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Soil multifunctionality is essential for the enhancement of soil carbon sequestration, but disturbances such as thinning practices can influence soil microbial activity and carbon cycling. Microbial residues, particularly microbial residue carbon (MRC), are important contributors to soil organic carbon (SOC), but the effects of thinning intensity on MRC accumulation remain poorly understood. This study evaluated the impact of four thinning treatments—control (CK, 0%), light-intensity thinning (LIT, 20%), medium-intensity thinning (MIT, 30%), and high-intensity thinning (HIT, 45%)—on soil multifunctionality in Chinese fir plantations five years after thinning. Soil nutrient provision, microbial biomass, enzyme activity, and microbial residue carbon were assessed. The results showed that thinning intensity significantly affected soil nutrient provision and microbial biomass, with MIT and HIT showing higher nutrient levels than CK and LIT. Specifically, MIT's and HIT's total nutrient provision increased by 0.04 and 0.15 compared to that of CK. Enzyme activity was highest in LIT (+0.89), followed by MIT (+0.07), with HIT showing a decline (−0.84). Microbial biomass, including bacterial PLFAs (B-PLFAs), fungal PLFAs (F-PLFAs), microbial biomass carbon (MBC), and nitrogen (MBN), was highest in CK and MIT, and lowest in HIT, with MIT showing a 0.13 increase compared to CK. Microbial residue carbon (MRC) accumulation was positively correlated with soil organic carbon (SOC), total nitrogen (TN), available nitrogen (AN), and easily oxidized organic carbon (EOC). The highest MRC content in the 0–20 cm soil layer was observed in MIT and CK (10.46 and 11.66 g/kg, respectively), while the MRC in LIT and HIT was significantly lower, reduced by 24% and 12%, respectively. These findings highlight the significant role of thinning intensity in microbial activity and carbon cycling. Medium-intensity thinning (MIT, 30%) was identified as the most effective approach for promoting microbial biomass and enhancing carbon cycling in Chinese fir forest soils, making it an optimal approach for forest management aimed at increasing soil carbon sequestration. [ABSTRACT FROM AUTHOR]

Dipeptidyl peptidase 4 (DPP4) is a serine protease widely distributed in membrane-bound and soluble forms in various tissues and organs throughout the body. DPP4 plays a role in inflammation, immune regulation, cell growth, migration and differentiation. The role of DPP4 in tumors has garnered increasing attention. Previous research has demonstrated that DPP4 contributes to the promotion of cancer in most cancers, and it may play a specific biological function through the variation in tumor cell types and expression forms. However, the expression of DDP4 in different tumor types and its specific mechanism remains unclear. In this review, we describe the structure of DPP4, summarize the recent research progress of its expression and potential mechanisms in common tumors, and discuss the development prospects of DPP4 inhibitors in tumor therapy. Although current research emphasizes the potential of DPP4 as a drug target, the incomplete understanding of its regulatory mechanisms impedes the discovery and development of new therapies against it. Further research on DPP4-related tumors is anticipated to promote its clinical application as a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Tumor-derived exosomes bind to organ resident cells, activating S100 molecules during the remodeling of the local immune microenvironment. However, little is known regarding how organ resident cell S100A10 mediates cancer metastatic progression. Here, we provided evidence that S100A10 plays an important role in regulating the lung immune microenvironment and cancer metastasis. S100A10-deficient mice reduced cancer metastasis in the lung. Furthermore, the activation of S100A10 within lung fibroblasts via tumor-derived exosomes increased the expression of CXCL1 and CXCL8 chemokines, accompanied by the myeloid-derived suppressor cells (MDSCs) recruitment. S100A10 inhibitors such as 1-Substituted-4-Aroyl-3-hydroxy-5-Phenyl-1 H-5-pyrrol-2(5 H)-ones inhibit lung metastasis in vivo. Our findings highlight the crucial role of S100A10 in driving MDSC recruitment in order to remodel the lung immune microenvironment and provide potential therapeutic targets to block cancer metastasis to the lung. [ABSTRACT FROM AUTHOR]

