The genomic origins of the Bronze Age Tarim Basin mummies.

The identity of the earliest inhabitants of Xinjiang, in the heart of Inner Asia, and the languages that they spoke have long been debated and remain contentious1. Here we present genomic data from 5 individuals dating to around 3000-2800 BC from the Dzungarian Basin and 13 individuals dating to around 2100-1700 BC from the Tarim Basin, representing the earliest yet discovered human remains from North and South Xinjiang, respectively. We find that the Early Bronze Age Dzungarian individuals exhibit a predominantly Afanasievo ancestry with an additional local contribution, and the Early-Middle Bronze Age Tarim individuals contain only a local ancestry. The Tarim individuals from the site of Xiaohe further exhibit strong evidence of milk proteins in their dental calculus, indicating a reliance on dairy pastoralism at the site since its founding. Our results do not support previous hypotheses for the origin of the Tarim mummies, who were argued to be Proto-Tocharian-speaking pastoralists descended from the Afanasievo1,2 or to have originated among the Bactria-Margiana Archaeological Complex3 or Inner Asian Mountain Corridor cultures4. Instead, although Tocharian may have been plausibly introduced to the Dzungarian Basin by Afanasievo migrants during the Early Bronze Age, we find that the earliest Tarim Basin cultures appear to have arisen from a genetically isolated local population that adopted neighbouring pastoralist and agriculturalist practices, which allowed them to settle and thrive along the shifting riverine oases of the Taklamakan Desert.

Pentraxin 3 promotes oxLDL uptake and inhibits cholesterol efflux from macrophage-derived foam cells.

BACKGROUND: The objective of this study was to determine the effects of pentraxin3 (PTX3) on human oxidized low density lipoprotein (oxLDL) uptake and cholesterol efflux from human macrophage foam cells, which may play a critical role in atherogenesis. METHODS: The effects of PTX3 on oxLDL uptake and cholesterol efflux were determined after transfection of human THP-1 macrophages with pSG5hPTX3 or PTX3siRNA plasmids. To evaluate the role of specific signaling pathways, human THP-1 cells were pre-treated with inhibitors of the extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), phosphatidylinositide 3-kinases (PI3-K), and p38 mitogen-activated protein kinase (MAPK) pathways (PD98059, LY294002, and SB203580, respectively), and then exposed to oxLDL for the uptake assay or oxLDL and [(3)H]-cholesterol and apolipoprotein A-I (apoA-I) for the cholesterol efflux assay. RESULTS: PTX3 overexpression not only promoted oxLDL uptake but also significantly reduced cholesterol efflux to apoA-I; it also significantly decreased the expression of peroxisome proliferator-activated receptor-γ (PPARγ), liver X receptor alpha (LXRα) and ATP-binding membrane cassette transporter A-1 (ABCA1), which was increased with PTX3 silencing. Furthermore, PTX3 significantly increased p-ERK1/2 levels in THP-1-derived foam cells, and inhibition of ERK1/2 by PD98059 significantly reduced the oxLDL uptake and promoted the cholesterol efflux induced by PTX3 overexpression. CONCLUSION: Here, we demonstrate that PTX3 affects lipid accumulation in human macrophages, increasing oxLDL uptake and inhibiting cholesterol efflux. That is the underlying possible mechanisms of PTX3 contribution to the progression of atherosclerosis.

Correlation of Forkhead Box c2 with subtypes and invasive ability of invasive breast cancer.

