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To enhance the performance and widespread use of solid oxide fuel cells (SOFCs), addressing the low-temperature (< 650 °C) electrochemical performance and operational stability issues of cathode materials is crucial. Here, we propose an innovative approach to enhance oxygen ion mobility and electrochemical performance of perovskite oxide by substituting some oxygen sites with chlorine anions. The designed SrTa0.1Fe0.9O3-δ-xClx (x = 0.05 and 0.10) exhibits improved performance compared to SrTa0.1Fe0.9O3-δ (STF). SrTa0.1Fe0.9O2.95-δCl0.05 (STFCl0.05) shows the lowest area-specific resistance (ASR) value on Sm0.2Ce0.8O1.9 (SDC) electrolyte. At 600 °C, STFCl0.05 achieves an ASR value of 0.084 Ω·cm2, and a single cell with STFCl0.05 reaches a higher peak power density (PPD) value (1143 mW·cm-2) than that with STF (672 mW·cm-2). Additionally, besides exhibiting excellent oxygen reduction reaction (ORR) activity at lower temperatures, the STFCl0.05 cathode demonstrates good CO2 tolerance and operational stability. Symmetrical cell operation lasts for 150 h, and single cell operation endures for 720 h without significant performance decline. The chlorine doping approach effectively enhances ORR activity and stability, making STFCl0.05 a promising cathode material for low-temperature SOFCs. [ABSTRACT FROM AUTHOR]

To explore highly active and thermomechanical stable air electrodes for intermediate-temperature solid oxide fuel cells (IT-SOFCs), 10mol% Ta5+ doped in the B site of strontium ferrite perovskite oxide (SrTa0.1Fe0.9O3−δ, STF) is investigated and optimized. The effects of Ta5+ doping on structure, transition metal reduction, oxygen nonstoichiometry, thermal expansion, and electrical performance are evaluated systematically. Via 10mol% Ta5+ doping, the thermal expansion coefficient (TEC) decreased from 34.1 × 10−6 (SrFeO3−δ) to 14.6 × 10−6 K−1 (STF), which is near the TEC of electrolyte (13.3 × 10−6 K−1 for Sm0.2Ce0.8O1.9, SDC), indicates excellent thermomechanical compatibility. At 550–750°C, STF shows superior oxygen vacancy concentrations (0.262 to 0.331), which is critical in the oxygen-reduction reaction (ORR). Oxygen temperature-programmed desorption (O2-TPD) indicated the thermal reduction onset temperature of iron ion is around 420°C, which matched well with the inflection points on the thermos-gravimetric analysis and electrical conductivity curves. At 600°C, the STF electrode shows area-specific resistance (ASR) of 0.152 Ω·cm2 and peak power density (PPD) of 749 mW·cm−2. ORR activity of STF was further improved by introducing 30wt% Sm0.2Ce0.8O1.9 (SDC) powder, STF + SDC composite cathode achieving outstanding ASR value of 0.115 Ω·cm2 at 600°C, even comparable with benchmark cobalt-containing cathode, Ba0.5Sr0.5Co0.8Fe0.2O3−δ (BSCF). Distribution of relaxation time (DRT) analysis revealed that the oxygen surface exchange and bulk diffusion were improved by forming a composite cathode. At 650°C, STF + SDC composite cathode achieving an outstanding PPD of 1117 mW·cm−2. The excellent results suggest that STF and STF + SDC are promising air electrodes for IT-SOFCs. [ABSTRACT FROM AUTHOR]

The oxygen reduction reaction (ORR) catalyzed by efficient and economical catalysts is critical for sustainable energy devices. Although the newly-emerging atomically dispersed platinum catalysts are highly attractive for maximizing atomic utilization, their catalytic selectivity and durability are severely limited by the inflexible valence transformation between Pt and supports. Here, we present a structure by anchoring Pt atoms onto valence-adjustable CuOx/Cu hybrid nanoparticle supports (Pt1-CuOx/Cu), in which the high-valence Cu (+2) in CuOx combined with zero-valent Cu (0) serves as a wide-range valence electron reservoir (0‒2e) to dynamically adjust the Pt 5d valence states during the ORR. In situ spectroscopic characterizations demonstrate that the dynamic evolution of the Pt 5d valence electron configurations could optimize the adsorption strength of *OOH intermediate and further accelerate the dissociation of O = O bonds for the four-electron ORR. As a result, the Pt1-CuOx/Cu catalysts deliver superior ORR performance with a significantly enhanced four-electron selectivity of over 97% and long-term durability. The electrochemical oxygen reduction reaction catalyzed by efficient and economical catalysts is critically important for sustainable energy devices. Here the authors report anchoring Pt atoms onto valence-adjustable CuOx/Cu hybrid nanoparticle to dynamically tune the Pt 5d valence states at the initial reaction stage for optimizing oxygen reduction performance. [ABSTRACT FROM AUTHOR]

Shellfish waste with non-metallic fractions from waste printed circuit boards (D-NMFs and W-NMFs) were used to reinforce polypropylene (PP). Thermal stability and mechanical properties were investigated, supplemented by finite element analysis, to investigate the reinforcement mechanism. Thermal property studies revealed a significant strengthening of the PP matrix upon NMFs incorporation. Final decomposition temperature increased from 391ºC for pure PP to 415ºC and 420ºC with 15 wt.% NMFs, and further reached ~ 435ºC and ~ 430ºC with clam and crab shell. Regarding mechanical properties, NMFs inclusion, especially W-NMFs, significantly elevated the composites' stiffness. Tensile modulus, along with flexural strength and flexural modulus increased from 917.31 MPa, 33.02 MPa, and 509.24 MPa for pure PP to 1368.82 MPa, 54.95 MPa, and 1678.12 MPa, respectively, for composites with 15 wt.% W-NMFs. NMFs/PP composites filled with shells, especially clam shells, could further improve the filling effect. The tensile modulus, along with flexural strength, increased from 1379.04 MPa, 52.97 MPa, and 1103.49 MPa to 1579.05 MPa, 54.72 MPa, and 1918.96 MPa, respectively, for composites containing 10 wt.% W-NMFs and 15 wt.% clam shell. [ABSTRACT FROM AUTHOR]

