HLA-DRB5 promotes immune thrombocytopenia via activating CD8+ T cells.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by a low platelet (PLT) count and a high risk of bleeding, the clinical treatment for which still needs to be upgraded. Based on the critical role of human leukocyte antigen class II heterodimer ß5 (HLA-DRB5) in immune system, we herein investigated its effect on ITP. ITP murine models were established by the injection of guinea pig anti-mouse platelet serum (GP-APS), and the PLT of mouse peripheral blood was counted during the modeling. Quantitative real-time reverse transcription polymerase chain reaction, western blot and immunofluorescence assay was performed to quantify expressions of HLA-DRB5, major histocompatibility complex II (MHC-II) and co-stimulatory molecules (CD80, CD86). Flow cytometry was conducted to analyze the percentage of CD8+ T cells. As a result, the PLT count was decreased in mouse peripheral blood. Expressions of HLA-DRB5, MHC-II and co-stimulatory molecules, as well as the percentage of CD8+ T cells were elevated in peripheral blood of ITP mice. HLA-DRB5 knockdown mitigated ITP by increasing peripheral PLT level, downregulating expressions of MHC-II and co-stimulatory molecules and inactivating CD8+ T cells. Collectively, the downregulation of HLA-DRB5 restores the peripheral PLT count in ITP mice by reducing MHC-II-mediated antigen presentation of macrophages to inhibit the activation of CD8+ T cells.

HLA-DRB5 Overexpression Promotes Platelet Reduction in Immune Thrombocytopenia Mice Model by Facilitating MHC-II-Mediated Antigen Presentation.

INTRODUCTION: Major histocompatibility complex II (MHC-II)-mediated antigen presentation contributes to the pathogenesis of immune thrombocytopenia (ITP). Human leukocyte antigen (HLA)-DRB5 is an MHC-II molecule and this study aims to investigate its role and mechanisms in ITP development. METHODS: Guinea pig anti-mouse platelet (PLT) serum-induced ITP mice received tail vein injection of HLA-DRB5 overexpressing adenoviral vector/immune receptor expressed on myeloid cells-1 (IREM-1) monoclonal antibody (mAb). PLT count changes in mice blood were assessed by a hematology analyzer. MHC-II/CD80/CD86 expression in mice blood was measured by quantitative real-time-PCR and immunofluorescence assay. CD8+ T-cell proportion in mice blood was detected by flow cytometry. RESULTS: HLA-DRB5 overexpression exacerbated PLT reduction since the 5th day of the establishment of ITP mice model and enhanced MHC-II/CD80/CD86 expression upregulation as well as CD8+ T-cell ratio elevation in the blood of ITP mice, while its effects were reversed by IREM-1 mAb. CONCLUSION: HLA-DRB5 overexpression upregulates MHC-II-mediated antigen presentation to CD8+ T cells, thus lowering PLT count in the ITP mice model.

Investigation of the mixed origins of the MGC-803 cell line reveals that it is a hybrid cell line derived from HeLa.

Human cancer cell lines have an essential role in cancer research, but only authentic cell lines should be used as biological models. Authentication testing using short tandem repeat (STR) loci has shown that MGC-803 cells, which were reported to come from gastric adenocarcinoma, are similar to HeLa. In this study, we confirmed that the MGC-803 cell line contains genetic material from HeLa, including genetic sequence from human papilloma virus 18 (HPV18). Additional alleles were present on STR analysis that remained stable after extensive passaging and generation of mono-clones. This behavior is consistent with a hybrid cell line arising from cell-cell fusion. Further genetic analysis revealed that MGC-803 originated from donors with different genetic ancestries, one African (HeLa) and the other Asian. Transcriptomic analysis demonstrated that MGC-803 closely resembles HeLa and another nasopharyngeal-HeLa hybrid cell line CNE-2. Based on these findings, we conclude that MGC-803 is a hybrid cell line derived from HeLa and other cells, the latter derived from a different patient with Asian genetic ancestry.

Optimizing milling and sintering parameters for mild synthesis of highly conductive Li5.5PS4.5Cl1.5 solid electrolyte.

