Close relatives of MERS-CoV in bats use ACE2 as their functional receptors.

Middle East respiratory syndrome coronavirus (MERS-CoV) and several bat coronaviruses use dipeptidyl peptidase-4 (DPP4) as an entry receptor1-4. However, the receptor for NeoCoV-the closest known MERS-CoV relative found in bats-remains unclear5. Here, using a pseudotype virus entry assay, we found that NeoCoV and its close relative, PDF-2180, can efficiently bind to and use specific bat angiotensin-converting enzyme 2 (ACE2) orthologues and, less favourably, human ACE2 as entry receptors through their receptor-binding domains (RBDs) on the spike (S) proteins. Cryo-electron microscopy analysis revealed an RBD-ACE2 binding interface involving protein-glycan interactions, distinct from those of other known ACE2-using coronaviruses. We identified residues 337-342 of human ACE2 as a molecular determinant restricting NeoCoV entry, whereas a NeoCoV S pseudotyped virus containing a T510F RBD mutation efficiently entered cells expressing human ACE2. Although polyclonal SARS-CoV-2 antibodies or MERS-CoV RBD-specific nanobodies did not cross-neutralize NeoCoV or PDF-2180, an ACE2-specific antibody and two broadly neutralizing betacoronavirus antibodies efficiently inhibited these two pseudotyped viruses. We describe MERS-CoV-related viruses that use ACE2 as an entry receptor, underscoring a promiscuity of receptor use and a potential zoonotic threat.

Detection of genomic variations and selection signatures in Wagyu using whole-genome sequencing data.

Wagyu is recognized for producing marbled beef with high nutritional value and flavor. Reportedly, Wagyu has been widely used to improve the meat quality of local breeds around the world. However, studies on the genetic mechanism of meat quality in Wagyu at the whole-genome level are rarely reported. Here, whole-genome sequencing data of 11 Wagyu and 115 other individuals were used to explore the genomic variations and genes under selection pressure in Wagyu. A total of 31 349 non-synonymous variants and 53 102 synonymous variants were identified in Wagyu. The population structure analysis showed that Wagyu had the closest genetic relationship with Mishima-Ushi cattle and was apparently separated from other cattle breeds. Then, composite likelihood ratio (CLR), integrated haplotype score, fixation index and cross-population composite likelihood ratio (XP-CLR) tests were performed to identify the candidate genes under positive selection in Wagyu. In total, 770 regions containing 312 genes were identified by at least three methods. Among them, 97 regions containing 27 genes were detected by all four methods. We specifically illustrate a list of interesting genes, including LRP2BP, GAA, CACNG6, CXADR, GPCPD1, KLF2, KLF13, SOX5, MYBPC1, SLC25A10, ATP8A1 and MYH15, which are associated with lipid metabolism, fat deposition, muscle development, bone development, feed intake and growth traits in Wagyu. This is the first study to explore the genomic variations and selection signatures of Wagyu at the whole-genome level. These results will provide significant help to beef cattle improvement and breeding.

Late lactation in small mammals is a critically sensitive window of vulnerability to elevated ambient temperature.

Predicted increases in global average temperature are physiologically trivial for most endotherms. However, heat waves will also increase in both frequency and severity, and these will be physiologically more important. Lactating small mammals are hypothesized to be limited by heat dissipation capacity, suggesting high temperatures may adversely impact lactation performance. We measured reproductive performance of mice and striped hamsters (Cricetulus barabensis), including milk energy output (MEO), at temperatures between 21 and 36 °C. In both species, there was a decline in MEO between 21 and 33 °C. In mice, milk production at 33 °C was only 18% of that at 21 °C. This led to reductions in pup growth by 20% but limited pup mortality (0.8%), because of a threefold increase in growth efficiency. In contrast, in hamsters, MEO at 33 °C was reduced to 78.1% of that at 21 °C, yet this led to significant pup mortality (possibly infanticide) and reduced pup growth by 12.7%. Hamster females were more able to sustain milk production as ambient temperature increased, but they and their pups were less capable of adjusting to the lower supply. In both species, exposure to 36 °C resulted in rapid catastrophic lactation failure and maternal mortality. Upper lethal temperature was lowered by 3 to 6 °C in late lactation, making it a critically sensitive window to high ambient temperatures. Our data suggest future heat wave events will impact breeding success of small rodents, but this is based on animals with a long history in captivity. More work should be performed on wild rodents to confirm these impacts.

Two-dimensional Supramolecular Polymers Based on Selectively Recognized Aromatic Cation-π and Donor-Acceptor Motifs for Photocatalytic Hydrogen Evolution.

