172766

ABSTRACT

Steroid hormone 20-hydroxyecdysone (20E) plays critical roles in reproductive development in dipterans and several other insect species. Ecdysteroidogenesis in the glands of larval or nymphal insects and other arthropods has been extensively studied, but that in the adult gonads remains largely unknown. Here we identified a proteasome ß3 subunit (PSMB3) from a highly invasive pest Bactrocera dorsalis, and found that this gene was crucial for ecdysone production during female reproduction. PSMB3 was enriched in the ovary, and it was upregulated during sexual maturation. RNAi-mediated depletion of PSMB3 resulted in retarded ovarian development and decreased fecundity. Additionally, knockdown of PSMB3 reduced 20E titer in hemolymph of B. dorsalis. Molecularly, RNA sequencing and qPCR validation revealed that PSMB3 depletion suppressed the expression of 20E biosynthetic genes in the ovary and 20E responsive genes in the ovary and fat body. Furthermore, exogenous 20E rescued the inhibition of the ovarian development caused by PSMB3 depletion. Taken together, this study provides new insights into the adult reproductive development-related biological processes controlled by PSMB3, and proposed a potential eco-friendly control strategy against this notorious agricultural pest.


Subject(s)
Sexual Maturation , Tephritidae , Animals , Female , Proteasome Endopeptidase Complex/genetics , Proteasome Endopeptidase Complex/metabolism , Base Sequence , Ecdysterone/metabolism , Reproduction , Tephritidae/physiology , Insect Proteins/genetics , Insect Proteins/metabolism
8.
Materials (Basel) ; 16(10)2023 May 09.
Article in English | MEDLINE | ID: mdl-37241240

ABSTRACT

This study investigated the effect of hollow 304 stainless-steel fiber on the corrosion resistance and mechanical properties of ultra-high-performance concrete (UHPC), and prepared copper-coated-fiber-reinforced UHPC as the control group. The electrochemical performance of the prepared UHPC was compared with the results of X-ray computed tomography (X-CT). The results reveal that cavitation can improve the distribution of steel fibers in the UHPC. Compared with solid steel fibers, the compressive strength of UHPC with hollow stainless-steel fibers did not exhibit significant change, but the maximum flexural strength increased by 45.2% (2 vol% content, length-diameter ratio of 60). Hollow stainless-steel fiber could better improve the durability of UHPC compared with copper-plated steel fiber, and the gap between the two continued to increase as the durability test progressed. After the dry-wet cycle test, the flexural strength of the copper-coated-fiber-reinforced UHPC was 26 MPa, marking a decrease of 21.9%, while the flexural strength of the UHPC mixed with hollow stainless-steel fibers was 40.1 MPa, marking a decrease of only 5.6%. When the salt spray test had run for seven days, the difference in the flexural strength between the two was 18.4%, but when the test ended (180 days), the difference increased to 34%. The electrochemical performance of the hollow stainless-steel fiber improved, owing to the small carrying capacity of the hollow structure, and more uniform distribution in the UHPC and lower interconnection probability were achieved. According to the AC impedance test results, the charge transfer impedance of the UHPC doped with solid steel fiber is 5.8 KΩ, while that of the UHPC doped with hollow stainless-steel fiber is 8.8 KΩ.

9.
Nat Mater ; 22(7): 832-837, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36894772

ABSTRACT

The scaling of silicon-based transistors at sub-ten-nanometre technology nodes faces challenges such as interface imperfection and gate current leakage for an ultrathin silicon channel1,2. For next-generation nanoelectronics, high-mobility two-dimensional (2D) layered semiconductors with an atomic thickness and dangling-bond-free surfaces are expected as channel materials to achieve smaller channel sizes, less interfacial scattering and more efficient gate-field penetration1,2. However, further progress towards 2D electronics is hindered by factors such as the lack of a high dielectric constant (κ) dielectric with an atomically flat and dangling-bond-free surface3,4. Here, we report a facile synthesis of a single-crystalline high-κ (κ of roughly 16.5) van der Waals layered dielectric Bi2SeO5. The centimetre-scale single crystal of Bi2SeO5 can be efficiently exfoliated to an atomically flat nanosheet as large as 250 × 200 µm2 and as thin as monolayer. With these Bi2SeO5 nanosheets as dielectric and encapsulation layers, 2D materials such as Bi2O2Se, MoS2 and graphene show improved electronic performances. For example, in 2D Bi2O2Se, the quantum Hall effect is observed and the carrier mobility reaches 470,000 cm2 V-1 s-1 at 1.8 K. Our finding expands the realm of dielectric and opens up a new possibility for lowering the gate voltage and power consumption in 2D electronics and integrated circuits.


