Effects of a low-sodium diet in patients with idiopathic hyperaldosteronism: a randomized controlled trial.

Background: Idiopathic hyperaldosteronism (IHA) is one of the most common types of primary aldosteronism (PA), an important cause of hypertension. Although high dietary sodium is a major risk factor for hypertension, there is no consensus on the recommended dietary sodium intake for IHA. Objective: This study investigated the effect of a low-sodium diet on hemodynamic variables and relevant disease biomarkers in IHA patients, with the aim of providing a useful reference for clinical treatment. Methods: Fifty IHA patients were evenly randomized into two groups and provided, after a 7-day run-in period (100 mmol/d sodium), either a low-sodium diet (50 mmol/d sodium) or a normal sodium diet (100 mmol/d sodium) for an additional 7 days. After the 14-day intervention (conducted without potassium supplementation), changes in blood pressure (BP) and serum potassium were evaluated in both groups. Results: After the dietary intervention, the low sodium group exhibited, compared to the normal sodium group, decreased BP (SBP: 121.8 ± 12.8 vs. 129.9 ± 12.1 mmHg, p < 0.05; DBP: 82.6 ± 7.6 vs. 86.4 ± 8.2 mmHg, p < 0.05; MAP: 95.7 ± 8.8 vs. 100.9 ± 8.4 mmHg, p < 0.05) and increased serum potassium levels (3.38 ± 0.33 vs. 3.07 ± 0.27 mmol/L, p < 0.001). The low sodium group showed also better control of both BP and serum potassium: BP <140/90 mmHg in 70.0% of total patients (76.0% vs. 64.0%, in the low and normal sodium groups, respectively; p > 0.05), BP <130/85 mmHg in 38.0% of total patients (56.0% vs. 20.0%, p < 0.05), BP <120/80 mmHg in 28.0% of total patients (44.0% vs. 12.0%, p < 0.05); serum potassium ≥3.5 mmol/L in 22.0% of total patients (32.0% vs. 12.0% in the low and normal sodium groups, respectively; p = 0.088). There were differences between the controlled BP group (<120/80 mmHg) and the non-controlled BP group (≥120/80 mmHg) in gender, BP at baseline, and type of diet (low vs. normal sodium). Female gender and low-sodium diet were protective factors for BP control. Conclusions: A low-sodium diet is effective in lowering BP and elevating serum potassium in IHA patients. Female patients on a low-sodium diet are more likely to achieve BP control (<120/80 mmHg). We advocate a dietary sodium intake of 50 mmol/d for IHA patients. Clinical trial registration: https://clinicaltrials.gov, Identifier NCT05649631.

Involvement of branched RG-I pectin with hemicellulose in cell-cell adhesion of tomato during fruit softening.

Cell adhesion of four cultivars of tomato fruit, "Micro Tom (MT)", "Heinz 1706 (H1706)", "Money Maker (MM)", "Ailsa Craig (AC)" were evaluated and cell walls were analyzed in order to assess the possible contribution of pectic and hemicellulosic polysaccharides to the softening and altered cell adhesion at two different stages of ripeness. Cell wall material (CWM) and solubilised fractions of green and red ripe fruit were analyzed by chemical, enzymatic techniques. In comparison with the four cultivars of tomato fruits, H1706 and MM are harder than MT and AC at both green and red ripe stage. The ripening-associated solubilisation of rhamnogalacturonan-riched pectic polysaccharides was reduced in H1706 and MM, and the content of side -chain sugars from RG-I reduced by more than 50% in MT and AC. In addition to recognized pectic modifying enzymes, RGase had a good effect on cell separation of H1706 and MM fruit at red ripe stage. The higher RG-I content and branching degree have been associated with increased cell adhesion and reduced cell wall porosity, thus maintained fruit firmness.

Simultaneous removal of fluoride, manganese and iron by manganese oxide supported activated alumina: characterization and optimization via response surface methodology.