Two-dimensional (2D) organic polymers have recently received considerable interest, especially those whose architectures are held together via supramolecular engineering. However, current approaches toward supramolecular 2D structures usually suffer from mutual interference of noncovalent interactions and lack of intrinsic functions. Herein, we report well-regulated 2D supramolecular polymers (2DSPs) through an aromatics-selective recognition strategy of cation-π and donor-acceptor (D-A) motifs, which are derived from C4 -symmetric cationic monomers and electron-withdrawing molecules. By subtly designing the strength and direction of noncovalent driving forces, the mutual interference between cation-π and D-A interactions is effectively avoided, enabling the construction of 2DSPs in aqueous solution. On this basis, the resultant 2DSPs possess boosted photocatalytic hydrogen evolution activity at a rate of 600 µmol g-1 h-1 , which is mainly ascribed to the specific stacking mode of cation-π/D-A motifs and the ordered 2D structures.

Detection of selection signatures in South African Mutton Merino sheep using whole-genome sequencing data.

The South African Mutton Merino (SAMM), a dual-purpose (meat and wool) sheep breed, is characterized by its excellent performance on growth, carcass traits and meat quality compared to other fine-wool Merino breeds. Nowadays, the SAMM breed has been widely used to cross with commercial and indigenous fine-wool or coarse-wool breeds to improve the growth and meat performance in many countries. To date, however, little is known about the genetic basis for its prominent characteristics. In this study, whole-genome sequences of 10 SAMM were sequenced and the selection signatures were analyzed together with those of 39 Australian Merino and Chinese Merino (wool-type Merino) by FST , iHS, and XP-EHH methods. In total, 313 genes in 277 regions were identified by at least 2 methods with the signal of selection and 21 of them were identified by all three methods. We highlighted a list of interesting genes, including GHR, LCORL, SMO, NCAPG, DCC, IBSP, PPARGC1A, PACRGL, PRDM5, XYLB, AHCYL2, TEFM, AFG1L, and FAM184B, which have been shown to be involved in growth, carcass traits, and meat quality by previous studies. Herein, GHR, encoding a transmembrane receptor for growth hormone, is the most notable one. We report the first study on selection signatures analysis of SAMM at whole-genome sequence level. These results provide new insights into the genetic mechanisms underlying the growth and carcass traits in SAMM.

Facile fabrication of reinforced sub-micron fibrous media with hierarchical structure compounded thermally for effective air purification in application.

Air pollution has steadily worsened in recent years, and the coronavirus disease 2019 has been spreading since 2020. The electrospun fibrous filters present superior filtration performance, while the low mechanical property and yield of them limit their applications, which must be addressed urgently. Herein, polyacrylonitrile (PAN) sub-micron fibrous membrane with hierarchical structure was easily manufactured using free surface electrospinning in mass production for air purification. The "sandwich" structured fibrous filter was thermally bonded with bi-component nonwoven through traditional bonding procedures, due to melting and bonding of the cortex of bi-component fibers, in which the electrospun fibrous web as the mid layer with tortuous channels showed superior filtration performance for aerosol particles with diameter of 260 nm, which could effectively intercept different-sized particles suspended in the air. In addition, the impact of the processing parameters on the characteristics and filtration mechanisms of thermally bonded composite materials was thoroughly investigated. The results showed that composite material with "dendrites" and "axon" morphologies presented the best formability, outstanding peeling strength and breaking strength, and steady filtration performance, following an easy through-air bonding procedure, making it useful for post-processing in air purification. The reinforced composite filter, which is thermally bonded with sub-micron fibers with high yield and nonwoven, is save-energy and has a low operation cost, indicating its promising commercial possibilities.

Demand-side consequences of unemployment and horizontal skill mismatches across national contexts: An employer-based factorial survey experiment.

With growing flexibilization in the labour market, continuous and consistent career trajectories have become less the norm, and workers facing unemployment may need to look for employment opportunities outside the occupation they are trained in. But what are their employment chances? And what are the chances of returning to the occupation they were trained in after having worked in a different occupation? Despite much research on how employers evaluate job candidates with vertical skill mismatches (e.g. over-qualification and under-qualification) and unemployment, there is little research to investigate how employers view horizontal mismatch in comparison to unemployment, and whether a combination of both generates multiplicative negative effects. Using data gathered from an employer survey experiment in Switzerland and Greece, we find that in Switzerland both unemployment and horizontal mismatch significantly reduce employment chances, but the scarring effect of horizontal mismatch is much stronger. In contrast, in Greece horizontal mismatch significantly reduces employment chances but unemployment does not. Furthermore, we found that horizontal mismatch scarring is significantly stronger in Switzerland than in Greece. These findings suggest that the scarring effects of both unemployment and horizontal mismatch vary across contexts. Further analyses show that, rather than experiencing multiplicative scarring effects, unemployment does not add further disadvantages to mismatched candidates in either country, highlighting the importance of occupational specificity of skills in labour market matching. Overall, these findings facilitate a more nuanced understanding of demand-side labour market processes, highlighting the distinct interactive effects of unemployment and horizontal mismatch across national contexts.

