Metabolism response mechanism in the gill of Oreochromis mossambicus under salinity, alkalinity and saline-alkalinity stresses.

Saline-alkalinity is one of the important ecological parameter that has an impact function on the physiological metabolism, osmoregulation, survival, growth, development and distribution of teleost fish. Oreochromis mossambicus, a species of euryhaline that can withstand a wide variety of salinities, may be used as a research model animal in environmental studies. In order to detect the metabolism responses and mechanisms of different osmotic stresses tolerance in the gills of O. mossambicus, in present study, the metabolic responses of O. mossambicus subjected to salinity (25 g/L, S_S), alkalinity (4 g/L, A_S) and saline-alkalinity stress (salinity: 25 g/L, alkalinity: 4 g/L; SA_S) with the control environment (freshwater, C_S) were investigated by LC-MS/MS-based metabolomics. The metabolism results indicated that numerous metabolites were identified between the stress groups and the control group. In addition, under three osmotic stresses, the amino acid and carbohydrate metabolism, levels of amino acids, osmolytes and energy substances, such as L-lysine, arachidonic acid, docosahexaenoic acids, creatine and taurine, were significantly affected and changed in the metabolism of the gills of O. mossambicus. The metabolism data indicated that signal transduction and regulation pathways, including FoxO signaling pathway, mTOR signaling pathway and prolactin signaling pathway, were enriched in the gill during adaptation to high salinity, alkalinity and saline-alkalinity stress. The results of this study provide more comprehensive and reliable data for the osmotic pressure regulation mechanism and biological response of euryhaline teleost, and provide reliable scientific basis for the breeding and research of high salinity tolerance population, and further promote the development and utilization of saline-alkalinity water resources.

Transcriptomic response to three osmotic stresses in gills of hybrid tilapia (Oreochromis mossambicus female × O. urolepis hornorum male).

BACKGROUND: Osmotic stress is a widespread phenomenon in aquatic animal. The ability to cope with salinity stress and alkaline stress is quite important for the survival of aquatic species under natural conditions. Tilapia is an important commercial euryhaline fish species. What's more tilapia is a good experimental material for osmotic stress regulation research, but the molecular regulation mechanism underlying different osmotic pressure of tilapia is still unexplored. RESULTS: To elucidate the osmoregulation strategy behind its hyper salinity, alkalinity and salinity-alkalinity stress of tilapia, the transcriptomes of gills in hybrid tilapia (Oreochromis mossambicus ♀ × O. urolepis hornorum ♂) under salinity stress (S: 25‰), alkalinity stress(A: 4‰) and salinity-alkalinity stress (SA: S: 15‰, A: 4‰) were sequenced using deep-sequencing platform Illumina/HiSeq-2000 and differential expression genes (DEGs) were identified. A total of 1958, 1472 and 1315 upregulated and 1824, 1940 and 1735 downregulated genes (P-value < 0.05) were identified in the salt stress, alkali stress and saline-alkali stress groups, respectively, compared with those in the control group. Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway analyses were conducted in the significant different expression genes. In all significant DEGs, some of the typical genes involved in osmoregulation, including carbonic anhydrase (CA), calcium/calmodulin-dependent protein kinase (CaM kinase) II (CAMK2), aquaporin-1(AQP1), sodium bicarbonate cotransporter (SLC4A4/NBC1), chloride channel 2(CLCN2), sodium/potassium/chloride transporter (SLC12A2 / NKCC1) and other osmoregulation genes were also identified. RNA-seq results were validated with quantitative real-time PCR (qPCR), the 17 random selected genes showed a consistent direction in both RNA-Seq and qPCR analysis, demonstrated that the results of RNA-seq were reliable. CONCLUSIONS: The present results would be helpful to elucidate the osmoregulation mechanism of aquatic animals adapting to saline-alkali challenge. This study provides a global overview of gene expression patterns and pathways that related to osmoregulation in hybrid tilapia, and could contribute to a better understanding of the molecular regulation mechanism in different osmotic stresses.

Highly efficient and controllable photoluminescence emission on a suspended MoS2-based plasmonic grating.

