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Abstract Coronary artery disease has a high mortality rate and is a striking public health concern, affecting a substantial portion of the global population. On the early onset of myocardial ischemia, thrombolytic therapy and coronary revascularization could promptly restore the bloodstream and nutrient supply to the ischemic tissue, efficiently preserving less severely injured myocardium. However, the abrupt re-establishment of blood flow triggers the significant discharge of previously accumulated oxidative substances and inflammatory cytokines, leading to further harm referred to as ischemia/reperfusion (I/R) injury. Diabetes significantly raises the vulnerability of the heart to I/R injury due to disrupted glucose and lipid processing, impaired insulin sensitivity and metabolic signaling, and increased inflammatory responses. Numerous studies have indicated that adipokines are crucial in the etiology and pathogenesis of obesity, diabetes, hyperlipidemia, hypertension, and coronary artery disease. Adipokines such as adiponectin, adipsin, visfatin, chemerin, omentin, and apelin, which possess protective properties against inflammatory activity and insulin resistance, have been shown to confer myocardial protection in conditions such as atherosclerosis, myocardial hypertrophy, myocardial I/R injury, and diabetic complications. On the other hand, adipokines such as leptin and resistin, known for their pro-inflammatory characteristics, have been linked to elevated cardiac lipid deposition, insulin resistance, and fibrosis. Meteorin-like (metrnl) exhibits opposite effects in various pathological conditions. However, the data on adipokines in myocardial I/R, especially in diabetes, is still incomplete and controversial. This review focuses on recent research regarding the categorization and function of adipokines in the heart muscle, and the identification of different signaling pathways involved in myocardial I/R injury under diabetic conditions, aiming to facilitate the exploration of therapeutic strategies against myocardial I/R injury in diabetes.

The increase in extreme precipitation (EP) may pose a serious threat to the health and safety of population in arid and semi-arid regions. The current research on the impact of EP on population in Central Asia (CA) is insufficient and there is an urgent need for a comprehensive assessment. Hence, we opted for precipitation and temperature data under two Shared Socioeconomic Pathways (SSP2–4.5 and SSP5–8.5) from ten Global Climate Models (GCMs), which were obtained from the NASA Earth Exchange Global Daily Downscaled Projections (NEX-GDDP-CMIP6). By integrating population data in 2020 and 2050 (SSP2 and SSP5), we investigated the future changes in EP and population exposure in CA under 1.5 °C and 2 °C global warming scenarios (GWSs). Our analysis indicates that EP in CA is projected to increase with global warming. Under the SSP5–8.5, the maximum daily precipitation (Rx1day) exhibits an average response rate to global warming of 3.58 %/K (1.99–4.06 %/K). With rising temperatures, an increasing number of areas and populations in CA will be impacted by EP, especially in the Fergana valley. Approximately 25% of the population (land area) in CA is exposed to Rx1day with increases of more than 8.31% (9.32%) under 1.5 °C GWS and 14.18% (13.25%) under 2 °C GWS. Controlling temperature rise can be effective in reducing population exposures to EP. For instance, limiting the temperature increase to 1.5 °C instead of 2 °C results in a 2.79% (1.75%–4.59%) reduction in population exposure to Rx1day. Finally, we found that climate change serves as the predominant factor influencing the population exposure to EP, while the role of population redistribution, although relatively minor, should not be disregarded. Particularly for prolonged drought, the role of population redistribution manifests negatively.

BackgroundCommon side effect of Herpes Zoster, postherpetic neuralgia (PHN), causes persistent pain that seriously affects quality of life. Lack of dependable biomarkers makes the clinical diagnosis and treatment of PHN difficult, so complicating the assessment of therapeutic efficacy. Blood metabolites are becoming more and more well known as significant disease markers. With an aim to find possible biomarkers for diagnosis and treatment, this work investigates the causal link between blood metabolites and PHN using Mendelian randomization.MethodsThis work evaluated causal relationships between PHN and 1,091 plasma metabolites using Mendelian randomization (MR). Complementing MR-Egger and weighted median approaches, the main causality analysis was done using inverse variance weighted (IVW) and Wald ratio (WR) approaches. Robustness was checked using sensitivity analyses including CAUSE, Cochran’s Q tests, leave-one-out analysis, MR-PRESSO, and MR-Egger intercept analysis. Reverse MR analysis and linkage disequilibrium score regression (LDSC) was used to assess significant correlations as well. Two-step MR analysis was also used to look at the mediating function of positively correlated metabolites in the causal pathway.ResultsThe results of this study indicated a significant association between N-acetyl-aspartyl-glutamate (NAAG) and PHN, with an odds ratio (OR) of 0.83 (95% CI: 0.76–0.91, p = 2.68E-05). Moreover, five potential associated metabolites were identified: Gamma-glutamylthreonine (OR = 1.60, 95% CI: 1.16–2.20, p = 0.004), 3-hydroxyphenylacetoylglutamine (OR = 1.43, 95% CI: 1.00–2.05, p = 0.048), Caprate (10:0) (OR = 1.86, 95% CI: 1.11–3.12, p = 0.018), X-12013 (OR = 1.64, 95% CI: 1.03–2.60, p = 0.035), and X-17328 (OR = 1.50, 95% CI: 1.04–2.18, p = 0.032). Additionally, NAAG likely acts as a complete mediator between FOLH1(CGPII) and postherpetic neuralgia in the causal pathway.ConclusionThe results of this study indicated a significant association between N-acetyl-aspartyl-glutamate (NAAG) and PHN, with an odds ratio (OR) of 0.83 (95% CI: 0.76–0.91, p = 2.68E-05). Furthermore five possible related metabolites were found: Glutamylthreonine gamma-wise (OR = 1.60, 95% CI: 1.16–2.20, p = 0.004), 3-hydroxyphenylacetoylglutamine (OR = 1.43, 95% CI: 1.00–2.05, p = 0.048), Caprate (10:0) (OR = 1.86, 95% CI: 1.11–3.12, p = 0.018), X-12013 (OR = 1.64, 95% CI: 1.03–2.60, p = 0.035), and X-17328 (OR = 1.50, 95% CI: 1.04–2.18, p = 0.032). Furthermore, in the causal pathway NAAG most certainly serves as a complete mediator between FOLH1(CGPII) and postherpetic neuralgia.

