Knowledge, attitude, and willingness toward breast magnetic resonance imaging screening among women at high risk of breast cancer in Beijing, China.

BACKGROUND: Annual breast magnetic resonance imaging (MRI) is highly recommended to assist mammography for women at high risk of breast cancer (BC). This study explored the knowledge, attitude, and willingness toward breast MRI screening among women at high risk of BC. METHODS: This cross-sectional study enrolled women at high risk of BC between August 2022 and January 2023 in Beijing, China. A structural equation model (SEM) was used to analyze the relationships among knowledge, attitude, and willingness. RESULTS: A total of 596 questionnaires were collected, and 412 questionnaires (69.13%) were valid. The women's knowledge and attitude scores were 7.75 ± 2.79 (possible range: 0-12) and 48.53 ± 6.31 (possible range: 13-65). Among the women, 297 (72.09%) were willing to undergo regular breast MRI screening. The SEM showed that knowledge had direct effect on attitude [ß = 0.77, 95% CI: (0.57, 0.98), P < 0.001], the attitude had direct effect on willingness [ß = 0.02, 95% CI: (0.01, 0.02), P < 0.001], knowledge had an indirect effect on willingness through attitude [ß = 0.01, 95% CI: (0.01,0.02), P < 0.001], and the direct effect of knowledge on practice was not significant. CONCLUSIONS: The women at high risk of BC had insufficient knowledge and a relatively positive attitude toward breast MRI screening. Most of them were willing to undergo regular breast MRI screening. Advertising and public health education programs should be designed to improve their knowledge and attitude, therefore improving their willingness and practice.

Increased adrenal steroidogenesis and suppressed corticosteroid responsiveness in critical COVID-19.

BACKGROUND: The effect of coronavirus disease 2019 (COVID-19) on adrenal endocrine metabolism in critically ill patients remains unclear. This study aimed to investigate the alterations in adrenal steroidogenic activity, elucidate underlying mechanisms, provide in situ histopathological evidence, and examine the clinical implications. METHODS: The comparative analyses of the adrenal cortices from 24 patients with fatal COVID-19 and 20 matched controls were performed, excluding patients previously treated with glucocorticoids. SARS-CoV-2 and its receptors were identified and pathological alterations were examined. Furthermore, histological examinations, immunohistochemical staining and ultrastructural analyses were performed to assess corticosteroid biosynthesis. The zona glomerulosa (ZG) and zona fasciculata (ZF) were then dissected for proteomic analyses. The biological processes that affected steroidogenesis were analyzed by integrating histological, proteomic, and clinical data. Finally, the immunoreactivity and responsive genes of mineralocorticoid and glucocorticoid receptors in essential tissues were quantitatively measured to evaluate corticosteroid responsiveness. FINDINGS: The demographic characteristics of COVID-19 patients were comparable with those of controls. SARS-CoV-2-like particles were identified in the adrenocortical cells of three patients; however, these particles did not affect cellular morphology or steroid synthesis compared with SARS-CoV-2-negative specimens. Although the adrenals exhibited focal necrosis, vacuolization, microthrombi, and inflammation, widespread degeneration was not evident. Notably, corticosteroid biosynthesis was significantly enhanced in both the ZG and ZF of COVID-19 patients. The increase in the inflammatory response and cellular differentiation in the adrenal cortices of patients with critical COVID-19 was positively correlated with heightened steroidogenic activity. Additionally, the appearance of more dual-ZG/ZF identity cells in COVID-19 adrenals was in accordance with the increased steroidogenic function. However, activated mineralocorticoid and glucocorticoid receptors and their responsive genes in vital tissues were markedly reduced in patients with critical COVID-19. INTERPRETATION: Critical COVID-19 was characterized by potentiated adrenal steroidogenesis, associated with increased inflammation, enhanced differentiation and elevated dual-ZG/ZF identity cells, alongside suppressed corticosteroid responsiveness. These alterations implied the reduced effectiveness of conventional corticosteroid therapy and underscored the need for evaluation of the adrenal axis and corticosteroid sensitivity.

Identification of hypoxic macrophages in glioblastoma with therapeutic potential for vasculature normalization.

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.

Industrial fluoride emissions and their spatial characteristics in the Nansi Lake Basin, Eastern China.

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.

Disorganized adrenocortical zonational structure in COVID-19 patients: Implications of critical illness duration.

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.

Can humidifier reservoir bacteria colonize the circuit during mechanical ventilation: An in vitro study.

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.

Effect of Hollow 304 Stainless Steel Fiber on Corrosion Resistance and Mechanical Properties of Ultra-High Performance Concrete (UHPC).

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.

Proteasome ß3 subunit (PSMB3) controls female reproduction by promoting ecdysteroidogenesis during sexual maturation in Bactrocera dorsalis.

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.

Comparison of the Mechanical Properties and Crack Expansion Mechanism of Different Content and Shapes of Brass-Coated Steel Fiber-Reinforced Ultra-High-Performance Concrete.

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.

Single-crystalline van der Waals layered dielectric with high dielectric constant.

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.

COVID-19-associated monocytic encephalitis (CAME): histological and proteomic evidence from autopsy.

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.

RNA sequencing identifies an ovary-enriched microRNA, miR-311-3p, involved in ovarian development and fecundity by targeting Endophilin B1 in Bactrocera dorsalis.

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.

Series of Benzoquinone-Bridged Dicobalt(II) Single-Molecule Magnets.

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.

A map of the spatial distribution and tumour-associated macrophage states in glioblastoma and grade 4 IDH-mutant astrocytoma.

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.

Dicer deficiency impairs proliferation but potentiates anti-tumoral effect of macrophages in glioblastoma.

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.

Lessons learned and recommendations for data coordination in collaborative research: The CSER consortium experience.

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.

Spatial region-resolved proteome map reveals mechanism of COVID-19-associated heart injury.

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.