Miracle-dz/UniFAR-FTUs huggingface dataset:
Angiotensinogen in hepatocytes contributes to Western diet-induced liver steatosis[S]

Nonalcoholic fatty liver disease (NAFLD) is considered as a liver manifestation of metabolic disorders. Previous studies indicate that the renin-angiotensin system (RAS) plays a complex role in NAFLD. As the only precursor of the RAS, decreased angiotensinogen (AGT) profoundly impacts RAS bioactivity. Here, we investigated the role of hepatocyte-derived AGT in liver steatosis. AGT floxed mice (hepAGT+/+) and hepatocyte-specific AGT-deficient mice (hepAGT−/−) were fed a Western diet and a normal laboratory diet for 12 weeks, respectively. Compared with hepAGT+/+ mice, Western diet-fed hepAGT−/− mice gained less body weight with improved insulin sensitivity. The attenuated severity of liver steatosis in hepAGT−/− mice was evidenced by histologic changes and reduced intrahepatic triglycerides. The abundance of SREBP1 and its downstream molecules, acetyl-CoA carboxylase and FASN, was suppressed in hepAGT−/− mice. Furthermore, serum derived from hepAGT+/+ mice stimulated hepatocyte SREBP1 expression, which could be diminished by protein kinase B (Akt)/mammalian target of rapamycin (mTOR) inhibition in vitro. Administration of losartan did not affect diet-induced body weight gain, liver steatosis severity, and hepatic p-Akt, p-mTOR, and SREBP1 protein abundance in hepAGT+/+ mice. These data suggest that attenuation of Western diet-induced liver steatosis in hepAGT−/− mice is associated with the alternation of the Akt/mTOR/SREBP-1c pathway.
Proteomic analysis of Escherichia coli detergent-resistant membranes (DRM)

Membrane microdomains or lipid rafts compartmentalize cellular processes by laterally organizing membrane components. Such sub-membrane structures were mainly described in eukaryotic cells, but, recently, also in bacteria. Here, the protein content of lipid rafts in Escherichia coli was explored by mass spectrometry analyses of Detergent Resistant Membranes (DRM). We report that at least three of the four E. coli flotillin homologous proteins were found to reside in DRM, along with 77 more proteins. Moreover, the proteomic data were validated by subcellular localization, using immunoblot assays and fluorescence microscopy of selected proteins. Our results confirm the existence of lipid raft-like microdomains in the inner membrane of E. coli and represent the first comprehensive profiling of proteins in these bacterial membrane platforms.
Fetal Congenital Heart Disease Echocardiogram Screening Based on DGACNN: Adversarial One-Class Classification Combined with Video Transfer Learning

Fetal congenital heart disease (FHD) is a common and serious congenital malformation in children. In Asia, FHD birth defect rates have reached as high as 9.3%. For the early detection of birth defects and mortality, echocardiography remains the most effective method for screening fetal heart malformations. However, standard echocardiograms of the fetal heart, especially four-chamber view images, are difficult to obtain. In addition, the pathophysiological changes in fetal hearts during different pregnancy periods lead to ever-changing two-dimensional fetal heart structures and hemodynamics, and it requires extensive professional knowledge to recognize and judge disease development. Thus, research on the automatic screening for FHD is necessary. In this paper, we proposed a new model named DGACNN that shows the best performance in recognizing FHD, achieving a rate of 85%. The motivation for this network is to deal with the problem that there are insufficient training datasets to train a robust model. There are many unlabeled video slices, but they are tough and time-consuming to annotate. Thus, how to use these un-annotated video slices to improve the DGACNN capability for recognizing FHD, in terms of both recognition accuracy and robustness, is very meaningful for FHD screening. The architecture of DGACNN comprises two parts, that is, DANomaly and GACNN (Wgan-GP and CNN). DANomaly, similar to the ALOCC network, but incorporates cycle adversarial learning to train an end-to-end one-class classification (OCC) network that is more robust and has a higher accuracy than ALOCC in screening video slices. For the GACNN architecture, we use FCH (four chamber heart) video slices at around the end-systole, as screened by DANomaly, to train a WGAN-GP for the purpose of obtaining ideal low-level features that can robustly improve the FHD recognition accuracy. A few annotated video slices, as screened by DANomaly, can also be used for data augmentation so as to improve the FHD recognition further. The experiments show that the DGACNN outperforms other state-of-the-art networks by 1%–20% in recognizing FHD. A comparison experiment shows that the proposed network already outperforms the performance of expert cardiologists in recognizing FHD, reaching 84% in a test. Thus, the proposed architecture has high potential for helping cardiologists complete early FHD screenings.
Agrobacteria reprogram virulence gene expression by controlled release of host-conjugated signals