The multistep dynamic process of metastasis is the primary cause of breast cancer deaths. C‐terminal Eps15‐homology domain‐containing protein 1 (EHD1), a translocator associated with endocytic recycling, has been implicated in various oncogenic processes. However, the precise molecular mechanisms of EHD1‐induced breast cancer metastases remain largely unexplored. Here we found that the upregulation of EHD1 in breast cancer was positively associated with distant lymph node metastasis in patients. Meanwhile, EHD1 promoted epithelial‐mesenchymal transition (EMT), invasion, and metastasis of breast cancer cells in both two‐dimensional (2D) and three‐dimensional (3D) culture models in vitro, as well as in vivo. Remarkably, EHD1 can activate the AKT–mTOR pathway to upregulate the protein expression of hypoxia‐inducible factor 2α (HIF2α) under normoxic conditions and subsequently enhance the invasive and metastatic breast cancer. Our findings indicated EHD1 as a new regulator of HIF2α and a potential therapeutic target for inhibiting breast cancer metastasis. [ABSTRACT FROM AUTHOR]

Karst ecosystems are characterized by the dissolution of soluble rocks, displaying distinctive landscape features such as rugged peaks, steep slopes, and deep valleys. Afforestation is an effective approach for improving soil quality in rocky desertification areas because plants have evolved unique adaptations to thrive in such environments. However, the effects of tree species composition and cultivation patterns on the soil quality, microbial diversity, stability, and functions in rocky desertification areas remain unclear. In this work, four study plots including three types of forests—pure Pinus massoniana plantations, Toona sinensis plantations, mixed coniferous and broadleaf plantations (Pinus massoniana–Betula luminifera forests), and unforested area as the control—were established in a karst desertification area in the Hunan province of China. Soil properties including soil bulk density, soil organic carbon, total nitrogen, total phosphate, soil ammonium nitrogen, nitrate, available phosphate, soil pH, and soil microbial diversity were investigated in the study area. The results showed that the forests significantly increased the soil organic carbon, total nitrogen, and ammonium nitrogen compared to the unforested area. The microbial diversity indicators in mixed forests were significantly higher than those in the Pinus massoniana forests. The dominant bacteria phyla included Proteobacteria, Acidobacteria, and Actinobacteria, while fungi species such as Ascomycota and Basidiomycota were identified in all study plots. In addition, the AVD index evaluation revealed that the mixed forests enhanced the stability of the soil microbial communities compared to the monoculture plantations and unforested plots in rocky desertification areas. The research results indicated that, among the various forest types, the mixed forest was the most effective choice for afforestation in terms of improving the soil quality by changing the soil's physiological properties in rocky desertification areas. Our study provided guidance and insights for afforestation technology and the optimal allocation of different tree species in the cultivation and management of plantation forests in rocky desertification regions. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are essential regulators of numerous biological processes in animals, including adipogenesis. Despite the abundance of miRNAs associated with adipogenesis, their exact mechanisms of action remain largely unknown. Our study highlights the role of bta-miR-484 as a major regulator of adipocyte proliferation, apoptosis, and differentiation. Here, we demonstrated that the expression of bta-miR-484 initially increased during adipogenesis before decreasing. Overexpression of bta-miR-484 in adipocytes ultimately inhibited cell proliferation and differentiation, reduced the number of EdU fluorescence-stained cells, increased the number of G1 phase cells, reduced the number of G2 and S phase cells, and downregulated the expression of proliferation markers (CDK2 and PCNA) and differentiation markers (CEBPA, FABP4, and LPL). Additionally, overexpression of bta-miR-484 promoted the expression of apoptosis-related genes (Caspase 3, Caspase 9, and BAX), and increased the number of apoptotic cells observed via flow cytometry. In contrast, bta-miR-484 inhibition in adipocytes yielded opposite effects to those observed during bta-miR-484 overexpression. Moreover, luciferase reporter assays confirmed SFRP1 as a target gene of bta-miR-484, and revealed that bta-miR-484 downregulates SFRP1 mRNA expression. These findings offer compelling evidence that bta-miR-484 targets SFRP1, inhibits proliferation and differentiation, and promotes apoptosis. Therefore, these results offer novel insights into the bta-miR-484 regulation of adipocyte growth and development. [ABSTRACT FROM AUTHOR]