Subject(s)
Graphite , Silicon , Electronics , Semiconductors
10.
Materials (Basel) ; 16(6)2023 Mar 11.
Article in English | MEDLINE | ID: mdl-36984137

ABSTRACT

Steel fiber-reinforced ultra-high-performance concrete (UHPC) is becoming an important type of concrete reinforcement. After mixing with the reinforced steel fibers, the UHPC has perfect flex resistance, shear strength, crack resistance, shock resistance, and anti-seepage. In this study, the influence of straight, corrugated, and hooked brass-coated steel fibers (BCSFs) on the microstructure, mechanical properties, and crack expansion mechanism of ultra-high-performance concrete (UHPC) with varying content of 1-6 wt.% under different curing times were investigated. Field emission scanning electron microscopy and energy dispersive X-ray spectrometry were employed to characterize the microstructure of the BCSF-reinforced UHPC mix specimens. X-ray computed tomography was employed to determine the porosity of the BCSF-reinforced UHPC mix specimens. The obtained results indicate the flexural strength and compressive strength of BCSF-reinforced UHPC mix specimens are enhanced, along with increasing the content of BCSFs reinforcement with different shapes (straight, corrugated, and hooked). The embedded BCSFs play a major role in the adhesive property and stress transfer of the BCSFs-UHPC matrix interface. Different from many studies, the flexural strength of mix UHPC with straight BCSFs is higher than those with corrugated and hooked BCSFs. However, the compressive strength of UHPC with corrugated BCSFs is higher than those with straight and hooked BCSFs. The flexural strength of mix UHPC with 6 wt.% straight BCSFs at 28 days reaches the maximum value of 26.2 MPa, and the compressive strength of UHPC with 6 wt.% corrugated BCSFs at 28 days reaches the maximum value of 142.3 MPa. With the increase in straight BCSF content from 1 wt.% to 6 wt.%, the porosity in mix UHPC reduces gradually from 18.4% to 8.3%. The length of average crack spacing is dependent on the straight BCSF content. With the increase in straight BCSF content from 1 wt.% to 6 wt.%, the average crack length reduces gradually from 34.2 mm to 12.1 mm, and the average crack width reduces gradually from 0.78 mm to less than 0.1 mm. During crack extension, part of the energy in the UHPC mixture specimen with the 6 wt.% BCSF content flows into the crack tip region converted into the work dissipated during the bridging process. The crack propagation resistance of the UHPC mixture with straight BCSFs was improved compared with those with corrugated and hooked BCSFs. The bond strength between the BCSFs and UHPC matrix was enhanced by using vibrational mixing, and the brass film coated on the BCSFs contributes to increase the flexural and compressive strength of the UHPC mixture.

