Shearing and Mixing Performance of Ultrahigh-Molecular-Weight Hydrolyzed Polyacrylamide (HPAM) Solution in a Helixes Static Mixer

Static mixers have been widely used to dilute high viscosity, high-molecular-weight polymer mother liquor for polymer flooding, in which the mixing performance plays a critical role. In this work, a novel mixing configuration, named as Helixes static mixer, was proposed to reduce high viscosity degradation rate of polyacrylamide solution resulting from mechanical shear during mixing process. Computational fluid dynamics simulations along with experiments were performed to investigate the mixing process. Several criteria such as the intensity of segregation, mixing distance, pressure loss, and shear strain rate were used to evaluate the mixing and shear performance of static mixers. Compared to the SMX and Kenics static mixer, a longer mixing distance is needed for the Helixes static mixer to achieve an ideal mixture. A lower shear strain rate along with less viscosity degradation rate is obtained in flow field of Helixes static mixer. The spiral-lead and helical directions of mixing elements were optimized to improve mixing performance. Experimental results are in good agreement with the numerical simulations on the intensity of segregation. The viscosity degradation rate of HPAM solution which flows through Helixes static mixer is lower than that of SMX and Kenics static mixers

Discovery of selective inhibitors of Glutaminase-2, which inhibit mTORC1, activate autophagy and inhibit proliferation in cancer cells

Glutaminase, which converts glutamine to glutamate, is involved in Warburg effect in cancer cells. Two human glutaminase genes have been identified, GLS (GLS1) and GLS2. Two alternative transcripts arise from each glutaminase gene: first, the kidney isoform (KGA) and glutaminase C (GAC) for GLS; and, second, the liver isoform (LGA) and glutaminase B (GAB) for GLS2. While GLS1 is considered as a cancer therapeutic target, the potential role of GLS2 in cancer remains unclear. Here, we discovered a series of alkyl benzoquinones that preferentially inhibit glutaminase B isoform (GAB, GLS2) rather than the kidney isoform of glutaminase (KGA, GLS1). We identified amino acid residues in an allosteric binding pocket responsible for the selectivity. Treatment with the alkyl benzoquinones decreased intracellular glutaminase activity and glutamate levels. GLS2 inhibition by either alkyl benzoquinones or GLS2 siRNA reduced carcinoma cell proliferation and anchorage-independent colony formation, and induced autophagy via AMPK mediated mTORC1 inhibition. Our findings demonstrate amino acid sequences for selective inhibition of glutaminase isozymes and validate GLS2 as a potential anti-cancer target

Fatty Acid Binding Protein 5 (FABP5) Promotes Aggressiveness of Gastric Cancer Through Modulation of Tumor Immunity.

PurposeGastric cancer (GC) is the second most lethal cancer globally and is associated with poor prognosis. Fatty acid-binding proteins (FABPs) can regulate biological properties of carcinoma cells. FABP5 is overexpressed in many types of cancers; however, the role and mechanisms of action of FABP5 in GC remain unclear. In this study, we aimed to evaluate the clinical and biological functions of FABP5 in GC.Materials and methodsWe assessed FABP5 expression using immunohistochemical analysis in 79 patients with GC and evaluated its biological functions following in vitro and in vivo ectopic expression. FABP5 targets relevant to GC progression were determined using RNA sequencing (RNA-seq).ResultsElevated FABP5 expression was closely associated with poor outcomes, and ectopic expression of FABP5 promoted proliferation, invasion, migration, and carcinogenicity of GC cells, thus suggesting its potential tumor-promoting role in GC. Additionally, RNA-seq analysis indicated that FABP5 activates immune-related pathways, including cytokine-cytokine receptor interaction pathways, interleukin-17 signaling, and tumor necrosis factor signaling, suggesting an important rationale for the possible development of therapies that combine FABP5-targeted drugs with immunotherapeutics.ConclusionsThese findings highlight the biological mechanisms and clinical implications of FABP5 in GC and suggest its potential as an adverse prognostic factor and/or therapeutic target