Forkhead Box c2 (FOXC2) is a member of forkhead/winged-helix family of transcription factors. The relationship between FOXC2 and invasive breast cancers, including basal-like breast cancer (BLBC, a subtype of breast cancer), remains to be elucidated. In this study, immunohistochemistry was used to detect the expression of FOXC2 in samples from 103 cases of invasive breast cancers and 15 cases of normal mammary glands. The relationship between FOXC2 and clinical parameters of invasive breast cancers such as patient's age, tumor size, lymph node metastasis, tumor grade, the expression of ER, PR, HER-2 and p53, and Ki-67 labeling index (LI) was evaluated. The expression of FOXC2 was detected in parent MCF7 cells, MCF cells transfected with FOXC2 expression vectors and MDA-MB-435 cells by immunohistochemistry and Western blotting. Transwell assay was used to determine the invasive ability of these cells. The results showed that FOXC2 was strongly expressed in basal epithelial cells in normal mammary glands and weakly expressed or even not expressed in glandular epithelial cells. The majority of invasive breast cancers (71.8%, 74/103) had negative or weak expression of FOXC2. However, FOXC2 was strongly expressed in 60.7% of BLBCs. Moreover, FOXC2 was related with tumor grade, p53 expression, ki-67 LI and lymph nodes metastasis. It was expressed in FOXC2-transfected MCF cells and MDA-MB-435 cells but not in parent MCF cells. Transwell assay revealed that MCF cells transfected with FOXC2 expression vectors were more aggressive than the parent MCF cells, suggesting a positive correlation between FOXC2 and the invasion of breast cancer. It was concluded that there is a significant association between FOXC2 and the metastasis of invasive breast cancer. FOXC2 may be used as a new marker for the diagnosis and prognosis prediction of different subtypes of invasive breast cancers.

Linear chromosome-generating system of Agrobacterium tumefaciens C58: protelomerase generates and protects hairpin ends.

Agrobacterium tumefaciens C58, the pathogenic bacteria that causes crown gall disease in plants, harbors one circular and one linear chromosome and two circular plasmids. The telomeres of its unusual linear chromosome are covalently closed hairpins. The circular and linear chromosomes co-segregate and are stably maintained in the organism. We have determined the sequence of the two ends of the linear chromosome thus completing the previously published genome sequence of A. tumefaciens C58. We found that the telomeres carry nearly identical 25-bp sequences at the hairpin ends that are related by dyad symmetry. We further showed that its Atu2523 gene encodes a protelomerase (resolvase) and that the purified enzyme can generate the linear chromosomal closed hairpin ends in a sequence-specific manner. Agrobacterium protelomerase, whose presence is apparently limited to biovar 1 strains, acts via a cleavage-and-religation mechanism by making a pair of transient staggered nicks invariably at 6-bp spacing as the reaction intermediate. The enzyme can be significantly shortened at both the N and C termini and still maintain its enzymatic activity. Although the full-length enzyme can uniquely bind to its product telomeres, the N-terminal truncations cannot. The target site can also be shortened from the native 50-bp inverted repeat to 26 bp; thus, the Agrobacterium hairpin-generating system represents the most compact activity of all hairpin linear chromosome- and plasmid-generating systems to date. The biochemical analyses of the protelomerase reactions further revealed that the tip of the hairpin telomere may be unusually polymorphically capable of accommodating any nucleotide.

Differential diagnosis of lymphoma with 18F-FDG PET/CT in patients with fever of unknown origin accompanied by lymphadenopathy.

PURPOSE: To investigate the value of 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the differential diagnosis of lymphoma in patients with fever of unknown origin (FUO) accompanied by lymphadenopathy and to develop a simple scoring system to distinguish lymphoma from other etiologies. METHODS: A prospective study was conducted on patients with classic FUO accompanied by lymphadenopathy. After standard diagnostic procedures, including PET/CT scan and lymph-node biopsy, 163 patients were enrolled and divided into lymphoma and benign groups according to the etiology. The diagnostic utility of PET/CT imaging was evaluated, and beneficial parameters that could improve diagnostic effectiveness were identified. RESULTS: The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PET/CT in diagnosing lymphoma in patients with FUO accompanied by lymphadenopathy were 81.0, 47.6, 59.3, and 72.7%, respectively. The lymphoma prediction model combining high SUVmax of the "hottest" lesion, high SUVmax of the retroperitoneal lymph nodes, old age, low platelet count, and low ESR had an area under the curve of 0.93 (0.89-0.97), a sensitivity of 84.8%, a specificity of 92.9%, a PPV of 91.8%, and an NPV of 86.7%. There was a lower probability of lymphoma for patients with a score < 4 points. CONCLUSIONS: PET/CT scans show moderate sensitivity and low specificity in diagnosing lymphoma in patients with FUO accompanied by lymphadenopathy. The scoring system based on PET/CT and clinical parameters performs well in differentiating lymphoma and benign causes and can be used as a reliable noninvasive tool. REGISTRATION NUMBER: This study on FUO was registered on http://www. CLINICALTRIALS: gov on January 14, 2014, with registration number NCT02035670.

