In plants, multiple detached tissues are capable of forming a pluripotent cell mass, termed callus, when cultured on media containing appropriate plant hormones. Recent studies demonstrated that ...callus resembles the root-tip meristem, even if it is derived from aerial organs. This finding improves our understanding of the regeneration process of plant cells; however, the molecular mechanism that guides cells of different tissue types to form a callus still remains elusive. Here, we show that genome-wide reprogramming of histone H3 lysine 27 trimethylation (H3K27me3) is a critical step in the leaf-to-callus transition. The Polycomb Repressive Complex 2 (PRC2) is known to function in establishing H3K27me3. By analyzing callus formation of mutants corresponding to different histone modification pathways, we found that leaf blades and/or cotyledons of the PRC2 mutants curly leaf swinger (clf swn) and embryonic flower2 (emf2) were defective in callus formation. We identified the H3K27me3-covered loci in leaves and calli by a ChIP-chip assay, and we found that in the callus H3K27me3 levels decreased first at certain auxin-pathway genes. The levels were then increased at specific leaf genes but decreased at a number of root-regulatory genes. Changes in H3K27me3 levels were negatively correlated with expression levels of the corresponding genes. One possible role of PRC2-mediated H3K27me3 in the leaf-to-callus transition might relate to elimination of leaf features by silencing leaf-regulatory genes, as most leaf-preferentially expressed regulatory genes could not be silenced in the leaf explants of clf swn. In contrast to the leaf explants, the root explants of both clf swn and emf2 formed calli normally, possibly because the root-to-callus transition bypasses the leaf gene silencing process. Furthermore, our data show that PRC2-mediated H3K27me3 and H3K27 demethylation act in parallel in the reprogramming of H3K27me3 during the leaf-to-callus transition, suggesting a general mechanism for cell fate transition in plants.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In this paper, a novel broadband Doherty power amplifier based on the continuous-mode technique (C-DPA) is proposed. The amplifier is focused on manipulating harmonic components in a Doherty power ...amplifier (DPA) structure to achieve improved bandwidth and efficiency. In a conventional DPA, harmonic isolation is typically required between the two transistors to prevent them from modulating each other at harmonic frequencies. However, as presented in this paper, such isolation is not actually necessary. On the contrary, by allowing the two transistors to modulate each other at harmonic frequencies with the help of a properly designed postharmonic tuning network, a series of highly efficient DPA modes can be created over a continuous frequency band, leading to a broadband C-DPA. Based on the proposed method, an example of a C-DPA working from 1.65 to 2.75 GHz was designed. According to the measured results, the designed C-DPA exhibits a 52%-66% efficiency at a -6 dB power backoff and a power utilization factor higher than 1.08 over the 1.1-GHz band. In addition, when simulated by a 7.5-dB peak-to-average power ratio 20-MHz LTE signal, the example C-DPA exhibits an efficiency of 46%-62% while maintaining an adjacent channel power ratio below -45 dBc after linearization over the full 1.1-GHz band. To the best of our knowledge, this is the first proposed C-DPA and a state-of-the-art performance for broadband DPAs.