Targeting a ribonucleoprotein complex containing the caprin-1 protein and the c-Myc mRNA suppresses tumor growth in mice: an identification of a novel oncotarget

Tylophorine compounds have been the focus of drug development for decades. Tylophorine derivatives exhibit anti-cancer activities but their cellular targets remain unknown. We used a biotinylated tylophorine derivative to probe for the interacting cellular target(s) of tylophorine. Tylophorine directly binds to caprin-1 and consequently enhances the recruitment of G3BP1, c-Myc mRNA, and cyclin D2 mRNA to form a ribonucleoprotein complex. Subsequently, this tylophorine targeted ribonucleoprotein complex is sequestered to the polysomal fractions and the protein expressions of the associated mRNA-transcripts are repressed. Caprin-1 depleted carcinoma cells become more resistant to tylophorine, associated with decreased formation of the ribonucleoprotein complex targeted by tylophorine. Consequently, tylophorine downregulates c-Myc and cyclins D1/D2, causing hypophosphorylation of Rb and suppression of both processing-body formation and the Warburg effect. Gene expression profiling and gain-of-c-Myc-function experiments also revealed that the downregulated c-Myc contributes to the anti-oncogenic effects of tylophorine compounds. Furthermore, the potent tylophorine derivative dibenzoquinoline-33b elicited a similar effect, as c-Myc protein levels were also decreased in xenograft tumors treated with dibenzoquinoline-33b. Thus, tylophorine compounds exert anti-cancer activity predominantly by targeting and sequestering the caprin-1 protein and c-Myc mRNA associated ribonucleoprotein complex

The genetic load for hereditary hearing impairment in Chinese population and its clinical implication

AbstractObjectiveTo understand the genetic load in the Chinese population for improvement in diagnosis, prevention and rehabilitation of deafness.MethodsDNA samples, immortalized cell lines as well as detailed clinical and audiometric data were collected through a national genetic resources collecting network. Two conventional genetic approaches were used in the studies. Linkage analysis in X chromosome and autosomes with microsatellite markers were performed in large families for gene mapping and positional cloning of novel genes. Candidate gene approach was used for screening themtDNA 12SrRNA, GJB2andSLC26A4mutations in population–based samples.ResultsA total of 2, 572 Chinese hearing loss families or sporadic cases were characterized in the reported studies, including seven X–linked, one Y–linked, 28 large and multiplex autosomal dominant hearing loss families, 607 simplex autosomal recessive hereditary hearing loss families, 100 mitochondrial inheritance families, 147GJB2induced hearing loss cases, 230 cases with enlarged vestibular aqueduct (EVA) syndrome, 169 sporadic cases with auditory neuropathy, and 1, 283 sporadic sensorineural hearing loss cases. Through linkage analysis or sequence analysis, two X–linked families were found transmitting two novel mutations in thePOU3F4gene, while another X–linked family was mapped onto a novel locus, nominated asAUNX1(auditory neuropathy, X–linked locus 1). The only Y–linked family was mapped onto theDFNY1locus (Y–linked locus 1,DFNY1). Eight of the 28 autosomal dominant families were linked to various autosomal loci. In population genetics studies, 2, 567 familial cases and sporadic patients were subjected to mutation screening for three common hearing loss genes:mtDNA 12S rRNA 1555G, GJB2andSLC26A4.The auditory neuropathy cases in our samples were screened forOTOFgene mutations.ConclusionsThese data show that the Chinese population has a genetic load on hereditary hearing loss. Establishing personalized surveillance and prevention models for hearing loss based on genetic research will provide the opportunity to decrease the prevalence of deafness in the Chinese population

Cross-National Differences in Victimization : Disentangling the Impact of Composition and Context

