Transcriptional regulation of SARS-CoV-2 receptor ACE2 by SP1.

Angiotensin-converting enzyme 2 (ACE2) is a major cell entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The induction of ACE2 expression may serve as a strategy by SARS-CoV-2 to facilitate its propagation. However, the regulatory mechanisms of ACE2 expression after viral infection remain largely unknown. Using 45 different luciferase reporters, the transcription factors SP1 and HNF4α were found to positively and negatively regulate ACE2 expression, respectively, at the transcriptional level in human lung epithelial cells (HPAEpiCs). SARS-CoV-2 infection increased the transcriptional activity of SP1 while inhibiting that of HNF4α. The PI3K/AKT signaling pathway, activated by SARS-CoV-2 infection, served as a crucial regulatory node, inducing ACE2 expression by enhancing SP1 phosphorylation-a marker of its activity-and reducing the nuclear localization of HNF4α. However, colchicine treatment inhibited the PI3K/AKT signaling pathway, thereby suppressing ACE2 expression. In Syrian hamsters (Mesocricetus auratus) infected with SARS-CoV-2, inhibition of SP1 by either mithramycin A or colchicine resulted in reduced viral replication and tissue injury. In summary, our study uncovers a novel function of SP1 in the regulation of ACE2 expression and identifies SP1 as a potential target to reduce SARS-CoV-2 infection.

Single-Molecule Protein Analysis by Centrifugal Droplet Immuno-PCR with Magnetic Nanoparticles.

Detecting proteins in ultralow concentrations in complex media is important for many applications but often relies on complicated techniques. Herein, a single-molecule protein analyzer with the potential for high-throughput applications is reported. Gold-coated magnetic nanoparticles with DNA-labeled antibodies were used for target recognition and separation. The immunocomplex was loaded into microdroplets generated with centrifugation. Immuno-PCR amplification of the DNA enabled the quantification of proteins at the level of single molecules. As an example, ultrasensitive detection of α-synuclein, a biomarker for neurodegenerative diseases, is achieved. The limit of detection was determined to be ∼50 aM in buffer and ∼170 aM in serum. The method exhibited high specificity and could be used to analyze post-translational modifications such as protein phosphorylation. This study will inspire wider studies on single-molecule protein detection, especially in disease diagnostics, biomarker discovery, and drug development.

Indole produced during dysbiosis mediates host-microorganism chemical communication.

An imbalance of the gut microbiota, termed dysbiosis, has a substantial impact on host physiology. However, the mechanism by which host deals with gut dysbiosis to maintain fitness remains largely unknown. In Caenorhabditis elegans, Escherichia coli, which is its bacterial diet, proliferates in its intestinal lumen during aging. Here, we demonstrate that progressive intestinal proliferation of E. coli activates the transcription factor DAF-16, which is required for maintenance of longevity and organismal fitness in worms with age. DAF-16 up-regulates two lysozymes lys-7 and lys-8, thus limiting the bacterial accumulation in the gut of worms during aging. During dysbiosis, the levels of indole produced by E. coli are increased in worms. Indole is involved in the activation of DAF-16 by TRPA-1 in neurons of worms. Our finding demonstrates that indole functions as a microbial signal of gut dysbiosis to promote fitness of the host.

Dirac semimetal-assisted near-field radiative thermal rectifier and thermostat based on phase transition of vanadium dioxide.