11.
Signal Transduct Target Ther ; 8(1): 24, 2023 01 06.
Article in English | MEDLINE | ID: mdl-36609561

ABSTRACT

Severe neurological symptoms are associated with Coronavirus disease 2019 (COVID-19). However, the morphologic features, pathological nature and their potential mechanisms in patient brains have not been revealed despite evidence of neurotropic infection. In this study, neuropathological damages and infiltrating inflammatory cells were quantitatively evaluated by immunohistochemical staining, ultrastructural examination under electron microscopy, and an image threshold method, in postmortem brains from nine critically ill COVID-19 patients and nine age-matched cadavers of healthy individuals. Differentially expressed proteins were identified by quantitative proteomic assays. Histopathological findings included neurophagocytosis, microglia nodules, satellite phenomena, extensive edema, focal hemorrhage, and infarction, as well as infiltrating mononuclear cells. Immunostaining of COVID-19 brains revealed extensive activation of both microglia and astrocytes, severe damage of the blood-brain barrier (BBB) and various degrees of perivascular infiltration by predominantly CD14+/CD16+/CD141+/CCR7+/CD11c+ monocytes and occasionally CD4+/CD8+ T lymphocytes. Quantitative proteomic assays combined with bioinformatics analysis identified upregulated proteins predominantly involved in immune responses, autophagy and cellular metabolism in COVID-19 patient brains compared with control brains. Proteins involved in brain development, neuroprotection, and extracellular matrix proteins of the basement membrane were downregulated, potentially caused by the activation of transforming growth factor ß receptor and vascular endothelial growth factor signaling pathways. Thus, our results define histopathological and molecular profiles of COVID-19-associated monocytic encephalitis (CAME) and suggest potential therapeutic targets.


Subject(s)
COVID-19 , Encephalitis , Humans , Monocytes , COVID-19/genetics , Autopsy , Proteomics , Vascular Endothelial Growth Factor A
12.
Pest Manag Sci ; 79(2): 688-700, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36239581

ABSTRACT

BACKGROUND: The oriental fruit fly, Bactrocera dorsalis, is a highly invasive pest in East Asia and the Pacific. With the development of pesticides resistance, environment-friendly pesticides are urgently needed. MicroRNAs (miRNAs) are critical regulators of numerous biological processes, including reproduction. Thus, it is significant to identify reproductive-related miRNAs in this notorious pest to facilitate its control, such as RNAi-based biopesticides targeting essential miRNAs. RESULTS: A high-throughput sequencing was carried out to identify miRNAs involved in reproduction from the ovary and fat body at four developmental stages [1 day (d), 5, 9, and 13 days post-eclosion] in female B. dorsalis. Results showed that 98 and 74 miRNAs were differentially expressed in ovary and fat body, respectively, during sexual maturation. Gene ontology analysis showed that target genes involved in oogenesis and lipid particle accounted for 33% and 15% of the total targets, respectively. Among these differentially expressed miRNAs, we found by qPCR that miR-311-3p was enriched in the ovary and down-regulated during sexual maturation. Injection of agomir-miR-311-3p resulted in arrested ovarian development, reduced egg deposition and progeny viability. Endophilin B1 was confirmed to be the target of miR-311-3p, via dual-luciferase assay and expression profiling. Knockdown of Endophilin B1 resulted in reproductive defects similar to those caused by injection of miR-311-3p agomir. Thus, miR-311-3p might play a critical role in female reproduction by targeting Endophilin B1. CONCLUSION: Our data not only provides knowledge on the abundance of reproductive-related miRNAs and target genes, but also promotes new control strategies for this pest. © 2022 Society of Chemical Industry.


Subject(s)
Fertility , MicroRNAs , Tephritidae , Animals , Female , Fertility/genetics , Gene Expression Profiling , High-Throughput Nucleotide Sequencing/methods , MicroRNAs/genetics , MicroRNAs/metabolism , Ovary/metabolism , Sequence Analysis, RNA , Tephritidae/genetics , Tephritidae/metabolism
13.
Inorg Chem ; 61(39): 15392-15397, 2022 Oct 03.
Article in English | MEDLINE | ID: mdl-36134570

ABSTRACT

Mononuclear complexes within a particular coordination geometry have been well recognized for high-performance single-molecule magnets (SMMs), while the incorporation of such well-defined geometric ions into multinuclear complexes remains less explored. Using the rigid 2-(di(1H-pyrazol-1-yl)methyl)-6-(1H-pyrazol-1-yl)pyridine (PyPz3) ligand, here, we prepared a series of benzoquinone-bridged dicobalt(II) SMMs [{(PyPz3)Co}2(L)][PF6]2, (1, L = 2,5-dioxo-1,4-benzoquinone (dhbq2-); 2, L = chloranilate (CA2-); and 3, L = bromanilate (BA2-)), in which each Co(II) center adopts a distorted trigonal prismatic (TPR) geometry and the distortion increases with the sizes of 3,6-substituent groups (H (1) < Cl (2) < Br (3)). Accordingly, the magnetic study revealed that the axial anisotropy parameter (D) of the Co ions decreased from -78.5 to -56.5 cm-1 in 1-3, while the rhombic one (E) increased significantly. As a result, 1 exhibited slow relaxation of magnetization under a zero dc field, while both 2 and 3 showed only the field-induced SMM behaviors, likely due to the increased rhombic anisotropy that leads to the serious quantum tunneling of the magnetization. Our study demonstrated that the relaxation dynamics and performances of a multinuclear complex are strongly dependent on the coordination geometry of the local metal ions, which may be engineered by modifying the substituent groups.