Fluoride, iron and manganese simultaneous exceedance of standard can be observed in groundwater in northeastern China. This work aims to apply a highly efficient method combining adsorption and oxidation for the synchronous removal of the inorganic ions. An innovative adsorbent (manganese-supported activated alumina) was synthesized by the impregnation method and showed a significant adsorption capacity better than that of fresh activated alumina. The characterization (scanning electron microscope; Brunauer, Emmett and Teller; X-ray diffraction and Fourier transform infrared spectroscopy) results verified the successful introduction of MnOOH and MnO2, and the improvement of surface microstructure enhanced the removal ability. The effect of single factors, such as pH value, reaction time or dosage on the removal performance has been verified. The maximum removal efficiencies of fluoride, iron and manganese were optimized via Response surface methodology considering the independent factors in the range of MO@AA dosage (5-9 g/L), pH (4-6) and contact time (4-12 h). Noted that compared with control, MO@AA exhibited 59.4% of improved fluoride performance. At pH of 5.79, contacting time of 12 h and 8.21 g/L of MO@AA, fluoride, iron and manganese removal were found to be 91, 100 and 23%, respectively. Herein, MO@AA was distinguished as good applicability for the treatment of fluoride-, iron- and manganese-containing groundwater.

Modified citrus pectin prevents isoproterenol-induced cardiac hypertrophy associated with p38 signalling and TLR4/JAK/STAT3 pathway.

Modified citrus pectin (MCP) is a specific inhibitor of galectin-3 (Gal-3) that is regarded as a new biomarker of cardiac hypertrophy, but its effect is unclear. The aim of this study is to investigate the role and mechanism of MCP in isoproterenol (ISO)-induced cardiac hypertrophy. Rats were injected with ISO to induce cardiac hypertrophy and treated with MCP. Cardiac function was detected by ECG and echocardiography. Pathomorphological changes were evaluated by the haematoxylin eosin (H&E) and wheat germ agglutinin (WGA) staining. The hypertrophy-related genes for atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and ß-myosin heavy chain (ß-MHC), and the associated signal molecules were analysed by qRT-PCR and western blotting. The results show that MCP prevented cardiac hypertrophy and ameliorated cardiac dysfunction and structural disorder. MCP also decreased the levels of ANP, BNP, and ß-MHC and inhibited the expression of Gal-3 and Toll-like receptor 4 (TLR4). Additionally, MCP blocked the phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), but it promoted the phosphorylation of p38. Thus, MCP prevented ISO-induced cardiac hypertrophy by activating p38 signalling and inhibiting the Gal-3/TLR4/JAK2/STAT3 pathway.

Alternative splicing perturbation landscape identifies RNA binding proteins as potential therapeutic targets in cancer.

Alternative splicing (AS) plays an important role in gene regulation, and AS perturbations are frequently observed in cancer. RNA binding protein (RBP) is one of the molecular determinants of AS, and perturbations in RBP-gene network activity are causally associated with cancer development. Here, we performed a systematic analysis to characterize the perturbations in AS events across 18 cancer types. We showed that AS alterations were prevalent in cancer and involved in cancer-related pathways. Given that the extent of AS perturbation was associated with disease severity, we proposed a computational pipeline to identify RBP regulators. Pan-cancer analysis identified a number of conserved RBP regulators, which play important roles in regulating AS of genes involved in cancer hallmark pathways. Our application analysis revealed that the expression of 68 RBP regulators helped in cancer subtyping. Specifically, we identified four subtypes of kidney cancer with differences in cancer hallmark pathway activities and prognosis. Finally, we identified the small molecules that can potentially target the RBP genes and suggested potential candidates for cancer therapy. In summary, our comprehensive AS perturbation landscape analysis identified RBPs as potential therapeutic targets in cancer and provided novel insights into the regulatory functions of RBPs in cancer.

Network pharmacology integrated with molecular docking reveals the common experiment-validated antipyretic mechanism of bitter-cold herbs.