The Li5.5PS4.5Cl1.5 electrolyte gains significant attention due to its ultrahigh ionic conductivity and cost-effectiveness in halogen-rich lithium argyrodite solid electrolytes. The conventional synthetic method for obtaining the electrolyte involves mechanical milling followed by post-annealing. However, these synthesis methods typically involve high milling speeds, elevated temperatures, and prolonged durations, resulting in both high energy consumption and potential damage to the electrolyte. In this study, we successfully obtained Li5.5PS4.5Cl1.5 with a high conductivity of 7.92 mS cm-1 using a milling speed of 400 rpm and annealing at 400 °C for 5 hours. When incorporated into a Li4Ti5O12-based all-solid-state battery, this electrolyte demonstrates stable cycling performance across varying temperatures.

SEMA3B-AS1 suppresses colorectal carcinoma progression by inhibiting Semaphorin 3B-dependent VEGF signaling pathway activation.

Mounting evidence has demonstrated the considerable regulatory effects of long noncoding RNAs (lncRNAs) in the tumorigenesis and progression of various carcinomas. LncRNA Semaphorin 3B (SEMA3B) antisense RNA 1 (SEMA3B-AS1) has been found to be dysregulated in a few carcinomas recently. However, its potential function and mechanism in colorectal carcinoma (CRC) have not yet been examined. Here we show that SEMA3B-AS1 acts as a crucial regulator of CRC progression. We found that SEMA3B-AS1 expression was downregulated in CRC cell lines and tissues. Downregulation of SEMA3B-AS1 was significantly associated with poor survival in CRC patients. Overexpression of SEMA3B-AS1 reduced the cell growth and metastasis of CRC in vivo and in vitro. In addition, SEMA3B-AS1 promoted the expression of its sense-cognate gene SEMA3B, a member of the Semaphorin family (SEMAs), by recruiting EP300 to induce H3K9 acetylation at the SEMA3B promoter. Furthermore, we proved that SEMA3B-AS1 suppressed CRC angiogenesis by affecting the vascular endothelial growth factor signaling pathway activation which was regulated by the SEMA3B-NRP1 axis. Our work unravels a novel mechanism of SEMA3B-AS1 in the inhibition of CRC malignant progression and highlights its probability as a new promising diagnostic marker and therapeutic target for CRC interventions.

Full Endoscopy Combined with Allogeneic Bone Grafting for Benign Spinal Lesions: Technical Notes and Preliminary Clinical Results.

Benign lesions of the spine include benign tumors and tumor-like lesions of the spine, which usually occur in the thoracic and lumbar vertebrae. The incidence rate is low, accounting for about 1% of primary bone tumors. Few cases of endoscopic treatment of benign spinal lesions have been reported in the literature. Here, we introduce a new surgical technique using full endoscopy and allogeneic bone grafting to treat benign spinal lesions. All patients in this study successfully underwent the operation, and their pain was significantly relieved postoperatively. The patient VAS scores decreased from 3.07 ± 0.70 preoperatively to 0.33 ± 0.49 at the last follow-up visit (p < 0.05). The mean total blood loss (including drainage blood) was 16.67 ± 6.98 mL. The mean operative time was 63.33 ± 7.23 min. No patients developed numbness in the corresponding segmental distribution after surgery, none of the patients had serious postoperative complications, and none had focal recurrence during follow-up requiring reoperation. Patients reported symptom relief throughout the whole follow-up period. We believe that endoscopic surgery preserves the ligaments and soft tissues around the vertebral body, and that this technique is feasible with minimal trauma, rapid recovery, and good outcomes at short-term follow-up. This minimally invasive treatment modality offers a new option for the treatment of patients with benign spinal lesions.

Synthesis of temperature- and humidity-induced dual stimulation film PU-PNIPAm n and its independent film formation as a smart window application.