Nuclear receptor subfamily 3 group C member 2 (NR3C2) has been revealed to affect the progression of multiple inflammatory diseases, while NR3C2's efficacy in coronary artery disease (CAD) remains ...largely unsolved. The study intended to elucidate the possible mechanisms of NR3C2 in oxidised low density lipoprotein (ox-LDL)-induced inflammation in human coronary endothelial cells (HCAECs) via regulating NACHT, LRR, and PYD domains-containing protein 3 (NLRP3). Patients who underwent CT angiography or coronary angiography for suspected CAD in our hospital were collected. The patients were divided into the CAD and the non-CAD (NCAD) groups. The expression of NR3C2 and NLRP3 in the peripheral blood of patients in both groups was examined by RT-qPCR. HCAECs were treated with ox-LDL to establish the model. The expression of NR3C2 and NLRP3 in ox-LDL-induced HCAECs was tested by RT-qPCR. The proliferation of HCAECs was measured using CCK-8 assay, the apoptosis of HCAECs was assessed by flow cytometry, and the levels of inflammation-related factors IL-1β and IL-18 in the cell supernatant were evaluated by ELISA. The molecular mechanisms of these factors in the proliferation and apoptosis of HCAECs and in the inflammatory response were further determined by knockdown and overexpression systems. The relationship between NR3C2 and NLRP3 was determined by ChIP and luciferase activity assays and bioinformatics analysis. NR3C2 and NLRP3 levels were elevated in the serum of CAD patients. The ox-LDL treatment elevated NR3C2 levels, evoked apoptosis and inflammation, and impeded cell viability in HCAECs, whereas downregulation of NR3C2 increased cell viability and reduced apoptosis and inflammatory response in ox-LDL-induced inflammation in HCAECs. NR3C2 levels were positively correlated with NLRP3, and NR3C2 elevated NLRP3 expression through transcription. Overexpression of NLRP3 counteracted the impacts of silencing NR3C2 on cell viability, cell apoptosis, and inflammatory response in ox-LDL-induced HCAECs. Our research stresses that NR3C2 transcription promotes NLRP3 to induce inflammatory responses in ox-LDL-induced HCAECs.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
We prepared new two-dimensional 3R TaS2 nanomaterials and investigated their application in hydrogen evolution reaction (HER) under acidic condition for the first time. The partial orientation ...aligned 3R TaS2 nanosheets show excellent electrocatalytic performance toward HER and outperform the corresponding 1T and 2H TaS2. Benefiting from the broken inversion symmetry and large exposed edge sites, the obtained 3R TaS2 nanomaterial exhibits optimized electrocatalytic activity for HER with onset overpotential as low as 106 mV, low Tafel slope of 85 mV decade–1 and high current density of 10 mA cm–2 at η = 196 mV. First-principles calculations suggest that the 3R TaS2 has more adsorption energies than 1T and 2H TaS2, confirming that the polymorph structures of TaS2 do influence their HER electrocatalytic performance. We expect that the control of polymorph structures can be an effective way to enhance the catalytic performance of transition-metal dichalcogenides (TMDs) in hydrogen evolution reaction and 3R TaS2 nanosheet is one of the most promising electrocatalysts for hydrogen production.
Background In China, mitral valve regurgitation (MR) is the most common cardiovascular valve disease. However, patients in China typically experience a high incidence of this condition, coupled with ...a low level of health knowledge and a relatively low rate of surgical treatment. TikTok hosts a vast amount of content related to diseases and health knowledge, providing viewers with access to relevant information. However, there has been no investigation or evaluation of the quality of videos specifically addressing MR. Objective This study aims to assess the quality of videos about MR on TikTok in China. Methods A cross-sectional study was conducted on the Chinese version of TikTok on September 9, 2023. The top 100 videos on MR were included and evaluated using quantitative scoring tools such as the modified DISCERN (mDISCERN), the Journal of the American Medical Association (JAMA) benchmark criteria, the Global Quality Score (GQS), and the Patient Education Materials Assessment Tool for Audio-Visual Content (PEMAT-A/V). Correlation and stepwise regression analyses were performed to examine the relationships between video quality and various characteristics. Results We obtained 88 valid video files, of which most (n=81, 92%) were uploaded by certified physicians, primarily cardiac surgeons, and cardiologists. News agencies/organizations and physicians had higher GQS scores compared with individuals (news agencies/organizations vs individuals, P=.001; physicians vs individuals, P=.03). Additionally, news agencies/organizations had higher PEMAT understandability scores than individuals (P=.01). Videos focused on disease knowledge scored higher in GQS (P<.001), PEMAT understandability (P<.001), and PEMAT actionability (P<.001) compared with videos covering surgical cases. PEMAT actionability scores were higher for outpatient cases compared with surgical cases (P<.001). Additionally, videos focused on surgical techniques had lower PEMAT actionability scores than those about disease knowledge (P=.04). The strongest correlations observed were between thumbs up and comments (r=0.92, P<.001), thumbs up and favorites (r=0.89, P<.001), thumbs up and shares (r=0.87, P<.001), comments and favorites (r=0.81, P<.001), comments and shares (r=0.87, P<.001), and favorites and shares (r=0.83, P<.001). Stepwise regression analysis identified “length (P<.001),” “content (P<.001),” and “physicians (P=.004)” as significant predictors of GQS. The final model (model 3) explained 50.1% of the variance in GQSs. The predictive equation for GQS is as follows: GQS = 3.230 − 0.294 × content − 0.274 × physicians + 0.005 × length. This model was statistically significant (P=.004) and showed no issues with multicollinearity or autocorrelation. Conclusions Our study reveals that while most MR-related videos on TikTok were uploaded by certified physicians, ensuring professional and scientific content, the overall quality scores were suboptimal. Despite the educational value of these videos, the guidance provided was often insufficient. The predictive equation for GQS developed from our analysis offers valuable insights but should be applied with caution beyond the study context. It suggests that creators should focus on improving both the content and presentation of their videos to enhance the quality of health information shared on social media.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Endocytosis and autophagy are the main pathways to deliver cargoes in vesicles and autophagosomes, respectively, to vacuoles/lysosomes in eukaryotes. Multiple positive regulators but few negative ...ones are reported to regulate the entry of vesicles and autophagosomes into vacuoles/lysosomes. In yeast, the Rab5 GTPase Vps21 and the ESCRT (endosomal sorting complex required for transport) are positive regulators in endocytosis and autophagy. During autophagy, Vps21 regulates the ESCRT to phagophores (unclosed autophagosomes) to close them. Phagophores accumulate on vacuolar membranes in both vps21∆ and ESCRT mutant cells under a short duration of nitrogen starvation. The vacuolar transport chaperon (VTC) complex proteins are recently found to be negative regulators in endocytosis and autophagy. Phagophores in vps21∆ cells are promoted to enter vacuoles when the VTC complex proteins are absent. Phagophores are easily observed inside vacuoles when any of these VTC complex proteins (Vtc1, 2, 4, 5) are removed. However, it is unknown whether the removal of VTC complex proteins will also promote the entry of phagophores into vacuoles in ESCRT mutant cells under the same conditions. Snf7 is a core subunit of ESCRT subcomplex III (ESCRT-III), and phagophores accumulate in snf7∆ cells under a short duration of nitrogen starvation. We used green fluorescence protein (GFP) labeled Atg8 to display phagophores and FM4-64-stained or Vph1-GFP-labeled membrane structures to show vacuoles, then examined fluorescence localization and GFP-Atg8 degradation in snf7∆ and snf7∆vtc4∆ cells. Results showed that Vtc4 depletion promoted the entry of phagophores in snf7∆ cells into vacuoles as it did for vps21∆ cells, although the promotion level was more obvious in vps21∆ cells. This observation indicates that the VTC complex proteins may have a widespread role in negatively regulating cargos to enter vacuoles in yeast.
Nonalcoholic steatohepatitis (NASH) is a key turning point during the progression of nonalcoholic fatty liver disease (NAFLD). Recent studies have shown that serum miRNA tests may be effective in the ...diagnosis of NAFLD. We conducted a meta-analysis to assess the evidence for the diagnostic efficacy of serum miRNAs in patients with NAFLD and its subtype, NASH, in particular.
After a systematic review, sensitivity, specificity, and area under the receiver operating characteristics curve (AUROC) were pooled to determine the efficacy of serum miRNA test for the diagnosis of NAFLD and NASH. Clinical utility was evaluated by Fagan's nomogram and likelihood ratio scattergram. Heterogeneity was evaluated by subgroup analysis and meta-regression. Publication bias was detected by Deeks' funnel plot.
We included 27 trials containing 1775 NAFLD patients (including simple steatosis and NASH) and 586 NASH patients. For NAFLD vs NASH, the pooled sensitivity, specificity, and AUROC were (0.71 vs. 0.74), (0.76 vs. 0.85) and (0.80 vs. 0.86), respectively. Serum miRNA had high accuracy for distinguishing NASH from simple steatosis, with an AUROC of 0.91. Among the most commonly studied serum miRNAs, miRNA-34a showed moderate diagnostic accuracy for NAFLD and the lowest heterogeneity (sensitivity I
= 5.73%, specificity I
= 33.16%, AUROC = 0.85). According to subgroup analysis and meta-regression, a lower BMI (< 30 kg/m
) might be a crucial source of heterogeneity.
As a novel non-invasive method, serum miRNA test exhibited robust diagnostic efficacy for NASH. Among these well-studied miRNAs, miRNA-34a was more available for diagnosis. Diagnosis of NAFLD by serum miRNA is more likely to be accurate in patients with BMI ≥ 30 kg/m
.
