Existing weakly-supervised semantic segmentation methods using image-level annotations typically rely on initial responses to locate object regions. However, such response maps generated by the ...classification network usually focus on discriminative object parts, due to the fact that the network does not need the entire object for optimizing the objective function. To enforce the network to pay attention to other parts of an object, we propose a simple yet effective approach that introduces a self-supervised task by exploiting the sub-category information. Specifically, we perform clustering on image features to generate pseudo sub-categories labels within each annotated parent class, and construct a sub-category objective to assign the network to a more challenging task. By iteratively clustering image features, the training process does not limit itself to the most discriminative object parts, hence improving the quality of the response maps. We conduct extensive analysis to validate the proposed method and show that our approach performs favorably against the state-of-the-art approaches.
Human PUF-A/PUM3 is a RNA and DNA binding protein participating in the nucleolar processing of 7S to 5.8S rRNA. The nucleolar localization of PUF-A redistributes to the nucleoplasm upon the exposure ...to genotoxic agents in cells. However, little is known regarding the roles of PUF-A in tumor progression. Phosphoprotein database analysis revealed that Y259 phosphorylation of PUF-A is the most prevalent residue modified. Here, we reported the importance of PUF-A's phosphorylation on Y259 in tumorigenesis. PUF-A gene was knocked out by the Crispr/Cas9 method in human cervix epithelial HeLa cells. Loss of PUF-A in HeLa cells resulted in reduced clonogenic and lower transwell invasion capacity. Introduction of PUF-AY259F to PUF-A deficient HeLa cells was unable to restore colony formation. In addition, the unphosphorylated mutant of PUF-A, PUF-AY259F, attenuated PUF-A protein stability. Our results suggest the important role of Y259 phosphorylation of PUF-A in cell proliferation.
Maternal chronic kidney disease (CKD) during pregnancy causes adverse fetal programming. Nitric oxide (NO) deficiency, gut microbiota dysbiosis, and dysregulated renin-angiotensin system (RAS) during ...pregnancy are linked to the development of hypertension in adult offspring. We examined whether maternal adenine-induced CKD can program hypertension and kidney disease in adult male offspring. We also aimed to identify potential mechanisms, including alterations of gut microbiota composition, increased trimethylamine-N-oxide (TMAO), reduced NO bioavailability, and dysregulation of the RAS. To construct a maternal CKD model, female Sprague-Dawley rats received regular chow (control group) or chow supplemented with 0.5% adenine (CKD group) for 3 weeks before pregnancy. Mother rats were sacrificed on gestational day 21 to analyze placentas and fetuses. Male offspring (
= 8/group) were sacrificed at 12 weeks of age. Adenine-fed rats developed renal dysfunction, glomerular and tubulointerstitial damage, hypertension, placental abnormalities, and reduced fetal weights. Additionally, maternal adenine-induced CKD caused hypertension and renal hypertrophy in adult male offspring. These adverse pregnancy and offspring outcomes are associated with alterations of gut microbiota composition, increased uremic toxin asymmetric and symmetric dimethylarginine (ADMA and SDMA), increased microbiota-derived uremic toxin TMAO, reduced microbiota-derived metabolite acetate and butyrate levels, and dysregulation of the intrarenal RAS. Our results indicated that adenine-induced maternal CKD could be an appropriate model for studying uremia-related adverse pregnancy and offspring outcomes. Targeting NO pathway, microbiota metabolite TMAO, and the RAS might be potential therapeutic strategies to improve maternal CKD-induced adverse pregnancy and offspring outcomes.
Ag-doped Bi2WO6-graphene based photocatalysts were found to exhibit hydrogen production activity. The performance of Bi2WO6-graphene based photocatalysts were investigated and optimized in this ...study. The activity can be further improved by Ag-doping. The morphology, surface chemistry, and phase structure of the photocatalysts were investigated by Field emission scanning electron microscopy, Transmission electron microscopy, X-ray photoelectron spectroscopy, Raman spectra, and X-ray diffraction. UV–vis diffuse reflectance spectroscopy and zeta potential were measured to study the optical properties, bandgap and dispersion stability of the photocatalysts. The effects of forming Bi2WO6-graphene contact and Ag doping on the light absorption, band gap, dispersion stability, and photocatalytic H2 production performance of the composite photocatalysts were evaluated. The improved photocatalytic performance is mainly owing to the Ag doping and high electrical conductivity of graphene.