ETHNOPHARMACOLOGICAL RELEVANCE: Bitter-cold herbs have been used to clearing heat and expelling damp in clinical practice in China for thousands of years. AIM OF THE STUDY: This study aimed to investigate the common molecular mechanism of bitter-cold herbs through network pharmacology analysis, molecular docking and experimental validation in vivo. MATERIALS AND METHODS: Network pharmacological analysis integrated with molecular docking was employed to identify the active compounds and core action targets of the bitter-cold herbs. Then, the yeast-induced pathological model was established, and the antipyretic effect of the herbs was evaluated by checking rectal temperatures of the mice hourly. Lastly, the protein expression of core targets was examined to reveal the antipyretic mechanism. RESULTS: A total of 52 lead compounds from the four bitter-cold herbs, Phellodendri Chinensis Cortex (PCC), Sophorae Flavescentis Radix (SFR), Gentianae Radix Et Rhozima (GRER) and Coptidis Rhizoma (CR), and 248 compounds-related targets were screened out with PTGS2 ranking the first. The results from molecular docking showed that 22 compounds adopted the same orientation as aspirin and had an excellent stability in the active site pocket of PTGS2. Furthermore, these herbs exerted potential therapeutic effects through 38 related pathways. On the other hand, the outcome of animal experiments showed that they could significantly attenuate the yeast-induced mice fever with dose-dependent relationship. Further experimental results demonstrated that administration of yeast suspension raised protein expression of PTGS2 significantly, which was evidently inhibited in the high or low-dose groups of GRER as well as in the low-dose group of SFR (P < 0.01) though a higher expression of PTGS2 was shown in the low-dose group of CR compared with FM group (P < 0.01). CONCLUSIONS: The bitter-cold herbs can alleviate fever response and their antipyretic effect may mainly be attributed to regulating the expression of PTGS2 after the formation of ligand-receptor/PTGS2 complexes, and their active compounds might be nominated as antipyretic lead-ligand candidates.

Modulome-Fangjiome Association Study (MoFAS) reveals differential target distribution among four similar fangjis (formulas).

ETHNOPHARMACOLOGICAL RELEVANCE: Precise target distribution is a key issue for further appropriate applications of fangjis (formulas) with similar efficacy and herbal constituents to maximize efficacy and minimize toxicity. AIM OF THE STUDY: To develop an algorithm for investigating the differential target distributions and characteristic mechanisms of fangjis. MAIN METHODS: In this study, we proposed a Modulome-Fangjiome Association Study (MoFAS) for comparing fangjis from qi-invigorating and xue-nourishing fangjiome (represented by four fangjis: FEJ, SDT, LYG and QOL). Firstly, the database-driven target network of these 4 fangjis was constructed as qi-xue network and decomposed into modules. Then, the modular map with functional landscape were constructed based on consistency score and enrichment analysis. Finally, we employed a targeting rate (TR) matrix to assess the contribution of this fangjiome to modulome (a set of modules) and compared characteristic effect of fangjis by principal component analysis (PCA). RESULTS: A qi-xue network constituted by 579 proteins and 23 modules were constructed. In the functional landscape, 3 primary modules were mainly involved in the endocrine system and environmental adaptation. For the target distribution, SDT and QOL were more similar; the FEJ and LYG were located distant from other fangjis according to PCA. The common effects of FEJ, SDT, and QOL focused on stress response and organism development in environmental perturbation, but the FEJ was superior in regulating critical targets, primarily focusing on hormone and neurotransmitter processes. SDT and QOL were concentrated on the majority scale of the qi-xue network, especially for the mitotic cell cycle and development. LYG only targeted lymphocyte costimulation and icosanoid biosynthetic processes. CONCLUSION: In this study, for the first time, we investigated the difference in the target distribution of qi-invigorating and xue-nourishing fangjiome and provided direct evidence for the characteristic therapeutic effect of these fangjis, which may promote the precise application of fangjis and support the identification of appropriate populations.