Being a new class of materials, transition metal dichalcogenides are paving the way for applications in atomically thin optoelectronics. However, the intrinsically weak light-matter interaction and the lack of manipulation ability has lead to poor light emission and tunable behavior. Here, we investigate the fluorescence characteristic of monolayer molybdenum disulfide on a metal narrow-slit grating, where a highly efficient, 471 times photoluminescence enhancement are realized, based on the hybrid surface plasmon polaritons resonances and the decreased influence of substrate. Moreover, the emitted intensity and polarization are controllable due to the polarization-dependent characteristic and anisotropy of grating. The manipulations of light-matter interactions in this special system provide a new insight into the fluorescent emission process and open a new avenue for high-performance low dimensional materials devices designs.

Characterization and expression of Na+/K+-ATPase in gills and kidneys of the Teleost fish Oreochromis mossambicus, Oreochromis urolepis hornorum and their hybrids in response to salinity challenge.

Tilapia (Oreochromis mossambicus, O. urolepis hornorum, their hybrids O. mossambicus♀ × O. hornorum♂ and O. hornorum♀ × O. mossambicus♂) were exposed to a high salinity environment to evaluate their osmoregulatory responses. The plasma osmolality of all the tilapia species were elevated with the salinity challenge. The activities of Na+/K+-ATPase (NKA) in both the gill and kidney showed a similar increased change tendency compared with the control. The distribution of NKA α1 mRNA in all the examined tissues suggested that NKA α1 has a possible housekeeping role for this isoform. The amount of NKA α1 mRNA in the gill and kidney was elevated in the four fishes with similar expression patterns after transfer from freshwater to seawater. The NKAα1 mRNA expression levels in the gill reached their peak level at 24 h after transfer (P < 0.01) compared to the freshwater group, following decreases in the pretreatment level at 48 h (P > 0.05). However, the NKAα1 mRNA expression levels in the kidney were not significantly affected with increasing environmental salinity (P > 0.05). The differences in the responses to saltwater challenge may be associated with differences in saltwater tolerance between the four tilapia. The drastic increase in the plasma osmolality, NKA activities and mRNA expression suggested that the hybrids (O. mossambicus♀ × O. hornorum♂) possess heterosis in salinity responsiveness compared to that of both the parents, indicating a maternal effect on the salinity tolerance of the tilapia hybrids. This study provides a theoretical basis to further study the mechanism of fish osmoregulation response to salinity challenge.

Intrinsic brain network abnormalities in codeine-containing cough syrup-dependent male individuals revealed in resting-state fMRI.

PURPOSE: To identify codeine-containing cough syrups (CCS)-related modulations of intrinsic connectivity network (ICN) and to investigate whether these changes of ICN can be related to duration of CCS use and to impulsivity behavior in CCS-dependent individuals. MATERIALS AND METHODS: Resting-state functional magnetic resonance imaging (fMRI) data in 41 CCS-dependent individuals and 34 healthy controls (HC) were scanned at 1.5T and analyzed using independent component analysis (ICA), in combination with a "dual-regression" technique to identify the group differences of three important resting-state networks, the default mode network (DMN), the executive control network (ECN), and the salience network (SN) between the CCS-dependent individuals and HC. RESULTS: Compared with the HC, CCS-dependent individuals had aberrant intrinsic connectivity within the DMN, ECN, and SN (P < 0.05, AlphaSim corrected). Furthermore, a longer duration of CCS use was associated with greater abnormalities in the intrinsic network functional connectivity (FC, P < 0.05, Bonferroni correction). Intrinsic network FC also correlated with higher impulsivity in CCS-dependent individuals (P < 0.05, AlphaSim corrected). CONCLUSION: Our findings revealed aberrant DMN, ECN, and SN connectivity patterns in CCS-dependent patients, which may provide new insight into how neuronal communication and information integration are disrupted among DMN, ECN, and SN key structures due to long duration of CCS use. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:177-186.

Larger corpus callosum and reduced orbitofrontal cortex homotopic connectivity in codeine cough syrup-dependent male adolescents and young adults.