Abstract Heatwaves represent a significant and growing threat to natural ecosystems and socio‐economic structures, making heatwave risk mitigation and prevention an important area of research. In exploring heatwave frequency and intensity from 1901 to 2020, the present study finds a sharp increase in both. The study also finds that the spatial distribution of heatwaves is unequal, the volatility of intensity characteristics has become more prominent over time, and the Gini coefficients of four key heatwave indictors have become larger due to increasing dryness. Although heatwaves occur more frequently in drylands, there is greater cumulative heat in humid areas, resulting in a higher heatwave risk in those areas. The global heatwave risk over the past three decades (1991–2020) has increased nearly five‐fold compared to the early 20th century (1901–1930). Furthermore, GeoDetector analysis indicates that the Palmer drought severity index (PDSI) and downward surface shortwave radiation (Srad) contributing the most in drylands and humid areas (0.29 and 0.41, respectively). The contribution of relative humidity (RH), wind speed (WS), soil moisture (SM), and the normalized difference vegetation index (NDVI) is also significant in humid areas, but is much smaller in drylands. Composite analysis shows that the years with anomalously high heatwave risk correspond to positive anomalies of 500hPa geopotential height and surface pressure. The inhibition of cloud formation due to sinking air and the resulting increase in temperature in the atmosphere may be increasing the risk of heatwave occurrence. This study emphasizes the urgent need to address worsening climate change impacts.

Study area: The Manas River Basin (84°01′−86°32′E, 42°27′−45°21′N) on the northern slopes of the Tianshan Mountains and the Kaidu River Basin (82°18′−85°57′E, 40°54′−44°30′N) on the southern slopes. Study focus: Traditional gap filling models struggle to accurately simulate daily streamflow in data-scarce regions. The underutilize of multi-source data leads to insufficient simulation ability for extremely high values of streamflow. Currently, a quantitative relationship between daily streamflow and hydro-meteorological factors has not been systematically established, despite the potential for improving accuracy of hydrological models through such relationships. To address this, a Denoising Diffusion Probabilistic Model were employed to investigate the driving factors of daily streamflow data. This study tested and compared the gap filling efficiency of mainstream models in the Tianshan Mountains region and provided a quantitative gap filling model for data-scarce areas. New hydrological insights for the region: This study has revealed a strong correlation between the missing rate and the efficiency of gap filling models. It is revealed that the DDPM model accurately simulates streamflow in the climatic conditions of the region and outperformed other models in terms of all missing rates, which holds significant implications for gaining a deeper understanding of the water balance process and enhancing hydrological and meteorological simulations in data-scarce regions.

Abstract Digital image watermarking is one of the effective schemes to protect the copyrights of still images. However, the existing watermarking schemes are still not robust enough to the common geometric transformation attacks such as arbitrary rotation, scaling and shifting with desirable hiding capacity. To address this issue, we propose a robust watermarking scheme based on geometric correction codes (GCCs). In this scheme, the watermark and pre‐set GCCs are combined and embedded into a cover image to obtain the watermarked image. At the stage of watermark extraction, the watermarked image, under a variety of geometric transformation attacks, can be geometrically corrected by minimising the difference between the extracted and the original GCCs, then the watermark is extracted from the watermarked image. The experiments demonstrate that, compared to the typical watermarking schemes, the proposed scheme achieves much higher robustness to the common geometric transformation attacks and comparable invisibility with the same embedding capacity.

In order to develop a kind of turmeric bovine colostrum fermented milk with high antioxidant capacity, the formula of turmeric bovine colostrum fermented milk was optimized by response surface analysis on the basis of single factors, with sensory evaluation as the response value, and the physicochemical indexes and antioxidant activity of the product were analyzed. The results showed that the optimal fermentation process of turmeric bovine colostrum was as follows: Curcumin microcapsule dosage of 0.5%, inoculum dosage of 2%, colostrum dosage of 30%, sucrose dosage of 6%, and the sensory score of fermented milk reached 91.24. The hardness of turmeric colostrum fermented milk was 0.97 N, elasticity was 3.96 mm, viscosity was 0.83 N, cohesion was 0.83, viscosity was 0.62 mJ, acidity was 88.63 °T, protein content was 3.98 g/100 g, fat content was 0.46 g/100 g, lactic acid bacteria count was 6.59×108 CFU/mL, no pathogenic bacteria were detected. When the concentration of yogurt was 25%, the scavenging rates of DPPH·, ABTS+· and hydroxyl free radical of turmeric bovine colostrum fermented milk were 89.59%, 95.39% and 63.26%, respectively. The antioxidant capacity of turmeric bovine colostrum fermented milk was significantly better than that of ordinary fermented milk.