•Ag doped Bi2WO6–graphene photocatalysts exhibited H2 production activity.•H2 production activity was improved by Ag doping and forming Bi2WO6-graphene contact.•Ag doping leads to decreased bandgap and increased light absorption.•Dispersion stability of Ag-doped sample deteriorated due to decreased zeta potential.•80% activity can be retained when the photocatalyst was recycled after 3 cycles.
PHRF1 is involved in transforming growth factor β (TGF-β) signaling to constrain the formation of acute promyelocytic leukemia (APL) in mouse APL models. PHRF1 also participates in modulating ...non-homologous end-joining. However, the role of PHRF1 in mammalian dendrite architecture and synaptic plasticity is unclear. Here, we investigated the role of PHRF1 in dendritic formation in the murine hippocampus using Camk2a promoter driven-iCre recombinase to conduct a PHRF1 conditional knockout, namely PHRF1
, in the forebrain region. PHRF1
mice developed normally, but exhibited anxiety-like behaviors and displayed defective spatial memory. Alterations of dendritic complexity in apical and basal dendrites of pyramidal neurons were noticed in PHRF1
mutants. Furthermore, electrical stimulation in the hippocampal CA1 region after the TGF-β1 treatment showed a reduced synaptic plasticity in PHRF1
mice. Immunoblotting analysis indicated that PHRF1 ablation affected the TGF-β signaling. Collectively, our results demonstrate that PHRF1 is important for the dendritic architecture and required for spatial memory formation in the hippocampus.
Lithium-ion batteries (LIBs) are widely used in applications ranging from electric vehicles to wearable devices. Before the invention of secondary LIBs, the primary lithium-thionyl chloride ...(Li-SOCl2) battery was developed in the 1970s using SOCl2 as the catholyte, lithium metal as the anode and amorphous carbon as the cathode1-7. This battery discharges by lithium oxidation and catholyte reduction to sulfur, sulfur dioxide and lithium chloride, is well known for its high energy density and is widely used in real-world applications; however, it has not been made rechargeable since its invention8-13. Here we show that with a highly microporous carbon positive electrode, a starting electrolyte composed of aluminium chloride in SOCl2 with fluoride-based additives, and either sodium or lithium as the negative electrode, we can produce a rechargeable Na/Cl2 or Li/Cl2 battery operating via redox between mainly Cl2/Cl- in the micropores of carbon and Na/Na+ or Li/Li+ redox on the sodium or lithium metal. The reversible Cl^NaCl or Cl2/LiCl redox in the microporous carbon affords recharge-ability at the positive electrode side and the thin alkali-fluoride-doped alkali-chloride solid electrolyte interface stabilizes the negative electrode, both are critical to secondary alkali-metal/Cl2 batteries.
Predictive maintenance techniques can determine the conditions of equipment in order to evaluate when maintenance should be performed. Thus, it minimizes the unexpected device downtime, lowers the ...maintenance costs, extends equipment lifecycle, etc. Therefore, this article developed a predictive maintenance mechanism with the construction of a test platform and data analysis along with machine learning. The information transmission of sensors was based on Raspberry Pi via the TCP/IP (Transmission Control Protocol/Internet Protocol) communication protocol. The sensors used for environmental sensing were implemented on the programmable interface controller and the data were stored in time sequence. A statistical analysis software platform was adopted for data preprocessing, modelling, and prediction to provide necessary maintenance decision. Using multivariate analysis users can obtain more information about the equipment's status, and the administrator can also determine the operational situation before unexpected device anomalies. The developed modules are decisively helpful in preventing unpredictable losses, thus improving the quality of services.
Tangeretin, 4′,5,6,7,8-pentamethoxyflavone, is one of the major polymethoxyflavones (PMFs) existing in citrus fruits, particularly in the peels of sweet oranges and mandarins. Tangeretin has been ...reported to possess several beneficial bioactivities including anti-inflammatory, anti-proliferative and neuroprotective effects. To achieve a thorough understanding of the biological actions of tangeretin in vivo, our current study is designed to investigate the pharmacokinetics, bioavailability, distribution and excretion of tangeretin in rats. After oral administration of 50 mg/kg bw tangeretin to rats, the Cmax, Tmax and t1/2 were 0.87 ± 0.33 μg/mL, 340.00 ± 48.99 min and 342.43 ± 71.27 min, respectively. Based on the area under the curves (AUC) of oral and intravenous administration of tangeretin, calculated absolute oral bioavailability was 27.11%. During tissue distribution, maximum concentrations of tangeretin in the vital organs occurred at 4 or 8 h after oral administration. The highest accumulation of tangeretin was found in the kidney, lung and liver, followed by spleen and heart. In the gastrointestinal tract, maximum concentrations of tangeretin in the stomach and small intestine were found at 4 h, while in the cecum, colon and rectum, tangeretin reached the maximum concentrations at 12 h. Tangeretin excreted in the urine and feces was recovered within 48 h after oral administration, concentrations were only 0.0026% and 7.54%, respectively. These results suggest that tangeretin was mainly eliminated as metabolites. In conclusion, our study provides useful information regarding absorption, distribution, as well as excretion of tangeretin, which will provide a good base for studying the mechanism of its biological effects.