OBJECTIVES: To characterize interhemispheric functional and anatomical connectivity and their relationships with impulsive behaviour in codeine-containing cough syrup (CCS)-dependent male adolescents and young adults. METHODS: We compared volumes of corpus callosum (CC) and its five subregion and voxel-mirrored homotopic functional connectivity (VMHC) in 33 CCS-dependent male adolescents and young adults and 38 healthy controls, group-matched for age, education and smoking status. Barratt impulsiveness scale (BIS.11) was used to assess participant impulsive behaviour. Abnormal CC subregions and VMHC revealed by group comparison were extracted and correlated with impulsive behaviour and duration of CCS use. RESULTS: We found selective increased mid-posterior CC volume in CCS-dependent male adolescents and young adults and detected decreased homotopic interhemispheric functional connectivity of medial orbitofrontal cortex (OFC). Moreover, impairment of VMHC was associated with the impulsive behaviour and correlated with the duration of CCS abuse in CCS-dependent male adolescents and young adults. CONCLUSIONS: These findings reveal CC abnormalities and disruption of interhemispheric homotopic connectivity in CCS-dependent male adolescents and young adults, which provide a novel insight into the impact of interhemispheric disconnectivity on impulsive behaviour in substance addiction pathophysiology. KEY POINTS: • CCS-dependent individuals (patients) had selective increased volumes of mid-posterior corpus callosum • Patients had attenuated interhemispheric homotopic FC (VMHC) of bilateral orbitofrontal cortex • Impairment of VMHC correlated with impulsive behaviour in patients • Impairment of VMHC correlated with the CCS duration in patients.

Aberrant interhemispheric functional and structural connectivity in heroin-dependent individuals.

Models of heroin addiction emphasize the role of disrupted frontostriatal circuitry supporting cognitive control processes. However, heroin addiction-related alterations in functional and structural interactions among brain regions, especially between the cerebral hemispheres, are rarely examined directly. Resting-state functional magnetic resonance imaging (fMRI) approaches, which reveal patterns of coherent spontaneous fluctuations in the fMRI signal, offer a means to quantify directly functional interactions between the hemispheres. The corpus callosum (CC), which connects homologous regions of the cortex, is the major conduit for information transfer between the cerebral hemispheres and represents a structural connectivity index between hemispheres. We compared interhemispheric voxel-mirrored homotopic connectivity (VMHC) and CC volume between 45 heroin dependent-individuals (HDIs) and 35 non-addict individuals. We observed significant reduction of VMHC in a number of regions, particularly the striatum/limbic system regions, and significant decrease in splenium and genu sub-regions of CC in HDI. Importantly, within HDI, VMHC in the dorsal lateral prefrontal cortex (DLPFC) correlated with genu CC volume, VMHC in the putamen, VMHC in the DLPFC and genu CC volume and splenium CC volume were negatively correlated with heroin duration and impulsivity traits. Further analyses demonstrated that impairment of VMHC of bilateral DLPFC partially mediated the association between genu CC volumes decreased and increased impulsivity in HDI. Our results reveal a substantial impairment of interhemispheric coordination in the HDI. Further, interhemispheric connectivity correlated with the duration of heroin abuse and higher impulsivity behavior in HDI. Our findings provide insight into a heroin addicts' related pathophysiology and reinforce an integrative view of the interhemispheric cerebral functional and structural organization.

Short-term UROD treatment on cerebral function in codeine-containing cough syrups dependent male individuals.

OBJECTIVE: To investigate alterations of resting brain function in codeine-containing cough syrups (CCS) dependent individuals before and after ultra-rapid opioid detoxification under general anaesthesia (UROD) combined with naltrexone treatment (NMT). METHODS: Fourteen CCS-dependent individuals were scanned using resting-state fMRI. After UROD and 2 weeks of NMT, CCS-dependent individuals were rescanned. Fourteen matched controls were studied at baseline and compared. The amplitude of low frequency fluctuations (ALFF) and seed-based functional connectivity (FC) were used to characterize resting-state cerebral function. RESULTS: After UROD and 2 weeks of NMT, CCS-dependent individuals had increased ALFF in the bilateral parahippocampal gyrus and right medial orbitofrontal cortex (mOFC), decreased ALFF in the left post-central gyrus (PoCG), left middle occipital cortex (MOC) and left dorsal lateral prefrontal cortex (DLPFC), and reduced FC between right mOFC and right DLPFC, and between left DLPFC and left inferior parietal lobe relative to pretreatment. Decreased ALFFs in the left PoCG and left MOC were associated with decreased withdrawal syndrome severity in CCS-dependent individuals. CONCLUSIONS: We offer the first report describing how regional and integral synchronous neural activity occurs after UROD and short-term NMT, accompanied by decreased withdrawal syndrome severity. These findings contribute to the understanding of complex systems involved in UROD-NMT effects. KEY POINTS: • CCS-dependent individuals had reduced ALFF and increased FC at baseline. • UROD treatment can change the regional and integral brain function of CCS-dependent individuals. • Attenuated ALFFs are correlated with the withdrawal syndrome after treatment.

