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BACKGROUND: The etiology and mechanism of persistent geotropic horizontal direction-changing positional nystagmus (DCPN) are still unclear. Whether this pattern of nystagmus is a subtype of benign paroxysmal positional vertigo (BPPV) remains controversial. OBJECTIVE: The goal of this study was to observe the clinical characteristics of persistent geotropic horizontal DCPN involving the lateral semicircular canal. METHODS: The analysis was performed to participants with episodic positional vertigo in our clinic from 2014 to 2021. Participants were included via positional test. We observed and summarized the distribution data, vertigo history, follow-up tests, and recurrence situations of 189 persistent geotropic horizontal DCPN participants. RESULTS: The mean age at the first time showing of persistent geotropic horizontal DCPN was 56±14.7 and more women than men were affected by persistent geotropic horizontal DCPN (female-to-male ratio 2.4 : 1). Overall, 58.7% (57/94) of participants who came for the first-week follow-up test were asymptomatic. Thirty-three participants experienced recurrence (female-to-male ratio: 4.5 : 1). Fifty-three (28.0%) participants experienced the conversion of the patterns of DCPN in the history, the follow-up tests and the recurrence compared to the first showing of persistent geotropic horizontal DCPN. 24(12.1%) participants still experienced persistent geotropic horizontal DCPN attack in the follow-up tests and the recurrences without benign paroxysmal positional vertigo history. CONCLUSION: Persistent geotropic horizontal DCPN affected more women than men. The persistent geotropic horizontal DCPN that with conversion to transient geotropic horizontal DCPN or to persistent apogeotropic horizontal DCPN might be a subtype of BPPV or in a stage of BPPV process. However, the persistent geotropic horizontal DCPN without conversion might be an independent disease that is not related to BPPV.

Small and medium-sized enterprises play an important role in promoting social and economic growth, which is an important foundation for the development of China’s national economy. From the perspective of bank interests, this paper uses the invoice data of small and medium-sized enterprises to evaluate their credit risk and formulates corresponding bank credit strategies for these enterprises in different industries and properties. Firstly, the credit risk identification factor system is constructed by using feature engineering, and the quantitative model of enterprise credit risk is built based on back propagation (BP) neural network to predict the default probability of enterprises. On this basis, the k-prototypes clustering algorithm is used to classify enterprises. According to the default probability of each enterprise and the loss rate under different interest rates, a nonlinear programming model, with the maximum expected profit of banks as the goal, is constructed. The simulated annealing algorithm is used to obtain the optimal solution of the credit strategy.

Summary This contribution deals with the record and description of one new species and record of one known species of the genus Laimaphelenchus from Shanxi province, north China. The type population of L. piceae sp. n. is characterised by having females 642-807 μm long, the cephalic region with six labial sectors divided by ribs, stylet 12-14 μm long, lateral field with four incisures, postvulval uterine sac (PUS) 114-161 μm long, vulva with a well-developed anterior flap, tail with a single stalk at tip, bearing four pedunculate tubercles, each tubercle including 5-7 finger-like protrusions; males spicules 18-24 μm long and three pairs of caudal papillae present. The new species looks closely similar to L. persicus, representing its cryptic species, being separated by differences in some morphological indices and partial large subunit (LSU) rDNA sequences. Its morphological differences from other relevant species were discussed. L. sinensis was also recorded from Shanxi province for the first time. The phylogenetic relationships of the recovered populations were reconstructed using sequences of the near full length small subunit (SSU) and D2-D3 segments of LSU rDNA, and the relationships of both species were discussed.

With the widespread application of Voltage Source Converter (VSC) in the power system with high penetration of renewable resources, the problem of wideband oscillations caused by the interaction between the power converters and the power grid has drawn large attention. This paper presents a new methodology for simplifying the mathematical derivations of the impedance model of VSC. Using the new simplified model, the stability and the spectrum characteristic of the performance of the VSC can be clearly analyzed. The proposed second-order d-q impedance model of the grid connected VSC at presence of PLL, not only mathematically proves that the wideband oscillatory modes always occurs in conjugate pairs, but also deliver a clear vision of the physical essence of the wideband oscillations. The classic modal analysis is executed in the paper to demonstrate the stability and frequency spectral characteristics of the wideband oscillations in the VSC integrated system. The impact of control parameters of the VSC on the wideband oscillatory stability is thouroughly analyzed using the results of the modal analysis. The methodology can be considered a powerful tool for the control design of VSC in the modern power system.

Hypoxia is a common characteristic of many solid tumors. The hypoxic microenvironment stabilizes hypoxia-inducible transcription factor 1α (HIF1α) and 2α (HIF2α/EPAS1) to activate gene transcription, which promotes tumor cell survival. The majority of human genes are alternatively spliced, producing RNA isoforms that code for functionally distinct proteins. Thus, an effective hypoxia response requires increased HIF target gene expression as well as proper RNA splicing of these HIF-dependent transcripts. However, it is unclear if and how hypoxia regulates RNA splicing of HIF targets. This study determined the effects of hypoxia on alternative splicing (AS) of HIF and non-HIF target genes in hepatocellular carcinoma cells and characterized the role of HIF in regulating AS of HIF-induced genes. The results indicate that hypoxia generally promotes exon inclusion for hypoxia-induced, but reduces exon inclusion for hypoxia-reduced genes. Mechanistically, HIF activity, but not hypoxia per se is found to be necessary and sufficient to increase exon inclusion of several HIF targets, including pyruvate dehydrogenase kinase 1 (PDK1). PDK1 splicing reporters confirm that transcriptional activation by HIF is sufficient to increase exon inclusion of PDK1 splicing reporter. In contrast, transcriptional activation of a PDK1 minigene by other transcription factors in the absence of endogenous HIF target gene activation fails to alter PDK1 RNA splicing.Implications: This study demonstrates a novel function of HIF in regulating RNA splicing of HIF target genes. Mol Cancer Res; 12(9); 1233–43. ©2014 AACR.

S3. HIF activity is sufficient to promote AS of HIF target genes.

Description for supplemental files and supplemental figures

Supplemental File 2: genes in each pathway

S4. Activation of endogenous HIF target genes promotes AS of PDK1 minigene.

Supplemental File 1: genes that are hypoxia induced or exhibit alternative splicing under hypoxia

S2. Hypoxia regulates AS of additional HIF target genes in Hep3B cells.

S1. Hypoxia regulates AS of the HIF target gene, ANGPTL4.