Abstract Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer, with limited therapeutic options readily available. Immunotherapy such as immune checkpoint inhibition has been investigated in TNBC but still encounters low overall response. Neutrophils, the most abundant leukocytes in the body, are increasingly recognized as an active cancer-modulating entity. In the bloodstream, neutrophils escort circulating tumor cells to promote their survival and stimulate their proliferation and metastasis. In the tumor microenvironment, neutrophils modulate the immune milieu through polarization between the anti-tumor and the pro-tumor phenotypes. Through a comprehensive review of recently published literature, it is evident that neutrophils are an important player in TNBC immunobiology and can be used as an important prognostic marker of TNBC. Particularly, in their pro-tumor form, neutrophils facilitate TNBC metastasis through formation of neutrophil extracellular traps and the pre-metastatic niche. These findings will help advance the potential utilization of neutrophils as a therapeutic target in TNBC.

In this study, oil bodies (OBs) loaded with curcumin (Cur) were successfully prepared via an ultrasonic and pH-driven method. Ultrasonic treatment significantly improved the encapsulation efficiency (EE) and loading capacity (LC) of Cur, producing OB particles with small size, uniform distribution, and high ζ-potential absolute values. When the ultrasonic power was 200 W, the EE, LC, and ζ-potential absolute value were the greatest (88.27 %, 0.044 %, and −25.71 mV, respectively), and the OBs possessed the highest yellowness, representing the best treatment result. The confocal laser scanning microscopy (CLSM) and cryo-scanning electron microscopy (cryo-SEM) results was also intuitionally shown that. Moreover, circular dichroism (CD) proved that ultrasonic treatment could unfold the surface protein structure, further enhancing the stability. Therefore, the cream index (CI), peroxide value (POV), and thiobarbituric acid reactive substances (TBARS) were the lowest when the ultrasonic power was 200 W. In this case, the Cur loaded in OBs was well protected against hostile conditions, evidenced by the highest Cur retention rate and the lowest degradation rate constant. Finally, the in vitro gastrointestinal digestion simulation results showed that the ultrasonic treatment effectively increased the release of FFA, bioaccessibility, and stability of Cur, especially when the ultrasonic power was 200 W. This research offers a new OB-based delivery system to stabilize, deliver, and protect Cur for food processing.

Climate change is exacerbating the occurrence of compound droughts and heatwaves (CDHWs), which pose a serious threat to human health and socio-economic development. Using daily maximum temperature (Tmax) and monthly self-calibrating Palmer drought severity index (sc-PDSI) dataset, the evolution patterns of CDHWs and compound wet-heatwave events, the dominant drivers and the relative contributions of droughts and heatwaves in the drylands and humid areas from 1961 to 2020 were compared and analyzed. The results show that the CDHWs are stronger in drylands than in humid areas, the growth rate of CDHWs in drylands was almost twice that of the humid areas, the CDHWs are greater than the multi-year average intensity of compound wet-heatwave events by up to 2.4 times. Moreover, CDHWs has increased significantly from the past period (1961–1990) to the recent warm period (1991–2020), and the heatwave threshold has increased by about 5 °C. In most drylands, the contribution of heatwaves to CDHWs dominates, whereas in humid areas, the droughts contribution to CDHWs does. The compounding effects of droughts and heatwaves may exacerbate the severity of CDHWs regionally and are most pronounced in drylands, taking into account optimal lags. The study findings could provide scientific and technological support to actively address global climate change risks.

Every year more and more people is suffering from hyperuricemia in China, but the drugs used in clinical to lower uric acid have certain side effects and the treatment costs are relatively high. Reduction of uric acid can be achieved by consuming some foods. This paper introduces the research progress on the effects and mechanism of some ingredients in foods that reduce uric acid such as flavonoids, phenolic acids, alkaloids, saponins, polysaccharides and probiotic etc. The effect of flavonoids on lowering uric acid mainly lies in inhibiting the formation and reabsorption of uric acid. On this basis, phenolic acids and alkaloids can also promote uric acid excretion. The research on the mechanism of uric acid lowering by glycosides is in the preliminary stage. Whether polysaccharides can be used as additives in uric acid lowering functional foods needs to be verified by more pharmacological studies due to the increase of uric acid caused by polysaccharide metabolism. Probiotics can not only reduce uric acid level but also alleviate renal function injury, which can be used as the superior substances of uric acid lowering functional products.