Earliest systematic coal exploitation for fuel extended to ~3600 B.P.

Coal has long fueled human civilizations. The history of systematic coal fuel exploitation has been traced back to the late third millennium before present (post-2500 B.P.). Although sporadic combustion of coal for fuel was reported in some prehistoric archaeological sites, evidence for the systematic exploitation of coal for fuel before 2500 B.P. remains lacking. Here, we report comprehensive understanding for the earliest systematic exploitation of coal for fuel at the Jirentaigoukou site in Xinjiang, northwestern China, at ~3600 B.P. The main body of the site witnessed systematic exploitation of bituminous coals, illustrating a complete chaîne opératoire with selective mining, planned storage, and extensive combustion. Our results transform the knowledge of energy history by extending the upper limit of the systematic exploitation of coal for fuel by approximately a millennium, and provide a precedent of energy transition under intense conflict between social demand and environmental deterioration.

TGF-ß1-induced LPP expression dependant on Rho kinase during differentiation and migration of bone marrow-derived smooth muscle progenitor cells.

Lipoma preferred partner (LPP) has been identified as a protein which is highly selective for smooth muscle progenitor cells (SMPCs) and regulates differentiation and migration of SMPCs, but mechanisms of LPP expression are not elucidated clearly. The aim of the present study was to discuss the mechanisms by which LPP expression is regulated in the differentiation and migration of SMPCs induced by TGF-ß1. It was found that TGF-ß1 could significantly increase the expression of LPP, smooth muscle α-actin, smooth muscle myosin heavy chain (SM-MHC), and smoothelin in SMPCs. Moreover, inactivation of Rho kinase (ROK) with ROK inhibitors significantly inhibited LPP mRNA expression in TGF-ß1-treated SMPCs and mouse aortic smooth muscle cells (MAoSMCs). At the same time, LPP silencing with short interfering RNA significantly decreased SMPCs migration. In conclusion, LPP appears to be a ROK-dependant SMPCs differentiation marker that plays a role in regulating SMPCs migration.

Diagnostic models for fever of unknown origin based on 18F-FDG PET/CT: a prospective study in China.

BACKGROUND: This study aims to analyze the 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) characteristics of different causes of fever of unknown origin (FUO) and identify independent predictors to develop a suitable diagnostic model for distinguishing between these causes. A total of 524 patients with classical FUO who underwent standard diagnostic procedures and PET/CT were prospectively studied. The diagnostic performance of PET/CT imaging was analyzed, and relevant clinical parameters that could improve diagnostic efficacy were identified. The model was established using the data of 369 patients and the other 155 patients comprised the validation cohort for verifying the diagnostic performance of the model. RESULTS: The metabolic characteristics of the "hottest" lesion, the spleen, bone marrow, and lymph nodes varied for various causes. PET/CT combined with clinical parameters achieved better discrimination in the differential diagnosis of FUO. The etiological diagnostic models included the following factors: multisite metabolic characteristics, blood cell counts, inflammatory indicators (erythrocyte sedimentation rate, C-reactive protein, serum ferritin, and lactate dehydrogenase), immunological indicators (interferon gamma release assay, antinuclear antibody, and anti-neutrophil cytoplasm antibody), specific signs (weight loss, rash, and splenomegaly), and age. In the testing cohort, the AUCs of the infection prediction model, the malignancy diagnostic model, and the noninfectious inflammatory disease prediction model were 0.89 (95% CI 0.86-0.92), 0.94 (95% CI 0.92-0.97), and 0.95 (95% CI 0.93-0.97), respectively. The corresponding AUCs for the validation cohort were 0.88 (95% CI 0.82-0.93), 0.93 (95% CI 0.89-0.98), and 0.95 (95% CI 0.92-0.99), respectively. CONCLUSIONS: 18F-FDG PET/CT has a certain level of sensitivity and accuracy in diagnosing FUO, which can be further improved by combining it with clinical parameters. Diagnostic models based on PET/CT show excellent performance and can be used as reliable tools to discriminate the cause of FUO. Trial registration This study (a two-step method apparently improved the physicians' level of diagnosis decision-making for adult patients with FUO) was registered on the website http://www.clinical-trials.gov on January 14, 2014, with registration number NCT02035670.