Dynamic windows, which switch between transparent and opaque states as the temperature changes, can be applied in buildings to reduce building energy consumption. Poly(N-isopropylacrylamide) (PNIPAm) is the most studied thermochromic hydrogel for climate-resilient smart window applications. In addition to its poor mechanical properties and low reaction rate, the PNIPAm hydrogel must be sandwiched between two pieces of glass to form an interlayer in practical applications. Here, durable PU-PNIPAm n copolymers for smart windows were synthesized by reacting the synthesized poly-NIPAm diols with isocyanate (-NCO) monomer, which greatly improved the mechanical properties of the hydrogel and it was able to form a film alone. These temperature-sensitive films can switch between transparent (>80% transmittance) and opaque (<5% transmittance) states in less than 10 minutes, with no degradation in optical contrast, switching speed, or uniformity after at least 100 switching cycles.

PINK1/Parkin-mediated mitophagy inhibits osteoblast apoptosis induced by advanced oxidation protein products.

Osteoblast apoptosis plays an important role in age-related bone loss and osteoporosis. Our previous study revealed that advanced oxidation protein products (AOPPs) could induce nicotinamide adenine dinucleotide phosphate oxidase (NOX)-derived reactive oxygen species (ROS) production, cause mitochondrial membrane potential (ΔΨm) depolarization, trigger the mitochondria-dependent intrinsic apoptosis pathway, and lead to osteoblast apoptosis and ultimately osteopenia and bone microstructural destruction. In this study, we found that AOPPs also induced mitochondrial ROS (mtROS) generation in osteoblastic MC3T3-E1 cells, which was closely related to NOX-derived ROS, and aggravated the oxidative stress condition, thereby further promoting apoptosis. Removing excessive ROS and damaged mitochondria is the key factor in reversing AOPP-induced apoptosis. Here, by in vitro studies, we showed that rapamycin further activated PINK1/Parkin-mediated mitophagy in AOPP-stimulated MC3T3-E1 cells and significantly alleviated AOPP-induced cell apoptosis by eliminating ROS and damaged mitochondria. Our in vivo studies revealed that PINK1/Parkin-mediated mitophagy could decrease the plasma AOPP concentration and inhibit AOPP-induced osteoblast apoptosis, thus ameliorating AOPP accumulation-related bone loss, bone microstructural destruction and bone mineral density (BMD) loss. Together, our study indicated that therapeutic strategies aimed at upregulating osteoblast mitophagy and preserving mitochondrial function might have potential for treating age-related osteoporosis.

Tumor-suppressing effects of miR-381-3p in pediatric acute myeloid leukemia via ROCK1 downregulation.

MicroRNA (miR)-381-3p is the newly discovered tumor-associated miRNA, which is frequently associated with diverse human malignancies; but, it is still unknown about its effect on acute myeloid leukemia (AML) in children. This work focused on exploring miR-381-3p's effect on childhood AML and identifying the possible mechanisms facilitating new treatment development. Using qRT-PCR analysis, miR-381-3p expression remarkably reduced in pediatric AML patients and AML cell lines (HL-60 and U937). Following transfection of miR-381-3p mimic or inhibitor into HL-60 and U937 cells, we conducted MTT assay to evaluate cell proliferation, flow cytometry (FCM) to measured cell apoptosis and cell cycle, whereas Transwell assays to detect cell invasion and migration. Our results demonstrated that miR-381-3p overexpression remarkably repressed cell growth, invasion and migration; additionally, miR-381-3p overexpression resulted in arrest of cell cycle and enhanced cell apoptosis. In contrast, miR-381-3p knockdown led to an opposite effect. Moreover, we predicted miR-381's target gene and validated it by luciferase reporter assay and TargetScan, separately. We identified miR-381-3p's binding site in ROCK1 3'-UTR. As revealed by Western-blot (WB) assay, miR-381-3p overexpression notably suppressed ROCK1 level. Moreover, restoring ROCK1 expression abolished miR-381-3p's inhibition on cell proliferation, invasion and migration. Data in this work indicated the role of miR-381-3p as the tumor suppressor within pediatric AML by targeting ROCK1. Therefore, miR-381-3p might serve as a potential therapeutic target for the treatment of pediatric AML.