Marine heatwaves (MHWs) are extreme events characterized by abnormally high sea surface temperatures, and they have significant impacts on marine ecosystems and human society. The rapid and accurate forecasting of MHWs is crucial for preventing and responding to the impacts they can lead to. However, the research on relevant forecasting methods is limited, and a dedicated forecasting system specifically tailored for the South China Sea (SCS) region has yet to be reported. This study proposes a novel forecasting system utilizing U-Net and ConvLSTM models to predict MHWs in the SCS. Specifically, the U-Net model is used to forecast the intensity of MHWs, while the ConvLSTM model is employed to predict the probability of their occurrence. The indication of an MHW relies on both the intensity forecasted by the U-Net model exceeding threshold T and the occurrence probability predicted by the ConvLSTM model surpassing threshold P. Incorporating sensitivity analysis, optimal thresholds for T are determined as 0.9 °C, 0.8 °C, 1.0 °C, and 1.0 °C for 1-, 3-, 5-, and 7-day forecast lead times, respectively. Similarly, optimal thresholds for P are identified as 0.29, 0.30, 0.20, and 0.28. Employing these thresholds yields the highest forecast accuracy rates of 0.92, 0.89, 0.88, and 0.87 for the corresponding forecast lead times. This innovative approach gives better predictions of MHWs in the SCS, providing invaluable reference information for marine management authorities to make well-informed decisions and issue timely MHW warnings. [ABSTRACT FROM AUTHOR]

Background: Starch is a major component of carbohydrates and a major energy source for monogastric animals. Starch is composed of amylose and amylopectin and has different physiological functions due to its different structure. It has been shown that the energy supply efficiency of amylose is lower than that of amylopectin. However, there are few studies on the effect of starch structure on the available energy of pigs. The purpose of this study was to measure the effect of different structures of starch in the diet on the net energy (NE) of pigs using a comparative slaughter method and to establish a prediction equation to estimate the NE of starch with different structures. Fifty-six barrows (initial BW 10.18 ± 0.11 kg) were used, and they were housed and fed individually. Pigs were divided into 7 treatments, with 8 replicates for each treatment and 1 pig for each replicate. One of the treatments was randomly selected as the initial slaughter group (ISG). Pigs in the remaining treatments were assigned to 6 diets, fed with basic diet and semi-pure diets with amylose/amylopectin ratio (AR) of 3.09, 1.47, 0.25, 0.15 and 0.12, respectively. The experiment lasted for 28 d. Results: Results showed that compared with the high amylose (AM) groups (AR 3.09 and 1.47), the high amylopectin (AP) group (AR 0.15) significantly increased the final BW, average daily weight gain and average daily feed intake of pigs (P < 0.05), but the F:G of the AM group was lower (P < 0.01). In addition, AR 0.15 and 0.12 groups have higher (P < 0.01) nutrient digestibility of dry matter, crude protein, gross energy and crude ash. Meanwhile, compared with other groups, AR 0.15 group has a higher (P < 0.05) NE intake and energy retention (RE). The regressive equation for predicting with starch structures was established as RE = 1,235.243 − 48.298AM/AP (R2 = 0.657, P = 0.05). Conclusions: In conclusion, NE intake and RE of pigs augmented with the increase of dietary amylopectin content, indicating that diets high in amylopectin were more conducive to promoting the growth of pigs in the late conservation period. [ABSTRACT FROM AUTHOR]

Multiple cancers have been reported to be associated with angiogenesis and are sensitive to anti‐angiogenic therapies. Vascular normalization, by restoring proper tumor perfusion and oxygenation, could limit tumor cell invasiveness and improve the effectiveness of anticancer treatments. However, the underlying anticancer mechanisms of antiangiogenic drugs are still unknown. Metformin (MET) and simvastatin (SVA), two metabolic‐related drugs, have been shown to play important roles in modulating the hypoxic tumor microenvironment and angiogenesis. Whether the combination of MET and SVA could exert a more effective antitumor effect than individual treatments has not been examined. The antitumor effect of the synergism of SVA and MET was detected in mouse models, breast cancer patient‐derived organoids, and multiple tumor cell lines compared with untreated, SVA, or MET alone. RNA sequencing revealed that the combination of MET and SVA (but not MET or SVA alone) inhibited the expression of endothelin 1 (ET‐1), an important regulator of angiogenesis and the hypoxia‐related pathway. We demonstrate that the MET and SVA combination showed synergistic effects on inhibiting tumor cell proliferation, promoting apoptosis, alleviating hypoxia, decreasing angiogenesis, and increasing vessel normalization compared with the use of a single agent alone. The MET and SVA combination suppressed ET‐1‐induced hypoxia‐inducible factor 1α expression by increasing prolyl hydroxylase 2 (PHD2) expression. Furthermore, the MET and SVA combination showed a more potent anticancer effect compared with bosentan. Together, our findings suggest the potential application of the MET and SVA combination in antitumor therapy. [ABSTRACT FROM AUTHOR]

