Explore the vast range of titles available.

Cumulus cells (CCs) originating from undifferentiated granulosa cells (GCs) differentiate in mural granulosa cells (MGCs) and CCs during antrum formation in the follicle by the distribution of location. CCs are supporting cells of the oocyte that protect the oocyte from the microenvironment, which helps oocyte growth and maturation in the follicles. Bi-directional communications between an oocyte and CCs are necessary for the oocyte for the acquisition of maturation and early embryonic developmental competence following fertilization. Follicle-stimulation hormone (FSH) and luteinizing hormone (LH) surges lead to the synthesis of an extracellular matrix in CCs, and CCs undergo expansion to assist meiotic resumption of the oocyte. The function of CCs is involved in the completion of oocyte meiotic maturation and ovulation, fertilization, and subsequent early embryo development. Therefore, understanding the function of CCs during follicular development may be helpful for predicting oocyte quality and subsequent embryonic development competence, as well as pregnancy outcomes in the field of reproductive medicine and assisted reproductive technology (ART) for infertility treatment.

Abstract The lack of highly efficient, inexpensive catalysts severely hinders large-scale application of electrochemical hydrogen evolution reaction (HER) for producing hydrogen. MoS 2 as a low-cost candidate suffers from low catalytic performance. Herein, taking advantage of its tri-layer structure, we report a MoS 2 nanofoam catalyst co-confining selenium in surface and cobalt in inner layer, exhibiting an ultra-high large-current-density HER activity surpassing all previously reported heteroatom-doped MoS 2 . At a large current density of 1000 mA cm −2 , a much lower overpotential of 382 mV than that of 671 mV over commercial Pt/C catalyst is achieved and stably maintained for 360 hours without decay. First-principles calculations demonstrate that inner layer-confined cobalt atoms stimulate neighbouring sulfur atoms while surface-confined selenium atoms stabilize the structure, which cooperatively enable the massive generation of both in-plane and edge active sites with optimized hydrogen adsorption activity. This strategy provides a viable route for developing MoS 2 -based catalysts for industrial HER applications.

Identifying novel drug targets to overcome resistance to tyrosine kinase inhibitors (TKIs) and eradicating leukemia stem/progenitor cells are required for the treatment of chronic myelogenous leukemia (CML). Here, we show that ubiquitin-specific peptidase 47 (USP47) is a potential target to overcome TKI resistance. Functional analysis shows that USP47 knockdown represses proliferation of CML cells sensitive or resistant to imatinib in vitro and in vivo. The knockout of Usp47 significantly inhibits BCR-ABL and BCR-ABL -induced CML in mice with the reduction of Lin Sca1 c-Kit CML stem/progenitor cells. Mechanistic studies show that stabilizing Y-box binding protein 1 contributes to USP47-mediated DNA damage repair in CML cells. Inhibiting USP47 by P22077 exerts cytotoxicity to CML cells with or without TKI resistance in vitro and in vivo. Moreover, P22077 eliminates leukemia stem/progenitor cells in CML mice. Together, targeting USP47 is a promising strategy to overcome TKI resistance and eradicate leukemia stem/progenitor cells in CML.

Under investigation in this paper are the (2+1)-dimensional Davey–Stewartson-like equations, which can be used to describe the slow modulation of (2+1)-dimensional electrostatic wave packets in the ultra-relativistic degenerate dense plasmas. With figures plotted, stable propagation of the one solitons and elastic collisions between the two solitons are, respectively, analyzed. Moreover, influences of the parameters χ 1 and χ 5 on the dark solitons are illustrated in detail, where χ 1 arises because of the evolution of the electrostatic wave packets and wave group dispersion, and χ 5 rests with the zeroth harmonic static field of the plasmas: Widths of the solitons become narrower with the value of χ 1 increasing; meanwhile, amplitudes of the one solitons become lower and velocities of the two solitons alter. With the decrease of χ 5 , amplitudes become lower for the one solitons but higher for the two solitons.