Purpose: Adrenal and extra-adrenal paragangliomas (PGLs) are a group of neuroendocrine tumors (NETs) with strong heterogeneity, which often express somatostatin receptor subtype 2 A (SSTR2A). However, the association between SSTR2A expression and genetic status of PGLs remains unclear. The purpose of the study was to identify whether various pathogenic variants (PVs) had an impact on SSTR2A expression in PGLs. Methods: This retrospective study included 184 patients with pathologically confirmed PGLs. The immunohistochemical expression of SSTR2A were studied in 184 tumors and PVs were tested in 159 tumor samples. Clinical and genetic data were compared in SSTR2A positive and negative PGLs. Results: SSTR2A was positive in 63.6% (117/184) of all tumors. PGLs with negative SSTR2A were more likely to be extra-adrenal (37.0% vs 18.0%; P = 0.005) and exhibited a considerably greater proportion of PVs (75.4% vs. 49.0%; P = 0.001) than those with positive SSTR2A. Compared to those without PVs, a higher proportion of PGLs with PVs in cluster 1B (P = 0.004) and cluster 2 (P = 0.004) genes, especially VHL (P = 0.009), FGFR1 (P = 0.010) and HRAS (P = 0.007), were SSTR2A negative. SSTR2A was positive in all tumors (4/4) with SDHx PVs and in 87.5% (7/8) of metastatic PGLs. Conclusions: SSTR2A negativity was correlated with extra-adrenal tumor location and PVs in cluster 1B and cluster 2 genes such as VHL, FGFR1 and HRAS. Immunohistochemistry of SSTR2A should be taken into consideration in the personalized management of PGLs. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC), a globally common cancer, often presents late and shows high resistance to chemotherapy, resulting in suboptimal treatment efficacy. Components from traditional Chinese medicines have been recognized for their anti-cancer properties. Objective: Exploring the mechanism of Schisandra chinensis lignans and acteoside in suppressing Epithelial-Mesenchymal Transition (EMT) in hepatoma cells through the Extracellular signal-Regulated Kinases (ERK)1/2 pathway and identifying biomarkers, molecular subtypes, and targets via multi-omics for precision oncology. Methods: Proliferation was assessed using cell counting kit-8 (CCK-8) assays, with scratch and transwell assays for evaluating invasion and migration. Flow cytometry quantified apoptosis rates. Expression levels of CCL20, p-ERK1/2, c-Myc, Vimentin, and E-cadherin/N-cadherin were analyzed by real-time PCR and Western blot. Tumor volume was calculated with a specific formula, and growth. Results: The Schisandra chinensis lignans and acteoside combination decreased CCL20 expression, inhibited hepatoma proliferation and migration, and enhanced apoptosis in a dose- and time-dependent manner. Molecular analysis revealed increased E-cadherin and decreased N-cadherin, p-ERK1/2, c-Myc, and Vimentin expression, indicating ERK1/2 pathway modulation. In vivo, treated nude mice showed significantly reduced tumor growth and volume. Conclusion: Schisandra chinensis lignans and acteoside potentially counteract CCL20-induced EMT, invasion, and migration in hepatocellular carcinoma cells via the ERK1/2 pathway, enhancing apoptosis. Multi-omics analysis further aids in pinpointing novel biomarkers for precision cancer therapy. [ABSTRACT FROM AUTHOR]

Air pollution poses a serious challenge to public health and simultaneously exacerbating regional & intergenerational health inequality. This research introduces PM2.5 pollution into the intergenerational health transmission model, and estimates its impact on health inequality in China using Ordered Logit Regression (OLR) and Multi-scale Geographically Weighted Regression (MGWR) model. The results indicate that PM2.5 pollution exacerbate the intergenerational health inequality, and its impacts show inconsistency across family income levels, parental health insurance status, and area of residence. Specifically, it is more difficult for offspring in low-income families to escape from the influence of unhealthy family to become upwardly mobile. Additionally, this health inequality is more significant in households in which at least one parent does not have health insurance. Moreover, the intergenerational solidification caused by PM2.5 pollution is higher in the east and lower in the west. Both the PM2.5 level and solidification effect are high in Beijing–Tianjin–Hebei region, Yangtze River Delta region and central areas of China, which is the focus of air pollution management. These findings suggest that more emphasis should be placed on family-based health promotion. In areas with high PM2.5 pollution levels, resources, subsidies and air pollution protection should be provided for less healthy families with lower incomes and no health insurance. [ABSTRACT FROM AUTHOR]

Semantic segmentation has wide applications in computer vision tasks. Due to the high labor cost of pixel-level annotation, weakly supervised semantic segmentation(WSSS) methods based on image-level labels have become an important research topic. However, existing WSSS based on image-level labels has problems such as sparse segmentation results and inaccurate object boundaries. To overcome these problems, we propose a novel locate-then-segment framework that separates the localization process and segmentation process of WSSS. During the localization process we use class activation map(CAM) to locate the rough position of the object as most WSSS methods do. During the segmentation process, we focused on designing the object segmenter to refine the CAM to obtain the pseudo mask. The object segmenter consists of a dual localization feature fusion module and a boundary enhancement decoder. The former effectively extracts the semantic features of the object and finds the whole object; the latter judges long-range pixels to search for the exact object boundary. Additionally, we utilize extra pixel-level labels to train our object segmenter and add some constraints to optimize its training process. Finally, we apply the trained object segmenter to weakly supervised segmented data to improve the prediction results of CAM. Experimental results show that our proposed method significantly improves the quality of pseudo masks and obtains competitive segmentation results. Compared to existing methods, our method has the best result on the PASCAL VOC 2012 validation set with 68.8 % mIoU and the competitive result on the test set with 67.9 % mIoU. Our method outperforms all CNN-based methods on the MS COCO 2014 validation set, second only to transformer-based methods, achieving 36.5 % mIoU. Code is available at https://github.com/wjlbnw/SegmentationFromLocalization. [ABSTRACT FROM AUTHOR]

RAS oncogenes (collectively NRAS, HRAS and especially KRAS) are among the most frequently mutated genes in cancer, with common driver mutations occurring at codons 12, 13 and 611. Small molecule inhibitors of the KRAS(G12C) oncoprotein have demonstrated clinical efficacy in patients with multiple cancer types and have led to regulatory approvals for the treatment of non-small cell lung cancer2,3. Nevertheless, KRASG12C mutations account for only around 15% of KRAS-mutated cancers4,5, and there are no approved KRAS inhibitors for the majority of patients with tumours containing other common KRAS mutations. Here we describe RMC-7977, a reversible, tri-complex RAS inhibitor with broad-spectrum activity for the active state of both mutant and wild-type KRAS, NRAS and HRAS variants (a RAS(ON) multi-selective inhibitor). Preclinically, RMC-7977 demonstrated potent activity against RAS-addicted tumours carrying various RAS genotypes, particularly against cancer models with KRAS codon 12 mutations (KRASG12X). Treatment with RMC-7977 led to tumour regression and was well tolerated in diverse RAS-addicted preclinical cancer models. Additionally, RMC-7977 inhibited the growth of KRASG12C cancer models that are resistant to KRAS(G12C) inhibitors owing to restoration of RAS pathway signalling. Thus, RAS(ON) multi-selective inhibitors can target multiple oncogenic and wild-type RAS isoforms and have the potential to treat a wide range of RAS-addicted cancers with high unmet clinical need. A related RAS(ON) multi-selective inhibitor, RMC-6236, is currently under clinical evaluation in patients with KRAS-mutant solid tumours (ClinicalTrials.gov identifier: NCT05379985).RMC-7977, a compound that exhibits potent inhibition of the active states of mutant and wild-type KRAS, NRAS and HRAS variants has a strong anti-tumour effect on RAS-addicted tumours and is well tolerated in preclinical models. [ABSTRACT FROM AUTHOR]

Broad-spectrum RAS inhibition has the potential to benefit roughly a quarter of human patients with cancer whose tumours are driven by RAS mutations1,2. RMC-7977 is a highly selective inhibitor of the active GTP-bound forms of KRAS, HRAS and NRAS, with affinity for both mutant and wild-type variants3. More than 90% of cases of human pancreatic ductal adenocarcinoma (PDAC) are driven by activating mutations in KRAS4. Here we assessed the therapeutic potential of RMC-7977 in a comprehensive range of PDAC models. We observed broad and pronounced anti-tumour activity across models following direct RAS inhibition at exposures that were well-tolerated in vivo. Pharmacological analyses revealed divergent responses to RMC-7977 in tumour versus normal tissues. Treated tumours exhibited waves of apoptosis along with sustained proliferative arrest, whereas normal tissues underwent only transient decreases in proliferation, with no evidence of apoptosis. In the autochthonous KPC mouse model, RMC-7977 treatment resulted in a profound extension of survival followed by on-treatment relapse. Analysis of relapsed tumours identified Myc copy number gain as a prevalent candidate resistance mechanism, which could be overcome by combinatorial TEAD inhibition in vitro. Together, these data establish a strong preclinical rationale for the use of broad-spectrum RAS-GTP inhibition in the setting of PDAC and identify a promising candidate combination therapeutic regimen to overcome monotherapy resistance.RMC-7977, a multi-selective RAS(ON) inhibitor, exhibits potent tumour-selective activity in multiple pre-clinical models of pancreatic ductal adenocarcinoma through a combination of pharmacology and oncogene dependence. [ABSTRACT FROM AUTHOR]