Homo sapiens circular RNA 0003602 (Hsa_circ_0003602) accelerates the tumorigenicity of acute myeloid leukemia by modulating miR-502-5p/IGF1R axis.

Acute myeloid leukemia (AML) has become a worldwide malignant cancer. We intended to investigate the critical roles and mechanism underlying homo sapiens circular RNA 0003602 (hsa_circ_0003602) in AML progression, especially in tumor cell proliferation, migration, invasion, and apoptosis. Real-time PCR was applied to identify the differential expression of hsa_circ_0003602 and miR-502-5p in AML bone marrow tissues and cell lines. In addition, western blot analysis was employed to determine the levels insulin-like growth factor 1 receptor (IGF1R) protein. The biological behaviors were assessed by CCK-8 cell viability assay, flow cytometry assay for apoptosis detection, and Transwell migration and invasion assay. The relationships between target miRNA and downstream mRNA were investigated by bioinformatics, luciferase reporter assay, and biotin-labeled RNA pull-down assay. Hsa_circ_0003602 was upregulated and predicted poor survival in AML. Knockdown of hsa_circ_0003602 in AML cell lines induced the inhibition of proliferation, migration, and invasion and caused apoptosis. Hsa_circ_0003602 sequestered miR-502-5p by functioning as a competitive endogenous RNA (ceRNA), thereby regulating IGF1R expression. Hsa_circ_0003602 acted as a tumor promoter in AML via miR-502-5p/IGF1R axis. Our study provides evidence that hsa_circ_0003602, miR-502-5p, and IGF1R might form a regulatory axis to affect the carcinogenicity of AML cells and provide potential targets for the treatment of AML.

Enhancing Moisture and Electrochemical Stability of the Li5.5PS4.5Cl1.5 Electrolyte by Oxygen Doping.

Chlorine-rich argyrodite-type solid electrolyte Li5.5PS4.5Cl1.5 has been a promising choice for solid-state batteries (SSBs) because of its ultrafast Li-ion conduction. However, the poor air/moisture stability and low electrochemical stability with pristine high-voltage cathodes hinder their applications. Herein, O-substituted Li5.5PS4.5-xOxCl1.5 (x = 0, 0.075, 0.175, and 0.25) solid electrolytes are successfully synthesized. Among them, Li5.5PS4.425O0.075Cl1.5 delivers high ionic conductivity, improved moisture resistance, and enhanced electrochemical stability in higher voltage windows. SSBs using Li5.5PS4.425O0.075Cl1.5 show higher capacities and superior cyclability than those using Li5.5PS4.5Cl1.5 combined with a pristine LiNi0.8Mn0.1Co0.1O2 cathode when operated at a high end-of-charge voltage of 4.5 V (vs Li+/Li0). Moreover, the batteries exhibit outstanding performance in a wide temperature range. This work provides a strategy to modify the inherent drawbacks of sulfide electrolytes, promoting their practical applications.

[Reactivation of Passivated Biochar/Nanoscale Zero-Valent Iron by an Electroactive Microorganism for Cooperative Hexavalent Chromium Removal and Mechanisms].

Nanoscale zero-valent iron (nZVI) shows excellent reduction of Cr(Ⅵ), but the passivation on its outer surface can restrict its longevity and performance. To tackle this problem, this work introduced Shewanella oneidensis MR-1, a dissimilatory iron-reducing bacterium, into the chemical reduction system of aged nZVI/biochar (B) and Cr(Ⅵ). The potential synergistic effect of Cr(Ⅵ) reduction of aged nZVI/B and MR-1 was systematically investigated under varying conditions. The results indicated that aged nZVI/B and MR-1 exhibited a synergistic effect at a pH of 7, and the removal rate of Cr(Ⅵ) increased by 51.3%. Further research showed that the synergistic effect could be attenuated with the increase in the initial Cr(Ⅵ) concentration and enhanced with the increase in the MR-1 concentration. The XPS spectra confirmed that Cr(Ⅵ) was mainly removed through reduction. The dissimilatory iron-reducing ability of MR-1 played a key role in enhancing the Cr(Ⅵ) reduction. The reductive dissolution of the oxidation layers not only released reactive sites inside the nZVI, but also reduced Cr(Ⅵ) by producing ferrous ions. Moreover, B promoted the reduction by dispersing the nZVI and mediating the extracellular electron transfer. This study provides a new insight into solving the passivation problem of the long-term application of nZVI for Cr(Ⅵ) removal, which is considered a promising solution for synergistically improving the performance of nZVI in environmental remediation.