Bronze and Iron Age population movements underlie Xinjiang population history.

The Xinjiang region in northwest China is a historically important geographical passage between East and West Eurasia. By sequencing 201 ancient genomes from 39 archaeological sites, we clarify the complex demographic history of this region. Bronze Age Xinjiang populations are characterized by four major ancestries related to Early Bronze Age cultures from the central and eastern Steppe, Central Asian, and Tarim Basin regions. Admixtures between Middle and Late Bronze Age Steppe cultures continued during the Late Bronze and Iron Ages, along with an inflow of East and Central Asian ancestry. Historical era populations show similar admixed and diverse ancestries as those of present-day Xinjiang populations. These results document the influence that East and West Eurasian populations have had over time in the different regions of Xinjiang.

Foxc2 overexpression enhances benefit of endothelial progenitor cells for inhibiting neointimal formation by promoting CXCR4-dependent homing.

OBJECTIVE: Endothelial progenitor cells (EPCs) are capable of enhancing re-endothelialization and attenuating neointimal formation. However, inefficient homing limits the therapeutic efficacy of EPCs transplantation. CXCR4 plays a critical role in regulating EPCs homing. Here, we studied the effect of Foxc2 overexpression on CXCR4 expression and the homing capacity of EPCs as well as the EPCs-mediated therapeutic benefit after artery injury. METHODS: Bone marrow-derived EPCs were transfected with Foxc2 expression vector (Foxc2-EPCs) or empty control vector (Ctrl-EPCs) and examined 48 hours later. CXCR4 expression of EPCs was detected by flow cytometry and quantitative reverse transcriptase-polymerase chain reaction. The migration of EPCs toward SDF-1α was evaluated in a transwell migration assay, and the adhesion to fibronectin was determined using a static adhesion assay. For in vivo studies, EPCs were injected intravenously into the mice subjected to carotid injury. At 3 days after green fluorescent protein (GFP)/EPCs delivery, the recruited cells to the injury sites were detected by fluorescent microscopy. Re-endothelialization and neointimal formation were, respectively, assessed by Evans blue dye at 7 days and by the morphometric analysis for neointima and media area ratio (N/M) at 28 days after EPCs transfusion. RESULTS: Foxc2 overexpression significantly increased the surface expression of CXCR4 on EPCs (about 1.9-fold of Ctrl-EPCs, P < .05). Foxc2-EPCs showed an increased migration toward SDF-1α (P < .05); Foxc2 overexpression increased also the adhesion capacity of EPCs (P < .05). In vivo, the number of recruited GFP cells was significantly higher in the mice transfused with Foxc2-GFP/EPCs compared with Ctrl-GFP/EPCs (about 2-fold of Ctrl-GFP/EPCs). The degree of re-endothelialization was higher in mice transfused with Foxc2-EPCs compared with Ctrl-EPCs (90.3% ± 1.6% vs 57.2% ± 1.3%; P < .05). Foxc2-EPCs delivery resulted in a greater inhibition of neointimal hyperplasia than Ctrl-EPCs administration (N/M: 0.38 ± 0.03 vs 0.67 ± 0.05, P < .05). Preincubation with CXCR4-Ab, AMD3100, or LY294002 significantly attenuated the enhanced in vitro and in vivo effects of Foxc2-EPCs. CONCLUSIONS: Our findings indicate that Foxc2 overexpression increases CXCR4 expression of EPCs and efficiently enhances the homing potential of EPCs, thereby improving EPCs-mediated therapeutic benefit after endothelial injury. Foxc2 may be a novel molecular target for improving the therapeutic efficacy of EPCs transplantation.