DPP4 (dipeptidyl peptidase 4) is expressed in many cancers, but the relationship between DPP4 and thyroid carcinoma (THCA) is incompletely understood. We aim to explore the expression of DPP4 in THCA and the correlation between DPP4 expression with the prognosis of THCA and antitumor immunity. We systematically analyzed data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO) databases and explored DPP4 expression, its impact on prognosis, and its relationship with antitumor immunity in THCA. Next, we collected 18 pairs of fresh THCA and adjacent paracancerous tissues and performed RT-qPCR to validate the DPP4 mRNA level. Concurrently, immunohistochemistry (IHC) analysis was performed on 12 pairs of paraffin-embedded tissues of medullary thyroid carcinoma (MTC) and paracancerous tissues to validate the DPP4 protein level. Bioinformatics analysis showed that DPP4 mRNA expression in THCA was significantly higher than that in paracancerous tissues (p < 0.01). DPP4 was expressed at the highest levels in MTC than in other pathological types. The DPP4 expression level was different between groups with different clinical characteristics. The higher the DPP4 expressed in THCA, the lower the disease-free survival (DFS) was (HR = 1.8, p = 0.048). DPP4 was significantly correlated with immune cell infiltration and immune response and was positively associated with 21 immune checkpoint genes (ICGs) in THCA (p < 0.05). The results of RT-qPCR showed that the relative mRNA expression of DPP4 was significantly upregulated in 18 THCA tissues compared to that in paracancerous tissues (p = 0.011). IHC results showed that the DPP4 protein level was higher in 12 MTC tissues than in paracancerous tissues (p = 0.011). In conclusion, DPP4 is a potential prognostic marker of THCA and may become an effective target for immunotherapy. [ABSTRACT FROM AUTHOR]

The proliferation and differentiation of pre‐adipocytes are regulated by microRNAs (miRNAs) and other factors. In this study, the potential functions of bta‐miR‐6517 in the regulation of pre‐adipocyte proliferation and differentiation were explored. The qRT‐PCR, oil red O staining and CCK‐8 assay were used to evaluate the role of bta‐miR‐6517. Further, the target gene of bta‐miR‐6517 was identified using bioinformatics analysis, dual‐luciferase reporter system and qRT‐PCR system. The results found that the overexpression of bta‐miR‐6517 promoted the expression of proliferation marker genes and substantially increased the adipocyte proliferation vitality in the CCK‐8 assay, whereas suppressing of bta‐miR‐6517 had the opposite effect. Overexpression bta‐miR‐6517 suppressed the expression of adipogenic genes, which inhibited lipid accumulation, whereas suppressing of bta‐miR‐6517 had the opposite effect. Furthermore, the dual‐fluorescent reporter experiment results demonstrated that bta‐miR‐6517 directly targeted phosphofructokinase, liver type (PFKL). When bta‐miR‐6517 was either overexpressed or suppressed, it negatively regulated PFKL. In conclusion, we observed that bta‐miR‐6517 promoted adipocyte proliferation and inhibited differentiation by targeting PFKL. [ABSTRACT FROM AUTHOR]

Electrocatalytic CO2 reduction reaction (CO2RR) is one of the most effective methods to convert CO2 into useful fuels. Introducing defects into metal nanostructures can effectively improve the catalytic activity and selectivity towards CO2RR. This review provides the recent progress on the use of metal nanomaterials with defects towards electrochemical CO2RR and defects engineering methods. Accompanying these ideas, we introduce the structure of defects characterized by electron microscopy techniques as the characterization and analysis of defects are relatively difficult. Subsequently, we present the intrinsic mechanism of how the defects affect CO2RR performance. Finally, to promote a wide and deep study in this field, the perspectives and challenges concerning defects engineering in metal nanomaterials towards CO2RR are put forward. [ABSTRACT FROM AUTHOR]

Finely modulating the morphology of bimetallic nanomaterials plays a vital role in enhancing their catalytic activities. Among the various morphologies, concave structures have received considerable attention due to the three advantageous features of high-index facets, high surface areas, and high curvatures, which contribute greatly to enhancing the catalytic performance. However, concave morphologies are not the products generated from thermodynamically controlled growth with minimized surface energy. Additionally, most nanocrystals with concave shapes are currently in the state of mono-metals or alloys with disordered arrangements of atoms. The synthesis of alloy structures with ordered atom arrangements, intermetallic compounds, which tend to display superior catalytic performance on account of their optimal geometric and electronic effects, has rarely been reported as high-temperature annealing is usually needed, which constrains the modulation of morphology and surface structure. In this work, concave one-dimensional Au–Cu nanorods with a partially ordered intermetallic structure were synthesized via a facile wet chemical method. By simply adjusting the reaction kinetics via the concentrations of the corresponding metal precursors, the degree of concavity of the one-dimensional Au–Cu nanorods could be regulated. In both the p-nitrophenol reduction and CO2 electro-reduction reactions, the concave-shaped Au–Cu nanorods demonstrated superior catalytic activity compared to corresponding non-concave samples with the same structure due to the morphological advantages provided by the concave structure. [ABSTRACT FROM AUTHOR]