Rational assembly of GO-based heterocyclic sulfur- and nitrogen-containing aerogels and their adsorption properties toward rare earth elementals.

An aromatic heterocyclic compound, 2-aminobenzothiazole (ABT), was used to decorate graphene oxide (GO) by a facile hydrothermal self-assembly procedure. The developed three-dimensional (3D) GO-ABT composite aerogels could be utilized as high-powered and sustainable adsorbents for the enrichment and recovery of low concentration rare earth elements (REEs) from aqueous solutions. The composition and microstructure of GO-ABT composites were explored various characterization methods. The enrichment properties of GO-ABT composites for REEs were investigated in detail, revealing the existence of S-, N- and -NH2 in ABT, as well as the carboxyl and hydroxyl groups of GO which might act as the major REE binding sites. The adsorption of GO-ABT composites for low concentration REEs could reach equilibrium in 30 min. Our investigations confirmed that the optimal pH value of GO-ABT composites for REEs was pH 4.0-5.0. For the adsorbent regeneration study, 50.0 mg of GO-ABT15:1/120 °C/6 h composite was used toward 20.0 mL of Er3+ solutions. After ten regeneration cycles, the adsorption rates of GO-ABT composites for Er3+ remained around 100%, and the desorption rates maintained over 90%. The long-term storage of the adsorbent did not affect its adsorption ability, while desorption rates increased, indicating it possessed relatively higher stability.

Influence Factors and Prediction Model of Bond Strength of Tunnel Fireproof Coating under Freeze-Thaw Cycles.

The freeze-thaw resistant performance of a tunnel fireproof coating (TFC) has an important impact on bonding property and durability. The influence of redispersible emulsion powder, polypropylene fiber and air-entraining agent on TFCs was studied. Transverse fundamental frequency and ultrasonic sound velocity were used to evaluate the damage degree of TFC, and the mechanism was revealed by SEM and pore structure. The results show that the most beneficial effect on bond strength of TFC is redispersible emulsion powder, followed by air-entraining agent, and then polypropylene fiber. After freeze-thaw cycles, the cumulative pore volume of micropores in the TFC increases obviously, while the porosity of macropores does not change significantly. A prediction model was proposed, which can calculate the bond strength from the damage degree of TFC under freeze-thaw cycles. The achievement can promote the application of TFC in cold regions.

Cryptosporidium of birds in pet markets in Wuhan city, Hubei, China.

Cryptosporidium is a group of protistan parasites of a range of vertebrates including mammals and birds. Stimulated by previous work that revealed "zoonotic" Cryptosporidium meleagridis subtypes (i.e. IIIbA26G1R1b and IIIbA22G1R1c) in diarrhoeic children and domestic chickens in Wuhan city and environs in Hubei Province, China, here we explored whether zoonotic C. meleagridis subtypes might also occur in pet birds in Wuhan city. From 11 bird markets in this city, we collected 322 faecal samples from 48 species of birds (representing six taxonomic orders), isolated genomic DNA and then conducted PCR-based sequencing of genetic markers in the small subunit (SSU) of the nuclear ribosomal RNA and the 60 kDa glycoprotein (gp60) genes of Cryptosporidium. Using SSU, Cryptosporidium was detected in 55 (17%) of the 322 samples. Cryptosporidium avium, C. baileyi, C. meleagridis, C. muris and C. proventriculi were characterised in 18%, 47%, 11%, 2% and 20% of the 55 samples, respectively, and a novel Cryptosporidium galli-like taxon in one sample. Using gp60, only one subtype (IIIeA17G2R1) of C. meleagridis was identified, which had not been detected in a previous study of diarrhoeic children in Wuhan. However, IIIe subtypes have been found in both humans and birds around the world. The relatively high prevalence and genetic diversity of Cryptosporidium recorded here in pet birds raise awareness about possible reservoirs of zoonotic variants of Cryptosporidium in birds in Wuhan, and potentially, other provinces in China.