Existing monocular depth estimation driving datasets are limited in the number of images and the diversity of driving conditions. The images of datasets are commonly in a low resolution and the depth maps are sparse. To overcome these limitations, we produce a Synthetic Digital City Dataset (SDCD) which was collected under 6 different weather driving conditions, and 6 common adverse perturbations caused by the data transmission. SDCD provides a total of 930 K high-resolution RGB images and corresponding perfect observed depth maps. The evaluation shows that depth estimation models which are trained on SDCD provide a clearer, smoother, and more precise long-range depth estimation compared to those trained on one of the best-known driving datasets KITTI. Moreover, we provide a benchmark to investigate the performance of depth estimation models in different adverse driving conditions. Instead of collecting data from the real world, we generate the SDCD under severe driving conditions with perfect observed data in the digital world, enhancing depth estimation for autonomous driving. [ABSTRACT FROM AUTHOR]

Methyltransferase-like protein 7A (METTL7A) is an m6A RNA methyltransferase that has been linked to cancer prognosis and drug resistance. However, a comprehensive analysis of METTL7A is lacking. The expression of METTL7A, prognostic performance, correlation with microsatellite instability (MSI), tumor mutational burden (TMB), and immune infiltration was investigated in The Cancer Genome Atlas (TCGA). Immunohistochemistry staining was applied to detect METTL7A in 6 tumors. METTL7A was significantly decreased in 19 cancers in TCGA including LUAD. Alterations of METTL7A include amplification and mutation, and epigenetic alterations revealed increased promoter methylation may result in down-regulation of METTL7A in LUAD. We also found that METTL7A was linked to both TMB and MSI in LUAD. METTL7A was increasingly correlated with invasive immune cells, while being negatively associated with Macrophages M0, Mast cells activated, activated memory CD4 T cells, CD8 T cells, and follicular helper T cells in several tumors. Additionally, METTL7A showed similar correlation with immune therapy-related genes across cancers. Our biological validation found that the protein levels of METTL7A were down-regulated in breast cancer (BRCA), endometrioid cancer (UCEC), colon cancer (COAD), prostate cancer (PRAD), and kidney clear cell carcinoma (KIRC), as detected by immunohistochemistry staining. Overall, our work indicates that METTL7A may serve as promising diagnostic and prognostic indicator of LUAD, and our work sheds light on the potential immunological and prognostic roles of METTL7A in human cancers. [ABSTRACT FROM AUTHOR]

Partly interval censoring is frequently encountered in clinical trials when the failure time of an event is observed exactly for some subjects but is only known to fall within an observed interval for others. Although this kind of censoring has drawn recent attention in survival analysis, available methods typically assume that the observed interval is independent of the failure time and that all potential predictors can be fully observable. However, the above assumptions may not be valid in practice. This paper considers a new joint modeling approach to simultaneously model the failure and observation times and correlate these two stochastic processes through shared latent factors. The proposed model comprises a transformation model for the failure time of interest, a proportional hazards model for the length of censoring interval, and a factor analysis model for characterization of the latent factors. A multi-stage data augmentation procedure is introduced to tackle the challenges posed by the complex model and data structure. A Bayesian approach coupled with monotone spline approximation and Markov chain Monte Carlo techniques is developed to estimate the unknown parameters and nonparametric functions. The satisfactory performance of the proposed method is demonstrated through simulations, and it is then applied to a Framingham Heart study. [ABSTRACT FROM AUTHOR]

Benefiting from large-scale pretrained vision language models (VLMs), the performance of visual question answering (VQA) has approached human oracles. However, finetuning such models on limited data often suffers from overfitting and poor generalization issues, leading to a lack of model robustness. In this paper, we aim to improve input robustness from an information bottleneck perspective when adapting pretrained VLMs to the downstream VQA task. Input robustness refers to the ability of models to defend against visual and linguistic input variations, as well as shortcut learning involved in inputs. Generally, the representations obtained by pretrained VLMs inevitably contain irrelevant and redundant information for a specific downstream task, resulting in statistically spurious correlations and insensitivity to input variations. To encourage representations to converge to a minimal sufficient statistic in multimodal learning, we propose Correlation Information Bottleneck (CIB), which seeks a tradeoff between compression and redundancy in representations by minimizing the mutual information (MI) between inputs and representations while maximizing the MI between outputs and representations. Moreover, we derive a tight theoretical upper bound for the mutual information between multimodal inputs and representations, incorporating different internal correlations that guide models to learn more robust representations and facilitate modality alignment. Extensive experiments consistently demonstrate the effectiveness and superiority of the proposed CIB in terms of input robustness and accuracy. [ABSTRACT FROM AUTHOR]

TRP channels have an important role in regulating the function of gastrointestinal epithelial cells. The aim of this study was to investigate the molecular mechanisms of genes associated with TRP channels in Crohn's disease (CD) by bioinformatics approach and to identify potential key biomarkers. In our study, we identified TRP channel-related differentially expressed genes (DEGs) based on the GSE95095 dataset and the TRP channel-related gene set from the GeneCards database. Hub genes (CXCL8, HIF1A, NGF, JUN, IL1A) were identified by the PPI network and validated by the external GSE52746 dataset. Immune infiltration analysis revealed that CXCL8 was significantly correlated with B cells memory, NK cells activated, Mast cells resting, Mast cells activated, and Neutrophils. GSEA of CXCL8 results showed inositol phosphate metabolism, RNA polymerase, propanoate metabolism, MAPK signaling pathway, base excision repair, and Calcium signaling pathway. In addition, we constructed a lncRNA-miRNA-mRNA ceRNA network and a drug–gene interaction network. Finally, we performed in vitro experiments to verify that LPS induced CXCL8 expression in HT-29 cells and that knockdown of CXCL8 inhibited the inflammatory stimulatory effects of LPS. This study reveals that CXCL8 plays an important role in the pathogenesis of Crohn's disease and is expected to be a novel biomarker. [ABSTRACT FROM AUTHOR]

Glucose tetrasaccharide (Glc4) and maltotetraose (M4) are important biomarkers for Pompe disease and other glycogen storage diseases (GSDs). With the development of new treatments for GSDs, more specific and sensitive bioanalytical methods are needed to determine biomarkers. In recent years, differential mobility spectrometry (DMS) has become an effective analytical technique with high selectivity and specificity. This study aimed to develop an efficient analytical method for the two urinary tetrasaccharide metabolites using DMS and apply it to patients with GSDs (type Ib and II). Urine samples were directly diluted and injected into liquid chromatography-differential mobility spectrometry tandem mass spectrometry (LC-DMS-MS/MS). Chromatographic separation was performed on an Acquity™ UPLC BEH Amide column (2.1 × 50 mm, 1.7 μm) with a short gradient elution of 2.6 min. DMS-MS/MS was used to detect two urinary tetrasaccharide metabolites in a negative multiple reaction monitoring mode with isopropanol as a modifier. A total of 20 urine samples from 6 healthy volunteers and 10 patients with GSDs (type Ib and II) were collected for analysis. The method was linear over a concentration range of 0.5~100.0 µg/mL for each urinary tetrasaccharide (r≥0.99). The intra- and inter-day precision RSD% were less than 14.3%, and the accuracy RE% were in the range of −14.3~13.4%. The relative matrix effect was between 86.6 and 114.3%. No carryover or interference was observed. Patients with GSDs (type Ib and II) had significantly higher median urinary Glc4 (P=0.001) and M4 (P=0.012) excretion than healthy subjects. The developed method was simple, rapid, sensitive, and specific. It was successfully applied to healthy volunteers and patients with GSDs (type Ib and II). DMS technology greatly improved analysis efficiency and provided high sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Intestinal microbiota plays an important role in promoting digestion, metabolism, and immunity. Intestinal microbiota and fatty acids are important indicators to evaluate the health and nutritional composition of Procambarus clarkii. They have been shown to be strongly influence by environmental and genetic factors. However, it is not clear whether environmental factors have a greater impact on the intestinal microbiota and fatty acid composition of crayfish. The link between the intestinal microbial communities and fatty acid (FA) compositions of red swamp crayfish from different geographical has not yet been studied. Thus, the current paper focuses on the influence of different environments on the fatty acids in muscles of crayfish and the possible existence between gut microbiota and fatty acids. Therefore, in this study, we compared the fatty acid compositions and intestinal microbiota of five crayfish populations from different geographical locations. The results were further analyzed to determine whether there is a relationship between geographical location, fatty acid compositions and intestinal microbiota. The gut microbial communities of the crayfish populations were characterized using 16S rRNA high-throughput gene sequencing. The results showed that there were significant differences in FA compositions of crayfish populations from different geographical locations. A similar trend was observed in the gut microbiome, which also varied significantly according to geographic location. Interestingly, the analysis revealed that there was a relationship between fatty acid compositions and intestinal microbes, revealed by alpha diversity analysis and cluster analysis. However, further studies of the interactions between the P. clarkii gut microbiota and biochemical composition are needed, which will ultimately reveal the complexity of microbial ecosystems with potential applications in aquaculture and species conservation. [ABSTRACT FROM AUTHOR]