14.
J Pathol ; 258(2): 121-135, 2022 10.
Article in English | MEDLINE | ID: mdl-35723032

ABSTRACT

Tumour-associated macrophages (TAMs) abundantly infiltrate high-grade gliomas and orchestrate immune response, but their diversity in isocitrate dehydrogenase (IDH)-differential grade 4 gliomas remains largely unknown. This study aimed to dissect the transcriptional states, spatial distribution, and clinicopathological significance of distinct monocyte-derived TAM (Mo-TAM) and microglia-derived TAM (Mg-TAM) clusters across glioblastoma-IDH-wild type and astrocytoma-IDH-mutant-grade 4 (Astro-IDH-mut-G4). Single-cell RNA sequencing was performed on four cases of human glioblastoma and three cases of Astro-IDH-mut-G4. Cell clustering, single-cell regulatory network inference, and gene set enrichment analysis were performed to characterize the functional states of myeloid clusters. The spatial distribution of TAM subsets was determined in human glioma tissues using multiplex immunostaining. The prognostic value of different TAM-cluster specific gene sets was evaluated in the TCGA glioma cohort. Profiling and unbiased clustering of 24,227 myeloid cells from glioblastoma and Astro-IDH-mut-G4 identified nine myeloid cell clusters including monocytes, six Mo/Mg-TAM subsets, dendritic cells, and proliferative myeloid clusters. Different Mo/Mg-TAM clusters manifest functional and transcriptional diversity controlled by specific regulons. Multiplex immunostaining of subset-specific markers identified spatial enrichment of distinct TAM clusters at peri-vascular/necrotic areas in tumour parenchyma or at the tumour-brain interface. Glioblastoma harboured a substantially higher number of monocytes and Mo-TAM-inflammatory clusters, whereas Astro-IDH-mut-G4 had a higher proportion of TAM subsets mediating antigen presentation. Glioblastomas with a higher proportion of monocytes exhibited a mesenchymal signature, increased angiogenesis, and worse patient outcome. Our findings provide insight into myeloid cell diversity and its clinical relevance in IDH-differential grade 4 gliomas, and may serve as a resource for immunotherapy development. © 2022 The Pathological Society of Great Britain and Ireland.


Subject(s)
Astrocytoma , Brain Neoplasms , Glioblastoma , Glioma , Astrocytoma/genetics , Astrocytoma/pathology , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Glioblastoma/genetics , Glioblastoma/pathology , Glioma/genetics , Humans , Isocitrate Dehydrogenase/genetics , Mutation , Tumor-Associated Macrophages
15.
HGG Adv ; 3(3): 100120, 2022 Jul 14.
Article in English | MEDLINE | ID: mdl-35707062

ABSTRACT

Integrating data across heterogeneous research environments is a key challenge in multi-site, collaborative research projects. While it is important to allow for natural variation in data collection protocols across research sites, it is also important to achieve interoperability between datasets in order to reap the full benefits of collaborative work. However, there are few standards to guide the data coordination process from project conception to completion. In this paper, we describe the experiences of the Clinical Sequence Evidence-Generating Research (CSER) consortium Data Coordinating Center (DCC), which coordinated harmonized survey and genomic sequencing data from seven clinical research sites from 2020 to 2022. Using input from multiple consortium working groups and from CSER leadership, we first identify 14 lessons learned from CSER in the categories of communication, harmonization, informatics, compliance, and analytics. We then distill these lessons learned into 11 recommendations for future research consortia in the areas of planning, communication, informatics, and analytics. We recommend that planning and budgeting for data coordination activities occur as early as possible during consortium conceptualization and development to minimize downstream complications. We also find that clear, reciprocal, and continuous communication between consortium stakeholders and the DCC is equally important to maintaining a secure and centralized informatics ecosystem for pooling data. Finally, we discuss the importance of actively interrogating current approaches to data governance, particularly for research studies that straddle the research-clinical divide.