Varying rates of criminal victimization across countries are assumed to be the outcome of countrylevel structural constraints that determine the supply ofmotivated o¡enders, as well as the differential composition within countries of suitable targets and capable guardianship. However, previous empirical tests of these ‘compositional’ and ‘contextual’ explanations of cross-national di¡erences have been performed upon macro-level crime data due to the unavailability of comparable individual-level data across countries. This limitation has had two important consequences for cross-national crime research. First, micro-/meso-level mechanisms underlying cross-national differences cannot be truly inferred from macro-level data. Secondly, the e¡ects of contextual measures (e.g. income inequality) on crime are uncontrolled for compositional heterogeneity. In this paper, these limitations are overcome by analysing individual-level victimization data across 18 countries from the International CrimeVictims Survey. Results from multi-level analyses on theft and violent victimization indicate that the national level of income inequality is positively related to risk, independent of compositional (i.e. micro- and meso-level) di¡erences. Furthermore, crossnational variation in victimization rates is not only shaped by di¡erences in national context, but also by varying composition. More speci¢cally, countries had higher crime rates the more they consisted of urban residents and regions with lowaverage social cohesion.

Screening mutations of OTOF gene in Chinese patients with auditory neuropathy, including a familial case of temperature-sensitive auditory neuropathy

International audienceBackgroundMutations in OTOF gene, encoding otoferlin, cause DFNB9 deafness and non-syndromic auditory neuropathy (AN). The aim of this study is to identify OTOF mutations in Chinese patients with non-syndromic auditory neuropathy.Methods73 unrelated Chinese Han patients with AN, including one case of temperature sensitive non-syndromic auditory neuropathy (TS-NSRAN) and 92 ethnicity-matched controls with normal hearing were screened. Forty-five pairs of PCR primers were designed to amplify all of the exons and their flanking regions of the OTOF gene. The PCR products were sequenced and analyzed for mutation identification.ResultsFive novel possibly pathogenic variants (c.1740delC, c.2975_2978delAG, c.1194T>A, c.1780G>A, c.4819C > T) were identified in the group of 73 AN patients, in which two novel mutant alleles (c.2975_2978delAG + c.4819C > T) were identified in one Chinese TS-NSRAN case. Besides, 10 non-pathogenic variants of the OTOF gene were found in AN patients and controls.ConclusionsScreening revealed that mutations in the OTOF gene account for AN in 4 of 73(5.5%) sporadic AN patients, which shows a lower genetic load of that gene in contrast to the previous studies based on other populations. Notably, we found two novel mutant alleles related to temperature sensitive non-syndromic auditory neuropathy. This mutation screening study further confirms that the OTOF gene contributes to ANs and to TS-NSRAN

ATOMS : ALMA Three-millimeter Observations of Massive Star-forming regions - I. Survey description and a first look at G9.62+0.19

The ATOMS, standing for ALMA Three-millimeter Observations of Massive Star-forming regions, survey has observed 146 active star-forming regions with ALMA band 3, aiming to systematically investigate the spatial distribution of various dense gas tracers in a large sample of Galactic massive clumps, to study the roles of stellar feedback in star formation, and to characterize filamentary structures inside massive clumps. In this work, the observations, data analysis, and example science of the ATOMS survey are presented, using a case study for the G9.62+0.19 complex. Toward this source, some transitions, commonly assumed to trace dense gas, including CS J = 2-1, HCO+ J = 1-0, and HCN J = 1-0, are found to show extended gas emission in low-density regions within the clump; less than 25 per cent of their emission is from dense cores. SO, CH3OH, (HCN)-C-13, and HC3N show similar morphologies in their spatial distributions and reveal well the dense cores. Widespread narrow SiO emission is present (over similar to 1 pc), which may be caused by slow shocks from large-scale colliding flows or HII regions. Stellar feedback from an expanding HII region has greatly reshaped the natal clump, significantly changed the spatial distribution of gas, and may also account for the sequential high-mass star formation in the G9.62+0.19 complex. The ATOMS survey data can be jointly analysed with other survey data, e.g. MALT90, Orion B, EMPIRE, ALMA IMF, and ALMAGAL, to deepen our understandings of 'dense gas' star formation scaling relations and massive protocluster formation.Peer reviewe