Clinical outcomes of hemodialysis patients infected with severe acute respiratory syndrome coronavirus 2 and impact of proactive chest computed tomography scans.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that first manifested in humans in Wuhan, Hubei Province, China, in December 2019, and has subsequently spread worldwide. METHODS: We conducted a retrospective, single-center case series of the seven maintenance hemodialysis (HD) patients infected with COVID-19 at Zhongnan Hospital of Wuhan University from 13 January to 7 April 2020 and a proactive search of potential cases by chest computed tomography (CT) scans. RESULTS: Of 202 HD patients, 7 (3.5%) were diagnosed with COVID-19. Five were diagnosed by reverse transcription polymerase chain reaction (RT-PCR) because of compatible symptoms, while two were diagnosed by RT-PCR as a result of screening 197 HD patients without respiratory symptoms by chest CT. Thirteen of 197 patients had positive chest CT features and, of these, 2 (15%) were confirmed to have COVID-19. In COVID-19 patients, the most common features at admission were fatigue, fever and diarrhea [5/7 (71%) had all these]. Common laboratory features included lymphocytopenia [6/7 (86%)], elevated lactate dehydrogenase [3/4 (75%)], D-dimer [5/6 (83%)], high-sensitivity C-reactive protein [4/4 (100%)] and procalcitonin [5/5 (100%)]. Chest CT showed bilateral patchy shadows or ground-glass opacity in the lungs of all patients. Four of seven (57%) received oxygen therapy, one (14%) received noninvasive and invasive mechanical ventilation, five (71%) received antiviral and antibacterial drugs, three (43%) recieved glucocorticoid therapy and one (14%) received continuous renal replacement therapy. As the last follow-up, four of the seven patients (57%) had been discharged and three patients were dead. CONCLUSIONS: Chest CT may identify COVID-19 patients without clear symptoms, but the specificity is low. The mortality of COVID-19 patients on HD was high.

Co-infection with SARS-CoV-2 and parainfluenza virus in a hemodialysis patient: A case report.

BACKGROUND: In December 2019, the 2019 novel coronavirus disease (COVID-19) caused by SARS-CoV-2 emerged in China and now has spread to many countries. Limited data are available for hemodialysis patients with COVID-19. CASE PRESENTATION: We report a 66-year-old man with confirmed COVID-19 and parainfluenza virus infection in Wuhan. We describe the clinical characteristics, radiological findings, and treatment of the hemodialysis patient, including the patient's initial pneumonia at presentation with progression to acute respiratory distress syndrome (ARDS). DISCUSSION AND CONCLUSION: Our case underscores the possibility of SARS-CoV-2 co-infection with other pathogens in hemodialysis patients and the importance of early identification of COVID-19.

COVID-19 in Hemodialysis Patients: A Report of 5 Cases.

In December 2019, an outbreak of coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in China and spread rapidly worldwide. It is unknown whether hemodialysis patients represent a distinct group of patients with certain characteristics that may make them susceptible to infection or severe disease. In this case report, we describe the clinical and epidemiologic features of COVID-19 infection in 201 maintenance hemodialysis patients in Zhongnan Hospital of Wuhan University, including 5 maintenance hemodialysis patients who contracted COVID-19 infection. Of the 5 patients with COVID-19 infection, one had a definite history of contact with an infected person. The age range of the patients was 47 to 67 years. Diarrhea (80%), fever (60%), and fatigue (60%) were the most common symptoms. Lymphopenia occurred in all patients. Computed tomography of the chest showed ground glass opacity in the lungs of all patients. Up to February 13, 2020, none of the patients had developed severe complications (acute respiratory distress syndrome, shock, or multiple organ dysfunction) or died.