HBX Protein-Induced Downregulation of microRNA-18a is Responsible for Upregulation of Connective Tissue Growth Factor in HBV Infection-Associated Hepatocarcinoma.

BACKGROUND This study was designed to improve our understanding of the role of miR-18a and its target (connective tissue growth factor (CTGF), which are mediators in HBX-induced hepatocellular carcinoma (HCC). MATERIAL AND METHODS We first investigated the expression of several candidate microRNAs (miRNAs) reported to have been aberrantly expressed between HepG2 and HepG2.2.15, which is characterized by stable HBV infection, while the CTGF is identified as a target of miR-18a. Furthermore, the expression of CTGF evaluated in HepG2 was transfected with HBX, while the HepG2.2.15 was transfected with miR-18a and CTGF siRNA. We examined the cell cycle at the same time. RESULTS We found that the expression of miR-18a was abnormally reduced in the HBV-positive HCC tissue samples compared with HBV-negative HCC samples. Through the use of a luciferase reporter system, we also identified CTGF 3'UTR (1046-1052 bp) as the exact binding site for miR-18a. We also observed a clear increase in CTGF mRNA and protein expression levels in HBV-positive HCC human tissue samples in comparison with the HBV-negative controls, indicating a possible negatively associated relationship between miR-18a and CTGF. Furthermore, we investigated the effect of HBX overexpression on miR-18a and CTGF, as well as the viability and cell cycle status of HepG2 cells. In addition, we found that HBX introduction downregulated miR-18a, upregulated CTGF, elevated the viability, and promoted cell cycle progression. We transfected HepG2.2.15 with miR-18a mimics and CTGF siRNA, finding that upregulated miR-18a and downregulated CTGF suppress the viability and cause cell cycle arrest. CONCLUSIONS Our study shows the role of the CTGF gene as a target of miR-18a, and identifies the function of HBV/HBX/miR-18a/CTGF as a key signaling pathway mediating HBV infection-induced HCC.

pH-Dependent Reversible Self-Assembly of ß-Lactoglobulin-Derived Reducing Peptides.

Peptide-based self-assembled nanostructures are emerging vehicles for nutrient delivery and interface engineering. The present study screened eight ß-lactoglobulin (ß-Lg) derived peptides and found that two reducing peptides [EQSLVCQCLV (EV-10) and VCQCLVR (VR-7)] demonstrated pH-dependent reversible fibrilization. EV-10 formed fibrils at pH 2.0 but became unordered aggregates at pH 7.0. VR-7 showed the opposite trend. Both peptides could undergo repetitive transitions between fibrils and unordered aggregates during consecutive pH-cycling. Fibrilization of both peptides was dominated by charges carried by N- and C-terminals. Both fibrils were characterized by a cross-ß sheet structure where the ß-sheet was arranged in an antiparallel manner. Fe3+ was reduced by Cys and EV-10 (pH 5.0 and 7.0) simultaneously upon mixing. In contrast, EV-10 fibrils released Fe3+ reducing capacity progressively, which were beneficial to long-term protection Fe2+. The EV-10 fibrils remained intact after simulated gastric digestion and finally dissociated after intestinal digestion. The results shed light on the mechanisms of fibrilization of ß-Lg derived peptides. This study was beneficial to the rational design of smart pH-responsive materials for drug delivery and antioxidants for nutrients susceptible to oxidation.

Abnormal regional homogeneity of resting-state brain activity in patients with HBV-related cirrhosis without overt hepatic encephalopathy.