Intermodule Coupling Analysis of Huang-Lian-Jie-Du Decoction on Stroke.

Huang-Lian-Jie-Du Decoction (HLJDD) is a "Fangji" made up of well-designed Chinese herb array and widely used to treat ischemic stroke. Here we aimed to investigate pharmacological mechanism by introducing an inter-module analysis to identify an overarching view of target profile and action mode of HLJDD. Stroke-related genes were obtained from OMIM (Online Mendelian Inheritance in Man). And the potential target proteins of HLJDD were identified according to TCMsp (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform). The two sets of molecules related to stroke and HLJDD were respectively imported into STRING database to construct the stroke network and HLJDD network, which were dissected into modules through MCODE, respectively. We analyzed the inter-module connectivity by quantify "coupling score" (CS) between HLJDD-modules (H-modules) and stroke-modules (S-module) to explore the pharmacological acting pattern of HLJDD on stroke. A total of 267 stroke-related proteins and 15 S-modules, 335 HLJDD putative targeting proteins, and 13 H-modules were identified, respectively. HLJDD directly targeted 28 proteins in stroke network, majority (16, 57.14%) of which were in S-modules 1 and 4. According to the modular map based on inter-module CS analysis, H-modules 1, 2, and 8 densely connected with S-modules 1, 3, and 4 to constitute a module-to-module bridgeness, and the enriched pathways of this bridgeness with top significance were TNF signaling pathway, HIF signaling pathway, and PI3K-Akt signaling pathway. Furthermore, through this bridgeness, H-modules 2 and 4 cooperatively work together to regulate mitochondrial apoptosis against the ischemia injury. Finally, the core protein in H-module 4 account for mitochondrial apoptosis was validated by an in vivo experiment. This study has developed an integrative approach by inter-modular analysis for elucidating the "shotgun-like" pharmacological mechanism of HLJDD for stroke.

Alteration of Phenolic Composition in Lettuce (Lactuca sativa L.) by Reducing Nitrogen Supply Enhances its Anti-Proliferative Effects on Colorectal Cancer Cells.

Consumption of vegetables rich in phenolic compounds has become a useful method to reduce the risk of developing several types of cancer. This study investigated the potential relationship between the alteration of phenolic compounds in lettuce induced by reduced nitrogen supply and its anti-proliferative effects on Caco-2 colorectal cancer cells. Our results showed that phenolic extracts from lettuce grown under low nitrogen conditions (LP) exhibited better anti-proliferative effects against Caco-2 cells, in part, by interfering with the cell cycle and inducing apoptosis, compared with those from lettuce supplied with adequate nitrogen. High performance liquid chromatography (HPLC) analysis and correlation analysis indicated that the better anticancer activity of LP may be not only related to the increased phenolic content, but also associated with the increased percentage contribution of quercetin to total phenolics. Taken together, alteration of phenolic composition by reduced nitrogen supply can be an effectively strategy for the development of healthy vegetables as anticancer products.

Activated scavenger receptor A promotes glial internalization of aß.

Beta-amyloid (Aß) aggregates have a pivotal role in pathological processing of Alzheimer's disease (AD). The clearance of Aß monomer or aggregates is a causal strategy for AD treatment. Microglia and astrocytes are the main macrophages that exert critical neuroprotective roles in the brain. They may effectively clear the toxic accumulation of Aß at the initial stage of AD, however, their functions are attenuated because of glial overactivation. In this study, we first showed that heptapeptide XD4 activates the class A scavenger receptor (SR-A) on the glia by increasing the binding of Aß to SR-A, thereby promoting glial phagocytosis of Aß oligomer in microglia and astrocytes and triggering intracellular mitogen-activated protein kinase (MAPK) signaling cascades. Moreover, XD4 enhances the internalization of Aß monomers to microglia and astrocytes through macropinocytosis or SR-A-mediated phagocytosis. Furthermore, XD4 significantly inhibits Aß oligomer-induced cytotoxicity to glial cells and decreases the production of proinflammatory cytokines, such as TNF-α and IL-1ß, in vitro and in vivo. Our findings may provide a novel strategy for AD treatment by activating SR-A.