Supplemental File 3: primer sequence

Background: Intrauterine hypoxia (IUH) increases the risk of cardiovascular diseases in offspring. As a reactive oxygen species (ROS) scavenger, polyamine spermidine (SPD) is essential for embryonic and fetal survival and growth. However, further studies on the SPD protection and mechanisms for IUH-induced heart damage in offspring are required. Objectives: This study aimed to investigate the preventive effects of prenatal SPD treatment on IUH-induced heart damage in newborn offspring rats and its underlying mitochondrial-related mechanism. Methods: The rat model of IUH was established by exposure to 10% O2 seven days before term. Meanwhile, for seven days, the pregnant rats were given SPD (5 mg.kg-1.d-1; ip). The one-day offspring rats were sacrificed to assess several parameters, including growth development, heart damage, cardiomyocytes proliferation, myocardial oxidative stress, cell apoptosis, and mitochondrial function, and have mitochondrial quality control (MQC), including mitophagy, mitochondrial biogenesis, and mitochondrial fusion/fission. In in vitro experiments, primary cardiomyocytes were subjected to hypoxia with or without SPD for 24 hours. Results: IUH decreased body weight, heart weight, cardiac Ki67 expression, the activity of SOD, and the CAT and adenosine 5'-triphosphate (ATP) levels and increased the BAX/BCL2 expression, and TUNEL-positive nuclei numbers. Furthermore, IUH also caused mitochondrial structure abnormality, dysfunction, and decreased mitophagy (decreased number of mitophagosomes), declined mitochondrial biogenesis (decreased expression of SIRT-1, PGC-1α, NRF-2, and TFAM), and led to fission/fusion imbalance (increased percentage of mitochondrial fragments, increased DRP1 expression, and decreased MFN2 expression) in the myocardium. Surprisingly, SPD treatment normalized the variations in the IUH-induced parameters. Furthermore, SPD also prevented hypoxia-induced ROS accumulation, mitochondrial membrane potential decay, and the mitophagy decrease in cardiomyocytes. Conclusion: Maternal SPD treatment caused IUH-induced heart damage in newborn offspring rats by improving the myocardial mitochondrial function via anti-oxidation and anti-apoptosis, and regulating MQC.

Conjugated linoleic acid (CLA) is a potential nutritional strategy to regulate meat quality in pigs and produce high-quality pork. However, the effects of CLA on nutritional quality, lipid dynamics, microbiota, and their metabolites in the gut of pigs remain unclear. Our study explored the effects of CLA on lipo-nutritional quality based on a Heigai pig model and investigated the regulatory mechanism using an integrated analysis of multiple omics. A total of 58 Heigai finishing pigs (body weight: 85.58 ± 10.39 kg) were randomly divided into 2 treatments and fed diets containing 1% soyabean oil and 1% CLA for 40 days. 1% CLA significantly decreased the backfat thickness (

Background In addition to its contractile properties and role in movement, skeletal muscle plays an important function in regulating whole-body glucose and lipid metabolism. A central component of such regulation is mitochondria, whose quality and function are essential in maintaining proper metabolic homeostasis, with defects in processes such as autophagy and mitophagy involved in mitochondria quality control impairing skeletal muscle mass and function, and potentially leading to a number of associated diseases. Cold exposure has been reported to markedly induce metabolic remodeling and enhance insulin sensitivity in the whole body by regulating mitochondrial biogenesis. However, changes in lipid metabolism and lipidomic profiles in skeletal muscle in response to cold exposure are unclear. Here, we generated lipidomic or transcriptome profiles of mouse skeletal muscle following cold induction, to dissect the molecular mechanisms regulating lipid metabolism upon acute cold treatment. Results Our results indicated that short-term cold exposure (3 days) can lead to a significant increase in intramuscular fat deposition. Lipidomic analyses revealed that a cold challenge altered the overall lipid composition by increasing the content of triglyceride (TG), lysophosphatidylcholine (LPC), and lysophosphatidylethanolamine (LPE), while decreasing sphingomyelin (SM), validating lipid remodeling during the cold environment. In addition, RNA-seq and qPCR analysis showed that cold exposure promoted the expression of genes related to lipolysis and fatty acid biosynthesis. These marked changes in metabolic effects were associated with mitophagy and muscle signaling pathways, which were accompanied by increased TG deposition and impaired fatty acid oxidation. Mechanistically, HIF-1α signaling was highly activated in response to the cold challenge, which may contribute to intramuscular fat deposition and enhanced mitophagy in a cold environment. Conclusions Overall, our data revealed the adaptive changes of skeletal muscle associated with lipidomic and transcriptomic profiles upon cold exposure. We described the significant alterations in the composition of specific lipid species and expression of genes involved in glucose and fatty acid metabolism. Cold-mediated mitophagy may play a critical role in modulating lipid metabolism in skeletal muscle, which is precisely regulated by HIF-1α signaling.

Fat deposition, especially the intramuscular (IM) fat deposition, is directly associated with meat quality. The cyclic adenosine monophosphate (cAMP)-responsive element binding-protein (CREB)-regulated transcription coactivator 3 (CRTC3) plays an important role in energy metabolism and various biological processes. The expression of porcine CRTC3 in skeletal muscle is positively associated with intramuscular fat deposition and possesses the capacity to control the intramuscular (IM) adipocyte morphology. However, the metabolic effects and transcriptional mechanism of CRTC3 in porcine intramuscular (IM) adipocytes as well as the regulatory mechanism of CRTC3 on porcine adipocyte differentiation have not been studied. Here, we utilized metabolomics and RNA sequencing (RNA-seq) to determine the metabolic and transcriptome profiles of CRTC3-overexpressing IM adipocytes. Moreover, the effect and regulation mechanism of CRTC3 on porcine IM and subcutaneous (SC) adipocyte differentiation were also studied. Our results showed that CRTC3 overexpression dramatically altered the metabolites in IM adipocytes. Glycerophospholipid (GP) metabolism and related genes were significantly changed in CRTC3-overexpressing IM adipocytes. Moreover, we demonstrated that CRTC3 overexpression promotes adipogenic differentiation by upregulating the Ca2+-cAMP signaling pathway in IM and SC adipocytes. We showed alterations in metabolites and in the expression of genes involved in lipid metabolism in CRTC3-overexpressing adipocytes and demonstrated the regulatory mechanism of CRTC3 on the adipogenic differentiation of porcine adipocytes. These results provide new insights into the regulatory roles of CRTC3 in porcine adipocytes, which could be an important target to regulate fat deposition in animals.