Aqueous copper-based batteries have many favourable properties and have thus attracted considerable attention, but their application is limited by their low operating voltage originating from the high potential of copper negative electrode (0.34 V vs. standard hydrogen electrode). Herein, we propose a coordination strategy for reducing the intrinsic negative electrode redox potential in aqueous copper-based batteries and thus improving their operating voltage. This is achieved by establishing an appropriate coordination environment through the electrolyte tailoring via Cl− ions. When coordinated with chlorine, the intermediate Cu+ ions in aqueous electrolytes are successfully stabilized and the electrochemical process is decoupled into two separate redox reactions involving Cu2+/Cu+ and Cu+/Cu0; Cu+/Cu0 results in a redox potential approximately 0.3 V lower than that for Cu2+/Cu0. Compared to the coordination with water, the coordination with chlorine also results in higher copper utilization, more rapid redox kinetics, and superior cycle stability. An aqueous copper-chlorine battery, harnessing Cl−/Cl0 redox reaction at the positive electrode, is discovered to have a high discharge voltage of 1.3 V, and retains 77.4% of initial capacity after 10,000 cycles. This work may open up an avenue to boosting the voltage and energy of aqueous copper batteries. Aqueous copper-based batteries suffer from low voltage due to the high copper negative electrode potential. Here, utilizing the coordination of chloride with copper ions, authors lower copper's redox potential by 0.3 V, resulting in a high-voltage aqueous copper-chlorine battery. [ABSTRACT FROM AUTHOR]

While photosynthesis transforms sunlight energy into sugar, aerobic and anaerobic respiration (fermentation) catabolizes sugars to fuel cellular activities. These processes take place within one cell across several compartments, however it remains largely unexplored how they interact with one another. Here we report that the weak acids produced during fermentation down-regulate both photosynthesis and aerobic respiration. This effect is mechanistically explained with an "ion trapping" model, in which the lipid bilayer selectively traps protons that effectively acidify subcellular compartments with smaller buffer capacities – such as the thylakoid lumen. Physiologically, we propose that under certain conditions, e.g., dim light at dawn, tuning down the photosynthetic light reaction could mitigate the pressure on its electron transport chains, while suppression of respiration could accelerate the net oxygen evolution, thus speeding up the recovery from hypoxia. Since we show that this effect is conserved across photosynthetic phyla, these results indicate that fermentation metabolites exert widespread feedback control over photosynthesis and aerobic respiration. This likely allows algae to better cope with changing environmental conditions. The processes of photosynthesis, aerobic and anaerobic respiration (fermentation) power life on Earth. Here, using mainly green alga Chlamydomonas, the authors find that the weak acids produced during fermentation could chemically suppress both photosynthesis and aerobic respiration. [ABSTRACT FROM AUTHOR]

Protonic ceramic fuel cells (PCFCs) are more suitable for operation at low temperatures due to their smaller activation energy (Ea). Unfortunately, the utilization of PCFC technology at reduced temperatures is limited by the lack of durable and high-activity air electrodes. A lot number of cobalt-based oxides have been developed as air electrodes for PCFCs, due to their high oxygen reduction reaction (ORR) activity. However, cobalt-based oxides usually have more significant thermal expansion coefficients (TECs) and poor thermomechanical compatibility with electrolytes. These characteristics can lead to cell delamination and degradation. Herein, we rationally design a novel cobalt-containing composite cathode material with the nominal composition of Sr4Fe4Co2O13+δ (SFC). SFC is composed of tetragonal perovskite phase (Sr8Fe8O23+δ, I4/mmm, 81 wt.%) and spinel phase (Co3O4, Fd3̄m, 19 wt.%). The SFC composite cathode displays an ultra-high oxygen ionic conductivity (0.053 S·cm−1 at 550 °C), superior CO2 tolerance, and suitable TEC value (17.01 × 10−6 K−1). SFC has both the O2−/e− conduction function, and the triple conducting (H+/O2−/e−) capability was achieved by introducing the protonic conduction phase (BaZr0.2Ce0.7Y0.1O3−δ, BZCY) to form SFC+BZCY (70 wt.%:30 wt.%). The SFC+BZCY composite electrode exhibits superior ORR activity at a reduced temperature with extremely low area-specific resistance (ASR, 0.677 Ω·cm2 at 550 °C), profound peak power density (PPD, 535 mW·cm−2 and 1.065 V at 550 °C), extraordinarily long-term durability (> 500 h for symmetrical cell and 350 h for single cell). Moreover, the composite has an ultra-low TEC value (15.96 × 10−6 K−1). This study proves that SFC+BZCY with triple conducting capacity is an excellent cathode for low-temperature PCFCs. [ABSTRACT FROM AUTHOR]

This paper investigates the relationship between digital finance and carbon emissions and explores the ecological effects of digital finance. Based on a panel data of 256 cities in China from 2011 to 2018, this paper investigates the impact of digital finance on carbon emissions and its intrinsic mechanisms. First, digital finance significantly suppresses the intensity of regional carbon emission, and the breadth of coverage, depth of use, and degree of digital support of digital finance together curb regional carbon emissions, with the strongest suppressive effect being the breadth of coverage. In addition, the regression results remain significant after a series of robustness tests. Second, it reveals the potential mechanism of digital finance to curb urban carbon emissions. These mechanisms include the three channels: promoting industrial advancement, green technology innovation, and optimizing labor resource allocation. Third, the heterogeneity test finds that the energy saving and emission reduction effects of digital finance are significantly stronger in non-low-carbon pilot cities with low urbanization rates, confirming the emission reduction utility of digital finance development. Therefore, we should take advantage of digital finance to improve the green development of financial services and adopt diverse policy measures according to local conditions to maximize the ecological effects of digital finance on energy saving and emission reduction. In the context of the development strategy of "carbon peaking and carbon neutral," this study has some implications for management in developing a regional green development system supported by digital finance. [ABSTRACT FROM AUTHOR]