The near-field thermal radiation has broad application prospects in micro-nano-scale thermal management technology. In this paper, we report the Dirac semimetal-assisted (AlCuFe quasicrystal) near-field radiative thermal rectifier (DSTR) and thermostat (DST), respectively. The DSTR is made of a Dirac semimetal-covered vanadium dioxide (VO2) plate and silicon dioxide (SiO2) plate separated by a vacuum gap. The left and right sides of DST are consisted of the SiO2 covered with Dirac semimetal, and the intermediate plate is the VO2. The strong coupling of the surface electromagnetic modes between the Dirac semimetal, SiO2, and insulating VO2 leads to enhance near-field radiative transfer. In the DSTR, the net radiative heat flux of VO2 in the insulating state is much larger than that in metallic state. When the vacuum gap distance d=100 nm, Fermi level EF=0.20 eV, and film thickness t=12 nm, the global rectification factor of DSTR is 3.5, which is 50% higher than that of structure without Dirac semimetal. In the DST, the equilibrium temperature of the VO2 can be controlled accurately to achieve the switching between the metallic and insulating state of VO2. When the vacuum gap distance d=60 nm, intermediate plate thickness δ=30 nm, and film thickness t=2 nm, with the modulation of Fermi level between 0.05-0.15 eV, the equilibrium temperature of VO2 can be controlled between 325-371 K. In brief, when the crystalline state of VO2 changes between the insulating and metallic state with temperature, the active regulation of near-field thermal radiation can be realized in both two-body and three-body parallel plate structure. This work will pave a way to further improve performance of near-field radiative thermal management and modulation.

Fenofibrate improves hepatic steatosis, insulin resistance, and shapes the gut microbiome via TFEB-autophagy in NAFLD mice.

Non-alcoholic fatty liver disease (NAFLD) is a major liver disease subtype worldwide, is commonly associated with insulin resistance and obesity. NAFLD is characterized by an excessive hepatic lipid accumulation, as well as hepatic steatosis. Fenofibrate is a peroxisome proliferator-activated receptor α agonist widely used in clinical therapy to effectively ameliorate the development of NAFLD, but its mechanism of action is incompletely understood. Here, we found that fenofibrate dramatically modulate the gut microbiota composition of high-fat diet (HFD)-induced NAFLD mouse model, and the change of gut microbiota composition is dependent on TFEB-autophagy axis. Furthermore, we also found that fenofibrate improved hepatic steatosis, and increased the activation of TFEB, which severed as a regulator of autophagy, thus, the protective effects of fenofibrate against NAFLD are depended on TFEB-autophagy axis. Our study demonstrates the host gene may influence the gut microbiota and highlights the role of TFEB and autophagy in the protective effect of NAFLD. This work expands our understanding of the regulatory interactions between the host and gut microbiota and provides novel strategies for alleviating obesity.

Ethanol mediates the interaction between Caenorhabditis elegans and the nematophagous fungus Purpureocillium lavendulum.

Accurately recognizing pathogens by the host is vital for initiating appropriate immune response against infecting microorganisms. Caenorhabditis elegans has no known receptor to recognize pathogen-associated molecular pattern. However, recent studies showed that nematodes have a strong specificity for transcriptomes infected by different pathogens, indicating that they can identify different pathogenic microorganisms. However, the mechanism(s) for such specificity remains largely unknown. In this study, we showed that the nematophagous fungus Purpureocillium lavendulum can infect the intestinal tract of the nematode C. elegans and the infection led to the accumulation of reactive oxygen species (ROS) in the infected intestinal tract, which suppressed fungal growth. Co-transcriptional analysis revealed that fungal genes related to anaerobic respiration and ethanol production were up-regulated during infection. Meanwhile, the ethanol dehydrogenase Sodh-1 in C. elegans was also up-regulated. Together, these results suggested that the infecting fungi encounter hypoxia stress in the nematode gut and that ethanol may play a role in the host-pathogen interaction. Ethanol production in vitro during fungal cultivation in hypoxia conditions was confirmed by gas chromatography-mass spectrometry. Direct treatment of C. elegans with ethanol elevated the sodh-1 expression and ROS accumulation while repressing a series of immunity genes that were also repressed during fungal infection. Mutation of sodh-1 in C. elegans blocked ROS accumulation and increased the nematode's susceptibility to fungal infection. Our study revealed a new recognition and antifungal mechanism in C. elegans. The novel mechanism of ethanol-mediated interaction between the fungus and nematode provides new insights into fungal pathogenesis and for developing alternative biocontrol of pathogenic nematodes by nematophagous fungi. IMPORTANCE Nematodes are among the most abundant animals on our planet. Many of them are parasites in animals and plants and cause human and animal health problems as well as agricultural losses. Studying the interaction of nematodes and their microbial pathogens is of great importance for the biocontrol of animal and plant parasitic nematodes. In this study, we found that the model nematode Caenorhabditis elegans can recognize its fungal pathogen, the nematophagous fungus Purpureocillium lavendulum, through fungal-produced ethanol. Then the nematode elevated the reactive oxygen species production in the gut to inhibit fungal growth in an ethanol dehydrogenase-dependent manner. With this mechanism, novel biocontrol strategies may be developed targeting the ethanol receptor or metabolic pathway of nematodes. Meanwhile, as a volatile organic compound, ethanol should be taken seriously as a vector molecule in the microbial-host interaction in nature.

