We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). ...Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT-PCR results and for the identification of asymptomatic infections.
A series of hyperbranched poly(arylene ether ketone) (HBPAEK) anion exchange membranes (AEMs) was synthesized by polycondensation and quaternization using ...1-(N′,N′-dimethylamino)−6,12-(N,N,N-trimethylammonium) dodecane bromide. The highest ionic conductivity of the HBPAEK-28-18 AEM with ionic exchange capacity of 2.21 meq g−1 is 122.5 mS cm−1 at 80 °C. The chemical stability of the AEMs was examined upon exposure to a 2 M KOH solution at 80 °C by monitoring the change in ionic conductivity, which decreased from 122.5 to 104.2 mS cm−1 after 500 h. 1H NMR spectra confirmed the chemical stability of the AEM during this period. The hyperbranched structure can not only improve the conductivity, but also increase the chemical stability of the AEMs. The H2/O2 single cell using HBPAEK-28-18 exhibits a maximum power density of 188.6 mW cm−2 under a current density of 450 mA cm−2 at 80 °C. Furthermore, the hyperbranched structure AEMs also exhibited good thermal stability and mechanical property
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•Hyperbranched polymer anion exchange membranes are fabricated.•Hyperbranched block copolymers can enhance the ionic conductivity.•Hyperbranched structure can improve the mechanical property and alkaline stability.
A series of highly alkaline durable crosslinked anion exchange membranes (AEMs) is prepared via elimination reaction using a sodium salt of 4,4′(5′)-di(hydroxybenzo)-18-crown-6 as the crosslinker, ...and quaternary ammonium (QA) as the cation group. The ionic conductivity, ionic exchange capacity (IEC) and mechanical property of the AEMs are investigated. The highest ionic conductivity (about 117 mS cm−1) of the PPO-CE0.10-QA0.90 membranes is obtained at 80 °C and 100% relative humidity. The alkaline stability of the AEMs is determined by inspecting the decline in ionic conductivity, mechanical property and the change in chemical structure after the alkaline stability test. The ionic conductivity has only a 6.0% decrease, the tensile strength has an 11.8 MPa reduction and the elongation at break has a 2.7% depression after 480 h test in 2 M KOH at 80 °C. 13C NMR spectra confirm a negligible change in chemical structure of the AEMs after the alkaline resistance test. The peak power density (about 195 mW cm−2) is achieved under a current density of 350 mA cm−2 at 80 °C. Additionally, the AEMs with a novel crosslinked structure decompose above 230 °C and exhibit decent thermal stability.
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•Novel AEMs were fabricated using crown ether as crosslinker.•Crown ether can promote the microphase separation of AEMs.•Crown ether as crosslinker can improve the mechanical property.•Crown ether as crosslinker can enhance alkaline stability of the AEMs.
The retrosplenial cortex (Rsp) is a transitional cortex located between the neocortex and archicortex, but the molecular mechanism specifying Rsp from the archicortex remains elusive. We here report ...that the transcription factor Satb2 is required for specifying Rsp identity during its morphogenesis. In Satb2 CKO mice, the boundary between the Rsp and archicortex i.e., subiculum (SubC) disappears as early as E17.5, and Rsp efferent projection is aberrant. Rsp-specific genes are lost, whereas SubC-specific genes are ectopically expressed in Rsp of Satb2 CKO mice. Furthermore, cell-autonomous role of Satb2 in maintaining Rsp neuron identity is revealed by inactivation of Satb2 in Rsp neurons. Finally, Satb2 represses the transcription of Nr4a2. The misexpression of Nr4a2 together with Ctip2 induces expression of SubC-specific genes in wild-type Rsp, and simultaneous knockdown of these two genes in Rsp Satb2-mutant cells prevents their fate transition to SubC identity. Thus, Satb2 serves as a determinant gene in the Rsp regionalization by repressing Nr4a2 and Ctip2 during cortical development.