pH is an important property of aerosol particles but is difficult to measure directly. Several studies have estimated the pH values for fine particles in northern China winter haze using thermodynamic models (i.e., E-AIM and ISORROPIA) and ambient measurements. The reported pH values differ widely, ranging from close to 0 (highly acidic) to as high as 7 (neutral). In order to understand the reason for this discrepancy, we calculated pH values using these models with different assumptions with regard to model inputs and particle phase states. We find that the large discrepancy is due primarily to differences in the model assumptions adopted in previous studies. Calculations using only aerosol-phase composition as inputs (i.e., reverse mode) are sensitive to the measurement errors of ionic species, and inferred pH values exhibit a bimodal distribution, with peaks between −2 and 2 and between 7 and 10, depending on whether anions or cations are in excess. Calculations using total (gas plus aerosol phase) measurements as inputs (i.e., forward mode) are affected much less by these measurement errors. In future studies, the reverse mode should be avoided whereas the forward mode should be used. Forward-mode calculations in this and previous studies collectively indicate a moderately acidic condition (pH from about 4 to about 5) for fine particles in northern China winter haze, indicating further that ammonia plays an important role in determining this property. The assumed particle phase state, either stable (solid plus liquid) or metastable (only liquid), does not significantly impact pH predictions. The unrealistic pH values of about 7 in a few previous studies (using the standard ISORROPIA model and stable state assumption) resulted from coding errors in the model, which have been identified and fixed in this study.

Leveraging data from various modalities to enhance multimodal segmentation tasks is a well-regarded approach. Recently, efforts have been made to incorporate an array of modalities, including depth and thermal imaging. Nevertheless, the effective amalgamation of cross-modal interactions remains a challenge, given the unique traits each modality presents. In our current research, we introduce the semantic guidance fusion network (SGFN), which is an innovative cross-modal fusion network adept at integrating a diverse set of modalities. Particularly, the SGFN features a semantic guidance module (SGM) engineered to boost bi-modal feature extraction. It encompasses a learnable semantic guidance convolution (SGC) designed to merge intensity and gradient data from disparate modalities. Comprehensive experiments carried out on the NYU Depth V2, SUN-RGBD, Cityscapes, MFNet, and ZJU datasets underscore both the superior performance and generalization ability of the SGFN compared to the current leading models. Moreover, when tested on the DELIVER dataset, the efficiency of our bi-modal SGFN displayed a mIoU that is comparable to the hitherto leading model, CMNEXT.

Coagulation factor IX (FIX) is a vitamin K dependent protein and its deficiency causes hemophilia B, an X-linked recessive bleeding disorder. More than 1000 mutations in the gene have been identified in hemophilia B patients. Here, we systematically summarize the structural and functional characteristics of FIX and the pathogenic mechanisms of the mutations that have been identified to date. The mechanisms of FIX deficiency are diverse in these mutations. Deletions, insertions, duplications, and indels generally lead to severe hemophilia B. Those in the exon regions generate either frame shift or inframe mutations, and those in the introns usually cause aberrant splicing. Regarding point mutations, the bleeding phenotypes vary from severe to mild in hemophilia B patients. Generally speaking, point mutations in the promoter region result in hemophilia B Leyden, and those in the introns cause aberrant splicing. Point mutations in the coding sequence can be missense, nonsense, or silent mutations. Nonsense mutations generate truncated FIX that usually loses function, causing severe hemophilia B. Silent mutations may lead to aberrant splicing or affect FIX translation. The mechanisms of missense mutation, however, have not been fully understood. They lead to FIX deficiency, often by affecting FIX's translation, protein folding, protein stability, posttranslational modifications, activation to FIXa, or the ability to form functional Xase complex. Understanding the molecular mechanisms of FIX deficiency will provide significant insight for patient diagnosis and treatment.