Significance Bacterial infection has been extensively investigated; however, little is known about how bacterial pathogens timely shut down infecting machinery after successful infections. Here, a previously unknown sucrose–SghR/SghA–SAG–SA signaling axis was identified which controls the timing to shut off bacterial virulence expression and fine-tune host immune response. Sucrose, salicylic acid (SA), and its storage form SAG are small chemicals produced in plants whereas SghR is a bacterial sensor of sucrose and SghA is a bacterial enzyme that releases SA from SAG. Given that SA is an imperative signaling molecule in defense against a variety of microbial pathogens, these results depict a previously unknown 2-way chemical signaling cross-talk during microbe–host coevolution and shed mechanistic insights into host–bacteria interaction. It is highly intriguing how bacterial pathogens can quickly shut down energy-costly infection machinery once successful infection is established. This study depicts that mutation of repressor SghR increases the expression of hydrolase SghA in Agrobacterium tumefaciens, which releases plant defense signal salicylic acid (SA) from its storage form SA β-glucoside (SAG). Addition of SA substantially reduces gene expression of bacterial virulence. Bacterial vir genes and sghA are differentially transcribed at early and later infection stages, respectively. Plant metabolite sucrose is a signal ligand that inactivates SghR and consequently induces sghA expression. Disruption of sghA leads to increased vir expression in planta and enhances tumor formation whereas mutation of sghR decreases vir expression and tumor formation. These results depict a remarkable mechanism by which A. tumefaciens taps on the reserved pool of plant signal SA to reprogram its virulence upon establishment of infection.
Enterococcus faecalis exploits the human fibrinolytic system to drive excess collagenolysis: implications in gut healing and identification of druggable targets.

Perforations, anastomotic leak and subsequent intraabdominal sepsis are among the most common and feared complications of invasive interventions in the colon and remaining intestinal tract. During physiologic healing, tissue protease activity is finely orchestrated to maintain the strength and integrity of the submucosa collagen layer in the wound. We have previously demonstrated in both mice and humans that the commensal microbe Enterococcus faecalis selectively colonizes wounded colonic tissues and disrupts the healing process by amplifying collagenolytic matrix-metalloprotease activity toward excessive degradation. Here we demonstrate for the first time a novel collagenolytic virulence mechanism by which E. faecalis is able to bind and locally activate the human fibrinolytic protease plasminogen (PLG), a protein present in high concentrations in healing colonic tissue. E. faecalis-mediated PLG activation leads to supraphysiologic collagen degradation; in this study, we demonstrate this concept both in vitro and in vivo. This pathoadaptive response can be mitigated with the PLG inhibitor tranexamic acid (TXA) in a fashion that prevented clinically significant complications in validated murine models of both E. faecalis- and P. aeruginosa mediated colonic perforation. TXA has a proven clinical safety record and is FDA approved for topical application in invasive procedures, albeit for the prevention of bleeding rather than infection. As such, the novel pharmacologic effect described in this study may be translatable to clinical trials for the prevention of infectious complications of colonic healing.
Spike Counts Based Low Complexity SNN Architecture With Binary Synapse