16.
Cell Rep ; 39(11): 110955, 2022 06 14.
Article in English | MEDLINE | ID: mdl-35679865

ABSTRACT

Direct myocardial and vascular injuries due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-driven inflammation is the leading cause of acute cardiac injury associated with coronavirus disease 2019 (COVID-19). However, in-depth knowledge of the injury characteristics of the heart affected by inflammation is lacking. In this study, using a quantitative spatial proteomics strategy that combines comparative anatomy, laser-capture microdissection, and histological examination, we establish a region-resolved proteome map of the myocardia and microvessels with obvious inflammatory cells from hearts of patients with COVID-19. A series of molecular dysfunctions of myocardia and microvessels is observed in different cardiac regions. The myocardia and microvessels of the left atrial are the most susceptible to virus infection and inflammatory storm, suggesting more attention should be paid to the lesion and treatment of these two parts. These results can guide in improving clinical treatments for cardiovascular diseases associated with COVID-19.


Subject(s)
COVID-19 , Heart Injuries , COVID-19/complications , Humans , Inflammation , Proteome , SARS-CoV-2
17.
Oncogene ; 41(30): 3791-3803, 2022 07.
Article in English | MEDLINE | ID: mdl-35764885

ABSTRACT

Glioblastoma is a lethal primary brain tumor with abundant immune-suppressive glioblastoma-associated macrophage (GAM) infiltration. Skewing immune suppressive GAMs towards an immune-activating phenotype represents a promising immunotherapeutic strategy against glioblastoma. Herein, we reported that genetic deletion of miRNA-processing enzyme Dicer in macrophages inhibited the growth of GL261 murine glioblastoma xenografts and prolonged survival of tumor-bearing mice. Single cell RNA sequencing (scRNA-seq) of the tumor-infiltrating immune cells revealed that Dicer deletion in macrophages reduced the proportion of cell-cycling GAM cluster and reprogramed the remaining GAMs towards a proinflammatory activation state (enhanced phagocytotic and IFN-producing signature). Dicer-deficient GAMs showed reduced level of cyclin-dependent kinases (CDK1 and CDK2) and increased expression of CDK inhibitor p27 Kip1, thus manifesting impaired proliferation. Dicer knockout enhanced phagocytotic activity of GAMs to eliminate GL261 tumor cells. Increased proinflammatory GAM clusters in macrophage Dicer-deficient mice actively interacted with tumor-infiltrating T cells and NK cells through TNF paracrine signaling to create a pro-inflammatory immune microenvironment for tumor cell elimination. Our work identifies the role of Dicer deletion in macrophages in generating an immune-activating microenvironment, which could be further developed as a potential immunotherapeutic strategy against glioblastoma.


Subject(s)
Brain Neoplasms , Glioblastoma , Animals , Brain Neoplasms/pathology , Cell Proliferation/genetics , Glioblastoma/metabolism , Humans , Killer Cells, Natural/metabolism , Macrophages/metabolism , Mice , T-Lymphocytes/metabolism , Tumor Microenvironment/genetics
18.
Insect Sci ; 29(6): 1583-1600, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35349758

ABSTRACT

The insulin and 20-hydroxyecdysone (20E) pathways coordinately regulate insect vitellogenesis and ovarian development. However, the detailed molecular mechanisms such as the genes mediating the cooperation of the interaction of these 2 pathways in regulating insect reproductive development are not well understood. In the present study, a small GTPase, Rab40C, was identified from the notorious agricultural pest Bactrocera dorsalis. In addition to the well-known RAB domain, it also has a unique SOCS-box domain, which is different from other Rab-GTPases. Moreover, we found that Rab40C was enriched in the ovaries of sexually mature females. RNA interference (RNAi)-mediated knockdown of BdRab40C resulted in a decrease in vitellogenin synthesis, underdeveloped ovaries, and low fertility. Furthermore, depletion of insulin receptor InR or the heterodimer receptor of 20E (EcR or USP) by RNAi significantly decreased the transcription of BdRab40C and resulted in lower fecundity. Further studies revealed that the transcription of BdRab40C could be upregulated by the injection of insulin or 20E. These results indicate that Rab40C participates in the insulin and 20E pathways to coordinately regulate reproduction in B. dorsalis. Our results not only provide new insights into the insulin- and 20E-stimulated regulatory pathways controlling female reproduction in insects but also contribute to the development of potential eco-friendly strategies for pest control.