The cost-effectiveness of conventional population-based breast cancer screening strategies (e.g. mammography) has been found controversial, while evidence shows that genetic testing for early detection of pathogenic variants is cost-effective. We aimed to review the economic evaluations of breast cancer screening in China to provide an information summary for future research on this topic. We searched the literature to identify the economic evaluations that examined breast cancer screening and testing in China, supplemented by hand-searching the reference lists of the included studies. We finally included five studies satisfying our inclusion criteria. Four articles examined mammography while the rest investigated multigene testing. The existing breast cancer screening programmes were found to be cost-effective among urban Chinese women, but one study concluded that they might cause harm to women in rural areas. Contextual factors, such as data absence, urban–rural disparity, willingness-to-pay threshold, and model design, imposed barriers to cost-effectiveness analysis. Multigene testing was found to be cost-effective and has a promising population impact among all women with breast cancer in China. Future research should investigate the cost-effectiveness of screening and identifying breast cancer through precision medicine technologies, including genetic testing, genome sequencing, cascade testing, and the return of secondary findings. [ABSTRACT FROM AUTHOR]

Taking the advantage of sun glitter (SG) observed from high-resolution satellites Gaofen-1 (GF-1) and Gaofen-6 (GF-6), a new method named Shield and Vortex 1-2 (SAV1-2) for extracting spatial texture information from sun glitter was established. Sea surface texture detail information around Diaoyu Dao and its affiliated islands was extracted using SAV1-2. Meanwhile, the dynamic characteristics of the water environment were analyzed by combining the water color, temperature and dynamic data. The results show the following information. (1) Stable westward shield effect and eastward Karman vortex streets, extracted from SG, appear upstream (westward) and downstream (eastward) of the Diaoyu Dao and its affiliated islands respectively. (2) The dominant direction of the Kuroshio Current in the Diaoyu Dao and its affiliated islands area is east, the Diaoyu Dao and its affiliated islands interacting with Kuroshio, inducing western shield and eastern shelter and wake. Furthermore, wave intervals of the shield in front of the island range from hundreds to thousands of metres, and extend wider than the island itself. (3) Combining with high-resolution sea surface temperature (SST) and chlorophyll a (Chl a) concentration, the directional changes of water color elements are mutually supported and proved with the stable shield (wave packet) effect in the west and vortex street effect in the east. The change of SST upstream of the island (western shield area) is not significant, the temperature in the downstream shelter area decreases slightly, and the SST in the downstream wake area shows a general trend of obvious decrease. The wake area is dominated by Karman vortex streets in shape, supplementing by vortices. The concentration of Chl a in the west shield of island is as low as that in downstream shelter area, while it increases significantly in the downstream wake area with shape in eddy or ribbon. (4) The SAV methods of extracting sea surface texture detail using SG can be widely used in different sea areas and water quality. This paper can provide reference for the protection and development of Diaoyu Dao and its affiliated islands and its surrounding waters. It is suggested that some kind of current buffer, such as marine wind farm, should be established in the western waters of Diaoyu Dao and its affiliated islands to protect the islands, and marine pasture should be developed in the downstream of eastern waters of Diaoyu Dao and its affiliated islands. [ABSTRACT FROM AUTHOR]

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Semiconductor photolysis of aquatic hydrogen has become a research hotspot in recent years. Cadmium sulfide (CdS) photocatalyst has been drawn widespread interest due to good visible light absorption, proper energy band potential, and excellent electron-hole pair production rate and mobility. In this work, three morphologies of CdS were synthesized successfully using different cadmium salts and sulfur sources by solvothermal methods. Compared with CdS nanospheres and nanorods, CdS nanosheets photocatalyst could suppressed the photoogenic electron holes better, resulting its high photocatalytic hydrogen generation activity. CdS nanosheets with good photostability showed the fastest photocatalytic hydrogen production rate (12.37 mmol h−1 g−1) with the support of simulated solar-light irradiation. These results indicated that the excellent photocatalytic performance of CdS nanosheets may be related to its exposed high index (002) lattice plane, which was main photocatalytic active lattice plane. This work optimized the catalytic properties of materials by regulating the morphology and the exposure of different lattice planes, which were of great significance for solar energy capture and conversion. [ABSTRACT FROM AUTHOR]

Levonorgestrel-releasing intrauterine system (LNG-IUS) insertion is the first-line treatment for atypical hyperplasia (AH) in young women who wish to retain their fertility. However, the procedure is not always effective, and may allow AH to progress to endometrioid endometrial cancer (EEC). Two young women with AH who wished to preserve their fertility developed EEC following 52-mg LNG-IUS in insertion at our institution. One was a 34-year-old woman diagnosed with endometrial cancer 2 years after LNG-IUS insertion. The second was a 30-year-old woman diagnosed 17 months after LNG-IUS insertion. Proactive molecular risk classification for endometrial cancer (ProMisE) classification revealed that the first and second patients had p53-abnormal (p53abn) EEC and mismatch repair deficient (MMR-d) EEC, respectively. MMR-d and p 53abn were frequently observed in both AH and EEC specimens. Studies suggest that MMR-d and p53abn are predictors of the occurrence adverse effects after fertility-preserving treatment for EEC. AH is a precursor of EEC. Therefore, p53 and mismatch repair (MMR) mutation may be used to identify women with AH who will not likely benefit from progestin therapy. Molecular assays in women with AH will likely be useful for identifying novel predictive biomarkers of progestin resistance and to improve the safety of conservative treatment. Combined assessment of progesterone receptor (PR) with these predictive molecular markers may improve the predictive ability. [ABSTRACT FROM AUTHOR]

The electrochemical oxygen reduction reaction (ORR) is at the heart of modern sustainable energy technologies. However, the linear scaling relationship of this multistep reaction now becomes the bottleneck for accelerating kinetics. Herein, we propose a strategy of using intermetallic-distance-regulated atomic-scale bimetal assembly (ABA) that can catalyse direct O‒O radical breakage without the formation of redundant *OOH intermediates, which could regulate the inherent linear scaling relationship and cause the ORR on ABA to follow a fast-kinetic dual-sites mechanism. Using in situ synchrotron spectroscopy, we directly observe that a self-adjustable N-bridged Pt = N2 = Fe assembly promotes the generation of a key intermediate state (Pt‒O‒O‒Fe) during the ORR process, resulting in high reaction kinetics and selectivity. The well-designed Pt = N2 = Fe ABA catalyst achieves a nearly two orders of magnitude enhanced kinetic current density at the half-wave potential of 0.95 V relative to commercial Pt/C and an almost 99% efficiency of 4-electron pathway selectivity, making it one of the potential ORR catalysts for application to the energy device of zinc‒air cells. This study provides a helpful design principle for developing and optimizing other efficient ORR electrocatalysts. Improving kinetics for electrochemical oxygen reduction reaction is relevant to important sustainable energy technologies. The authors propose an atomic-scale bimetal assembly consisting Pt and Fe dual sites to regulate the inherent scaling relationship between intermediates for fast kinetics. [ABSTRACT FROM AUTHOR]

Thyroid hormones (TH) regulate systemic glucose metabolism through incompletely understood mechanisms. Here, we show that improved glucose metabolism in hypothyroid mice after T3 treatment is accompanied with increased glucagon-like peptide-1 (GLP-1) production and insulin secretion, while co-treatment with a GLP-1 receptor antagonist attenuates the effects of T3 on insulin and glucose levels. By using mice lacking hepatic TH receptor β (TRβ) and a liver-specific TRβ-selective agonist, we demonstrate that TRβ-mediated hepatic TH signalling is required for both the regulation of GLP-1 production and the insulinotropic and glucose-lowering effects of T3. Moreover, administration of a liver-targeted TRβ-selective agonist increases GLP-1 and insulin levels and alleviates hyperglycemia in diet-induced obesity. Mechanistically, T3 suppresses Cyp8b1 expression, resulting in increased the levels of Farnesoid X receptor (FXR)-antagonistic bile acids, thereby potentiating GLP-1 production and insulin secretion by repressing intestinal FXR signalling. T3 correlates with both plasma GLP-1 and fecal FXR-antagonistic bile acid levels in people with normal thyroid function. Thus, our study reveals a role for hepatic TH signalling in glucose homeostasis through the regulation of GLP-1 production via bile acid-mediated FXR antagonism. Thyroid hormones regulate systemic glucose metabolism through incompletely understood mechanisms. Here the authors report that hepatic thyroid hormone receptor β mediates the effects of the thyroid hormone T3 on systemic glucose homeostasis by modulating GLP-1 levels through suppression of hepatic CYP8B1 expression and bile acid mediated inhibition of intestinal FXR signalling. [ABSTRACT FROM AUTHOR]