In this paper, we present an energy and area efficient spike neural network (SNN) processor based on novel spike counts based methods. For the low cost SNN design, we propose hardware-friendly complexity reduction techniques for both of learning and inferencing modes of operations. First, for the unsupervised learning process, we propose a spike counts based learning method. The novel learning approach utilizes pre- and post-synaptic spike counts to reduce the bit-width of synaptic weights as well as the number of weight updates. For the energy efficient inferencing operations, we propose an accumulation based computing scheme, where the number of input spikes for each input axon is accumulated without instant membrane updates until the pre-defined number of spikes are reached. In addition, the computation skip schemes identify meaningless computations and skip them to improve energy efficiency. Based on the proposed low complexity design techniques, we design and implement the SNN processor using 65 nm CMOS process. According to the implementation results, the SNN processor achieves 87.4% of recognition accuracy in MNIST dataset using only 1-bit 230 k synaptic weights with 400 excitatory neurons. The energy consumptions are 0.26 pJ/SOP and 0.31 μJ/inference in inferencing mode, and 1.42 pJ/SOP and 2.63 μJ/learning in learning mode of operations.
Cyclometalated Ir-Zr-MOFs as Recyclable Visible-Light Photocatalysts for Sulfide Oxidation into Sulfoxide in Water.

Aerobic photo-oxidation of sulfide into sulfoxide in water is of great interest in synthesis chemistry. In this study, three high stable Ir(III)-Zr(IV) metal-organic frameworks (Ir-Zr-MOFs), namely Zr6-Irbpy (bpy is 2,2'-bipyridine), Zr6-IrbpyOMe (bpyOMe is 4,4'-dimethoxy-2,2'-bipyridine), and Zr6-Irphen (phen is 1,10-phenanthroline), are constructed by using [Ir(pqc)2(L)2]Cl complexes (where pqc is 2-phenylquinoline-4-carboxylic acid, L is an ancillary ligand bpy, bpyOMe or phen) as linkers and Zr6 cluster as nodes. The constructed Ir-Zr-MOFs present high catalytic activity on aerobic photo-oxidation of sulfide into sulfoxide under visible light irradiation in water at room temperature. Moreover, the reaction is high chemoselectivity and functional group tolerance. The catalyst can be readily recycled and reused at least ten times without loss of catalytic activity. Mechanism studies demonstrate that superoxide radical is the reactive oxygen species in the sulfoxidation, which is generated by electron transfer from the excited triplet photosensitizer 3[Ir-Zr-MOF]* to O2. The high activity of photocatalytic sulfoxidation in water may be attributed to the sta-bilization of the persulfoxide intermediate by hydrogen bonds formation with water solvent, which accelerates the conversion of persulfoxide into sulfoxide and prevents further oxidation of sulfoxide into sulfone. This work provides a new strategy for green synthesis of sulfoxides using MOF as photosensitizer under ambient conditions.
Prevalence and factors associated with frailty among community-dwelling older people in rural Thanjavur district of South India: a cross-sectional study

Objective There is sparse data on the prevalence of frailty from rural parts of India. Our aim was to estimate prevalence of frailty among community-dwelling older people in rural South Indian population and explore socio-demographic factors associated with frailty. We further explored the associations between frailty with fear of falling and falls. Design Community based cross-sectional study. Setting Four villages in Thanjavur district of Southern India. Participants Random sample of adults aged 60 years and above from four villages. Methods We sampled community-dwelling older adults from the electoral list of four villages using stratified random sampling. We report prevalence of frailty as defined by physical definition (Fried’s Phenotype), accumulation of deficits (Frailty Index) and multi-domain definition (Tilburg Frailty Indicator). We report proportion of agreement of frailty status between the frailty tools. We used logistic regressions with robust SEs to examine the associations between socio-demographic determinants with frailty and the association between frailty with fear of falling and falls. Results Among the 408 participants, the weighted (non-response and poststratification for sex) prevalence and 95% CI of frailty was 28% (18.9 to 28.1) for physical definition, 59% (53.9 to 64.3) for accumulation of deficits and 63% (57.4 to 67.6) for multi-domain definition. Frailty Index and Tilburg Frailty Indicator had good agreement (80%). Age, female, lower education, lower socioeconomic status, minimum physical activity in routine work were independently associated with frailty irrespective of the frailty definitions. Frail elderly had higher odds of falls as well as fear of falling compared with non-frail, irrespective of the definitions. Conclusion Prevalence of frailty among older people in rural Thanjavur district of South India was high compared with low-income and middle-income countries. Understanding the modifiable determinants of frailty can provide a valuable reference for future prevention and intervention.
Age-Standardized Mortality of Persons on Probation, in Jail, or in State Prison and the General Population, 2001-2012