BackgroundCancer cells drastically increase the uptake of glucose and glucose metabolism by overexpressing class I glucose transporters (GLUT1-4) to meet their energy and biomass synthesis needs and are very sensitive and vulnerable to glucose deprivation. Although targeting glucose uptake via GLUTs has been an attractive anticancer strategy, the relative anticancer efficacy of multi-GLUT targeting or single GLUT targeting is unclear. Here, we report DRB18, a synthetic small molecule, is a potent anticancer compound whose pan-class I GLUT inhibition is superior to single GLUT targeting.MethodsGlucose uptake and MTT/resazurin assays were used to measure DRB18’s inhibitory activities of glucose transport and cell viability/proliferation in human lung cancer and other cancer cell lines. Four HEK293 cell lines expressing GLUT1-4 individually were used to determine the IC50values of DRB18’s inhibitory activity of glucose transport. Docking studies were performed to investigate the potential direct interaction of DRB18 with GLUT1-4. Metabolomics analysis was performed to identify metabolite changes in A549 lung cancer cells treated with DRB18. DRB18 was used to treat A549 tumor-bearing nude mice. TheGLUT1gene was knocked out to determine how the KO of the gene affected tumor growth.ResultsDRB18 reduced glucose uptake mediated via each of GLUT1-4 with different IC50s, which match with the docking glidescores with a correlation coefficient of 0.858. Metabolomics analysis revealed that DRB18 altered energy-related metabolism in A549 cells by changing the abundance of metabolites in glucose-related pathways in vitro and in vivo. DRB18 eventually led to G1/S phase arrest and increased oxidative stress and necrotic cell death. IP injection of DRB18 in A549 tumor-bearing nude mice at 10 mg/kg body weight thrice a week led to a significant reduction in the tumor volume compared with mock-treated tumors. In contrast, the knockout of theGLUT1gene did not reduce tumor volume.ConclusionsDRB18 is a potent pan-class I GLUT inhibitor in vitro and in vivo in cancer cells. Mechanistically, it is likely to bind the outward open conformation of GLUT1-4, reducing tumor growth through inhibiting GLUT1-4-mediated glucose transport and metabolisms. Pan-class I GLUT inhibition is a better strategy than single GLUT targeting for inhibiting tumor growth.

Background: The pathogenesis of chronic pancreatitis is still unclear. Trypsinogen activation is an active factor in acute pancreatitis that has not been studied in the occurrence of chronic pancreatitis. Methods: Immunofluorescence was used to detect the location and expression of trypsinogen in chronic pancreatitis and normal tissues. Microarray and single-cell RNA-seq (scRNA-seq) were used to screen core genes and pathways in pancreatic stellate cells (PSCs). Western blotting and immunofluorescence were used to verify trypsinogen expression in PSCs after silencing Rabep1. Immunofluorescence and flow cytometry were used to validate trypsinogen activation and PSC activation after intervening in the endocytosis pathway. Results: Endocytosed trypsinogen was found in PSCs in CP clinical samples. Bioinformatic analysis showed that Rabep1 is a core gene that regulates trypsinogen endocytosis through the endocytosis pathway, verified by Western blot and immunofluorescence. Immunofluorescence and flow cytometry analyses confirmed the activation of trypsinogen and PSCs through the endocytosis pathway in PSCs. Conclusion: This study discovered a new mechanism by which trypsinogen affects the activation of PSCs and the occurrence and development of CP. Through communication between pancreatic acinar cells and PSCs, trypsinogen can be endocytosed by PSCs and activated by the Rabep1 gene.

Endothelial cells (ECs) in vivo are subjected to three forms of shear stress induced by luminal blood flow, transendothelial flow and interstitial flow simultaneously. It is controversial that shear stress, especially the component induced by luminal flow, was thought to inhibit the initialization of angiogenesis and trigger arteriogenesis. Here, we combined microfabrication techniques and delicate numerical simulations to reconstruct the initial physiological microenvironment of neovascularization in vitro, where ECs experience high luminal shear stress, physiological transendothelial flow and various vascular endothelial growth factor (VEGF) distributions simultaneously. With the biomimetic microfluidic model, cell alignment and endothelial sprouting assays were carried out. We found that luminal shear stress inhibits endothelial sprouting and tubule formation in a dose-dependent manner. Although a high concentration of VEGF increases EC sprouting, neither a positive nor a negative VEGF gradient additionally affects the degree of sprouting, and luminal shear stress significantly attenuates neovascularization even in the presence of VEGF. Heparinase was used to selectively degrade the heparan sulfate proteoglycan (HSPG) coating on ECs and messenger RNA profiles in ECs were analyzed. It turned out that HSPGs could act as a mechanosensor to sense the change of fluid shear stress, modulate multiple EC gene expressions, and hence affect neovascularization. In summary, distraction from the stabilized state, such as decreased luminal shear stress, increased VEGF and the destructed mechanotransduction of HSPGs would induce the initiation of neovascularization. Our study highlights the key role of the magnitude and forms of shear stress in neovascularization.

Fat infiltration in skeletal muscle is observed in several myopathies, is associated with muscular dysfunction, and is strongly correlated with insulin resistance, diabetes, obesity, and aging. In animal production, skeletal muscle fat (also known as intermuscular and intramuscular fat) is positively related to meat quality including tenderness, flavor, and juiciness. Thus, understanding the cell origin and regulation mechanism of skeletal muscle fat infiltration is important for developing therapies against human myopathies as well as for improving meat quality. Notably, age, sarcopenia, oxidative stress, injury, and regeneration can activate adipogenic differentiation potential in myoblasts and affect fat accumulation in skeletal muscle. In addition, several transcriptional and nutritional factors can directly induce transdifferentiation of myoblasts into adipocytes. In this review, we focused on the recent progress in understanding the muscle-to-adipocyte differentiation and summarized and discussed the genetic, nutritional, and physiological factors that can induce transdifferentiation of myoblasts into adipocytes. Moreover, the regulatory roles and mechanisms of these factors during the transdifferentiation process were also discussed.

The ratio of monocyte to high-density lipoprotein cholesterol level (MHR) was a newly proposed inflammatory and oxidative stress marker. This study aimed to explore the association between MHR and Brachial-ankle pulse wave velocity (Ba-PWV) in adult Chinese participants. A total of 2029 participants were divided into two groups according to the Ba-PWV: a high Ba-PWV group (Ba-PWV ≥1400 cm/s) and a low Ba-PWV group (Ba-PWV < 1400 cm/s). According to the cut-off points of quartile of MHR, the participants were divided into four groups. The relationship between MHR and Ba-PWV was analyzed. After adjusting for potential confounders, a non-linear relationship between MHR and Ba-PWV was found in the participants, and the inflection point was 7.78 in the non-linear curve. On the left of the inflection point, MHR had a positive correlation with Ba-PWV (OR = 1.17, 95% confidence interval (CI): 1.08 to 1.28, p < 0.01). However, there was no obvious relationship between MHR and Ba-PWV on the right of the inflection point (OR = 0.96, 95% CI: 0.90 to 1.01, p = 0.117). Further demographic analysis demonstrated that the positive relationship between MHR and Ba-PWV was found in the female participants with hypertension family history, but without a current history of hypertension, smoking, or drinking (p < 0.05). An increased MHR is a risk factor of atherosclerosis, which may predict the potential development of atherosclerosis. When the MHR is close to 7.78, it has the highest predictive value for the risk of atherosclerosis occurrence.