Crop quality tends to decrease with an increasing grain yield. Nitrogen is an important nutrient and moderate nitrogen foliage application (NFA) can significantly improve the wheat yield and quality. The objective of this study was to investigate the effect of NFA on the grain yield and quality of wheat and its genotype-dependent variation. Eighteen wheat cultivars were used, and two NFA levels (N1 and N2; 10.70 and 21.40 kg N ha−1 two day−1, respectively) were applied. Significant genotypic differences in the yield and quality were observed among the 18 varieties, and their responses to NFA differed. For nine varieties in the experiment, N1 increased the grain yield, but N2 did not. In contrast, high concentrations of NFA had no effect on the grain yield in the other nine varieties. The protein content and composition and trace element (Fe, Zn, etc.) are all nutrient elements that notably affect the wheat grain quality and yield. NFA significantly increased the grain prolamin and glutelin concentrations in the grains, thereby increasing the total protein concentration. The prolamin, glutelin, and total protein concentrations in the grains of the lower-protein cultivars were more sensitive to NFA than those of the higher-protein cultivars. In addition, NFA significantly decreased the amylose concentration in the grains. By affecting the prolamin, glutelin, and amylose concentrations in the grains, NFA significantly increased the development and stability times of the corresponding wheat flour dough, thereby improving the dough quality. Moreover, NFA reduced the molar ratio of phytic acid to Fe and Zn, increasing the bioavailability of trace elements. The judicious application of nitrogen fertilizer resulted in the synergistic improvement in the yield and quality.

Abstract Background Archaea form a third domain of life that is distinct from Bacteria and Eukarya. So far, many scholars have elucidated considerable details about the typical promoter architectures of the three domains of life. However, a functional promoter from the archaeon Halobacterium salinarum has never been studied in Escherichia coli. Results This paper found that the promoter of Halobacterium salinarum showed a promoter function in Escherichia coli. This Escherichia coli promoter structure contains − 10 box, -10 box extension and − 29 elements, however, no -35 box. The − 29 element is exercised by the TATA box in archaea. And we isolated the RM10 fragment that possessed the fusion characteristics of bacteria and archaea, which was overlapped with functionality of TATA box and − 29 elements. Conclusions The − 29 element reflects the evolutionary relationship between the archaeal promoter and the bacterial promoter. The result possibly indicated that there may be a certain internal connection between archaea and bacteria. We hypothesized that it provided a new viewpoint of the evolutionary relationship of archaea and other organisms.

Background: Abnormalities in regulated cell death (RCD) are involved in multiple diseases. However, the role of RCD in intracranial aneurysms (IA) remains unknown. The aim of this study was to explore different RCD processes in the pathogenesis of IA. Methods: Four microarray datasets (GSE75436, GSE54083, GSE13353, GSE15629) and one RNA sequencing (RNA-seq) dataset (GSE122897) were extracted from the Gene Expression Omnibus (GEO) database. The microarray datasets were merged to form the training set, while the RNA-seq dataset was used as the validation set. Differentially expressed genes (DEGs), gene set enrichment analysis (GSEA), and gene set variation analysis (GSVA) were used to investigate the role of different types of RCD, including apoptosis, necroptosis, autophagy, ferroptosis and pyroptosis in the formation of IA. A novel cell death classification system for IA was established using an unsupervised consensus clustering algorithm based on cell death signature genes. Differences in functional enrichment, cell death-related regulators, and immune infiltration between two cell death clusters were evaluated. Finally, predictive genes were identified using the least absolute shrinkage and selection operator (LASSO) regression, random forest and logistic regression, allowing a prediction model to be constructed for IA rupture. Results: Multiple RCD processes were significantly activated in IAs compared to controls. A total of 33 signature genes related to cell death were identified. The IA samples were divided into two clusters based on the cell death signature. The cell death-high subtype had a relatively higher rate of rupture, and higher enrichment levels for multiple cell death processes and several signal transduction and immune-related pathways. Immune infiltration analysis showed that cell death scores were correlated with multiple immune cell types, including macrophages, mast cells, T cells and B cells. A six-gene prediction model was constructed to predict rupture. The area under curves (AUCs) for predicting rupture in the training and validation cohorts were 0.924 and 0.855, respectively. Conclusions: Comprehensively analysis of RCD in IA and found that multiple RCD types are likely to be involved in IA formation and rupture. These cell death processes were correlated with inflammation and immunity. We present novel insights into the mechanism of IA pathogenesis that should help to guide further research.

Climate change has significantly influenced water resource patterns in arid regions. Applying effective water-saving measures to improve irrigation efficiency and evaluate their future water-saving capabilities is crucial for ensuring the sustainable development of irrigation agriculture. Based on the daily meteorological data from 15 global climate models (GCMs) in the sixth phase of the Coupled Model Intercomparison Project (CMIP6), this study used the AquaCrop model to perform high-resolution (0.1° × 0.1°) grid simulations of cotton yields and irrigation requirements. The study also investigated the ability of film-mulched drip irrigation (FMDI) to improve future irrigation efficiency under two shared socio-economic pathways (SSP245 and SSP585) in the Tarim River Basin (TRB), Central Asia, from 2025 to 2100. The results showed that the cotton yield and irrigation water productivity (WPI) in the TRB exhibited an upward trend of 13.82 kg/ha/decade (80.68 kg/ha/decade) and 0.015 kg/m3/decade (0.068 kg/m3/decade), respectively, during the study period. The cotton yield and WPI were higher in the northern, northwestern plains, and northeastern intermountain basin areas, where they reach over 4000 kg/ha and 0.8 kg/m3/decade. However, the cotton yield and WPI were lower in the southwestern part of the study area. Therefore, large-scale cotton production was not recommended there. Furthermore, compared to flood irrigation, the use of FMDI can, on average, improve the WPI by approx. 25% and reduce irrigation water requirements by more than 550 m3/ha. Therefore, using FMDI can save a substantial amount of irrigation water in cotton production, which is beneficial for improving irrigation efficiency and ensuring the future stable production of cotton in the TRB. The research results provide a scientific reference for the efficient utilization and management of water resources for cotton production in the TRB and in similar arid regions elsewhere in the world.