Subject(s)
Ecdysterone , Monomeric GTP-Binding Proteins , Female , Animals , Ecdysterone/metabolism , Monomeric GTP-Binding Proteins/metabolism , Vitellogenins/metabolism , Fertility , Insulin , Insect Proteins/genetics , Insect Proteins/metabolism
19.
Front Oncol ; 12: 822756, 2022.
Article in English | MEDLINE | ID: mdl-35211414

ABSTRACT

BACKGROUND: Early identification of nasopharyngeal carcinoma (NPC) patients with high risk of failure to induction chemotherapy (IC) would facilitate prompt individualized treatment decisions and thus reduce toxicity and improve overall survival rate. This study aims to investigate the value of amide proton transfer (APT) imaging in predicting short-term response of NPC to IC and its potential correlation with well-established prognosis-related clinical characteristics. METHODS AND MATERIALS: A total of 80 pathologically confirmed NPC patients receiving pre-treatment APT imaging at 3T were retrospectively enrolled. Using asymmetry analysis, APT maps were calculated with mean (APTmean), 90th percentile (APT90) of APT signals in manually segmented NPC measured. APT values were compared among groups with different histopathological subtypes, clinical stages (namely, T, M, N, and overall stages), EBV-related indices (EBV-DNA), or responses to induction chemotherapy, using Mann-Whitney U test or Kruskal-Wallis H test. RESULTS: NPC showed significantly higher APTmean than normal nasopharyngeal tissues (1.81 ± 0.62% vs.1.32 ± 0.56%, P <0.001). APT signals showed no significant difference between undifferentiated and differentiated NPC subtypes groups, different EBV-DNA groups, or among T, N, M stages and overall clinical stages of II, III, IVA and IVB (all P >0.05). Similarly, baseline APT-related parameters did not differ significantly among different treatment response groups after IC, no matter if evaluated with RECIST criteria or sum volumetric regression ratio (SVRR) (all P >0.05). CONCLUSION: NPC showed significantly stronger APT effect than normal nasopharyngeal tissue, facilitating NPC lesion detection and early identification. However, stationary baseline APT values exhibited no significant correlation with histologic subtypes, clinical stages and EBV-related indices, and showed limited value to predict short-term treatment response to IC.

20.
Inorg Chem ; 61(4): 2265-2271, 2022 Jan 31.
Article in English | MEDLINE | ID: mdl-35044768

ABSTRACT

Novel 3D metal formate frameworks {[Ba4Cl][M3(HCO2)13]}n (M = Mn for 1, Co for 2, and Mg for 3) were successfully assembled via microwave-assisted synthesis. The complexes are rare coordination polymers crystallized at space group P4cc with the polar point group C4v. In the structure, the MII ions are bridged by two types of anti-anti formate in forming a 3D pcu framework, and additional formates coordinate to the unsaturated sites of the MII ions in the framework, giving an anionic M-formate net. Ba4Cl clusters take the cavities of the net as charge balance, in which the chloride ion deviates from the center of the barium ions. The asymmetric Ba4Cl structure is transmitted throughout the crystal resulting in polar structure, which is further confirmed by nonlinear optical and piezoelectric test. Nonlinear optical activity tests of 1 and 3 show SHG signals 0.32 and 0.28 times that of KDP, while 2 has a piezoelectric coefficient d33 of 6.8 pC/N along polar axis. Magnetic studies reveal antiferromagnetic coupling between MII ions in 1 and 2. Spin canting was found only in 2 with anisotropic CoII ions, and 2 is a canted antiferromagnetically with TN = 5 K. Further field-induced spin flop was also found in 2 with a critical field 0.9 T.

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