Changing fatty acid composition is a potential nutritional strategy to shape microbial communities in pigs. However, the effect of different n-6/n-3 polyunsaturated fatty acid (PUFA) ratios on serum fatty acid composition, microbiota, and their metabolites in the intestine of pigs remains unclear. Our study investigated the changes in serum fatty acid composition and metabolome–microbiome responses induced by dietary n-6/n-3 PUFA ratio based on a Heigai-pig model. A total of 54 Heigai finishing pigs (body weight: 71.59 ± 2.16 kg) fed with 3 types of diets (n-6/n-3 PUFA ratios are 8:1, 5:1, and 3:1) were randomly divided into 3 treatments with 6 replications (3 pigs per replication) for 75 days. Results showed that dietary n-6/n-3 PUFA ratio significantly affected biochemical immune indexes including glucose (Glu), triglycerides (TG), total cholesterol (TChol), non-esterified fatty acid (NEFA), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total thyroxine (TT4), and medium- and long-chain fatty acid composition, especially n-3 PUFA and n-6/n-3 PUFA ratio in the serum. However, no significant effects were found in the SCFAs composition and overall composition of the gut microbiota community. In the low dietary n-6/n-3 PUFA ratio group, the relative abundance of Cellulosilyticum, Bacteroides, and Alloprevotella decreased, Slackia and Sporobacter increased. Based on the metabolomic analysis, dietary n-6/n-3 PUFA ratio altered the metabolome profiles in the colon. Moreover, Pearson’s correlation analysis indicated that differential microbial genera and metabolites induced by different n-6/n-3 PUFA ratio had tight correlations and were correlated with the n-6 PUFA and n-3 PUFA content in longissimus dorsi muscle (LDM) and subcutaneous adipose tissue (SAT). Taken together, these results showed that lower dietary n-6/n-3 PUFA ratio improved serum fatty acid composition and metabolome–microbiome responses of Heigai pigs and may provide a new insight into regulating the metabolism of pigs and further better understanding the crosstalk with host and microbes in pigs.

Cold exposure promotes fat oxidation and modulates the energy metabolism in adipose tissue through multiple mechanisms. However, it is still unclear about heat-generating capacity and lipid mobilization of different fat depots without functional mitochondrial uncoupling protein 1 (UCP1). In this study, we kept finishing pigs (lack a functional UCP1 gene) under cold (5-7°C) or room temperature (22-25°C) and determined the effects of overnight cold exposure on fatty acid composition and transcriptional profiles of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). And the plasma metabolomes of porcine was also studied by LC-MS-based untargeted metabolomics. We found that the saturated fatty acids (SFAs) content was decreased in SAT upon cold exposure. While in VAT, the relative content of lauric acid (C12:0), myristic acid (C14:0) and lignoceric acid (C24:0) were decreased without affecting total SFA content. RNA-seq results showed SAT possess active organic acid metabolism and energy mobilization upon cold exposure. Compared with SAT, cold-induced transcriptional changes were far less broad in VAT, and the differentially expressed genes (DEGs) were mainly enriched in fat cell differentiation and cell proliferation. Moreover, we found that the contents of organic acids like creatine, acamprosate, DL-3-phenyllactic acid and taurine were increased in plasma upon overnight cold treatment, suggesting that cold exposure induced lipid and fatty acid metabolism in white adipose tissue (WAT) might be regulated by functions of organic acids. These results provide new insights into the effects of short-term cold exposure on lipid metabolism in adipose tissues without functional UCP1.

Uncoupling protein 1 (UCP1), the hallmark protein responsible for nonshivering thermogenesis in adipose tissue (especially brown adipose tissue) has regained researchers’ attention in the context of metabolic disorders following the realization that UCP1 can be activated in adult humans and reconstituted in pigs. Both skeletal muscle and adipose tissue are highly dynamic tissues that interact at the metabolic and hormonal level in response to internal and external stress, and they coordinate in maintaining whole-body metabolic homeostasis. Here, we utilized lipidomics and transcriptomics to identify the altered lipid profiles and regulatory pathways in skeletal muscles from adipocyte-specific UCP1 knock-in (KI) pigs. UCP1 KI changed the contents of glycerophospholipids and acyl carnitines of skeletal muscles. Several metabolic regulatory pathways were more enriched in the UCP1 KI skeletal muscle. Comparison of the transcriptomes of adipose and skeletal muscle suggested that nervous system or chemokine signaling might account for the crosstalk between these two tissues in UCP1 KI pigs. Comparison of the lipid biomarkers from UCP1 KI pigs and other mammals suggested associations between UCP1 KI-induced metabolic alternations and metabolic and muscle dysfunction. Our study reveals the lipid dynamics and transcriptional programs in the skeletal muscle of UCP1 KI pigs and suggests that a network regulates metabolic homeostasis between skeletal muscle and adipose tissue.

Skeletal muscle plays important roles in normal biological activities and whole-body energy homeostasis in humans. The growth and development of skeletal muscle also directly influence meat production and meat quality in animal production. Therefore, regulating the development and homeostasis of skeletal muscle is crucial for human health and animal production. Adipose tissue, which includes white adipose tissue (WAT) and brown adipose tissue (BAT), not only functions as an energy reserve but also has attracted substantial attention because of its role as an endocrine organ. The novel signalling molecules known as "adipokines" and "lipokines" that are secreted by adipose tissue were identified through the secretomic technique, which broadened our understanding of the previously unknown crosstalk between adipose tissue and skeletal muscle. In this review, we summarize and discuss the secretory role of adipose tissues, both WAT and BAT, as well as the regulatory roles of various adipokines and lipokines in skeletal muscle development and homeostasis. We suggest that adipokines and lipokines have potential as drug candidates for the treatment of skeletal muscle dysfunction and related metabolic diseases and as promising nutrients for improving animal production.