To address the problems of limited hiding capacity and inaccurate information extraction in the existing generative steganography methods, a novel generative steganography method was proposed based on auto-generation of contours, which consisted of two main stages, such as the contour generation driven by secret information and the contour-to-image transformation.Firstly, the contour generation model was built based on long short term memory (LSTM) for secret information-driven auto-generation of object contours.Then, a contour-to-image reversible transformation model was constructed based on pix2pix network to obtain the stego-image, and the model also supported the reversible transformations from the stego-image to contours for secret information extraction.Experimental results demonstrate that the proposed method not only achieves high hiding capacity and accurate information extraction simultaneously, but also effectively resists the attacks by steganalysis tools.It performs much better than the state-of-the-art generative steganographic methods.

Mycobacterium leprae is a kind of disease-causing bacteria and results in leprosy in human. Gamma delta (γδ) T cell is a T-cell subset that is presented in both human dermis and epidermis. These cells bridge innate and adaptive immune responses and play critical roles in regulating anti-microbial defense, wound healing, and skin inflammation. Here, we investigated skin resident γδ T cells in patients with leprosy. Our data showed that γδ T cells significantly accumulated in skin lesions of leprosy patients with tuberculoid (TT) form. IL-23 can predominantly stimulate dermal γδ T cells to produce interleukin 17 (IL-17), a cytokine which may lead to disease protection. These γδ T cells expressed a specific set of surface molecules, and majority of these cells were Vδ1+. Also, IL-23 can stimulate the expansion of dermal γδ T cells expansion. Moreover, our results revealed that the transcription factor RORγt was responsible for IL-17A expression in leprosy lesion. Therefore, these data indicated that IL-23–responsive dermal γδ T cells were the major resource of IL-17A production in the skin and could be a potential target in the treatment of leprosy.

Soil, sediment, and waters contaminated with heavy metals pose a serious threat to ecosystem function and human health, and microorganisms are an effective way to address this problem. In this work, sediments containing heavy metals (Cu, Pb, Zn, Mn, Cd, As) were treated differently (sterilized and unsterilized) and bio-enhanced leaching experiments were carried out with the addition of exogenous iron-oxidizing bacteria A. ferrooxidans and sulfur-oxidizing bacteria A. thiooxidans. The leaching of As, Cd, Cu, and Zn was higher in the unsterilized sediment at the beginning 10 days, while heavy metals leached more optimally in the later sterilized sediment. The leaching of Cd from sterilized sediments was favored by A. ferrooxidans compared to A. thiooxidans. Meanwhile, the microbial community structure was analyzed using 16S rRNA gene sequencing, which revealed that 53.4% of the bacteria were Proteobacteria, 26.22% were Bacteroidetes, 5.04% were Firmicutes, 4.67% were Chlamydomonas, and 4.08% were Acidobacteria. DCA analysis indicated that microorganisms abundance (diversity and Chao values) increased with time. Furthermore, network analysis showed that complex networks of interactions existed in the sediments. After adapting to the acidic environmental conditions, the growth of some locally dominant bacteria increased the microbial interactions, allowing more bacteria to participate in the network, making their connections stronger. This evidence points to a disruption in the microbial community structure and its diversity following artificial disturbance, which then develops again over time. These results could contribute to the understanding of the evolution of microbial communities in the ecosystem during the remediation of anthropogenically disturbed heavy metals.