Regulation of intracellular pH (pHi) in cardiomyocytes is crucial for cardiac function; however, currently known mechanisms for direct or indirect extrusion of acid from cardiomyocytes seem insufficient for energetically efficient extrusion of the massive H+ loads generated under in vivo conditions. In cardiomyocytes, voltage‐sensitive H+ channel activity mediated by the HVCN1 proton channel would be a highly efficient means of disposing of H+, while avoiding Na+ loading, as occurs during direct acid extrusion via Na+/H+ exchange or indirect acid extrusion via Na+–HCO3− cotransport. PCR and immunoblotting demonstrated expression of HVCN1 mRNA and protein in canine heart. Patch clamp analysis of canine ventricular myocytes revealed a voltage‐gated H+ current that was highly H+‐selective. The current was blocked by external Zn2+ and the HVCN1 blocker 5‐chloro‐2‐guanidinobenzimidazole. Both the gating and Zn2+ blockade of the current were strongly influenced by the pH gradient across the membrane. All characteristics of the observed current were consistent with the known hallmarks of HVCN1‐mediated H+ current. Inhibition of HVCN1 and the NHE1 Na+/H+ exchanger, singly and in combination, showed that either mechanism is largely sufficient to maintain pHi in beating cardiomyocytes, but that inhibition of both activities causes rapid acidification. These results show that HVCN1 is expressed in canine ventricular myocytes and provides a major H+ extrusion activity, with a capacity similar to that of NHE1. In the beating heart in vivo, this activity would allow Na+‐independent extrusion of H+ during each action potential and, when functionally coupled with anion transport mechanisms, could facilitate transport‐mediated CO2 disposal. Key points: Intracellular pH (pHi) regulation is crucial for cardiac function, as acidification depresses contractility and causes arrhythmias. H+ ions are generated in cardiomyocytes from metabolic processes and particularly from CO2 hydration, which has been shown to facilitate CO2 venting from mitochondria.Currently, the NHE1 Na+/H+ exchanger is viewed as the dominant H+ extrusion mechanism in cardiac muscle.We show that the HVCN1 voltage‐gated proton channel is present and functional in canine ventricular myocytes, and that HVCN1 and NHE1 both contribute to pHi regulation.HVCN1 provides an energetically efficient mechanism of H+ extrusion that would not cause Na+ loading, which can cause pathology, and that could contribute to transport‐mediated CO2 disposal.These results provide a major advance in our understanding of pHi regulation in cardiac muscle. [ABSTRACT FROM AUTHOR]

Carbohydrates are the main source of energy in the diet, accounting for the largest proportion in the diets of humans and monogastric animals. Although recent progress has been made in the study of intestinal carbohydrate digestion in piglets, there is a lack of comprehensive study on the dynamic changes in intestinal carbohydrate digestion with age in the early growth stage of piglets. To fill in this gap of knowledge, we collected samples of the small intestine, pancreatic tissues, and colonic digesta from 42 piglets during newborn [day (d) 0], lactation (d 7, 14), weaning (d 21), and nursery (d 28, 35, and 42) stages. Intestinal and pancreatic tissues and colonic digesta were collected at necropsy and analyzed for morphology, digestive enzyme activities, short-chain fatty acids (SCFA), and microbial abundance. Villus height reached a maximum at 1 week (d 7) in the duodenum and jejunum (P <0.01), and a higher ratio of villus height to crypt depth and lactase activity were observed on d 0 and 7 (P < 0.001) compared to other ages. However, the sucrase and maltase activities were increased with piglets' age. Similar activities of sucrase and maltase were found in the small intestine. In addition, amylase, lipase, and protease activities were assayed in the pancreas. The activity of amylase increased with age, while lipase and protease decreased gradually from birth to weaning (d 21, 28) and then increased after weaning (d 35, 42). Compared with d 0, d 42 increased the abundance of Firmicutes and Bacteroidetes with a higher concentration of total SCFA (P < 0.001) and decreased the abundance of Proteobacteria , but weaning (d 21, 28) increased the abundance of Proteobacteria in the colon. These results indicate that with the increase in piglet age, the carbohydrate digestive function gradually increased, but weaning hindered the development of intestinal function. These results provide us with new insights into the healthy development of piglets' intestines, which may help us to better regulate the physiological health of piglets in the future. [ABSTRACT FROM AUTHOR]