ATOMS : ALMA three-millimeter observations of massive star-forming regions - II. Compact objects in ACA observations and star formation scaling relations

We report studies of the relationships between the total bolometric luminosity (L-bol or L-TIR) and the molecular line luminosities of J = 1 - 0 transitions of (HCN)-C-13, (HCO+)-C-13, HCN, and HCO+ with data obtained from ACA observations in the 'ATOMS' survey of 146 active Galactic star-forming regions. The correlations between L-bol and molecular line luminosities L-mol' of the four transitions all appear to be approximately linear. Line emission of isotopologues shows as large scatters in L-bol-L-mol' relations as their main line emission. The log(L-bol/L-mol') for different molecular line tracers have similar distributions. The L-bol-to-L-mol' ratios do not change with galactocentric distances (R-GC) and clump masses (M-clump). The molecular line luminosity ratios (HCN-to-HCO+, (HCN)-C-13-to-(HCO+)-C-13, HCN-to-(HCN)-C-13, and HCO+-to-(HCO+)-C-13) all appear constant against L-bol, dust temperature (T-d), M-clump, and R-GC. Our studies suggest that both the main lines and isotopologue lines are good tracers of the total masses of dense gas in Galactic molecular clumps. The large optical depths of main lines do not affect the interpretation of the slopes in star formation relations. We find that the mean star formation efficiency (SFE) of massive Galactic clumps in the 'ATOMS' survey is reasonably consistent with other measures of the SFE for dense gas, even those using very different tracers or examining very different spatial scales.Peer reviewe

Cutaneous immunoprofiles of three spotted fever group Rickettsia cases

Spotted fever group rickettsia (SFGR) can cause mild to fatal illness. The early interaction between the host and rickettsia in skin is largely unknown, and the pathogenesis of severe rickettsiosis remains an important topic. A surveillance of SFGR infection by PCR of blood and skin biopsy specimens followed by sequencing and immunohistochemical (IHC) detection was performed on patients with a recent tick bite between 2013 and 2016. Humoral and cutaneous immunoprofiles were evaluated in different SFGR cases by serum cytokine and chemokine detection, skin IHC staining, and transcriptome sequencing (RNA-seq). A total of 111 SFGR cases were identified, including 79 “Candidatus Rickettsia tarasevichiae,” 22 Rickettsia raoultii, 8 Rickettsia sibirica, and 2 Rickettsia heilongjiangensis cases. The sensitivity to detect SFGR in skin biopsy specimens (9/24, 37.5%) was significantly higher than that in blood samples (105/2,671, 3.9%) (P 0.05). As early as 1 day after the tick bite, rickettsiae could be detected in the skin. R. sibirica infection was more severe than “Ca. Rickettsia” and R. raoultii infections. Increased levels of serum interleukin-18 (IL- 18), IP10, and monokine induced by gamma interferon (MIG) and decreased levels of IL-2 were observed in febrile patients infected with R. sibirica compared to those infected with “Ca. Rickettsia.” RNA-seq and IHC staining could not discriminate between SFGR-infected and uninfected tick bite skin lesions. However, the type I interferon (IFN) response was differently expressed between R. sibirica and R. raoultii infections at the cutaneous interface. It is concluded that skin biopsy specimens were more reliable for the detection of SFGR infection in human patients although the immunoprofile may be complicated by immunomodulators induced by the tick bite.The Natural Science Foundation of China (81621005 and 81773492) and the State Key Research Development Program of China (2016YFC 1200301).https://iai.asm.orgam2020Veterinary Tropical Disease