Celotno besedilo
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In this article, a fully integrated dual-band gallium nitride (GaN) Doherty power amplifier (DPA) based on multi-resonant circuits (MRCs) is presented. A lumped T-type network in combination with the ...output capacitances of the main and auxiliary transistors is able to realize the quarter-wavelength transformer (QWT) in DPA, and its component values are totally decided by the operating frequency, given a certain characteristic impedance. MRCs are proposed to exhibit the required component values at two different frequencies. By replacing each component in the T-type network with an MRC, a dual-band QWT can be achieved. An integrated dual-band DPA is implemented in a commercial 0.25-<inline-formula> <tex-math notation="LaTeX">\mu \text{m} </tex-math></inline-formula> GaN-HEMT process to validate the proposed method. The fabricated DPA shows a saturated output power of 43.8-44.7/44.4-44.8 dBm, a 6-dB back-off drain efficiency (DE) of 41%-46%/41.5%-47%, and a saturated DE of 49%-52%/56%-59% in 3.35-3.6/4.8-5.2 GHz, with a compact size of <inline-formula> <tex-math notation="LaTeX">2.8\times3.5 </tex-math></inline-formula> mm 2 . Applying a 100-MHz OFDM signal with a 7.8-dB peak-to-average power ratio (PAPR), an average efficiency of 37%/40% and an average power of 37/37 dBm are measured at 3.5/5.0 GHz, and the adjacent channel power ratio (ACPR) is better than −49 dBc after digital predistortion (DPD). To the best of our knowledge, the proposed DPA is the first demonstration of fully integrated dual-band GaN DPAs.
In the widespread adoption of chemotherapy, drug resistance has been the major obstacle to tumor elimination in cancer patients. Our aim was to explore the role of TGF-β in osteosarcoma-associated ...chemoresistance.
We performed a cytotoxicity analysis of methotrexate (MTX) and cisplatin (CIS) in TGF-β-treated osteosarcoma cells. Then, the metabolite profile of the core metabolic energy pathways in Saos-2 and MG-63 cell extracts was analyzed by
H-NMR. We detected the expression of succinate dehydrogenase (SDH), STAT1, and hypoxia-inducible factor 1α (HIF1α) in TGF-β-treated osteosarcoma cells and further tested the effects of these molecules on the cytotoxicity induced by chemotherapeutic agents. Using in vivo experiments, we examined the tumor growth and survival time of Saos-2-bearing mice treated with a combination of chemotherapeutic agents and a HIF1α inhibitor.
The metabolic analysis revealed enhanced succinate production in osteosarcoma cells after TGF-β treatment. We further found a decrease in SDH expression and an increase in HIF1α expression in TGF-β-treated osteosarcoma cells. Consistently, blockade of SDH efficiently enhanced the resistance of Saos-2 and MG-63 cells to MTX and CIS. Additionally, a HIF1α inhibitor significantly strengthened the anticancer efficacy of the chemotherapeutic drugs in mice with osteosarcoma cancer.
Our study demonstrated that TGF-β attenuated the expression of SDH by reducing the transcription factor STAT1. The reduction in SDH then caused the upregulation of HIF1α, thereby rerouting glucose metabolism and aggravating chemoresistance in osteosarcoma cells. Linking tumor cell metabolism to the formation of chemotherapy resistance, our study may guide the development of additional treatments for osteosarcoma.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The behavior of power amplifiers (PAs) driven by concurrent dual-band signals is analyzed theoretically in this paper. According to the analysis, the impedance matching at intermodulation (IM) ...frequency is very important for PAs working in concurrent mode. Based on the concept of IM impedance tuning, a family of new operation modes can be introduced, including concurrent Class-A, Class-AB, Class-B, and Class-C. The theoretical performance of these modes are derived and the overdrive effects of them are also discussed. A possible structure is proposed to implement the proposed IM impedance tuning, and a concurrent Class-AB dual-band example PA operating at 1.9-2.6-GHz long-term evolution (LTE) bands is demonstrated. Experimental results show good consistence with the theoretical analysis, and the concurrent Class-AB PA prototype exhibits higher than 36.1% power-added efficiency in concurrent mode when driven by 10- and 15-MHz LTE signals in two bands concurrently. To our best knowledge, this is the state-of-the-art efficiency performance of concurrent dual-band PAs, even higher than previously reported dual-band Doherty PAs. Additionally the proposed PA, which is fabricated using a 10-W GaN HEMT, can output more than 34.3-dBm power with a peak-to-average ratio of 7 dB in concurrent mode, showing a remarkable power utilization factor for concurrent dual-band PAs.