Integration of HIV and maternal healthcare in a high HIV-prevalence setting: analysis of client flow data over time in Swaziland.

OBJECTIVE: Maternal and child health (MCH) care may provide an entry point for HIV services in high HIV-prevalence settings. Our objective was to assess integration of HIV with MCH services in public sector facilities in Swaziland. DESIGN: In 2009, 2010 and 2012, client flow assessments (CFAs) were conducted over 5 days in the MCH units of eight government facilities, purposively selected as intervention or comparison sites. PARTICIPANTS: 8263 MCH visits with female clients were tracked: 3261 in 2009, 2086 in 2010 and 2916 in 2012. INTERVENTION: Activities and resources to strengthen integration of HIV services into postnatal care (PNC), 2009-2010. MAIN OUTCOME MEASURES: The proportion of all visits in which an HIV/sexually transmitted infection (STI) testing, counselling or treatment was received together with an MCH service; the proportion of all visits in which a client receives HIV counselling. RESULTS: Across facilities, the proportion of visits in which HIV/STI and MCH services were received varied considerably, for example, from 9% to 49% in 2009. HIV/STI services were integrated most frequently with child health (CH), antenatal care (ANC) and family planning (FP)-the most common reasons for women's attendance-and least often with PNC and cervical screening (CS). There was no meaningful difference in integration over time by design group and considerable heterogeneity across facilities. Receipt of integrated services increased in one intervention and two comparison facilities, where HIV counselling also rose, and fell in one intervention and two comparison facilities. CONCLUSIONS: Provision of HIV/STI services with MCH care occurred at all facilities, yet relatively few women receive integrated services. Increases in integration were driven by increases in HIV counselling, while sharp declines in some facilities indicate that integration is difficult to sustain. Opportunities for intensifying HIV integration lie with ANC, CH and FP, while HIV-PNC integration will remain limited until more women attend PNC. TRIAL REGISTRATION NUMBER: Current Controlled Trials NCT01694862.

Chinese medicine injection shuanghuanglian for treatment of acute upper respiratory tract infection: a systematic review of randomized controlled trials.

Acute upper respiratory tract infections (AURTIs) are the illnesses caused by an acute infection with various viruses and bacteria involving the upper respiratory tract. Shuanghuanglian (SHL) injection, a Chinese medicine intravenous preparation extracted from honeysuckle, Scutellaria baicalensis, and fructus forsythiae, is commonly used to treat AURTIs. Although it is used largely in Chinese hospitals, there is no substantial evidence to demonstrate its clinical effect on AURTIs. We conducted a systematic review to evaluate the effectiveness and safety of Shuanghuanglian injection for the treatment of acute upper respiratory tract infections.

CMOS-based carbon nanotube pass-transistor logic integrated circuits.

Field-effect transistors based on carbon nanotubes have been shown to be faster and less energy consuming than their silicon counterparts. However, ensuring these advantages are maintained for integrated circuits is a challenge. Here we demonstrate that a significant reduction in the use of field-effect transistors can be achieved by constructing carbon nanotube-based integrated circuits based on a pass-transistor logic configuration, rather than a complementary metal-oxide semiconductor configuration. Logic gates are constructed on individual carbon nanotubes via a doping-free approach and with a single power supply at voltages as low as 0.4 V. The pass-transistor logic configurarion provides a significant simplification of the carbon nanotube-based circuit design, a higher potential circuit speed and a significant reduction in power consumption. In particular, a full adder, which requires a total of 28 field-effect transistors to construct in the usual complementary metal-oxide semiconductor circuit, uses only three pairs of n- and p-field-effect transistors in the pass-transistor logic configuration.