We proposed and fabricated toroidal dipole (TD) metasurfaces(MSs) with a metamolecule of two coplanar U-shaped split ring resonators(USRRs) fabricated on polyimide substrate, and TD metamaterials (MMs) were the stacks of two TD MSs layers, whose frequencies, electromagnetic (EM) distributions and Q factor can be efficiently affected by the EM coupling effect in TD MSs/MMs. It was found that the resonances frequencies of TD MMs were shifted to lower frequencies due to the increase of inductance by the stacks of metallic layer. Meanwhile, the high-frequency TD resonance in TD MMs would be tailored by the periodicity. Considering the relation between TD resonances and the scattering power of TD (Ty), the Q factor depended highly on the value of Ty in the same metamolecule structure. The optimization in excitation of TD provide opportunity to further increase the Q-factor of metamaterial and pave a way for potential applications in terahertz sensor and other functional devices.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and lacks approved specific targeted therapies. One of the major reasons why TNBC is difficult to treat is the high proportion of cancer stem cells within the tumor tissue. Nucleolus is the location of ribosome biogenesis which is frequently overactivated in cancer cells and overactivation of ribosome biogenesis frequently drives the malignant transformation of cancer. Nucleolar and coiled-body phosphoprotein 1 (NOLC1) is a nucleolar protein responsible for nucleolus organization and rRNA synthesis and plays an important role in ribosome biogenesis. However, the correlation of NOLC1 expression with patient prognosis and its value as a therapeutic target have not been evaluated in TNBC. In the current study, based on bioinformatics analysis of the online databases, we found that the expression of NOLC1 was higher in breast cancer tissues than normal tissues, and NOLC1 was expressed at a higher level in TNBC than other subtypes of breast cancer. GSEA analysis revealed that stemness-related pathways were significantly enriched in breast cancer with high NOLC1 gene expression. Further analyses using gene expression profiling interactive analysis 2 (GEPIA2), tumor immune estimation resource (TIMER) and search tool for retrieval of interacting genes/proteins (STRING) demonstrated that NOLC1 was significantly associated with stemness in both all breast cancer and basal-like breast cancer/TNBC patients at both gene and protein levels. Knockdown of NOLC1 by siRNA decreased the protein level of the key stemness regulators MYC and ALDH and inhibited the sphere-forming capacity in TNBC cell line MDA-MB-231. Univariate and multivariate Cox regression analyses demonstrated that NOLC1 was an independent risk factor for overall survival in breast cancer. PrognoScan and Kaplan-Meier plotter analyses revealed that high expression of NOLC1 was associated with poor prognosis in both all breast cancer and TNBC patients. Further immunohistochemical analysis of breast cancer patient samples revealed that TNBC cells had a lower level of NOLC1 in the nucleus compared with non-TNBC cells. These findings suggest that NOLC1 is closely associated with the stemness properties of TNBC and represents a potential therapeutic target for TNBC.

After the Fukushima nuclear accident in Japan in 2011, the demand for new and innovative nuclear reactor technologies is increasing. The present work implements potential Accident Tolerant Fuels (ATF), U3Si2-FeCrAl, and innovative fuel designs, annular type, to small reactor systems. Neutronic analyses at both the assembly and core levels are performed for the traditional UO2-Zr system and the candidate ATF U3Si2-FeCrAl systems with cylindrical fuel rod as well as the annular fuel rod design. The whole core level studies show that with 10% enrichment fuel, the lifetime of the annular fuel can achieve up to 55 MWd/kg, whereas those of the cylindrical U3Si2-FeCrAl system and the UO2-Zr system are 60 and 67 MWd/kg, respectively. A larger thermal neutron penalty and higher 239Pu amount are observed in the ATF systems (more significant in the annular fuel design). Compared with the two cylindrical designs, the annular design leads to a higher power peak value and more heterogeneous power distribution in an assembly and in the core. The calculated negative fuel and moderator temperature coefficients throughout the whole life ensure the inherent safety of the core loaded with one of the three fuel assemblies. Therefore, the preliminary results indicate the rationality of the core design loaded with the traditional fuel and the U3Si2-FeCrAl system with both cylindrical and annular fuel designs.

Mushrooms containing Amanita peptide toxins are the major cause of mushroom poisoning, and lead to approximately 90% of deaths. Phallotoxins are the fastest toxin causing poisoning among Amanita peptide toxins. Thus, it is imperative to construct a highly sensitive quantification method for the rapid diagnosis of mushroom poisoning. In this study, we established a highly sensitive and automated magnetic bead (MB)-based chemiluminescence immunoassay (CLIA) for the early, rapid diagnosis of mushroom poisoning. The limits of detection (LODs) for phallotoxins were 0.010 ng/ml in human serum and 0.009 ng/ml in human urine. Recoveries ranged from 81.6 to 95.6% with a coefficient of variation

PurposeXanthomatous hypophysitis (XHP) is an extremely rare form of primary hypophysitis for which there is a lack of clinical experience. A comprehensive understanding of its clinical characteristics, diagnosis and treatment is needed.MethodsHere, we report a case study and conduct a systematic review of XHP. Thirty-six cases were included, and their clinical manifestations, endocrine assessment, imaging features, treatment and follow-up data were collected and analyzed.ResultsThe mean age at diagnosis was 39.1 years, and females were predominant (75.0%). The most common symptom was headache (68.6%), and 66.7% of female patients presented menstrual disorders. The most common pituitary dysfunction was growth hormone (GH) deficiency. More than half of patients exhibited central diabetes insipidus (CDI). The majority of patients had an imaging presentation of a cystic lesion with peripheral enhancement. Pituitary stalk thickening was observed in half of the patients. Total lesion resection was achieved in 57.1% of cases. The recurrence rate after partial resection and biopsy was significantly higher than that after total lesion resection (57.1% vs. 0.0%, P = 0.0147). The most common pituitary hormone abnormalities to resolve after surgery were hyperprolactinemia (100.0%) and GH deficiency (91.7%). The typical pathological feature was inflammatory infiltration of foamy histiocytes, which showed positivity for CD68.ConclusionDiagnosis of XHP is difficult when relying on clinical symptoms and imaging features. Therefore, surgical histopathology is necessary. Based on the available evidence, total lesion resection is recommended for treatment. However, the long-term prognosis for this rare disease remains unclear.