TRNSYS simulation study of the operational energy characteristics of a hot water supply system for the integrated design of solar coupled air source heat pumps.

To address the issues with solar water heating systems taking up a lot of space, unstable hot water supply, air source heat pumps susceptible to frost in the winter, and low energy efficiency. The TRNSYS tool is employed in this work to simulate a solar-coupled air source heat pump system. The heat pump operation is first investigated using the inverse Carnot cycle. The performance coefficient is then calculated by the second law of thermodynamics without considering the pipeline's pressure drop and heat loss. The output temperature of the hot water that the heat pump circulates is then determined. The daily hot water needs can be estimated roughly based on information about solar radiation. The heat balance equation for flat plate solar collectors was used to compute the intensity of solar diffused radiation. The Berlage calculation was used to determine the solar radiation received on the collector's surface. After a qualitative analysis of the heat from the heat source, the efficiency of the linked heat pump and the conventional air source heat pump was compared. Analyzing the water temperature change graph for each month's data reveals that the system can achieve 50 °C during the water supply time each month. The heat pump's annual energy consumption is 6252.01 kWh, while the system's annual energy consumption is 9100.47 kWh. The study findings may be used as a guide to improving the design and management of the whole system. In addition, they may improve the solar water supply system's performance.

Mapping intellectual structure and research hotspots in the field of fibroblast-associated DFUs: a bibliometric analysis.

Background: Diabetic foot ulcers (DFUs) are one of the most popular and severe complications of diabetes. The persistent non-healing of DFUs may eventually contribute to severe complications such as amputation, which presents patients with significant physical and psychological challenges. Fibroblasts are critical cells in wound healing and perform essential roles in all phases of wound healing. In diabetic foot patients, the disruption of fibroblast function exacerbates the non-healing of the wound. This study aimed to summarize the hotspots and evaluate the global research trends on fibroblast-related DFUs through bibliometric analysis. Methods: Scientific publications on the study of fibroblast-related DFUs from January 1, 2000 to April 27, 2022 were retrieved from the Web of Science Core Collection (WoSCC). Biblioshiny software was primarily performed for the visual analysis of the literature, CiteSpace software and VOSviewer software were used to validate the results. Results: A total of 479 articles on fibroblast-related DFUs were retrieved. The most published countries, institutions, journals, and authors in this field were the USA, The Chinese University of Hong Kong, Wound Repair and Regeneration, and Seung-Kyu Han. In addition, keyword co-occurrence networks, historical direct citation networks, thematic map, and the trend topics map summarize the research hotspots and trends in this field. Conclusion: Current studies indicated that research on fibroblast-related DFUs is attracting increasing concern and have clinical implications. The cellular and molecular mechanisms of the DFU pathophysiological process, the molecular mechanisms and therapeutic targets associated with DFUs angiogenesis, and the measures to promote DFUs wound healing are three worthy research hotspots in this field.

Gut microbiome determines therapeutic effects of OCA on NAFLD by modulating bile acid metabolism.

Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease, had no approved pharmacological agents yet. Obeticholic acid (OCA), a novel bile acid derivative, was demonstrated to ameliorate NAFLD-related manifestations. Regarding the role of gut-liver axis in liver disease development, this study aimed to explore the potential role of gut microbiota in the treatment of OCA in NAFLD mice induced by the high-fat diet (HFD). Antibiotic-induced microbiome depletion (AIMD) and fecal microbiota transplantation (FMT) confirmed the critical role of gut microbiota in OCA treatment for NAFLD by effectively alleviating histopathological lesions and restoring liver function impaired by HFD. Metagenomic analysis indicated that OCA intervention in HFD mice remarkably increased the abundance of Akkermansia muciniphila, Bifidobacterium spp., Bacteroides spp., Alistipes spp., Lactobacillus spp., Streptococcus thermophilus, and Parasutterella excrementihominis. Targeted metabolomics analysis indicated that OCA could modulate host bile acids pool by reducing levels of serum hydrophobic cholic acid (CA) and chenodeoxycholic acid (CDCA), and increasing levels of serum-conjugated bile acids, such as taurodeoxycholic acid (TDCA) and tauroursodesoxycholic acid (TUDCA) in the HFD-fed mice. Strong correlations were observed between differentially abundant microbes and the shifted bile acids. Furthermore, bacteria enriched by OCA intervention exhibited much greater potential in encoding 7alpha-hydroxysteroid dehydrogenase (7α-HSDs) producing secondary bile acids rather than bile salt hydrolases (BSHs) mainly responsible for primary bile acid deconjugation. In conclusion, this study demonstrated that OCA intervention altered gut microbiota composition with specially enriched gut microbes modulating host bile acids, thus effectively alleviating NAFLD in the mice.

Physical exercise attenuates age-related muscle atrophy and exhibits anti-ageing effects via the adiponectin receptor 1 signalling.

BACKGROUND: Although the adiponectin signalling exerts exercise-mimicking effects, whether this pathway contributes to the anti-ageing benefits of physical exercise has not been established yet. METHODS: Swim exercise training and wheel running were used to measure lifespan in the nematode Caenorhabditis elegans and skeletal muscle quality in mice, respectively. Muscle weight, muscle fibre cross-sectional area (CSA) and myonuclei number were used to evaluate muscle mass. RNA sequencing (RNA-Seq) analysis of skeletal muscle in exercised mice was used to study the underlying mechanisms. Western blot and immunofluorescence were performed to explore autophagy- and senescence-related markers. RESULTS: The C. elegans adiponectin receptor PAQR-1/AdipoR1, but not PAQR-2/AdipoR2, was activated (3.55-fold and 3.48-fold increases in p-AMPK on Days 1 and 6, respectively, P < 0.001), which was involved in lifespan extension in exercised worms. Exercise training increased skeletal muscle mass index (1.29-fold, P < 0.01), muscle weight (1.75-fold, P < 0.001), myonuclei number (1.33-fold, P < 0.05), muscle fibre CSA (1.39-fold, P < 0.05) and capillary abundance (2.19-fold, P < 0.001 for capillary density; 1.58-fold, P < 0.01 for capillary number) in aged mice. Physical exercise reduced protein (2.94-fold, P < 0.001) and mRNA levels (1.70-fold, P < 0.001) of p16INK4a , a marker for cellular senescence, in skeletal muscle of aged mice. These beneficial effects of exercise on skeletal muscle of mice were dependent on AdipoR1. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis for differentially expressed genes in skeletal muscle between exercised mice with and without AdipoR1 knockdown by RNA-Seq analysis revealed that several KEGG pathways, such as 'AMPK signalling pathway' (P < 0.001), 'FOXO signalling pathway' (P < 0.001) and 'autophagy' (P < 0.001) were overrepresented. Knockdown of FoxO3a inhibited exercise-mediated beneficial effects on skeletal muscle quality of mice by inhibiting autophagy/mitophagy (3.81-fold reduction in LC3-II protein, P < 0.001; 1.53-fold reduction in BNIP3 protein, P < 0.05). Knockdown of daf-16, the FoxO homologue in C. elegans, reduced autophagy (2.77-fold and 2.06-fold reduction in GFP::LGG-1 puncta in seam cells and the intestine, respectively, P < 0.05) and blocked lifespan extension by exercise in worms. CONCLUSIONS: Our findings provide insights into how the AdipoR1 pathway has an impact on the anti-ageing benefits of exercise and implicate that activation of the AdipoR1 signalling may represent a potential therapeutic strategy for reducing age-related loss of skeletal muscle.