Objectives: The number of adults in the United States being held on probation—persons convicted of crimes and serving their sentence in the community rather than in a correctional facility—approached 4 million at the end of 2016 and continues to grow, yet little is known about the health and well-being of this population. We compared the standardized mortality ratios of persons on probation in the United States with persons in jail, persons in state prison, and the general US population. Methods: We used administrative data from 2001-2012 from the Bureau of Justice Statistics and the Centers for Disease Control and Prevention WONDER database and indirect standardization techniques to compare the mortality rates of persons on probation in 15 states with the mortality rates of persons in jail, persons in state prison, and the general US population. We applied the age-specific mortality rates of 3 populations (general US population, persons in jail, and persons in state prison) to the age distribution of persons on probation to estimate standardized mortality ratios. Results: Persons on probation died at a rate 3.42 times higher than persons in jail, 2.81 times higher than persons in state prison, and 2.10 times higher than the general US population, after standardizing the age distribution of persons on probation relative to the other 3 groups. Conclusions: Public health interventions should target persons on probation, who have received less attention from the public health community than persons serving sentences in jails and prisons.
Does Drinking Together Promote Relationship Intimacy? Temporal Effects of Daily Drinking Events.

OBJECTIVE Although research has documented harms associated with drinking within intimate relationships, there is evidence that some drinking patterns-characterized by congruent or shared partner drinking-may be associated with positive relationship functioning. The present dyadic daily diary study allowed us to consider whether congruent drinking events and drinking with partner increase the likelihood of experiencing intimacy with one's partner within the next few hours. METHOD Within a sample of 119 community couples in which both partners drank regularly, we studied the temporal relationship between drinking events and intimacy experiences using 56 days of daily reports. To ensure that the pattern of results was robust, we tested the effects of congruent versus noncongruent drinking events using different characterizations. RESULTS Drinking episodes involving simultaneous drinking by both partners (but not solo drinking) increased the likelihood of intimacy in the next few hours. Similarly, drinking episodes in which partner was present (but not episodes when partner was absent) and drinking episodes that took place at home (but not away from home) increased the likelihood of intimacy. CONCLUSIONS Results provide the first evidence that some types of drinking events contribute to the occurrence of couple intimacy experiences within the next few hours and help to explain previously observed long-term effects of congruent drinking patterns on couple functioning.
Assessment of cerebral low-frequency oscillations in patients with retinal vein occlusion: a preliminary functional MRI study