Peritendinous adhesion (PA) around tendons are daunting challenges for hand surgeons. Tenotomy with various sutures are considered classical tendon repair models (TRM) of tendon adhesion as well as tendon healing. However, potential biomimetic therapies such as anti-adhesion barriers and artificial tendon sheaths to avoid recurrence of PA are sometimes tested in these models without considering tendon healing. Thus, our aim is to create a simplified model without sutures in this study by using three 6 mm longitudinal and parallel incisions called the longitudinal incision model (LCM) in the murine flexor tendon. We found that the adhesion score of LCM has no significant difference to that in TRM. The range of motion (ROM) reveals similar adhesion formation in both TRM and LCM groups. Moreover, mRNA expression levels of collagen I and III in LCM shows no significant difference to that in TRM. The breaking force and stiffness of LCM were significantly higher than that of TRM. Therefore, LCM can imitate flexor tendon adhesion formation without sutures compared to TRM, without significant side effects on biomechanics with an easy operation.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. Massive internal migration from rural to urban areas poses new challenges for leprosy control in Shanghai, China. This retrospective epidemiological study examined new cases of leprosy diagnosed in Shanghai from 2000 to 2019, with emphasis on internal migration cases. There were 145 cases of leprosy in the study period; the majority of cases (89.0%) were internal migrants. Migrant cases had a mean of 25.4 months lag time from onset of symptoms to diagnosis, which was significantly longer than that of resident cases (mean 10.8 months, p

Ectopic thyrotropin-secreting pituitary adenoma (ectopic TSH-oma) is a rare disorder that is easily misdiagnosed in clinical work. We report one patient who presented with hyperthyroidism and a suprasellar mass. In this case, preoperative diagnosis of suprasellar ectopic thyrotropin-secreting pituitary adenoma was challenging. A literature review revealed that a total of 11 patients with ectopic TSH-oma were previously reported, and only our one case was diagnosed in the microadenoma stage. Most of the patients with TSH-oma or ectopic TSH-oma were middle-aged. We described ectopic TSH-oma in a child at length. We recommend that ectopic TSH-oma should be considered in the differential diagnosis of thyrotoxicosis syndrome to achieve an accurate, early diagnosis. The somatostatin suppression test and imaging examinations, such as magnetic resonance imaging and positron emission tomography/magnetic resonance imaging, could contribute to the diagnosis. Once the diagnosis was highly suspected, tumor resection could achieve a satisfying long-term outcome in ectopic TSH-oma.

Drought is one of the most significant abiotic stresses that affects the growth and productivity of crops worldwide. Finger millet [Eleusine coracana (L.) Gaertn.] is a C4 crop with high nutritional value and drought tolerance. However, the drought stress tolerance genetic mechanism of finger millet is largely unknown. In this study, transcriptomic (RNA-seq) and proteomic (iTRAQ) technologies were combined to investigate the finger millet samples treated with drought at different stages to determine drought response mechanism. A total of 80,602 differentially expressed genes (DEGs) and 3,009 differentially expressed proteins (DEPs) were identified in the transcriptomic and proteomic levels, respectively. An integrated analysis, which combined transcriptome and proteome data, revealed the presence of 1,305 DEPs were matched with the corresponding DEGs (named associated DEGs-DEPs) when comparing the control to samples which were treated with 19 days of drought (N1-N2 comparison group), 1,093 DEGs-DEPs between control and samples which underwent rehydration treatment for 36 hours (N1-N3 comparison group) and 607 DEGs-DEPs between samples which were treated with drought for 19 days and samples which underwent rehydration treatment for 36 hours (N2-N3 comparison group). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified 80 DEGs-DEPs in the N1-N2 comparison group, 49 DEGs-DEPs in the N1-N3 comparison group, and 59 DEGs-DEPs in the N2-N3 comparison group, which were associated with drought stress. The DEGs-DEPs which were drought tolerance-related were enriched in hydrolase activity, glycosyl bond formation, oxidoreductase activity, carbohydrate binding and biosynthesis of unsaturated fatty acids. Co-expression network analysis revealed two candidate DEGs-DEPs which were found to be centrally involved in drought stress response. These results suggested that the coordination of the DEGs-DEPs was essential to the enhanced drought tolerance response in the finger millet.

Rosai-Dorfman disease (RDD) is an extremely rare histiocytic disorder characterized by cervical lymphadenopathy, while the involvement of sellar region is less observed. Here we report a pediatric patient who was initially suspected as sellar germinoma but later identified as RDD. We also conducted a systematic review about RDD involving sellar region. A total of only 14 cases were included and analyzed in our study in terms of clinical presentation, endocrine abnormality, radiological features, pathology, treatment, and follow up. The most common neurological manifestations of sellar RDD is diabetes insipidus and visual changes. Two typical kinds of MRI manifestations were presented in sellar RDD; one is like meningioma-like mass lesions, another showing infiltrative pattern that demonstrates hyperintense areas on T2WI. Currently, the treatment of RDD is tailored to the individual clinical circumstances. For sellar RDD, surgical treatment can be considered to completely remove or debulk the tumor.