Model of collective detachment in high-grade serous ovarian cancer demonstrates that tumor spheroids produce ECM to support metastatic processes.

High-grade serous ovarian cancer (HGSOC) metastasizes through transcoelomic spread, with both single cells and spheroids of tumor cells observed in patient ascites. These spheroids may form through single cells that detach and aggregate (Sph-SC) or through collective detachment (Sph-CD). We developed an in vitro model to generate and separate Sph-SC from Sph-CD to enable study of Sph-CD in disease progression. In vitro-generated Sph-CD and spheroids isolated from ascites were similar in size (mean diameter 51 vs 55 µm, p > 0.05) and incorporated multiple ECM proteins. Using the in vitro model, nascent protein labeling, and qRT-PCR, we determined that ECM was produced after detachment. As fibronectin plays a key role in many cell adhesion events, we confirmed that inhibiting RGD-based adhesion or fibronectin assembly reduced Sph-CD-mesothelial adhesion strength under shear stress. Our model will enable future studies to determine factors that favor formation of Sph-CD, as well as allow investigators to manipulate Sph-CD to better study their effects on HGSOC progression.

Vitellogenin accumulation leads to reproductive senescence by impairing lysosomal function.

The maintenance of proteostasis is essential for cellular and organism healthspan. How proteostasis collapse influences reproductive span remains largely unclear. In Caenorhabditis elegans, excess accumulation of vitellogenins, the major components in yolk proteins, is crucial for the development of the embryo and occurs throughout the whole body during the aging process. Here, we show that vitellogenin accumulation leads to reproduction cessation. Excess vitellogenin is accumulated in the intestine and transported into the germline, impairing lysosomal activity in these tissues. The lysosomal function in the germline is required for reproductive span by maintaining oocyte quality. In contrast, autophagy and sperm depletion are not involved in vitellogenin accumulation-induced reproductive aging. Our findings provide insights into how proteome imbalance has an impact on reproductive aging and imply that improvement of lysosomal function is an effective approach for mid-life intervention for maintaining reproductive health in mammals.

The metabolite alpha-ketobutyrate extends lifespan by promoting peroxisomal function in C. elegans.

Metabolism is intimately linked to aging. There is a growing number of studies showing that endogenous metabolites may delay aging and improve healthspan. Through the analysis of existing transcriptome data, we discover a link between activation of the transsulfuration pathway and a transcriptional program involved in peroxisome function and biogenesis in long-lived glp-1(e2141ts) mutant Caenorhabditis elegans worms. Subsequently, we show that supplementation with α-ketobutyrate, an intermediate of the transsulfuration pathway, extends lifespan in wild-type worms. Alpha-ketobutyrate augments the production of NAD+ via the lactate dehydrogenase LDH-1, leading to SIR-2.1/SIRT1-mediated enhanced peroxisome function and biogenesis, along with a concomitant increase in the expression of acox-1.2/ACOX1 in the peroxisomal fatty acid ß-oxidation pathway. ACOX-1.2/ACOX1 promotes H2O2 formation, thereby resulting in activation of SKN-1/NRF2. This transcription factor in turn extends the lifespan of worms by driving expression of autophagic and lysosomal genes. Finally, we show that α-ketobutyrate also delays the cellular senescence in fibroblast cells through the SIRT1-ACOX1-H2O2-NRF2 pathway. This finding uncovers a previously unknown role for α-ketobutyrate in organismal lifespan and healthspan by coordinating the NAD+-SIRT1 signaling and peroxisomal function.

The EGL-30 pathway regulates experience-dependent aversive behavior of Caenorhabditis elegans to the pathogenic bacterium Pseudomonas aeruginosa.