Chemotherapies often induce drug-resistance in cancer cells and simultaneously stimulate proliferation and activation of Myeloid-Derived Suppressor Cells (MDSCs) to inhibit anti-tumor T cells, thus ...result in poor prognosis of patients with breast cancers. To date, the mechanism underlying the expansion of MDSCs in response to chemotherapies is poorly understood. In the present study, we used in vitro cell culture and in vivo animal studies to demonstrate that doxorubicin-resistant breast cancer cells secret significantly more prostaglandin E2 (PGE2) than their parental doxorubicin-sensitive cells. The secreted PGE2 can stimulate expansion and polymerization of MDSCs by directly target to its receptors, EP2/EP4, on the surface of MDSCs, which consequently triggers production of miR-10a through activating PKA signaling. More importantly, activated MDSCs can inhibit CD4(+)CD25(-) T cells as evidenced by reduced proliferation and IFN-γ release. In order to determine the molecular pathway that involves miR-10a mediated activation of MDSCs, biochemical and pharmacological studies were carried out. We found that miR-10a can activate AMPK signaling to promote expansion and activation of MDSCs. Thus, these results reveal, for the first time, a novel role of PGE2/miR-10a/AMPK signaling axis in chemotherapy-induced immune resistance, which might be targeted for treatment of chemotherapy resistant tumors.
Circulating tumor cells (CTCs) are a burgeoning topic in cancer biomarker discovery research with minimal invasive blood draws. CTCs can be used as potential biomarkers for disease prognosis, early ...cancer diagnosis and pharmacodynamics. However, the extremely low abundance of CTCs limits their clinical utility because of technical challenges such as the isolation and subsequent detailed molecular and functional characterization of rare CTCs from patient blood samples.
In this study, we present a novel density gradient centrifugation method employing biodegradable gelatin nanoparticles coated on silicon beads for the isolation, release, and downstream analysis of CTCs from colorectal and breast cancer patients.
Using clinical patient/spiked samples, we demonstrate that this method has significant CTC-capture efficiency (>80%) and purity (>85%), high CTC release efficiency (94%) and viability (92.5%). We also demonstrate the unparalleled robustness of our method in downstream CTC analyses such as the detection of PIK3CA mutations.
The efficiency and versatility of the multifunctional density microbeads approach provides new opportunities for personalized cancer diagnostics and treatments.
Abstract
Objectives
Despite of strenuous research in the past decades, the etiology of schizophrenia (SCZ) still remains incredibly controversial. Previous genetic analysis has uncovered a close ...association of Unc-51 like kinase 4 (ULK4), a family member of Unc-51-like serine/threonine kinase, with SCZ. However, animal behavior data which may connect Ulk4 deficiency with psychiatric disorders, particularly SCZ are still missing.
Methods
We generated Emx1-Cre:Ulk4flox/flox conditional knockout (CKO) mice, in which Ulk4 was deleted in the excitatory neurons of cerebral cortex and hippocampus.
Results
The cerebral cellular architecture was maintained but the spine density of pyramidal neurons was reduced in Ulk4 CKO mice. CKO mice showed deficits in the spatial and working memories and sensorimotor gating. Levels of p-Akt and p-GSK-3α/β were markedly reduced in the CKO mice indicating an elevation of GSK-3 signaling. Mechanistically, Ulk4 may regulate the GSK-3 signaling via putative protein complex comprising of two phosphatases, protein phosphatase 2A (PP2A) and 1α (PP1α). Indeed, the reduction of p-Akt and p-GSK-3α/β was rescued by administration of inhibitor acting on PP2A and PP1α in CKO mice.
Conclusions
Our data identified potential downstream signaling pathway of Ulk4, which plays important roles in the cognitive functions and when defective, may promote SCZ-like pathogenesis and behavioral phenotypes in mice.
To determine the value of salivary pepsin in discriminating sub-types of gastroesophageal reflux disease (GERD) and GERD-related disorders.