BACKGROUND: Many studies have reported that cognitive deficits exist in cirrhotic patients without overt hepatic encephalopathy (OHE). However, the neurobiological mechanisms underlying these deficits are still not fully understood. AIM: To investigate regional activity abnormalities in patients with hepatitis B virus-related cirrhosis (HBV-RC) without OHE using resting-state functional MRI (Rs-fMRI), and to examine the relationship between regional activity abnormalities and impaired cognition. METHODS: A newly reported regional homogeneity (ReHo) approach was used to compare the local synchronization of Rs-fMRI signals in 32 patients with HBV-RC without OHE and 32 well-matched healthy controls. Cognition was measured in all patients using psychometric hepatic encephalopathy score (PHES) tests, and the relationship between ReHo variation and PHES was analysed. RESULTS: Relative to healthy controls, the cirrhosis group showed high ReHo in the prefrontal cortex, and widespread low ReHo in visual association areas (left lingual gyrus, middle temporal gyrus and right middle occipital gyrus), motor association areas (bilateral precentral gyrus and paracentral lobule) and the bilateral precuneus. Correlation analysis of the mean ReHo values in different brain areas and PHES in cirrhotic patients revealed a significantly positive correlation in the left lingual gyrus (r = 0.352; P = 0.048), right middle occipital gyrus (r = 0.453; P = 0.009) and bilateral precentral gyrus (left: r = 0.436, P = 0.013; right: r = 0.582, P < 0.001), paracentral lobule (r = 0.485; P = 0.005) and precuneus (r = 0.468; P = 0.007). CONCLUSIONS: Our results provide information on the pathophysiological mechanisms underlying cognitive alterations in cirrhotic patients and demonstrate the feasibility of using Rs-fMRI with ReHo analysis as a noninvasive modality with which to detect the progression of cognitive changes in cirrhotic patients.

Metabolism responses in the intestine of Oreochromis mossambicus exposed to salinity, alkalinity and salt-alkalinity stress using LC-MS/MS-based metabolomics.

Multiple abiotic stresses are imposed on fish as a result of unprecedented changes in temperature and precipitation patterns in recent decades. It is unclear how teleosts respond to severe ambient salinity, alkalinity, and saline-alkalinity in terms of their metabolic and molecular osmoregulation processes. The metabolic reactions in the intestine of Oreochromis mossambicus under salinity (25 g/L, S_C), alkalinity (4 g/L, A_C), and saline-alkalinity (salinity: 25 g/L & alkalinity: 4 g/L, SA_C) stresses were examined in this research utilizing LC-MS/MS-based metabolomics. The findings demonstrated that the three osmotic-stressed groups' metabolic profiles were considerably different from those of the control group. Osmolytes, energy sources, free amino acids, and several intermediate metabolites were all synthetically adjusted as part of the osmoregulation associated with the salinity, alkalinity, and saline-alkalinity stress. Following osmotic stress, osmoregulation-related pathways, including the mTOR signaling pathway, TCA cycle, glycolysis/gluconeogenesis, etc., were also discovered in the intestine of O. mossambicus. Overall, our findings can assist in better comprehending the molecular regulatory mechanism in euryhaline fish under various osmotic pressures and can offer a preliminary profile of osmotic regulation.

Inhibiting ice recrystallization by amyloid protein fibrils.

Ice recrystallization is harmful to the quality of frozen foods and the cryopreservation of cells and biological tissues, requiring biocompatible materials with ice recrystallization inhibition (IRI) activity. Emerging studies have associated IRI activity with amphiphilic structures. We propose amphiphilic amyloid protein fibrils (APFs) may be IRI-active. APFs were prepared from whey protein isolate (WPI) in water (W-APFs) and in trifluoroethanol (TFE-APFs). W-APFs and TFE-APFs were more IRI-active than WPI over a concentration range of 2.5-10.0 mg/mL. Both APFs showed stronger IRI activity at pH 3.0 than at pH 5.0, 7.0, and 10.0, which was ascribed to the effect of water dispersibility and fibril length. The reduced IRI activity of the two APFs with increasing NaCl content was caused by fibril aggregation. Ice binding by APFs was absent or very weak. Ordered water was observed for the two APFs, which might be essential for IRI activity. Our findings may lead to the use of APFs as novel ice recrystallization inhibitors.