Adipocytes are the key constituents of adipose tissue, and their de-differentiation process has been widely observed in physiological and pathological conditions. For obese people, the promotion of adipocyte de-differentiation or maintenance of an undifferentiated state of adipocytes may help to improve their metabolic condition. Thus, understanding the regulatory mechanisms of adipocyte de-differentiation is necessary for treating metabolic diseases. Attractively, in addition to intracellular signals regulating adipocyte de-differentiation, external factors such as temperature and pressure also affect adipocyte de-differentiation. In this review, we summarize the recent progress in the field and discuss the regulatory roles and mechanisms of involved endogenous and exogenous factors during the process of de-differentiation.

Cold exposure promotes glucose oxidation and modulates the lipid metabolism in adipose tissue, but it is still not fully clear whether cold exposure could affect meat quality and fatty acid metabolism in skeletal muscle of pig in vivo. Here, we kept finishing pigs under cold or room temperature overnight and determined the effects of cold exposure on meat quality, fatty acids composition and transcriptional changes in skeletal muscle of pigs. We found that cold exposure significantly reduced the meat colour24 h and pH24 h, without affecting carcass characteristics and other meat quality traits. Considerable changes were found in the proportions of individual fatty acids and the total content of saturated fatty acid, polyunsaturated fatty acids, monounsaturated fatty acid and n3-fatty acids. RNA-seq results showed upregulated fatty acid biosynthesis genes and downregulated mitochondrial beta-oxidation genes. The lipid metabolism in cold-treated longissimus dorsi muscle might be regulated by functions of the lipoprotein particle, the extracellular matrix, and the PPAR signaling pathways. Our study revealed the potential of cold exposure to regulate the lipid metabolism and fatty acid composition in skeletal muscle of farmed animals.

Polyunsaturated fatty acids (PUFAs) supplementation has been widely discussed as a strategy for improving meat quality in pig production, but the effects are inconsistent. This meta-analysis was performed to comprehensively evaluate its effects on the meat quality and growth performance of pigs. We searched the PubMed and the Web of Science databases (articles published from January 1, 2000 to October 16, 2020) and compared PUFAs-supplemented diets with control diets. We identified 1,670 studies, of which 14 (with data for 752 pigs) were included in our meta-analysis. The subgroup analysis was classified as PUFA source [conjugated linoleic acid (CLA) or linseed], concentration (high or low concentration), and initial stage (growing or finishing pigs). Our analysis found that PUFA supplementation increased the intramuscular fat (IMF) content (WMD = 0.467%, 95% CI: 0.312–0.621, p < 0.001), decreased the meat color L* (WMD = −0.636, 95% CI: −1.225 to −0.047, p = 0.034), and pH 24 h (WMD = −0.021, 95% CI: −0.032 to −0.009, p < 0.001) but had no influence on drip loss, meat color a* and b*, pH 45 min, and growth performance. CLA supplementation improved IMF content (WMD = 0.542%, 95% CI: 0.343–0.741, p < 0.001) and reduced meat color b* (WMD = −0.194, 95% CI: −0.344 to −0.044, p = 0.011). Linseed supplementation increased IMF content (WMD = 0.307%, 95% CI: 0.047–0.566, p = 0.021), decreased meat color L* (WMD = −1.740, 95% CI: −3.267 to −0.213, p = 0.026), and pH 24 h (WMD = 0.034, 95% CI: −0.049 to −0.018, p < 0.001). We discovered an increase on the IMF content in both high and low concentration PUFA supplementation (WMD = 0.461%, 95% CI: −0.344 to −0.044, p < 0.001; WMD = 0.456%, 95% CI: 0.276–0.635, p < 0.001). Furthermore, we also found the effects of PUFA supplementation on meat color L* and pH 24 h are concentration- and stage-dependent. PUFA supplementation can improve the meat quality of pigs, which mainly emerges in greatly increasing IMF content.

Microplastics are an emerging global pollutant type that poses a great health threat to animals due to their uptake and translocation in animal tissues and organs. Ecotoxicological effects of microplastics on the development of bird embryos are not known. The bird egg is a complete development and nutrition system, and the entire embryo development occurs in the eggshell. Therefore, a direct record of bird embryo development under the stress of pollutants such as microplastics is highly limited by the opaque eggshell in traditional hatching. In this study, the effects of microplastics on quail embryo development were visually monitored by hatching without an eggshell. The main steps include the cleaning and disinfection of fertilized eggs, the incubation before exposure, the short-term incubation after exposure, and the sample extraction. The results show that compared with the control group, the wet weight and body length of the microplastics-exposed group displayed a statistical difference and the liver proportion of the whole exposed group significantly increased. Additionally, we evaluated external factors that affect the incubation: temperature, humidity, egg rotation angle, and other conditions. This experimental method provides valuable information on the ecotoxicology of microplastics and a novel way to study the adverse effects of pollutants on the development of embryos.

Neovascularization is usually initialized from an existing normal vasculature and the biomechanical microenvironment of endothelial cells (ECs) in the initial stage varies dramatically from the following process of neovascularization. Although there are plenty of models to simulate different stages of neovascularization, an in vitro 3D model that capitulates the initial process of neovascularization under the corresponding stimulations of normal vasculature microenvironments is still lacking. Here, we reconstructed an in vitro 3D model that mimics the initial event of neovascularization (MIEN). The MIEN model contains a microfluidic sprouting chip and an automatic control, highly efficient circulation system. A functional, perfusable microchannel coated with endothelium was formed and the process of sprouting was simulated in the microfluidic sprouting chip. The initially physiological microenvironment of neovascularization was recapitulated with the microfluidic control system, by which ECs would be exposed to high luminal shear stress, physiological transendothelial flow, and various vascular endothelial growth factor (VEGF) distributions simultaneously. The MIEN model can be readily applied to the study of neovascularization mechanism and holds a potential promise as a low-cost platform for drug screening and toxicology applications.