Avoidance of harmful substances is survival strategy used cross invertebrates and vertebrates. For example, the nematode Caenorhabditis elegans evolves a sufficient avoidance response to pathogenic bacteria. Despite G protein has been found to exert neural plasticity for avoidance behaviours in C. elegans, the function of Gi/o and Gq subunit signalling in experience-dependent aversive behaviour remains unclear. In this study, we show that EGL-30/Gq coupled with EGL-8/UNC-13 regulates aversive behaviour of C. elegans to pathogenic bacterium Pseudomonas aeruginosa PA01 via acetylcholine and its receptor nAChR. Pyocyanin, a toxin secreted from P. aeruginosa, acts as a signal molecule to trigger aversive behaviour. ODR-3 and ODR-7 in AWA and AWC neurons function as upstream of EGL-30 to induce experience-dependent aversive behaviour to P. aeruginosa, respectively. These results suggested that a novel signalling pathway to regulate a behavioural response.

Influence of combined exposure levels of total arsenic and inorganic arsenic on arsenic methylation capacity among university students: findings from Bayesian kernel machine regression analysis.

The arsenic (As) methylation capacity is an important determinant of susceptibility to As-related diseases. Total As (TAs) or inorganic As (iAs) was reported to associated with As methylation capacity. We measured urinary concentrations of iAs, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) by using HPLC-HG-AFS and calculated the primary methylation capacity index (PMI) and secondary methylation capacity index (SMI) in 209 university students in Hefei, China, a non-As endemic area. Volunteers were given a standardized questionnaire asking about their sociodemographic characteristics. Bayesian kernel machine regression (BKMR) analysis was used to estimate the association of lnTAs and lniAs levels with methylation indices (ln%MMA, ln%DMA, lnPMI, lnSMI). The median concentrations of iAs, MMA, and DMA were 1.22, 0.92, and 12.17 µg/L, respectively; the proportions of iAs, MMA, and DMA were 8.76%, 6.13%, and 84.84%, respectively. Females had higher %DMA and lower %MMA than males. The combined levels of lnTAs and lniAs showed a decrease in the changes in ln%DMA and lnSMI. With regard to the single exposure level, the lnTAs showed positive correlations with ln%DMA, lnPMI, and lnSMI when lniAs was set at a specific level, while lniAs showed negative correlations with ln%DMA, lnPMI, and lnSMI when lnTAs was set at a specific level; all the dose-response relationships were nonlinear. Our results suggested that combined levels of TAs and iAs play an important role in reducing As methylation capacity, especially iAs, and the reduction only occurs when TAs and iAs are present up to a certain combined level.

Metformin Alleviates Hepatic Steatosis and Insulin Resistance in a Mouse Model of High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease by Promoting Transcription Factor EB-Dependent Autophagy.

Nonalcoholic fatty liver disease (NAFLD) results from an abnormal accumulation of lipids within hepatocytes, and is commonly associated with obesity, insulin resistance, and hyperlipidemia. Metformin is commonly used to treat type 2 diabetes mellitus and, in recent years, it was found to play a potential role in the amelioration of NAFLD. However, the mechanisms underlying the protective effect of metformin against NAFLD remain largely unknown. Transcription factor EB (TFEB) is a master transcriptional regulator of lysosomal biogenesis and autophagy and, when activated, is effective against disorders of lipid metabolism. However, the role of TFEB in hepatic steatosis is not well understood. In this report, we demonstrate that the activity of TFEB is reduced in the liver of mice fed a high-fat diet. Metformin treatment significantly reverses the activity of TFEB, and the protective effect of metformin against hepatic steatosis and insulin resistance is dependent on TFEB. We show that metformin-induced autophagy is regulated by TFEB, and our findings reveal that TFEB acts as a mediator, linking metformin with autophagy to reverse NAFLD, and highlight that TFEB may be a promising molecular target for the treatment of NAFLD.

Metabolic iron detection through divalent metal transporter 1 and ferroportin mediated cocktail fluorogenic probes.

A cocktail [1 + 2] dual-fluorescent probe system was developed to realize the real-time visualization of dynamic iron state changes between Fe2+ and Fe3+ at the cellular level and in multicellular organisms, providing insights into the effect of DMT1 and ferroportin on iron regulation.

Severe undernutrition in children affects tuberculin skin test performance in Southern India.