Delivery of curcumin in a carboxymethyl cellulose and hydroxypropyl methyl cellulose carrier: Physicochemical properties and biological activity.

Curcumin solid dispersions (Cur SDs) were prepared using hydroxypropyl methyl cellulose (HPMC) and sodium carboxymethyl cellulose (CMC) at different dosages. The results of Fourier transform infrared spectroscopy and Raman spectroscopy showed that the characteristic peak of curcumin shifted, and the addition of CMC enhanced this phenomenon. The addition of CMC reduced the contact angle, increased the surface free energy, and improved the solubility of Cur SDs. These changes were positively correlated with the amount of CMC. The surface morphology of Cur SDs changed from needle-like to sheet-like as observed by scanning electron microscopy. Cur SDs prepared by CMC and HPMC retained good biological activity. HT-29 human colon cancer cell analysis showed that the addition of CMC significantly improved the anti-proliferation effect of Cur SDs, thus enhancing the bioavailability of curcumin. Solid dispersions made with CMC and HPMC will be a promising hydrocolloid carrier to improve oral bioavailability and efficacy of curcumin.

Application of Biophysical Properties of Meridians in the Visualization of Pericardium Meridian.

Background: The biophysical properties of the meridian system, an important concept of traditional Chinese medicine, include low impedance, resounding voice, and high acoustic conductance, all of which are helpful for elucidating the essence of meridians. Objectives: To visualize the human pericardium meridian (PC) based on the resounding voice property of meridians. Methods: Visualization of the PC was performed by injection of fluorescein sodium at the PC6 acupoint (Neiguan) on the PC. Before injection, percussion active points (PAPs) were identified by the virtue of their resounding voice properties. After injection, the trajectories of fluorescein migration throughout the body surface were recorded and analyzed. The distribution of fluorescein in the tissue was further studied using cross-sections of hind limbs of mini-pigs, in which fluorescein was injected into low impedance points. Results: The identified PAP lines were colocalized with PC. Following intradermal fluorescein injection, 1-3 fluorescent lines, which were unrelated to the arm veins, were observed in 7 of 10 participants; 85.4% of fluorescent signals were coincident with PAPs and their intensity had a negative correlation with the body mass index (r = -0.56, p = 0.045). Cross-sections showed a Y-shaped fluorescence pattern where the two migration lines on the surface were the two vertices of the "Y." Conclusion: The trajectories of fluorescein in the body are suggestive of the anatomical structure of meridians. The PC is related to the deep horizontal interstitial channels that connect to the body surface through vertical interstitial spaces. These biophysical properties and techniques for meridian visualization are valuable for revealing the anatomical structure of meridians.

Sodium-Based Concave Metasurfaces for High Performing Plasmonic Optical Filters by Templated Spin-on-Sodiophobic-Glass.

Optical filters have aroused tremendous excitement in advanced photonic instruments and modern digital displays due to their flexible capability of spectrum manipulation. Plasmonic metasurfaces of narrow bandwidth, high spectral contrast, and robust structure tolerance are highly desired for optical filtration (especially in the visible regime) but rather challenging as large spectral broadening from intrinsic ohmic loss and design/fabrication deviations. Here the high-performing sodium-based metasurfaces are demonstrated for optical filtration across 450 to 750 nm by unique structure design of spatially decoupled concave surfaces and precise fabrication through templated solidification of liquid metals. Thanks to the distinct suppression of metallic loss as well as fabrication tolerance of interfacial structures, the as-prepared concave metasurfaces enable a minimum linewidth of ≈15 nm, a maximal optical contrast of ≈93%, and a high measure-to-design spectral match ratio ≈1500. These results have for the first time pushed the operation wavelengths of sodium-based plasmonic devices from infrared to visible which in turn demonstrates the capability of filling the blank of commercial dielectric optical filters thus far.

Altered Cerebral Blood Flow in the Progression of Chronic Kidney Disease.