Non-Small Cell Lung Cancer (NSCLC) is the most common type of lung cancer, accounting for 84% of all lung cancer diagnoses. While there are current standard treatments for NSCLC, these treatments may cause severe side effects, drug resistance, or lead to ineffective treatment, recurrence of the cancer, and death. It has been shown that most cancer types are “addicted” to glucose, and are sensitive and vulnerable to glucose deprivation, making the inhibition of glucose transport into these cells an attractive anticancer strategy. DRB18 is a small molecule proprietary compound that has been shown to target and inhibit class I glucose transporters (GLUTs, GLUT1-4), which are responsible for the uptake of glucose into cells, particularly these types of cancer cells. DRB18 has been shown to be effective in inhibiting cancer cell growth in vitro and in vivo without noticeable side effects.1 While this may be a promising anticancer therapy by itself, combining DRB18 with another anticancer drug that has a totally different anticancer mechanism should substantially increase the efficacy of the treatment while potentially minimizing the rate of resistance and recurrence of the cancer without increasing unwanted side effects. This research focuses on combining DRB18 with FDA-approved target drugs Trametinib and Brigatinib, the FDA-approved chemotherapy drug Paclitaxel, and a glutamine transporter inhibitor (V-9302). Thus, the treatment groups are vehicle, each of the previously mentioned drugs alone, as well as DRB18+Trametinib, DRB18+Brigatinib, DRB18+Paclitaxel, and DRB18+V-9302. This study tests the hypothesis that, due to their different anticancer mechanisms, the combination of DRB18 with these anticancer drugs will have a synergistic anticancer effect. Preliminary in vitro data and an in vivo pilot tumor study in nude mice, using human NSCLC A549 cells, have shown the improved anticancer efficacy of the combinatorial approach by further reducing tumor growth when compared with single drug treatment. The results of a larger nude mouse study, as well as basic mechanistic studies in vitro, that are currently underway will be presented later at the AACR meeting. This combination therapy has great therapeutic implications and the potential to benefit cancer patients for decades to come. 1. Shriwas P, Roberts D, Li Y, Wang L, Qian Y, Bergmeier S, Hines J, Adhicary S, Nielsen C, & Chen X. (2021). A small molecule pan-class I glucose transporter inhibitor reduces cancer cell proliferation in vitro and tumor growth in vivo by targeting glucose-based metabolism. Cancer and Metabolism, 9 (14). Citation Format: Lindsey M. Bachmann, Pratik Shriwas, Ryan A. Ward, Liyi Wang, Stephen C. Bergmeier, Yunsheng Li, Xiaozhuo Chen. Combinatorial anticancer therapy strategy using a pan-class I glucose transporter inhibitor with chemotherapy and target drugs in vitro and in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1047.

Additional file2: Figure S1. DRB18 binds to GLUT2-4 in outward open conformation. Figure S2. DRB18 docked to hGLUT1-4 in inward open conformation. Figure S3. DRB18 treatment leads to induced internalization of glucose via different endocytic mechanisms. FigureS4. DRB18 caused G1/S phase cell cycle arrest and necrotic cell death in A549 cells. Figure S5. Average body weights of nude mice bearing A549 xenograft tumors from control (n=10) and DRB18 (n=10) treated groups.

Background: Polyunsaturated fatty acids (PUFAs) supplementation has been widely discussed as a strategy for improving meat quality in pig production but the effects are inconsistent. This meta-analysis was performed to comprehensively evaluate its effects on the meat quality including intramuscular fat (IMF) content, drip loss, meat color, pH 45min and pH 24h of pigs.Methods: We searched the PubMed and Web of Science databases (articles published from Jan 1st, 2000, and Oct 16th, 2020) and compared PUFAs-supplemented diets with control diets. We identified 1670 studies, of which 14 (with data for 752 pigs) were included in our meta-analysis. We used a random-effects model and a fixed-effects model to calculate the weighted mean differences (WMDs) and 95% confidence intervals (CIs). We used sensitivity and subgroup analysis to ensure the pooled estimates are robust. The subgroup analysis was classified as treatment (conjugated linoleic acid (CLA) or linseed), concentration (high or low concentration) and initial stage (growing and finishing pigs).Results: Our analysis found that PUFAs supplementation increased the IMF content (WMD= 0.467%, 95% CI: 0.312 to 0.621, PP=0.034) and pH 24h (WMD= -0.021,95% CI: -0.032 to -0.009, PPP=0.011). Linseed supplementation increased IMF content (WMD= 0.307%, 95% CI: 0.047 to 0.566, P=0.021), decreased meat color L*(WMD= -1.740, 95% CI: -3.267 to -0.213, P=0.026) and pH 24h (WMD= -0.034, 95% CI: -0.049 to -0.018, PConclusions: PUFAs supplementation can improve meat quality of pigs which mainly emerge in greatly increasing IMF content.

Liver kinase B1 (LKB1) plays important and various roles in the differentiation and lipid metabolism of adipocytes. However, the current knowledge of the respective roles of LKB1 in subcutaneous fat (SCF) and intramuscular fat (IMF) adipocytes remains unclear. This study aimed to discover the different regulatory mechanisms of LKB1 in SCF and IMF adipocytes. We found that LKB1 overexpression inhibited adipogenesis in both SCF and IMF adipocytes, and SCF adipocytes were more sensitive to regulation by LKB1. Transcriptomics results showed that IMF adipocytes had many more differentially expressed genes (DEGs) than SCF adipocytes. Pathway analysis of the shared and distinct DEGs revealed that the main adipogenesis mechanism was similar between SCF and IMF adipocytes upon LKB1 overexpression, while regulatory and metabolic signaling pathways, such as MAPK, PPAR signaling pathways, were differently regulated by LKB1. Several cytokine-related pathways were only enriched in LKB1-overexpressing IMF adipocytes. Our study reveals different regulators and signaling pathways between SCF and IMF adipocytes under LKB1 overexpression, which may be potential targets to differentially control SCF and IMF deposition and improve our understanding of the regulatory mechanisms of IMF deposition.

The objective of this study was to investigate the effects of dietary supplementation with different n-6/n-3 polyunsaturated fatty acid (PUFA) ratios on growth performance, meat quality, and fatty acid profile in Heigai pigs. A total of 54 Heigai finishing pigs (body weight: 71.59 &plusmn, 2.16 kg) were randomly divided into three treatments with six replications (three pigs per replication) and fed diets containing different n-6/n-3 PUFA ratios: 8:1, 5:1, and 3:1. Pigs fed the dietary n-6/n-3 PUFA ratio of 8:1 had the highest feed to gain ratio (p &lt, 0.01), carcass weight (p &lt, 0.05), redness a* (p &lt, 0.01), and yellowness b* (p &lt, 0.01). Fatty acid compositions in longissimus dorsi muscle (LDM) and subcutaneous adipose tissue (SAT) were significantly changed (p &lt, 0.01). Notably, the meat from the pigs fed with the low dietary n-6/n-3 PUFA ratio had higher n-3 PUFA contents (p &lt, 0.01) and lower n-6/n-3 PUFA ratio (p &lt, 0.01). The triglyceride and total cholesterol contents were significantly decreased in SAT from the pigs fed with dietary n-6/n-3 PUFA ratios of 5:1 (p &lt, 0.05) and 3:1 (p &lt, 0.01). Reducing n-6/n-3 PUFA ratio upregulated the expression of HSL (p &lt, 0.05), CPT1 (p &lt, 0.01), and FABP4 (p &lt, 0.01) but downregulated ATGL (p &lt, 0.01) expression. These results demonstrate that the lower n-6/n-3 PUFA ratio regulates meat quality and enhances the deposition of n-3 PUFA in Heigai pigs.