Introduction Bisphenols are a group of chemicals with two hydroxyphenyl functionalities in the structure (Liao and Kannan 2013). Bisphenols are widely used in the manufacturing industry, with bisphenol A (BPA) [...], BACKGROUND: Bisphenol S (BPS) has increasingly been used as a substitute for bisphenol A (BPA) in some 'BPA-free' consumer goods and in thermal papers. Wide human exposure to BPS has been reported; however, the biological and potential toxic effects of BPS are poorly understood. OBJECTIVE: In this study, we sought to elucidate the sex-specific rapid effect of BPS in rat hearts and its underlying mechanism. METHODS: We examined the rapid effects of BPS in rat hearts using electrophysiology, confocal and conventional fluorescence imaging, and immunoblotting. Treatment was administered via acute perfusion of excised hearts or isolated cardiac myocytes. RESULTS: In female rat hearts acutely exposed to [10.sup.-9] M BPS, the heart rate was increased; in the presence of catecholamine-induced stress, the frequency of ventricular arrhythmia events was markedly increased. BPS-exposed hearts showed increased incidence of arrhythmogenic-triggered activities in female ventricular myocytes and altered myocyte [Ca.sup.2+] handling, particularly spontaneous [Ca.sup.2+] release from the sarcoplasmic reticulum. The dose responses of BPS actions were inverted U-shaped. The impact of BPS on myocyte [Ca.sup.2+] handling was mediated by estrogen receptor β signaling and by rapid increases in the phosphorylation of key [Ca.sup.2+] handling proteins, including ryanodine receptor and phospholamban. The proarrhythmic effects of BPS were female specific; male rat hearts were not affected by BPS at the organ, myocyte, or protein levels. CONCLUSION: Rapid exposure to low-dose BPS showed proarrhythmic impact on female rat hearts; these effects at the organ, cellular, and molecular levels are remarkably similar to those reported for BPA. Evaluation of the bioactivity and safety of BPS and other BPA analogs is necessary before they are used as BPA alternatives in consumer products. http://dx.doi.org/10.1289/ehp.l408679

INTRODUCTION Bisphenol A (BPA; CAS 80-05-7) is one of the highest production volume chemicals worldwide, with annual production exceeding 3 million metric tons. BPA is used in the production of [...], BACKGROUND: The need for mechanistic understanding of nonmonotonic dose responses has been identified as one of the major data gaps in the study of bisphenol A (BPA). Previously we reported that acute exposure to BPA promotes arrhythmogenesis in female hearts through alteration of myocyte [Ca.sup.2+] handling, and that the dose response of BPA was inverted U-shaped. OBJECTIVE: We sought to define the cellular mechanism underlying the nonmonotonic dose response of BPA in the heart. METHODS: We examined rapid effects of BPA in female rat ventricular myocytes using video-edge detection, confocal and conventional fluorescence imaging, and patch clamp. RESULTS: The rapid effects of BPA in cardiac myocytes, as measured by multiple end points, including development of arrhythmic activities, myocyte mechanics, and [Ca.sup.2+] transient, were characterized by nonmonotonic dose responses. Interestingly, the effects of BPA on individual processes of myocyte [Ca.sup.2+] handling were monotonic. Over the concentration range of [10.sup.-12] to [10.sup.-6] M, BPA progressively increased sarcoplasmic reticulum (SR) [Ca.sup.2+] release and [Ca.sup.2+] reuptake and inhibited the L-type [Ca.sup.2+] current ([I.sub.CaL]). These effects on myocyte [Ca.sup.2+] handling were mediated by estrogen receptor (ER)β signaling. The nonmonotonic dose responses of BPA can be accounted for by the combined effects of progressively increased SR [Ca.sup.2+] reuptake/release and decreased [Ca.sup.2+] influx through [I.sub.CaL]. CONCLUSION: The rapid effects of BPA on female rat cardiac myocytes are characterized by nonmonotonic dose responses as measured by multiple end points. The nonmonotonic dose response was produced by ERβ-mediated monotonic effects on multiple cellular [Ca.sup.2+] handling processes. This represents a distinct mechanism underlying the nonmonotonicity of BPA's actions. http://dx.doi.org/10.1289/ehp.1307491