Macrophages overexpressing VEGF, transdifferentiate into endothelial-like cells in vitro and in vivo.

Vascular endothelial growth factor (VEGF) induces endothelial cell differentiation. To investigate the role of VEGF overexpression in regulating the phenotype of macrophages, we transfected mouse macrophages with human VEGF(165) and examined the expression of the genes and proteins for various endothelial markers. Macrophages overexpressing VEGF significantly expressed fetal liver kinase 1 (FLK-1), vascular endothelial cadherin (VE-cadherin), CD31, Von Willebrand factor (vWF), endothelial nitric oxide synthase (eNOS) and CD105. Furthermore, in a model of myocardial infarction (MI), macrophages overexpressing VEGF incorporated into blood vessels. Thus macrophages overexpressing VEGF were transdifferentiate into endothelial-like cells (ELCs) both in vitro and in vivo.

Infection-associated Hemophagocytic Syndrome in Critically Ill Patients with COVID-19.

Infection-associated hemophagocytic syndrome (IAHS), a severe complication of various infections, is potentially fatal. This study aims to determine whether IAHS occurs in critically ill patients with coronavirus disease 2019 (COVID-19). We conducted a retrospective observational study on 268 critically ill patients with COVID-19 between February 1st, 2020 and February 26th, 2020. Demographics, clinical characteristics, laboratory results, information on concurrent treatments and outcomes were collected. A diagnosis of secondary hemophagocytic lymphohistiocytosis (sHLH) was made when the patients had an HScore greater than 169. Histopathological examinations were performed to confirm the presence of hemophagocytosis. Of 268 critically ill patients with confirmed SARS-CoV-2 infection, 17 (6.3%) patients had an HScore greater than 169. All the 17 patients with sHLH died. The interval from the onset of symptom of COVID-19 to the time of a diagnosis of sHLH made was 19 days and the interval from the diagnosis of sHLH to death was 4 days. Ten (59%) patients were infected with only SARS-CoV-2. Hemophagocytosis in the spleen and the liver, as well as lymphocyte infiltration in the liver on histopathological examinations, was found in 3 sHLH autopsy patients. Mortality in sHLH patients with COVID-19 is high. And SARS-CoV-2 is a potential trigger for sHLH. Prompt recognition of IAHS in critically ill patients with COVID-19 could be beneficial for improving clinical outcomes.

Ancient Xinjiang mitogenomes reveal intense admixture with high genetic diversity.

Xinjiang is a key region in northwestern China, connecting East and West Eurasian populations and cultures for thousands of years. To understand the genetic history of Xinjiang, we sequenced 237 complete ancient human mitochondrial genomes from the Bronze Age through Historical Era (41 archaeological sites). Overall, the Bronze Age Xinjiang populations show high diversity and regional genetic affinities with Steppe and northeastern Asian populations along with a deep ancient Siberian connection for the Tarim Basin Xiaohe individuals. In the Iron Age, in general, Steppe-related and northeastern Asian admixture intensified, with North and East Xinjiang populations showing more affinity with northeastern Asians and South Xinjiang populations showing more affinity with Central Asians. The genetic structure observed in the Historical Era of Xinjiang is similar to that in the Iron Age, demonstrating genetic continuity since the Iron Age with some additional genetic admixture with populations surrounding the Xinjiang region.

Oxidized low density lipoprotein-induced transdifferentiation of bone marrow-derived smooth muscle-like cells into foam-like cells in vitro.