Glucose transporters (GLUTs) facilitate glucose uptake and are overexpressed in most cancer cells Inhibition of glucose transport has been shown to be an effective method to slow the growth of cancer cells both in vitro and in vivo. We have previously reported on the anticancer activity of an ester derived glucose uptake inhibitor. Due to the hydrolytic instability of the ester linkage we have prepared a series of isosteres of the ester moiety. Of all of the isosteres prepared, the amine linkage showed the most promise. Several addition analogues of the amine-linked compounds were also prepared to improve the overall activity.

Myokines are muscle-derived cytokines and chemokines that act extensively on organs and exert beneficial metabolic functions in the whole-body through specific signal networks. Myokines as mediators provide the conceptual basis for a whole new paradigm useful for understanding how skeletal muscle communicates with other organs. In this review, we summarize and discuss classes of myokines and their physiological functions in mediating the regulatory roles of skeletal muscle on other organs and the regulation of the whole-body energy metabolism. We review the mechanisms involved in the interaction between skeletal muscle and nonmuscle organs through myokines. Moreover, we clarify the connection between exercise, myokines and disease development, which may contribute to the understanding of a potential mechanism by which physical inactivity affects the process of metabolic diseases via myokines. Based on the current findings, myokines are important factors that mediate the effect of skeletal muscle on other organ functions and whole-body metabolism.

The neutron Bragg-edge imaging is expected to be a new non-destructive energy-resolved neutron imaging technique for quantitatively two-dimensional or three-dimensional visualizing crystallographic information in a bulk material, which could be benefited from pulsed neutron source. Here we build a Bragg-edge imaging system on the General Purpose Powder Diffractometer at the China Spallation Neutron Source. The residual strain mapping of a bent Q235 ferrite steel sample has been achieved with a spectral resolution of 0.15% by the time-of-flight neutron Bragg-edge imaging on this system. The results show its great potential applications in materials science and engineering.

Plastic debris provides a stable substrate and novel ecological niche for microorganisms in the aquatic environment, which was referred to as "Plastisphere". Little is known about distribution patterns and responses of ecological function and structure of microbial communities in the plastisphere along rivers which usually have antibiotics pollution gradient. In this study, the differences in the community structure between the plastisphere and the planktonic bacteria, and their spatial variation of the community structure and function along a river with increased antibiotics pollution gradient was investigated at the watershed scale. The diversity of bacteria colonized on most plastic debris was higher than in surrounding water. Plastic debris could accumulate a higher abundance of some potential pathogens than surrounding water even at high antibiotics concentrations. The source tracking results showed that downstream plastisphere inherited much higher proportions of bacterial taxa from upstream than planktonic bacteria. About 92.3-99.7% of bacteria communities in downstream water were not from upstream but from the input of downstream human activities. On the contrary, high proportions of bacterial taxa in downstream plastisphere were closely connected to upstream. The plastisphere possesses higher ecological functional diversity than the planktonic bacteria. Seventy nine functional groups across plastisphere were predicted using functional annotation of prokaryotic taxa and only 65 functional groups were found in the planktonic bacteria. Plastisphere also acts as hotspot for biogeochemical cycling of nutrients such as N and S. Intensive human activities of urban and downstream agriculture and aquaculture had great effects on microbial community structure and functional groups of the Urumqi River. Pastisphere communities are much more resistant to human disturbance than planktonic bacteria. Compared to surrounding water, plastisphere increased inheritance from upstream microbial structure and function and also increased survival and propagation of pathogens in the downstream water with high concentrations of antibiotics.

Lakes in arid northwestern China are valuable freshwater resources that drive socioeconomic development. Environmental pollution can significantly influence the composition of microbial communities and the distribution of functional genes in lakes. This study investigated heavy metal pollution to identify possible correlations with metal resistance genes (MRGs) and bacterial community composition in water, sediment and biofilm samples from Bosten Lake and Ebi Lake in northwestern China. High levels of zinc were detected in all samples. However, the metals detected in the sediment samples of both lakes were determined to be at low risk levels according to an ecological index. The mercury resistance gene subtype merP had the greatest average abundance (4.61 × 10−3 copies per 16S rRNA) among all the samples, followed by merA and merC. The high abundance of merA in the pelagic zone rather than in benthic sediment suggests that the pelagic microbial community was important in mercury reduction. Proteobacteria were the main phylum found in the microbial communities in all samples. However, microbial communities in most of the water, sediment and biofilm samples had different compositions, indicating that the habitat niche plays an important role in shaping the bacterial communities in lakes. The microbial community, rather than the heavy metals, was the main driver of MRG distribution. The abundances of some bacterial genera involved in the decomposition of organic matter and the terrestrial nitrogen cycle were negatively correlated with heavy metals. This result suggests that metal pollution can adversely affect the biogeochemical processes that occur in lakes.