Objective: This study aimed to evaluate how leucine are associated with diabetic nephropathy (DN) in type 2 diabetes (T2D) patients and the gender difference of this association. Methods: We retrieved 1,031 consecutive patients with T2D who meet the inclusion and exclusion criteria from the same tertiary care center and extracted clinical information from electronic medical record. Plasma leucine was measured by liquid chromatography-mass spectrometer. Restricted cubic spline (RCS) was conducted to examine potential non-linear relationship between leucine and the risk of DN. Logistic regression was used to obtain odds ratio (OR) and confidence interval (CI). Additive interaction was used to estimate the interaction effect between leucine and gender for DN. Results: We found there was a negative correlation between leucine and the risk of DN. After stratifying all patients by gender, this relationship only remained significant in women (OR:0.57, CI:0.41–0.79). Conclusions: In conclusion, T2D patients with high levels of leucine have a lower risk of developing DN in female. [ABSTRACT FROM AUTHOR]

Nucleotide metabolism is the driving force of cell proliferation, and thymidylate synthase (TYMS) catalyzes a rate‐limiting step in the initial synthesis of nucleotides. Previous studies reported that TYMS activity significantly affected the proliferation of tumour cells. However, the diagnostic and prognostic significance of TYMS expression in breast cancer remains unclear. Here, we used the Breast Cancer Integrative Platform (BCIP) to investigate the relationship between progression and prognosis of breast cancer with TYMS expression, and then verified the database analysis using immunohistochemical staining. Our results indicated TYMS expression was greater in breast cancer than adjacent normal tissues and greater in triple‐negative breast cancer (TNBC) than non‐TNBC tissues. TYMS expression also had significant positive correlations with histological grade, tumour size, and ER negativity, and PR negativity. The increased copy number of the TYMS gene appears to be the reason for its upregulation in breast cancer. Breast cancer patients with higher TYMS expression had poorer prognosis. Our data suggest that TYMS has potential use as a diagnostic and prognostic marker for breast cancer patients. [ABSTRACT FROM AUTHOR]

Clinical value of ultrasonic imaging in diagnosis of hypopharyngeal cancer with cervical lymph node metastasis was investigated. Eighty-nine patients who were diagnosed with hypopharyngeal cancer in Qilu Hospital of Shandong University (Qingdao) from January 2014 to June 2016 were retrospectively analyzed. Sixty-eight patients were diagnosed with hypopharyngeal cancer with cervical lymph node metastasis by pathological sections. Twenty-one patients did not have cervical lymph node metastasis. All the patients were diagnosed by palpation and ultrasound. The lymph node ultrasound images were quantified by computer, and the long/short diameter ratio, the maximum systolic velocity, blood flow resistance of the metastatic and non-metastatic patients were compared. The diagnostic efficacy of palpation and ultrasound was analyzed in the diagnosis of hypopharyngeal cancer with cervical lymph node metastasis. A correlation analysis was carried out between the image features of ultrasound and lymph node metastasis. The long/short diameter ratio, maximum systolic velocity and resistance index of patients with lymph node metastasis were significantly higher than those without lymph node metastasis, with a significant difference (P<0.05). Forty-one patients were diagnosed with lymph node metastasis by palpation, fifty-nine patients were diagnosed with lymph node metastasis by ultrasound. The sensitivity and diagnostic coincidence rate of ultrasound in diagnosis of hypopharyngeal cancer with cervical lymph node metastasis were significantly higher than those of palpation (P<0.05). Statistically significant differences were observed in lymph node internal echo types, medullary echo characteristics, envelope definition, and blood flow distribution characteristics between the metastasis group and the non-metastasis group (P<0.05). Lymph node internal echo was heterogeneous. There was no medulla, and the disordered blood flow in the lymph node predicted lymph node metastasis. Preoperative ultrasound has a high diagnostic value in diagnosis of hypopharyngeal cancer with cervical lymph node metastasis. The diagnostic results of preoperative ultrasound can be used as a reference for the diagnosis and treatment of hypopharyngeal cancer with cervical lymph node metastasis. [ABSTRACT FROM AUTHOR]