Oxidized-low density lipoprotein (ox-LDL) is believed to contribute to atherogenesis in part by being taken up into smooth muscle cells (SMC) via specific scavenger receptors; however, it is not clear whether ox-LDL receptor(s) are expressed in bone marrow-derived smooth muscle-like cells (SMLCs) and whether they play a role in the process of SMLC development. Therefore, we examined the ox-LDL-induced transdifferentiation of SMLCs that is mediated by lectin-like ox-LDL receptor-1 (LOX-1). Smooth muscle progenitor cells (SMPCs) from bone marrow mesenchymal stem cells (BMSCs) were isolated using a tissue-specific promoter sorting method with a mouse SM22_ promoter (_480 bp)/green fluorescent protein recombinant plasmid. The SMPCs were myocardin+CD105+KDR+CD45(-)CD34(-), but did not express SMC-specific markers alpha-smooth muscle actin (alpha-SMA), SM22, smooth muscle myosin heavy chain (SM-MHC) and smoothelin. After long-term culture with platelet-derived growth factor-BB (PDGF-BB), SMPCs expressed alpha-SMA, SM22 and SM-MHC and differentiated into SMLCs. When SMLCs were incubated with different concentrations of ox-LDL, LOX-1 expression on the surface of SMLCs gradually increased with the increase of the ox-LDL concentration, but myocardin and SMC-specific marker genes decreased, accordingly. Furthermore, receptor-mediated endocytosis was enhanced and lipid droplets accumulated in the cytoplasm of SMLCs. A subpopulation of myocardin+CD105+KDR+CD45(-)CD34(-) SMPCs exist in BMSCs that can differentiate into SMLCs under induction with PDGF-BB. Moreover, LOX-1 contributes to the ox-LDL-induced transdifferentiation of bone marrow-derived SMLCs into foam-like cells.

CXCR4 positive bone mesenchymal stem cells migrate to human endothelial cell stimulated by ox-LDL via SDF-1alpha/CXCR4 signaling axis.

BACKGROUND: Bone mesenchymal stem cells (BMSCs) are attractive candidates for cell based therapies to cardiovascular disease such as infarction and atherosclerosis; however, the mechanisms responsible for stem cell chemotaxis and homing remain unknown. Chemokine stromal cell-derived factor 1 (SDF-1alpha) is involved in the process of atherogenesis. This study was aimed at investigating whether the SDF-1alpha of human umbilical vein endothelial cells (HUVECs) plays a role in migration of BM-derived CXCR4(+)(receptor for SDF-1alpha) stem cells. METHODS: HUVECs were cultured from human umbilical cords and was treated with ox-LDL. The mRNA and protein expression of SDF-1alpha was detected in HUVECs. CXCR4(+)BMSCs from bone marrow were isolated and were tested by migration and adhesion assays. RESULTS: It was found that ox-LDL induced HUVECs to increase the mRNA and protein expression of SDF-1alpha. Ox-LDL increased the migratory and adhesion response of CXCR4(+)BMSCs. When the neutralizing SDF-1alpha antibody abrogated the secreted SDF-1alpha, the migration and adhesion response of CXCR4(+)BMSCs markedly decreased. CONCLUSIONS: Our data indicated that the endothelial cells (ECs) stimulated by ox-LDL could increase the BMSCs migratory response via SDF-1alpha/CXCR4 signaling axis. These findings provide a new paradigm for biological effects of ox-LDL and have implications for novel stem cell therapeutic strategies for atherosclerosis.

SDF-1/CXCR4-mediated migration of transplanted bone marrow stromal cells toward areas of heart myocardial infarction through activation of PI3K/Akt.