Sulfobacillus and Leptospirillum occur frequently in leaching systems. Here we investigated the effects of cells of L. ferriphilum on biofilm formation and leaching performance by S. thermosulfidooxidans. The effects were caused by the presence of L. ferriphilum or an addition of pyrite leach liquor from L. ferriphilum. Data show that the number of attached S. thermosulfidooxidans on pyrite increases, if the pyrite had been pre-colonized by living biofilms of L. ferriphilum, while it decreases if the pre-colonized biofilms had been inactivated. Coaggregation between S. thermosulfidooxidans and L. ferriphilum occurs during the dual-species biofilm formation, but different effects on bioleaching were noted, if the preculture of L. ferriphilum had been different. If L. ferriphilum had been pre-colonized on a pyrite, significantly negative effect was shown. However, if the two species were simultaneously inoculated into a sterile leaching system, the bioleaching efficiency was better than that of a pure culture of S. thermosulfidooxidans. The effect might be related to a metabolic preference of S. thermosulfidooxidans. If S. thermosulfidooxidans performed leaching in a filtered pyrite leachate from L. ferriphilum, the cells preferred to oxidize RISCs instead of ferrous ion and the number of attached cells decreased compared with the control. This study gives an indication that in a short-term multi-species leaching system the role of S. thermosufidooxidans may be related to the time of its introduction.

Abstract: The current standard of care for acute myeloid leukemia (AML) is largely ineffective with very high relapse rates and low survival rates, mostly due to the inability to eliminate a rare population of leukemic stem cells (LSCs) that initiate tumor growth and are resistant to standard chemotherapy. RNA-sequencing analysis on isolated LSCs confirmed C-type lectin domain family 12 member A (CLL1, also known as CLEC12A) to be highly expressed on LSCs but not on normal hematopoietic stem cells (HSCs) or other healthy organ tissues. Expression of CLL1 was consistent across different types of AML. We developed CLT030 (CLL1-ADC), an antibody-drug conjugate (ADC) based on a humanized anti-CLL1 antibody with 2 engineered cysteine residues linked covalently via a cleavable linker to a highly potent DNA-binding payload, thus resulting in a site-specific and homogenous ADC product. The ADC is designed to be stable in the bloodstream and to release its DNA-binding payload only after the ADC binds to CLL1-expressing tumor cells, is internalized, and the linker is cleaved in the lysosomal compartment. CLL1-ADC inhibits in vitro LSC colony formation and demonstrates robust in vivo efficacy in AML cell tumor models and tumor growth inhibition in the AML patient-derived xenograft model. CLL1-ADC demonstrated a reduced effect on differentiation of healthy normal human CD34+ cells to various lineages as observed in an in vitro colony formation assay and in an in vivo xenotransplantation model as compared with CD33-ADC. These results demonstrate that CLL1-ADC could be an effective ADC therapeutic for the treatment of AML.

The soy protein isolates (SPI) extracted from different extruded full-fat soybean flakes (FFSF), and their conformational and functional properties were characterized. Overall, the free thiol (SH) content of SPI increased when the extrusion temperature was below 80 °C and decreased at higher temperatures. Soy glycinin (11S) showed higher stability than β-conglycinin (7S) during extrusion. Results also indicated that the increase in some hydrophobic groups was due to the movement of hydrophobic groups from the interior to the surface of the SPI molecules at extrusion temperatures from 60 to 80 °C. However, the aggregation of SPI molecules occurred at extrusion temperatures of 90 and 100 °C, with decreasing levels of hydrophobic groups. The extrusion temperature negatively affected the emulsifying activity index (EAI); on the other side, it positively affected the emulsifying stability index (ESI), compared to unextruded SPI.

BACKGROUND:The persistence of Mycobacterium leprae (M. leprae) infection is largely dependent on the types of host immune responses being induced. Macrophage, a crucial modulator of innate and adaptive immune responses, could be directly infected by M. leprae. We therefore postulated that M. leprae-infected macrophages might have altered immune functions. METHODOLOGY/PRINCIPAL FINDINGS:Here, we treated monocyte-derived macrophages with live or killed M. leprae, and examined their activation status and antigen presentation. We found that macrophages treated with live M. leprae showed committed M2-like function, with decreased interleukin 1 beta (IL-1beta), IL-6, tumor necrosis factor alpha (TNF-alpha) and MHC class II molecule expression and elevated IL-10 and CD163 expression. When incubating with naive T cells, macrophages treated with live M. leprae preferentially primed regulatory T (Treg) cell responses with elevated FoxP3 and IL-10 expression, while interferon gamma (IFN-gamma) expression and CD8+ T cell cytotoxicity were reduced. Chromium release assay also found that live M. leprae-treated macrophages were more resistant to CD8+ T cell-mediated cytotoxicity than sonicated M. leprae-treated monocytes. Ex vivo studies showed that the phenotype and function of monocytes and macrophages had clear differences between L-lep and T-lep patients, consistent with the in vitro findings. CONCLUSIONS/SIGNIFICANCE:Together, our data demonstrate that M. leprae could utilize infected macrophages by two mechanisms: firstly, M. leprae-infected macrophages preferentially primed Treg but not Th1 or cytotoxic T cell responses; secondly, M. leprae-infected macrophages were more effective at evading CD8+ T cell-mediated cytotoxicity.