Background: In chronic kidney disease (CKD), cognitive impairment is a definite complication. However, the mechanisms of how CKD leads to cognitive impairment are not clearly known. Methods: Cerebral blood flow (CBF) information was collected from 37 patients with CKD (18 in stage 3; 19 in stage 4) and 31 healthy controls (HCs). For CKD patients, we also obtained laboratory results as well as neuropsychological tests. We conducted brain perfusion imaging studies using arterial spin labeling and calculated the relationship between regional CBF changes and various clinical indicators and neuropsychological tests. We also generated receiver operator characteristic (ROC) curves to explore whether CBF value changes in certain brain regions can be used to identify CKD. Results: Compared with HCs, CBF decreased in the right insula and increased in the left hippocampus in the CKD4 group; through partial correlation analysis, we found that CBF in the right insula was negatively correlated with the number connection test A (NCT-A) (r = −0.544, p = 0.024); CBF in the left hippocampus was positively correlated with blood urea nitrogen (r = 0.649, p = 0.005) and negatively correlated with serum calcium level (r = −0.646, p = 0.005). By comparing the ROC curve area, it demonstrated that altered CBF values in the right insula (AUC = 0.861, p < 0.01) and left hippocampus (AUC = 0.862, p < 0.01) have a good ability to identify CKD. Conclusions: Our study found that CBF alterations in the left hippocampus and the right insula brain of adult patients with stage 4 CKD were correlated with disease severity or laboratory indicators. These findings provide further insight into the relationship between altered cerebral perfusion and cognitive impairment in patients with non-end-stage CKD as well as, additional information the underlying neuropathophysiological mechanisms.

Janus effects of NaCl on structure of egg yolk granules.

Egg yolk granules are supramolecular assembly of high-density lipoproteins and phosvitin driven by calcium bridges. However, applications of granules are severely restricted by the large particle size and poor water dispersibility. This study revealed the Janus effects of NaCl on structure of granules at varied pH values. Addition of 0.3-0.5 M NaCl led to the dissociation of at pH 5.0-7.0. At pH 5.0-10.0, dissociated granules demonstrated good colloidal stability with NaCl because of the adsorption of highly hydrated Na+ and Ca2+, which provided strong hydration repulsion when electrostatic repulsion was screened. In contrast, at pH 2.0 and 3.0, dissociated granules were positively charged with adsorption of poorly hydrated Cl- as counterions. Cl- failed to give sufficient hydration repulsion, leading to the phase separation with 0.3-0.5 M NaCl. Similar effects have been also found in LiCl, KCl, and CsCl, but Li+ might be less effective to disrupt calcium bridges.

Free-energy landscape of two-state protein acylphosphatase with large contact order revealed by force-dependent folding and unfolding dynamics.

Acylphosphatase (AcP) is a small protein with 98 amino acid residues that catalyzes the hydrolysis of carboxyl-phosphate bonds. AcP is a typical two-state protein with slow folding rate due to its relatively large contact order in the native structure. The mechanical properties and unfolding behavior of AcP has been studied by atomic force microscope. Here using stable magnetic tweezers, we measured the force-dependent folding rates within a force range 1-3 pN, and unfolding rates 15-40 pN. The obtained unfolding rates show different force sensitivities at forces below and above ∼27 pN, which determines a free-energy landscape with two energy barriers. Our results indicate that the free-energy landscape of small globule proteins have general Bactrian camel shape, and large contact order of the native state produces a high barrier dominate at low forces.

Boosting the performance of single-atom catalysts via external electric field polarization.

Single-atom catalysts represent a unique catalytic system with high atomic utilization and tunable reaction pathway. Despite current successes in their optimization and tailoring through structural and synthetic innovations, there is a lack of dynamic modulation approach for the single-atom catalysis. Inspired by the electrostatic interaction within specific natural enzymes, here we show the performance of model single-atom catalysts anchored on two-dimensional atomic crystals can be systematically and efficiently tuned by oriented external electric fields. Superior electrocatalytic performance have been achieved in single-atom catalysts under electrostatic modulations. Theoretical investigations suggest a universal "onsite electrostatic polarization" mechanism, in which electrostatic fields significantly polarize charge distributions at the single-atom sites and alter the kinetics of the rate determining steps, leading to boosted reaction performances. Such field-induced on-site polarization offers a unique strategy for simulating the catalytic processes in natural enzyme systems with quantitative, precise and dynamic external electric fields.