Stromal cell-derived factor-1 (SDF-1) and its receptor, CXCR4, are crucial for homing and migration of multiple stem cell types. Their potential role in mediating bone marrow-derived mesenchymal stem cell (BMSC) migration in areas of myocardial infarction (MI) has not been demonstrated. In this study, rat heart MI was created by left coronary artery ligation, and green fluorescent protein-labeled BMSCs were directly infused into the left ventricular cavity. Reverse transcriptase-polymerase chain reaction and Western blot analysis showed that SDF-1 was predominantly localized in the MI lesion, and its levels peaked by 3 to 7 days and were maintained at least 14 days. Additionally, this was matched with increased accumulation of BMSCs and an improvement in cardiac function. Furthermore, this effect was blocked by the phosphoinositide 3-kinase inhibitor, LY294002. In vitro experiments showed that CXCR4 expression by BMSCs was elevated during hypoxia and SDF-1 induced a concentration-dependent migration of BMSCs. This migration was CXCR4-dependent as confirmed by its total inhibition by AMD3100, a CXCR4-specific antagonist. Migration was also almost completely blocked by LY294002. Analysis showed that phosphorylated Akt was highly increased in SDF-1-treated BMSCs. Together these results demonstrated that SDF-1/CXCR4 may mediate the migration of BMSCs toward heart MI through activation of PI3K/Akt.

Synthesis and characterization of atherosclerotic target anti-CD47 functionalized by nano-polyelectrolyte complexes between chitosan and hyaluronic acid and in vivo and in vitro targeting experiments.

BACKGROUND: In several different atherosclerotic model mice, blocking CD47 with anti-CD47 antibody significantly reduced accumulation of arterial plaque. OBJECTIVES: We described the development of multifunctional positively charged polyelectrolyte complex (PEC) nanoparticles, designed to be stable at physiological salt concentrations and pH for effective targeted delivery in atherosclerosis. MATERIAL AND METHODS: These nanoparticles were obtained by charge neutralization using chitosan (CS) as the polycation and hyaluronic acid (HA) as the polyanion. An atherosclerotic-model antibody, the anti-CD47 antibody, was sorbed onto the particle surfaces in water and phosphate-buffered saline (PBS) for 4 h. The synthetic nanocarriers were exposed to vascular endothelial cells (VECs) in vitro to study their targeted adsorption to the cells, and the targeted distribution of nanocarriers was evaluated in vivo. RESULTS: We showed that the complexation process and the physicochemical properties of the resulting colloids were impacted by external parameters such as the charge mixing ratio and the polymer concentrations. Nonstoichiometric colloidal PECs were obtained in water or PBS (pH 7.4) and remained stable for 1 month. The morphology was studied with scanning electron microscopy (SEM). The average size of the CS-HA/CD47 nanoparticles was 375-620 nm, with a positive zeta potential. The CD47-targeted nanocarriers could be efficiently adsorbed to the surface of VECs in vitro, and their targeted distribution was evaluated in vivo. CONCLUSIONS: Targeted nanocarriers can be effectively adsorbed to the surface of a VEC line and atheromatous plaque in vitro and in vivo. These results demonstrated that CS-HA/CD47 can be an effective carrier for targeted drug delivery in atherosclerosis.

Correction to: Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China.

Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China.

Pathological changes in the lungs and lymphatic organs of 12 COVID-19 autopsy cases.

Systematic autopsy and comprehensive pathological analyses of COVID-19 decedents should provide insights into the disease characteristics and facilitate the development of novel therapeutics. In this study, we report the autopsy findings from the lungs and lymphatic organs of 12 COVID-19 decedents-findings that evaluated histopathological changes, immune cell signature and inflammatory factor expression in the lungs, spleen and lymph nodes. Here we show that the major pulmonary alterations included diffuse alveolar damage, interstitial fibrosis and exudative inflammation featured with extensive serous and fibrin exudates, macrophage infiltration and abundant production of inflammatory factors (IL-6, IP-10, TNFα and IL-1ß). The spleen and hilar lymph nodes contained lesions with tissue structure disruption and immune cell dysregulation, including lymphopenia and macrophage accumulation. These findings provide pathological evidence that links injuries of the lungs and lymphatic organs with the fatal systematic respiratory and immune malfunction in critically ill COVID-19 patients.