Stromal cells influence epithelial function in both health and disease. Myofibroblasts are abundant stromal cells that influence the cellular microenvironment by release of extracellular matrix (ECM) proteins, growth factors, proteases, cytokines, and chemokines. Cancer-associated myofibroblasts (CAMs) differ from adjacent tissue (ATMs) and normal tissue myofibroblasts (NTMs), but the basis of this is incompletely understood. We report now the differential expression of miRNAs in gastric cancer CAMs. MicroRNA arrays identified differences in the miRNA profile in gastric and esophageal NTMs and in CAMs from stomach compared with NTMs. miR-181d was upregulated in gastric CAMs. Analysis of differentially regulated miRNAs indicated an involvement in Wnt signaling. Examination of a microarray data set then identified Wnt5a as the only consistently upregulated Wnt ligand in gastric CAMs. Wnt5a stimulated miR-181d expression, and knockdown of miR-181d inhibited Wnt5a stimulation of CAM proliferation and migration. Analysis of miR-181d targets suggested a role in chemotaxis. Conditioned medium from CAMs stimulated gastric cancer cell (AGS) migration more than that from ATMs, and miR-181d knockdown reduced the effect of CAM-CM on AGS cell migration but had no effect on AGS cell responses to ATM conditioned media. The data suggest that dysregulation of miRNA expression in gastric CAMs, secondary to Wnt5a signaling, accounts at least in part for the effect of CAMs in promoting cancer cell migration. stromal cells have emerged in recent years as important determinants of epithelial cell function in the gastrointestinal mucosa in health and disease (7, 23, 25). There are multiple stromal cell types, including inflammatory and immune cells, fibroblasts, pericytes, and myofibroblasts. The latter are sparse in many tissues, but in the gut there is normally a sheath of myofibroblasts that surrounds intestinal crypts and gastric glands. They may arise from activation of fibroblasts, for example, by TGFβ, by transdifferentiation of mesenchymal stem cells (26), or by epithelial-mesenchymal transition (20). Physiologically, they play a role in wound healing. They may also influence tumor progression (26). Myofibroblasts are often operationally defined as expressing α-smooth muscle actin (SMA), vimentin, and fibroblast activation protein and are negative for cytokeratin and usually desmin (7). An emerging body of evidence from multiple experimental platforms supports the idea that there are marked differences between different myofibroblast populations in both health and disease. For example, microarray studies reveal differences between myofibroblasts from different regions of the normal gastrointestinal tract (12). Moreover, there are marked differences in cancer at the levels of transcripts, proteins, and functions. Previously, we showed that myofibroblasts from gastric or esophageal cancer differ from their counterparts in adjacent tissue with evidence that myofibroblasts from advanced gastric tumors promote more aggressive phenotypes in cancer cells (3, 13, 14, 17). We also showed that esophageal cancer-associated myofibroblasts (CAMs) exhibit increased secretion of the chemokine-like peptide chemerin, which plays a role in mesenchymal stem cell recruitment (17). MicroRNAs (miRNAs) are short RNAs of ∼22 nucleotides that act posttranscriptionally to determine mRNA stability and translation (1). They regulate an impressive diversity of biological processes and importantly may contribute to cancer initiation and progression. In stomach and esophagus, previous studies have identified differentially expressed miRNAs (8, 11, 19). However, it is not known whether miRNAs contribute to the differences in function of different myofibroblast populations. In view of differences in the secretomes and proteomes of gastric or esophageal cancer-derived myofibroblasts compared with their respective adjacent tissue myofibroblasts (ATMs), in the present study we sought to determine whether there might also be differences in their miRNA expression profiles compared both with each other and with normal tissue myofibroblasts (NTMs). We now report that gastric and esophageal NTM miRNA profiles are readily distinguishable, that gastric CAMs differ from their respective NTMs in their miRNA profiles, and that Wnt5a (which is upregulated in gastric CAMs) may act in part via miR-181d to influence mesenchymal-epithelial signaling.

The responses of Sea Surface Temperature (SST) to greenhouse gas (GHG) and anthropogenic aerosol in the North Pacific are compared based on the historical single and all-forcing simulations with Geophysical Fluid Dynamics Laboratory Climate Model version 3 (GFDL CM3). During 1860–2005, the effect of GHG forcing on the North Pacific SST is opposite to that of the aerosol forcing. Specifically, the aerosol cooling effect exceeds the GHG warming effect in the Kuroshio Extension (KE) region during 1950–2004 in the CM3 single forcing. The mid-latitude response of ocean circulation to the GHG (aerosol) forcing is to enhance (weaken) the Subtropical Gyre. Then the SST warming (cooling) lies on the zonal band of 40°N because of the increased (reduced) KE warm advection effect in the GHG (aerosol) forcing simulations, and the cooling effect to SST will surpass the warming effect in the KE region in the historical all-forcing simulations. Besides, the positive feedback between cold SST and cloud can also strengthen the aerosol cooling effect in the KE region during boreal summer, when the mixed layer depth is shallow. In the GHG (aerosol) forcing simulations, corresponding to warming (cooling) SST in the KE region, the weakened (enhanced) Aleutian Low appears in the Northeast Pacific. Consequently, the SST responses to all-forcing in the historical simulations are similar to the responses to aerosol forcing in sign and spatial pattern, hence the aerosol effect is quite important to the SST cooling in the mid-latitude North Pacific during the past 55 years.

Light intensity plays an important role in determining the distribution of submerged macrophyte. A modified SAVM (M-SAVM) was constructed to simulate the role of epiphyton and water level for the biomass and distribution of Potamogeton crispus in the Yuqiao Reservoir in China. M-SAVM is developed by modification of the light attenuation equation, which is determined by the water transparency (Secchi depth) and epiphyton. The model was calibrated and verified by biomass using two datasets, from the seedling establishment until dying out, in 2008 and 2009. Five hydraulic scenarios were simulated by M-SAVM to analyze the relationship between biomass and water depth. Results showed that epiphyton increase had a slightly low light intensity limitation coefficient to suppress plant growth in M-SAVM. Significant negative correlation ( p r = −0.97) between biomass and water depth existed in the reservoir. The biomass increases under low water levels due to increasing underwater light intensity and decreases when the water level is raised. M-SAVM could be a useful tool for submerged macrophyte management in the reservoir and for maintaining intermediate vegetation biomass by fluctuating water level strategies in shallow lakes.

in the paper, for the first time, the synthesis of aluminum nitrides microparticles with a hierarchically meso-macroporus structure were reported by an aluminum-magnesium alloy nitridization routine. The hierarchically meso-macroporous aluminum nitrogen with a specific surface area of 97.7 m 2 /g and a specific mesopore volume of 0.10 cm 3 /g was prepared by nitriding an aluminum-magnesium alloy with diameters between 75 µm and 150 µm at the temperature 500 °C for 8 h firstly and then 800 °C for 6 h.

Adrenomedullin (ADM) is important for tumor angiogenesis, tumor cell growth, and survival. Under normoxic conditions, the ADM gene was found to produce two alternative transcripts, a fully spliced transcript that produces AM and PAMP peptides and intron-3–retaining transcript that produces a less functionally significant PAMP peptide only. ADM is a well-established hypoxia inducible gene; however, it is not clear which ADM isoform is induced by hypoxia. In this study, it was determined that various cancer and normal cells express two predominant types of ADM transcripts, a AM/PAMP peptide producing full-length transcript in which all introns are removed, and a nonprotein producing I1-3 transcript in which all introns are retained. Interestingly, hypoxia preferentially induced the full-length isoform. Moreover, hypoxia-inducible factors (HIF), but not hypoxia per se, are necessary and sufficient to increase splicing of ADM pre-mRNA. ADM splicing reporters confirmed that transcriptional activation by HIF or other transcription factors is sufficient to enhance splicing. However, HIFs are more potent in enhancing ADM pre-mRNA splicing than other transcriptional activators. Thus, ADM intron retention is not a consequence of abnormal splicing, but is an important mechanism to regulate ADM expression. These results demonstrate a novel function of HIFs in regulating ADM expression by enhancing its pre-mRNA splicing. Importantly, using endogenous and cloned ADM gene, further evidence is provided for the coupling of transcription and RNA splicing. Implications: Here, a novel function of HIFs in regulating ADM gene expression is identified by enhancing ADM pre-mRNA splicing. Mol Cancer Res; 12(5); 728–41. ©2014 AACR.