Simple Summary: Carbohydrates are the most important energy source for monogastric animals, including humans, and dysregulation of carbohydrate metabolism has been associated with metabolic syndromes, such as type 2 diabetes mellitus (T2DM), hypertension, and obesity. Starch is the major carbohydrate source, consisting of amylose and amylopectin. This study investigated the effects of dietary starch structure on growth performance, serum glucose–insulin response, and intestinal health in weaned piglets, which may contribute to the principles of carbohydrate nutrition and facilitate the utilization of dietary starches. To investigate the effects of dietary starch structure (amylose/amylopectin ratio, AR) on serum glucose absorption metabolism and intestinal health, a total of ninety weaned piglets (Duroc × (Yorkshire × Landrace)) were randomly assigned to 5 dietary treatments and fed with a diet containing different AR (2.90, 1.46, 0.68, 0.31, and 0.14). The trial lasted for 21 d. In this study, the growth performance was not affected by the dietary starch structure (p > 0.05). Diets with higher amylose ratios (i.e., AR 2.90 and 1.46) led to a significant reduction of the serum glucose concentration at 3 h post-prandium (p < 0.01), while high amylopectin diets (AR 0.31 and 0.14) significantly elevated The expression of gene s at this time point (p < 0.01). High amylopectin diets also increased the apparent digestibility of crude protein (CP), ether extract (EE), dry matter (DM), gross energy (GE), and crude ash (p < 0.001). Interestingly, diet rich in amylose (AR 2.90) significantly elevated the butyric acid content (p < 0.05) and decreased the pH value (p < 0.05) in the cecal digesta. In contrast, diet rich in amylopectin (i.e., AR 0.14) significantly elevated the total bacteria populations in the cecal digesta (p < 0.001). Moreover, a high amylopectin diet (AR 0.14) tended to elevate the mRNA level of fatty acid synthase (FAS, p = 0.083), but significantly decreased the mRNA level of sodium-dependent glucose transporter 1 (SGLT1, p < 0.05) in the duodenal and jejunal mucosa, respectively. These results suggested that blood glucose and insulin concentrations were improved in high AR diets, and the diet also helped to maintain the intestinal health. [ABSTRACT FROM AUTHOR]

Turbulent motions in the thin ocean surface boundary layer control exchanges of momentum, heat and trace gases between the atmosphere and ocean. However, present parametric equations of turbulent motions that are applied to global climate models result in systematic or substantial errors in the ocean surface boundary layer. Significant mixing caused by surface wave processes is missed in most parametric equations. A Large Eddy Simulation model is applied to investigate the wave-induced mixed layer structure. In the wave-averaged equations, wave effects are calculated as Stokes forces and breaking waves. To examine the effects of wave parameters on mixing, a series of wave conditions with varying wavelengths and heights are used to drive the model, resulting in a variety of Langmuir turbulence and wave breaking outcomes. These experiments suggest that wave-induced mixing is more sensitive to wave heights than to the wavelength. A series of numerical experiments with different wind intensities-induced Stokes drifts are also conducted to investigate wave-induced mixing. As the wind speed increases, the influence depth of Langmuir circulation deepens. Additionally, it is observed that breaking waves could destroy Langmuir cells mainly at the sea surface, rather than at deeper layers. [ABSTRACT FROM AUTHOR]

The Bering Sea is located between the Aleutian Low and Siberian High, with strong seasonal variations in the oceanic circulation and the sea ice coverage. Within such a large-scale system, the physical processes in the Bering Sea carry interannual variability. The special topography in the Bering Sea traps a strong jet along the Bering Slope, whose instability enriches the eddy activity in the region. A Regional Oceanic Modeling System (ROMS), coupled with a sea ice module, is employed to study multiple-scale variability in the sea ice and oceanic circulation in the Bering Sea for interannual, seasonal, and intra-seasonal eddy variations. The model domain covers the whole Bering Sea and a part of the Chukchi Sea and south of Aleutian Islands, with an averaged spatial resolution of 5 km. The external forcings are momentum, heat, and freshwater flux at the surface and adaptive nudging to reanalysis fields at the boundaries. The oceanic model starts in an equilibrium state from a multiple year cyclical climatology run, and then it is integrated from years 1990 through 2004. The 15 year simulation is analyzed and assessed against the observational data. The model accurately reproduces the seasonal and interannual variations in the sea ice coverage compared with the satellite-observed sea ice data from the National Snow and Ice Data Center (NSIDC). Sea surface temperature and eddy kinetic energy patterns from the ROMS agree with satellite remote sensing data. The transportation through the Bering Strait is also comparable with the estimate of mooring data. The mechanism for seasonal and interannual variation in the Bering Sea is connected to the Siberia-Aleutian index. Eddy variation along the Bering Slope is discussed. The model also simulates polynya generation and evolution around the St. Lawrence Island. [ABSTRACT FROM AUTHOR]