As cancer is increasingly considered a metabolic disorder, it is postulated that serum metabolite profiling can be a viable approach for detecting the presence of cancer. By multiplexing mass spectrometry fingerprints from two independent nanostructured matrixes through machine learning for highly sensitive detection and high throughput analysis, we report a laser desorption/ionization (LDI) mass spectrometry-based liquid biopsy for pan-cancer screening and classification. The Multiplexed Nanomaterial-Assisted LDI for Cancer Identification (MNALCI) is applied in 1,183 individuals that include 233 healthy controls and 950 patients with liver, lung, pancreatic, colorectal, gastric, thyroid cancers from two independent cohorts. MNALCI demonstrates 93% sensitivity at 91% specificity for distinguishing cancers from healthy controls in the internal validation cohort, and 84% sensitivity at 84% specificity in the external validation cohort, with up to eight metabolite biomarkers identified. In addition, across those six different cancers, the overall accuracy for identifying the tumor tissue of origin is 92% in the internal validation cohort and 85% in the external validation cohort. The excellent accuracy and minimum sample consumption make the high throughput assay a promising solution for non-invasive cancer diagnosis. As cancer is increasingly considered a metabolic disorder, it is postulated that serum metabolite profiling can be a viable approach for detecting the presence of cancer. Here, the authors report a machine learning model using mass spectrometry-based liquid biopsy data for pan-cancer screening and classification. [ABSTRACT FROM AUTHOR]

Malignant pleural mesothelioma (MPM) is a rare malignancy with poor prognosis, for which chemotherapy with pemetrexed (PEM) is among the few clinical treatments. PEM suffers, however, fast clearance, moderate drug exposure, and dose-limiting toxicities. Here, we report on epidermal growth factor receptor (EGFR)-targeted disulfide-crosslinked biodegradable chimaeric polymersomes (EGFR-CPs) to firmly load PEM and boost chemotherapy of MPM. EGFR-CPs encapsulating 8.7–16.4 wt.% PEM (EGFR-CPs-PEM) showed diameters of 62–65 nm and reduction-responsive drug release property. EGFR-CPs-PEM was more efficiently taken up by EGFR-overexpressed MSTO-211H cells, inducing about 4.7-fold enhanced anticancer activity compared with non-targeted CPs-PEM control. Intriguingly, the in vivo experiments in MSTO-211H xenograft mouse model revealed that EGFR-CPs-PEM brought about superior tumor deposition and penetration to CPs-PEM, and significantly more potent tumor repression than CPs-PEM and free PEM. This polymersome-enabled EGFR-targeted delivery of PEM offers an appealing therapeutic strategy for MPM. [ABSTRACT FROM AUTHOR]

Because of insufficient liquidity, prices in the carbon market are more vulnerable to unexpected events, for which the impact duration lasts longer than that of the general market. The root reason for this phenomenon lies in the irrationality of quota distribution. The existing quota adjustment schemes and policies, e.g., the market stability reserve (MSR) and some recent adjustment measures, have poor timeliness and effectiveness, which has increased the risk of market crashes. Using the Hidden Markov Model (HMM), this paper develops a new dynamic quota adjustment scheme that can rapidly reduce the risk of quota supply by bridging quota price and quantity with price feedback as a response signal. To achieve this, we integrated the HMM algorithm and a two-step quota adjustment model by setting price thresholds and then connected the quota adjustment transition matrix and historical quota price. By comparing the MSR from 2013 to 2018, our scheme will help mitigate risks in quota price because the HMM can show the actual impact of price feedback on quota adjustment with merits of steady quota price and timely supply optimization. Moreover, our scheme, which recalculates the transition matrix, can be applied in other mature carbon markets. [ABSTRACT FROM AUTHOR]

Achieving carbon neutrality has become a global consensus, and plenty of measures and policies have been proposed in various industries to obtain this ambitious goal. As an innovative and radical environmental policy tool, personal carbon trading (PCT) policy which aims to reduce carbon emissions from the private consumption sector has aroused the attention. For a new policy tool, public support and acceptance is critical to obtain policy legitimacy and policy implementation. To implement PCT policy smoothly, the current research aims to explore the antecedents of public acceptance. From the emotional reaction perspective, this research mainly evaluated how political trust, perceived uncertainty and associated emotions matter for public acceptance of PCT policy. Based on the survey data, this research revealed that political trust has a direct positive impact on public acceptance of PCT policy. Meanwhile, political trust also has an indirect impact on public acceptance of PCT policy via emotions. Specifically, political trust is positively associated with positive emotions and negatively associated with negative emotions. Positive emotions promote public to accept PCT policy, while negative emotions inhibit public to accept PCT policy. The negative emotions exert a more powerful impact on public acceptance than positive emotions. Additionally, we found that perceived uncertainty exerts a negative effect on public acceptance and negatively regulates the relationship between political trust and public acceptance. That is, perceived uncertainty has a significant substitution effect on political trust. According to the research findings, policy implications to improve public acceptance of PCT policy were explored. [ABSTRACT FROM AUTHOR]

Haze pollution has drawn lots of public concern due to its potential damages to human health. Strategic interaction of environmental regulation among local governments may lead to a race to the bottom and hinder air quality improvement. Still, current empirical evidence is scarce, especially from developing countries. Based on province-level panel data from 2004 to 2015, the paper employs a dynamic fixed effect spatial Durbin model to identify interactive patterns of environmental regulation and then investigate its environmental impact. Empirical results indicate that regional differences are observed in environmental regulation and haze pollution, and high-high and low-low clusters dominate the spatial pattern. Interactive patterns of economically similar provinces are dominated by strategic substitution, whereas provinces sharing common borders or belonging to the same region are dominated by strategic complementation. Further, both race to the bottom and race to the top effect are discovered in the asymmetric test. The reaction coefficient values are much more extensive when competitors implement laxer policies, indicating a more significant racing trend to the bottom. Overall, after controlling for the spillover effect and hysteresis effect of haze pollution, the strategic interaction of environmental regulation among provinces is not conducive to improve air quality. The consequence might be correlated with low environmental standards, weak regulation enforcement, and the "free-ride" motive in China. These findings will be of great significance for optimizing local government behavior and improving air quality. [ABSTRACT FROM AUTHOR]

Mechanical ventilation may cause ventilator-induced lung injury (VILI) in patients requiring ventilator support. Inhibition of autophagy is an important approach to ameliorate VILI as it always enhances lung injury after exposure to various stress agents. This study aimed to further reveal the potential mechanisms underlying the effects of geranylgeranyl diphosphate synthase large subunit 1 (GGPPS1) knockout and autophagy in VILI using C57BL/6 mice with lung-specific GGPPS1 knockout that were subjected to mechanical ventilation. The results demonstrate that GGPPS1 knockout mice exhibit significantly attenuated VILI based on the histologic score, the lung wet-to-dry ratio, total protein levels, neutrophils in bronchoalveolar lavage fluid, and reduced levels of inflammatory cytokines. Importantly, the expression levels of autophagy markers were obviously decreased in GGPPS1 knockout mice compared with wild-type mice. The inhibitory effects of GGPPS1 knockout on autophagy were further confirmed by measuring the ultrastructural change of lung tissues under transmission electron microscopy. In addition, knockdown of GGPPS1 in RAW264.7 cells reduced cyclic stretch-induced inflammation and autophagy. The benefits of GGPPS1 knockout for VILI can be partially eliminated through treatment with rapamycin. Further analysis revealed that Rab37 was significantly downregulated in GGPPS1 knockout mice after mechanical ventilation, while it was highly expressed in the control group. Simultaneously, Rab37 overexpression significantly enhances autophagy in cells that are treated with cyclin stretch, including GGPPS1 knockout cells. Collectively, our results indicate that GGPPS1 knockout results in reduced expression of Rab37 proteins, further restraining autophagy and VILI. [ABSTRACT FROM AUTHOR]