BACKGROUND: Undernutrition impairs immunity to Mycobacterium tuberculosis and is a risk factor for tuberculosis disease (TB). We aim to investigate if severe undernutrition affects the tuberculin skin test (TST) response among household contacts (HHCs) of pulmonary TB cases. METHODS: We analyzed data from HHCs (> five years) of pulmonary TB cases in Southern India. Undernutrition was defined as per World Health Organization based on body mass index (BMI) for adults (undernutrition 16-18.4 and severe undernutrition <16 kg/m2) and BMI relative to the mean for children (undernutrition 2SD-3SD and severe undernutrition < 3SDs below mean). Univariate and multivariate models of TST positivity (> five mm) were calculated using logistic regression with generalized estimating equations. RESULTS: Among 1189 HHCs, 342 were children (age 5-17 years) and 847 were adults. Prevalence of TST positivity in well-nourished, undernourished and severely undernourished children was 135/251 (53.8%), 32/68 (47.1%), and 7/23 (30.4%) respectively; among adults, prevalence of TST positivity was 304/708 (42.9%), 43/112 (38.4%) and 12/26 (46.2%), respectively. Severe undernutrition in children was associated with decreased odds of TST positivity (adjusted odds ratio 0.3; 95%CI 0.1-0.9). CONCLUSION: Severe undernutrition in children was associated with decreased odds of TST positivity. False-negative TSTs may result from undernutrition; caution is warranted when interpreting negative results in undernourished populations.

Bilayer and three dimensional conductive network composed by SnCl2 reduced rGO with CNTs and GO applied in transparent conductive films.

Graphene oxide (GO), reduced graphene oxide (rGO) and carbon nanotubes (CNTs) have their own advantages in electrical, optical, thermal and mechanical properties. An effective combination of these materials is ideal for preparing transparent conductive films to replace the traditional indium tin oxide films. At present, the preparation conditions of rGO are usually harsh and some of them have toxic effects. In this paper, an SnCl2/ethanol solution was selected as the reductant because it requires mild reaction conditions and no harmful products are produced. The whole process of rGO preparation was convenient, fast and environmentally friendly. Then, SEM, XPS, Raman, and XRD were used to verify the high reduction efficiency. CNTs were introduced to improve the film conductive property. The transmittance and sheet resistance were the criteria used to choose the reduction time and the content ratios of GO/CNT. Thanks to the post-treatment of nitric acid, not only the by-product (SnO2) and dispersant in the film are removed, but also the doping effect occurs, which are all conducive to reducing the sheet resistances of films. Ultimately, by combining rGO, GO and CNTs, transparent conductive films with a bilayer and three-dimensional structure were prepared, and they exhibited high transmittance and low sheet resistance (58.8 Ω/sq. at 83.45 T%, 47.5 Ω/sq. at 79.07 T%), with corresponding [Formula: see text] values of 33.8 and 31.8, respectively. In addition, GO and rGO can modify the surface and reduce the film surface roughness. The transparent conductive films are expected to be used in photoelectric devices.

TOR functions as a molecular switch connecting an iron cue with host innate defense against bacterial infection.

As both host and pathogen require iron for survival, iron is an important regulator of host-pathogen interactions. However, the molecular mechanism by which how the availability of iron modulates host innate immunity against bacterial infections remains largely unknown. Using the metazoan Caenorhabditis elegans as a model, we demonstrate that infection with a pathogenic bacterium Salmonella enterica serovar Typhimurium induces autophagy by inactivating the target of rapamycin (TOR). Although the transcripts of ftn-1 and ftn-2 encoding two H-ferritin subunits are upregulated upon S. Typhimurium infection, the ferritin protein is kept at a low level due to its degradation mediated by autophagy. Autophagy, but not ferritin, is required for defense against S. Typhimurium infection under normal circumstances. Increased abundance of iron suppresses autophagy by activating TOR, leading to an increase in the ferritin protein level. Iron sequestration, but not autophagy, becomes pivotal to protect the host from S. Typhimurium infection in the presence of exogenous iron. Our results show that TOR acts as a regulator linking iron availability with host defense against bacterial infection.