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. However, there still remains a lack of effective diagnostic and therapeutic targets for this disease. Increasing evidence demonstrates that RNA modifications play an important role in the progression of HCC, but the role of the N7-methylguanosine (m7G) methylation modification in HCC has not been properly evaluated. Thus, the goal of the present study was to investigate the function and mechanism of the m7G methyltransferase WD repeat domain 4 (WDR4) in HCC as well as its clinical relevance and potential value. We first verified the high expression of WDR4 in HCC and observed that upregulated WDR4 expression increased the m7G methylation level in HCC. WDR4 promoted HCC cell proliferation by inducing the G2/M cell cycle transition and inhibiting apoptosis in addition to enhancing metastasis and sorafenib resistance through epithelial-mesenchymal transition (EMT). Furthermore, we observed that c-MYC (MYC) can activate WDR4 transcription and that WDR4 promotes CCNB1 mRNA stability and translation to enhance HCC progression. Mechanistically, we determined that WDR4 enhances CCNB1 translation by promoting the binding of EIF2A to CCNB1 mRNA. Furthermore, CCNB1 was observed to promote PI3K and AKT phosphorylation in HCC and reduce P53 protein expression by promoting P53 ubiquitination. In summary, we elucidated the MYC/WDR4/CCNB1 signalling pathway and its impact on PI3K/AKT and P53. Furthermore, the result showed that the m7G methyltransferase WDR4 is a tumour promoter in the development and progression of HCC and may act as a candidate therapeutic target in HCC treatment.

Previous studies have shown the potential of immunogenic cell death-related modalities in myeloma. The significance of IL5RA in myeloma and immunogenic cell death remains unknown. We analyzed IL5RA expression, the gene expression profile, and secretory protein genes related to IL5RA level using GEO data. Immunogenic cell death subgroup classification was performed using the ConsensusClusterPlus and pheatmap R package. Enrichment analyses were based on GO/KEGG analysis. After IL5RA-shRNA transfection in myeloma cells, cell proliferation, apoptosis, and drug sensitivity were detected. P < 0.05 was considered statistically significant. IL5RA was upregulated in myeloma and progressed smoldering myeloma. We observed enrichment in pathways such as the PI3K-Akt signaling pathway, and Natural killer cell mediated cytotoxicity in the high-IL5RA group. IL5RA was also closely associated with secretory protein genes such as CST6. We observed the enrichment of cellular apoptosis and hippo signaling pathway on differential genes in the immunogenic cell death cluster. Furthermore, IL5RA was associated with immune infiltration, immunogenic cell death-related genes, immune-checkpoint-related genes, and m6A in myeloma. In vitro and in vivo experiments showed the involvement of IL5RA in apoptosis, proliferation, and drug resistance of myeloma cells. IL5RA shows the potential to be an immunogenic cell death-related predictor for myeloma.

Abstract China’s nationwide monitoring network initiated in 2013 has witnessed continuous increases of urban summertime surface ozone to 2019 by about 5% year −1 , among the fastest ozone trends in the recent decade reported in the Tropospheric ozone assessment report. Here we report that surface ozone levels averaged over cities in eastern China cities decrease by 5.5 ppbv in May–August 2020 compared to the 2019 levels, representing an unprecedented ozone reduction since 2013. We combine the high-resolution GEOS-Chem chemical model and the eXtreme Gradient Boosting (XGBoost) machine learning model to quantify the drivers of this reduction. We estimate that changes in anthropogenic emissions alone decrease ozone by 3.2 (2.9–3.6) ppbv (57% of the total 5.5 ppbv reduction) averaged over cities in eastern China and by 2.5 ∼ 3.2 ppbv in the three key city clusters for ozone mitigation. These reductions appear to be driven by decreases in anthropogenic emissions of both nitrogen oxides (NO x ) and volatile organic compounds, likely reflecting the stringent emission control measures implemented by The Chinese Ministry of Environmental and Ecology in summer 2020, as supported by observed decline in tropospheric formaldehyde (HCHO) and nitrogen dioxides (NO 2 ) from satellite and by bottom-up emission estimates. Comparable to the emission-driven ozone reduction, the wetter and cooler weather conditions in 2020 decrease ozone by 2.3 (1.9–2.6) ppbv (43%). Our analyses indicate that the current emission control strategies can be effective for ozone mitigation in China yet tracking future ozone changes is essential for further evaluation. Our study also reveals important potential to combine the mechanism-based, state-of-art atmospheric chemical models with machine learning model to improve the attribution of ozone drivers.