Background: Bile acid diarrhoea or BAD is a common but little recognised cause of chronic diarrhoea. Few of these patients in China have been diagnosed due to a lack of diagnostic options. Aims: To clarify the diagnostic value of serum fibroblast growth factor19 (FGF19) in BAD patients. Methods: We reported on 60 chronic diarrhoea patients and 80 healthy volunteers (HV). Based on the 90th percentile levels of serum 7a-hydroxy-4-cholesten-3-one (C4) of HV, these patients were divided into BAD group (C4 ≥ 90th) and non-bile acid diarrhoea group (NBAD, C4 < 90th). Serum FGF19 in the two clinical groups and HV group were compared, as was distal ileum FGF19 in clinical groups. The diagnostic value of serum FGF19 for BAD was evaluated. Results: The 90th percentile of serum C4 in HV group was 65.87 ng/ml. Serum FGF19 concentrations in BAD group (Median 69.28 pg/ml; n = 23) were significantly lower than those in HV (Median 122.18 pg/ml; n = 80) and NBAD (Median 129.57 pg/ml; n = 29) groups. FGF19 mRNA of the distal ileum in BAD group, was lower than that in NBAD group, P = 0.002. The rate of FGF19 protein low expression of distal ileum in BAD and NBAD group were 78.3% and 48.3%, P = 0.027. Using an ROC curve, statistical analysis yielded a threshold FGF19 concentration of 117.3 pg/ml (AUC, 0.906; 91.3% sensitivity, 79.3% specificity) for a clinical diagnosis of BAD. Conclusions: Serum and distal ileum expression of FGF19 significantly decreased in BAD patients. The suggested clinical ranges for serum FGF19 < 117.3 pg/ml has high sensitivity and specificity for BAD patients with a normal structural and histological ileum. [ABSTRACT FROM AUTHOR]

Purpose: Paraganglioma of the urinary bladder (UBPGL) is a rare neuroendocrine tumor diagnosed in many patients only after surgery. We, therefore, assessed clinical clues relevant to presurgical diagnosis and clinical consequences in patients with a missed presurgical diagnosis of UBPGL. Materials and methods: Case reports describing a UBPGL (published from 1–1–2001 and 31–12–2020) were identified in Pubmed. Two authors independently performed data extraction and assessed data quality according to the PRISMA guideline. Patients were divided into two groups: UBPGL diagnosis before and after surgery. Results: We included 177 articles reporting 194 cases. In 90 (46.4%) patients, the UBPGL was diagnosed before and in 104 (53.6%) after surgery. In presurgically diagnosed UBPGL, hypertension and catecholamine-associated symptoms were 2- to 3-fold (p < 0.001) more frequent than in postsurgically diagnosed patients whereas hematuria was twofold (p = 0.003) more prevalent in those with postsurgical diagnosis. Hypertension was an independent factor for presurgical biochemical testing (OR 4.45, 95% CI 1.66–11.94) while hematuria (OR 0.23, 95% CI 0.09–0.60) was an independent factor for not performing presurgical biochemical testing. Most patients diagnosed after surgery were not pretreated with alpha-adrenoceptor blockade (95.2%), underwent more frequently transurethral resection instead of cystectomy (70.2% vs. 23.1%) and had more frequent peroperative complications and residual tumor mass. Conclusions: In nearly half of all patients with a UBPGL, the diagnosis was not established before surgery. Hypertension and hematuria contributed independently to a presurgical diagnosis. Postsurgical diagnosis, which was associated with suboptimal presurgical and surgical management, resulted in more peroperative complications and incomplete tumor resections. [ABSTRACT FROM AUTHOR]

Thyroid hormone (TH) and thyroid hormone receptor (THR) regulate stem cell proliferation and differentiation during development, as well as during tissue renewal and repair in the adult. THR undergoes posttranslational modification by small ubiquitin-like modifier (SUMO). We generated the THRA (K283Q/K288R)−/− mouse model for in vivo studies and used human primary preadipocytes expressing the THRA sumoylation mutant (K283R/K288R) and isolated preadipocytes from mutant mice for in vitro studies. THRA mutant mice had reduced white adipose stores and reduced adipocyte cell diameter on a chow diet, compared to wild-type, and these differences were further enhanced after a high fat diet. Reduced preadipocyte proliferation in mutant mice, compared to wt, was shown after in vivo labeling of preadipocytes with EdU and in preadipocytes isolated from mice fat stores and studied in vitro. Mice with the desumoylated THRA had disruptions in cell cycle G1/S transition and this was associated with a reduction in the availability of cyclin D2 and cyclin-dependent kinase 2. The genes coding for cyclin D1, cyclin D2, cyclin-dependent kinase 2 and Culin3 are stimulated by cAMP Response Element Binding Protein (CREB) and contain CREB Response Elements (CREs) in their regulatory regions. We demonstrate, by Chromatin Immunoprecipitation (ChIP) assay, that in mice with the THRA K283Q/K288R mutant there was reduced CREB binding to the CRE. Mice with a THRA sumoylation mutant had reduced fat stores on chow and high fat diets and reduced adipocyte diameter. [ABSTRACT FROM AUTHOR]

Retinal fundus diseases can lead to irreversible visual impairment without timely diagnoses and appropriate treatments. Single disease-based deep learning algorithms had been developed for the detection of diabetic retinopathy, age-related macular degeneration, and glaucoma. Here, we developed a deep learning platform (DLP) capable of detecting multiple common referable fundus diseases and conditions (39 classes) by using 249,620 fundus images marked with 275,543 labels from heterogenous sources. Our DLP achieved a frequency-weighted average F1 score of 0.923, sensitivity of 0.978, specificity of 0.996 and area under the receiver operating characteristic curve (AUC) of 0.9984 for multi-label classification in the primary test dataset and reached the average level of retina specialists. External multihospital test, public data test and tele-reading application also showed high efficiency for multiple retinal diseases and conditions detection. These results indicate that our DLP can be applied for retinal fundus disease triage, especially in remote areas around the world. Systems for automatic detection of a single disease may miss other important conditions. Here, the authors show a deep learning platform can detect 39 common retinal diseases and conditions. [ABSTRACT FROM AUTHOR]

Facing the growing pressure of climate change and environmental protection, integrated energy systems (IESs), which comprise different energy sources, have become promising candidates for future energy systems. However, the capacity configuration of each source remains challenging due to the various couplings, randomness of renewables and numerical optimization difficulty. In this paper, a hierarchical optimization framework is proposed to determine the component capacities of trigeneration IESs, i.e., systems involving combined cooling, heating and power (CCHP) generation. The potential variation in the demand and renewable resource availability are considered stochastic factors and captured as scenarios generated according to a probability function. In the first level, with the component capacities and scenarios defined, a mixed-integer linear programming (MILP) problem is formulated to minimize the total system cost. Then, in the second level, the Monte Carlo method is applied to calculate the expectation by feeding different scenarios into the MILP and sampling the minimal costs. Finally, as the second level returns the expected value of the system cost considering the given component capacities, a genetic algorithm is adopted in the third level to search the optimal component capacities. Compared to the conventional deterministic optimization method, the proposed stochastic optimization method reduces the annual operational cost while allowing a wider operational range. In addition, it is revealed that the inclusion of heat storage and grid connections yields notable benefits in terms of IES cost reduction. [ABSTRACT FROM AUTHOR]