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•Absolute oral bioavailability of tangeretin in rats was 27.11%.•Tangeretin was mainly concentrated in the kidney, lung and liver.•Less than 8% of tangeretin excreted in either urine or feces.
SARS-CoV-2 viruses, responsible for the COVID-19 pandemic, continues to evolve into new mutations, which poses a significant threat to public health. Current testing methods have some limitations, ...such as long turnaround times, high costs, and professional laboratory requirements. In this report, the novel Spin-Enhanced Lateral Flow Immunoassay (SELFIA) platform and fluorescent nanodiamond (FND) reporter were utilized for the rapid detection of SARS-CoV-2 nucleocapsid and spike antigens from different variants, including wild-type (Wuhan-1), Alpha (B.1.1.7), Delta (B.1.617.2), and Omicron (B.1.1.529). The SARS-CoV-2 antibodies were conjugated with FND via nonspecific binding, enabling the detection of SARS-CoV-2 antigens via both direct and competitive SELFIA format. Direct SELFIA was performed by directly adding the SARS-CoV-2 antibodies-conjugated FND on the antigens-immobilized nitrocellulose (NC) membrane. Conversely, the SARS-CoV-2 antigen-containing sample was first incubated with the antibodies-conjugated FND, and then dropped on the antigen-immobilized NC membrane to carry out the competitive SELFIA. The results suggested that S44F anti-S IgG antibody can be efficiently used for the detection of wild-type, Alpha, Delta, and Omicron variants spike antigens. Findings were comparable in direct SELFIA, competitive SELFIA, and ELISA. A detection limit of 1.94, 0.77, 1.14, 1.91, and 1.68 ng/mL can be achieved for SARS-CoV-2 N protein, wild-type, Alpha, Delta, and Omicron S proteins, respectively, via competitive SELFIA assay. These results suggest that a direct SELFIA assay can be used for antibody/antigen pair screening in diagnosis development, while the competitive SELFIA assay can serve as an accurate quantitative diagnostic tool. The simplicity and rapidity of the SELFIA platform were demonstrated, which can be leveraged in the detection of other infectious diseases in the near future.
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•Sensitive detection of SARS-CoV-2 N and S antigens from wild-type, Alpha, Delta, and Omicron variants in artificial saliva.•Our direct SELFIA assay can be used for antibody/antigen pair screening.•Our competitive SELFIA assay serves as a precise quantitative diagnostic tool.
Abstract
Background
Human angiotensin-converting enzyme 2 (hACE2) is the receptor mediating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. hACE2 expression is low in the ...lungs and is upregulated after SARS-CoV-2 infection. How such a hACE2-limited pulmonary environment supports efficient virus transmission and how dynamic hACE2 expression affects SARS-CoV-2 infection are unclear.
Methods
We generated stable cell lines with different expression levels of hACE2 to evaluate how the hACE2 expression level can affect SARS-CoV-2 transmission.
Results
We demonstrated that the hACE2 expression level controls the mode of SARS-CoV-2 transmission. The hACE2-limited cells have an advantage for SARS-CoV-2 shedding, which leads to cell-free transmission. By contrast, enhanced hACE2 expression facilitates the SARS-CoV-2 cell-to-cell transmission. Furthermore, this cell-to-cell transmission is likely facilitated by hACE2-containing vesicles, which accommodate numerous SARS-CoV-2 virions and transport them to neighboring cells through intercellular extensions.
Conclusions
This hACE2-mediated switch between cell-free and cell-to-cell transmission routes provides SARS-CoV-2 with advantages for either viral spread or evasion of humoral immunity, thereby contributing to the COVID-19 pandemic and pathogenesis.
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