Background There is increasing evidence that patients with retinal vein occlusion exhibit cerebral vascular changes and are at an increased risk of stroke. However, it remains unknown whether patients with retinal vein occlusion exhibit changes in intrinsic brain activity. Purpose This study investigated intrinsic brain activity changes in patients with retinal vein occlusion by assessing the amplitude of low-frequency fluctuations. Material and Methods Forty-five patients with retinal vein occlusion (22 men, 23 women, mean age 56.55 ± 6.97 years) and 43 healthy controls (13 men, 30 women; mean age 53.53 ± 8.19 years) closely matched in age, sex, and education level underwent resting-state MRI scans. The amplitude of low-frequency fluctuation method was used to compare intrinsic brain activity between the two groups. Results Compared with healthy controls, patients with retinal vein occlusion exhibited significantly lower amplitude of low-frequency fluctuation values in the left middle occipital gyrus, right middle occipital gyrus, and right calcarine. However, patients with retinal vein occlusion showed significantly higher amplitude of low-frequency fluctuations in the bilateral cerebellum 6, right hippocampus, left insula, and left fusiform (voxel-level P < 0.01, Gaussian random field correction, cluster-level P < 0.05). Conclusion Our results demonstrated that patients with retinal vein occlusion showed abnormal spontaneous neural activities in the visual cortices, cerebellum, and Papez circuit, which might indicate impaired vision, cognition, and emotional function in patients with retinal vein occlusion. These findings offer important insights into the neural mechanism of retinal vein occlusion.
Psychological Resilience in the Context of Disability: A Study With Turkish and Moroccan Young-Old Immigrants Living in the Netherlands.

BACKGROUND AND OBJECTIVES The disability paradox postulates that some individuals with severe functional limitations demonstrate psychological resilience, that is, good mental health and quality of life. Resilience to disabilities has been linked to psychological (e.g., mastery) and social factors (e.g., social provisions). It is, however, less clear whether cultural factors can provide additional resources for resilience building in older immigrants. We investigated the extent to which sociodemographic, psychosocial, and cultural factors contributed to psychological resilience to disabilities among immigrants of Turkish and Moroccan descent in the Netherlands. RESEARCH DESIGN AND METHOD The sample included 478 older immigrants aged 55-65 years. Data were analyzed using latent profile analysis and multinomial logistic regressions. RESULTS Five categories were identified: (a) High physical and emotional functioning; (b) High physical but poor emotional functioning; (c) Low physical but high emotional functioning (resilient); (d) Low physical and emotional functioning; and (e) Low physical and very low emotional functioning. Resilient functioning (reference category) was associated with poorer Dutch language proficiency, lower levels of loneliness, greater mastery, and more religious coping. DISCUSSION AND IMPLICATIONS Findings provide support for the disability paradox and highlight social provisions, mastery, and religiosity/spirituality as important resources for psychological resilience in older labor migrants. Poor Dutch language proficiency is discussed as a potential factor contributing to severe functional limitations in the resilient category.
The E3 ubiquitin ligase Pib1 regulates effective gluconeogenic shutdown upon glucose availability

Cells use multiple mechanisms to regulate their metabolic states in response to changes in their nutrient environment. One example is the response of cells to glucose. In Saccharomyces cerevisiae growing in glucose-depleted medium, the re-availability of glucose leads to the down-regulation of gluconeogenesis and the activation of glycolysis, leading to “glucose repression. ” However, our knowledge of the mechanisms mediating the glucose-dependent down-regulation of the gluconeogenic transcription factors is limited. Using the major gluconeogenic transcription factor Rds2 as a candidate, we identify here a novel role for the E3 ubiquitin ligase Pib1 in regulating the stability and degradation of Rds2. Glucose addition to cells growing under glucose limitation results in a rapid ubiquitination of Rds2, followed by its proteasomal degradation. Through in vivo and in vitro experiments, we establish Pib1 as the ubiquitin E3 ligase that regulates Rds2 ubiquitination and stability. Notably, this Pib1-mediated Rds2 ubiquitination, followed by proteasomal degradation, is specific to the presence of glucose. This Pib1-mediated ubiquitination of Rds2 depends on the phosphorylation state of Rds2, suggesting a cross-talk between ubiquitination and phosphorylation to achieve a metabolic state change. Using stable isotope-based metabolic flux experiments, we find that the loss of Pib1 results in an imbalanced gluconeogenic state, regardless of glucose availability. Pib1 is required for complete glucose repression and enables cells to optimally grow in competitive environments when glucose again becomes available. Our results reveal the existence of a Pib1-mediated regulatory program that mediates glucose repression when glucose availability is restored.