Purposes: To retrospectively compare the short-term refractive outcomes and corneal aberrations after small-incision lenticule extraction (SMILE) and femtosecond-assisted laser-assisted in situ keratomileusis (FS-LASIK) combined with smart pulse technology (SPT) in patients with compound myopic astigmatism. Methods: A total of 91 eyes (91 patients) were included, 43eyes in FS-LASIK group and 48 eyes in the SMILE group. Uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), refractive results and corneal topography were evaluated 1 and 3 months postoperatively. Corneal aberrations of anterior corneal surface were calculated from the topography data over 6 mm-diameter. Results: There was no significant difference in UCVA, BCVA, and refractive results between the two groups. There were no statistical difference in TIA (target induced astigmatism), SIA (surgery induced astigmatism), DV (difference vector), ME (magnitude of error), AE (angle of error), AE (absolute value) and CI (correction index) between both groups at 1 and 3 months. Coma and spherical aberration improved in all the patients in both groups at 1 and 3 months postoperatively. The amount of induced spherical aberrations was higher in FS-LASIK group compared to SMILE group. Conclusions: Both FS-LASIK and SMILE achieved similar refractive outcomes in patients with myopia and compound myopic astigmatism. FS-LASIK combined with SPT resulted in higher spherical aberration than SMILE in early postoperative period. [ABSTRACT FROM AUTHOR]

Purpose: Comprehensive understanding glioma metabolic characters is of great help for patient management. We aimed to compare amide proton transfer imaging (APTw) and magnetization transfer imaging (MT) in predicting glioma malignancy and reflecting tumor proliferation. Methods: Thirty low-grade gliomas (LGGs) and 39 high-grade gliomas (HGGs) were prospectively included, of which 58 samples Ki-67 levels were quantified. Anatomical MRI, APTw, and MT were scanned, and magnetization transfer ratio (MTR) and asymmetric magnetic transfer ratio at 3.5 ppm (MTRasym(3.5ppm)) were calculated. ROIs were semi-automatically drawn with ImageJ, from which histogram features, including 5th, 25th, 50th, mean, 70th, 90th, and 95th percentiles were extracted. The independent t test was used to test differences in LGGs and HGGs, and correlations between histogram features and tumor grades, Ki-67 were revealed by Spearman's rank or Pearson's correlation analysis. Results: The maximum correlation coefficient (R) values of APTw were 0.526 (p < 0.001) with tumor grades and 0.397 (p < 0.001) with Ki-67 at 90th percentiles, while only 5th and 25th percentiles of MT significantly correlated with tumor grades. Moreover, APTw features were significantly different in LGGs and HGGs, except 5th percentile. The most significantly different feature was 95th percentile, providing the excellent AUC of 0.808. However, the best feature in MTR was 5th percentiles with AUC of 0.703. Combing 5th and 95th of APTw achieved highest AUC Of 0.837. Conclusions: Both APTw and MT provide quantitative information for tumor metabolite imaging. However, APTw supplys more specific information in reflecting glioma biological behaviors than MT, and well differentiates glioma malignancy. [ABSTRACT FROM AUTHOR]

Rhamnolipids have extensive potential applications and are the most promising biosurfactants for commercialization. The efficient and accurate identification and analysis of these are important to their production, application and commercialization. Accordingly, significant efforts have been made to identify and analyse rhamnolipids during screening of producing strains, fermentation and application processes. Cationic cetyltrimethylammonium bromide–methylene blue (CTAB-MB) test combines a series of indirect assays to efficiently assist in the primary screening of rhamnolipids-producing strains, while the secretion of rhamnolipids by these strains can be identified through TLC, FTIR, NMR, electrospray ionization mass spectrometry (ESI-MS) and HPLC-MS analysis. Rhamnolipids can be quantified by colorimetric methods requiring the use of concentrated acid, and this approach has the advantages of reliability, simplicity, low-cost and excellent reproducibility with very low technological requirements. HPLC-MS can also be employed as required as a more accurate quantification method. In addition, HPLC-ELSD has been established as the internationally acceptable measure of rhamnolipids for commercial purposes. The preparation of well-accepted rhamnolipids standards and modifications of analysis operations are essential to further enhance the accuracy and improve the simplicity of rhamnolipid analysis. Key points • Current status of R&D works on determination of rhamnolipids is listed • Advantages and disadvantages of various types analysis are summarized • Limitations of current rhamnolipid quantification are discussed [ABSTRACT FROM AUTHOR]

Sodium alginate (SA), as the eco-friendly and human-safe biomass material not only can achieve effective dispersion of graphene nanoplatelets (GnPs), but also improve the interaction between GnPs and cellulose macromolecules. Based on this, a flexible and wearable GnPs/cellulose strain sensor with a special 2 × 2 double rib knitted fabric structure (KFGS) was prepared by a simple dip-coating method that could be used on a large scale. The KFGS exhibited dual sensing performance with high sensitivity (25.32 kPa−1 at 3 kPa pressure, gauge factor 32.62 at 25% tensile strain), stretchability (ε > 25%) and dynamic stability (signal drift < 6% after 300 cycles). Its potential application prospects were also predicted by the monitoring of human movement and physical parameters through a wireless Bluetooth connection. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate whether miR-148a-3p overexpression is associated with disrupted decidualization of recurrent implantation failure (RIF). Methods: Endometrial miRNA and mRNA expression profiles during the implantation window derived from women with and without RIF were identified using microarray and RT-qPCR. Immortalized human endometrial stromal cells (HESCs) were cultured for proliferation and in vitro decidualization assays after enhancing miR-148a-3p expression or inhibiting putative target gene homeobox C8 (HOXC8) expression. RT-qPCR, western blot, and luciferase reporter assays were used to confirm the relationship between miR-148a-3p and HOXC8 gene. Results: MiR-148a-3p was significantly upregulated in RIF endometrial tissues. Forced expression of miR-148a-3p notably attenuated HESC in vitro decidualization. Mechanistic studies revealed that miR-148a-3p directly bounds to the HOXC8 3′ untranslated region (3′UTR) and suppressed HOXC8 expressions in both mRNA and protein levels. Further investigations demonstrated that inhibition of HOXC8 in HESCs induced similar effects on decidual process as those induced by miR-148a-3p overexpression. Conclusion: Taken together, our findings suggested that elevated miR-148a-3p might account for flawed decidualization in RIF by negatively regulating HOXC8, raising the possibility that miR-148a-3p might be a novel therapeutic target in RIF. [ABSTRACT FROM AUTHOR]

Due to extensive morphological plasticity, the taxonomy of Cladophora species remains unclear. As one of the widely distributed species, C. gracilis was reported to hold many varieties, which make it difficult to identify the species. This study explored the morphology diversity of nine C. gracilis samples collected along the coast of western Yellow Sea. Some samples showed extremely varied characteristics, by which one cannot classify them correctly. Hence, 18S rDNA and nuclear ribosomal DNA internal transcribed spacer regions (ITS) sequences were employed to delimit species. For 18S rDNA, sequence similarity ranged from 99.6% to 100%. For ITS region, the similarity ranged from 98.7% to 100%. Molecular data strongly suggested that the morphologically heterogeneous samples were actually the same species. Characteristics comparison of the samples revealed that the taxonomy criteria including branching pattern and density, thallus color, height and texture varied widely, influenced by environmental conditions and age of alga. Besides, cell dimensions, as the relatively stable criterion, also exhibited intraspecific variance. Successful application of 18S rDNA and ITS sequences indicated that molecular method can be a powerful assistant as DNA barcodes to traditional morphology taxonomy. [ABSTRACT FROM AUTHOR]