Overall, 322 patients with different sub-types of GERD and ...45 healthy controls (HC) were studied. All patients took Gastroesophageal Reflux Disease Questionnaire (GerdQ) and underwent endoscopy and 24-hour esophageal pH monitoring and manometry. Salivary pepsin concentration (SPC) was detected by using colloidal gold double-antibody immunological sandwich assay. Oral esomeprazole treatment was administrated in the patients with non-erosive reflux disease (NERD) and extra-esophageal symptoms (EES).
Compared to HC, patients with erosive esophagitis, NERD, EES, EES plus typical GERD symptoms, or Barrett's esophagus had a higher prevalence of saliva and SPC (all
< 0.001). There was no significant difference in the positive rate for pepsin in patients with functional heartburn or GERD with anxiety and depression, compared to HC. After esomeprazole treatment, the positive rate and SPC were significantly reduced in NERD (both
< 0.001) and in EES (
= 0.001 and
= 0.002, respectively). Of the 64 NERD patients, 71.9% (n = 46) were positive for salivary pepsin, which was significantly higher than the rate (43.8%, n = 28) of pathological acid reflux as detected by 24-hour esophageal pH monitoring (
= 0.002).
Salivary pepsin has an important significance for the diagnosis of GERD and GERD-related disorders. Salivary pepsin and 24-hour esophageal pH monitoring may complement with each other to improve the diagnostic efficiency.
Previous studies used to enumerate circulating tumor cells to predict prognosis and therapeutic effect of colorectal cancer. However, increasing studies have shown that only circulating tumor cells ...enumeration was not enough to reflect the heterogeneous condition of tumor. In this study, we classified different metastatic-potential circulating tumor cells from colorectal cancer patients and measured FAM172A expression in circulating tumor cells to improve accuracy of clinical diagnosis and treatment of colorectal cancer. Blood samples were collected from 45 primary colorectal cancer patients. Circulating tumor cells were enriched by blood filtration using isolation by size of epithelial tumor cells, and in situ hybridization with RNA method was used to identify and discriminate subgroups of circulating tumor cells. Afterwards, FAM172A expression in individual circulating tumor cells was measured. Three circulating tumor cell subgroups (epithelial/biophenotypic/mesenchymal circulating tumor cells) were identified using epithelial–mesenchymal transition markers. In our research, mesenchymal circulating tumor cells significantly increased along with tumor progression, development of distant metastasis, and vascular invasion. Furthermore, FAM172A expression rate in mesenchymal circulating tumor cells was significantly higher than that in epithelial circulating tumor cells, which suggested that FAM172A may correlate with malignant degree of tumor. This hypothesis was further verified by FAM172A expression in mesenchymal circulating tumor cells, which was strictly related to tumor aggressiveness factors. Mesenchymal circulating tumor cells and FAM172A detection may predict highrisk stage II colorectal cancer. Our research proved that circulating tumor cells were feasible surrogate samples to detect gene expression and could serve as a predictive biomarker for tumor evaluation.
The reflection characteristics of radar waves in coastal high-rise buildings form a certain shielding area, which makes it difficult for vessel traffic service to control the ship dynamic situation ...in sheltered waters. To study the overshadowing influence of coastal buildings on the vessel traffic service radar, an expression model of shielding area is established based on the structure characteristics of buildings and the relative height of radar. Then, the coordinate system is established, and the range and height of the shelter area are calculated, according to the geometric relation. Based on the theory of radar electromagnetic wave diffraction, the target height is calculated. Finally, taking the prince’s Bay Cruise Terminal Building on the radar Shekou radar as an example, the shielding area and height are calculated and visualized by the numerical calculation model and verified by real vessel test and observation. The building with a height of 60 m has covered 973,090 m2 of sheltered area for Shekou radar. The results can be used not only to analyze the influence of buildings on existing vessel traffic service radar stations but also to provide an important reference for site selection of vessel traffic service radar stations.
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