In Vitro Assessment of Antimicrobial Resistance Dissemination Dynamics during Multidrug-Resistant-Bacterium Invasion Events by Using a Continuous-Culture Device.

Antimicrobial-resistant pathogens display significant public health threats by causing difficulties in clinical treatment of bacterial infection. Antimicrobial resistance (AMR) is transmissible between bacteria, significantly increasing the appearance of antimicrobial-resistant pathogens and aggravating the AMR problem. In this work, the dissemination dynamics of AMR from invading multidrug-resistant (MDR) Escherichia coli to a community of pathogenic Salmonella enterica was investigated using a continuous-culture device, and the behaviors of dissemination dynamics under different levels of antibiotic stress were investigated. Three MDR E. coli invasion events were analyzed in this work: MDR E. coli-S. enterica cocolonization, MDR E. coli invasion after antibiotic treatment of S. enterica, and MDR E. coli invasion before antibiotic treatment of S. enterica It was found that both horizontal gene transfer (HGT) and vertical gene transfer (VGT) play significant roles in AMR dissemination, although different processes contribute differently under different circumstances, that environmental levels of antibiotics promote AMR dissemination by enhancing HGT rather than leading to selective advantage for resistant bacteria, and that early invasion of MDR E. coli completely and quickly sabotages the effectiveness of antibiotic treatment. These findings contribute to understanding the drivers of AMR dissemination under different antibiotic stresses, the detrimental impact of environmental tetracycline contamination, and the danger of nosocomial presence and dissemination of MDR nonpathogens.IMPORTANCE Antimicrobial resistance poses a grave threat to public health and reduces the effectiveness of antimicrobial drugs in treating bacterial infections. Antimicrobial resistance is transmissible, either by horizontal gene transfer between bacteria or by vertical gene transfer following inheritance of genetic traits. The dissemination dynamics and behaviors of this threat, however, have not been rigorously investigated. In this work, with a continuous-culture device, we studied antimicrobial resistance dissemination processes by simulating antimicrobial-resistant Escherichia coli invasion to a pathogenic Salmonella enterica community. Using this novel tool, we provide evidence on the drivers of antimicrobial resistance dissemination, on the detrimental impact of environmental antibiotic contamination, and on the danger of antimicrobial resistance in hospitals, even if what harbors the antimicrobial resistance is not a pathogen. This work furthers our understanding of antimicrobial resistance and its dissemination between bacteria and of antibiotic therapy, our most powerful tool against bacterial infection.

Arabidopsis BRCA1 represses RRTF1-mediated ROS production and ROS-responsive gene expression under dehydration stress.

Reactive oxygen species (ROS) act as important secondary messengers in abscisic acid (ABA) signaling and induce stomatal closure under dehydration stress. The breast cancer susceptibility gene 1 (BRCA1), an important tumor suppressor in animals, functions primarily in the maintenance of genome integrity in animals and plants. However, whether and how the plant BRCA1 regulates intracellular ROS homeostasis in guard cells under dehydration stress remains unknown. Here, we found that Arabidopsis atbrca1 loss-of-function mutants showed dehydration stress tolerance. This stress tolerant phenotype of atbrca1 was a result of ABA- and ROS-induced stomatal closure, which was enhanced in atbrca1 mutants compared with the wild-type. AtBRCA1 downregulated the expression of ROS-responsive and marker genes. Notably, these genes were also the targets of the AP2/ERF transcriptional activator RRTF1/ERF109. Under normal conditions, AtBRCA1 physically interacted with RRTF1 and inhibited its binding to the GCC-box-like sequence in target gene promoters. Under dehydration stress, the expression of AtBRCA1 was dramatically reduced and that of RRTF1 was activated, thus inducing the expression of ROS-responsive genes. Overall, our study reveals a novel molecular function of AtBRCA1 in the transcriptional regulation of intracellular ROS homeostasis under dehydration stress.

Effects of heat stress on antioxidant status and immune function and expression of related genes in lambs.

The study was conducted to evaluate the effects of heat stress on antioxidant status, immune response, and related gene expression of lambs. Eighteen male lambs were randomly allocated into three treatment groups that were as follows: indoor temperature control group furnished with an air-conditioner (ITC), indoor temperature non-control group suffered intermittent and varying degrees of heat stress (ITNC), outdoor temperature non-control group in the external natural environment (OTNC). ITNC group presented a more severe and prolonged exposure to thermal stress than the other two groups. The trial lasted 28 days. Blood samples were collected on days 14 and 28 to analyze total superoxide dismutase (T-SOD), catalase (CAT), glutathione peroxidase (GPx) activities, malondialdehyde (MDA) concentrations, total antioxidant capacity (T-AOC), interleukin-1 (IL-1), interleukin-2 (IL-2), tumor necrosis factor-alpha (TNF-α), immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) concentrations and gene expressions of SOD1, SOD2, GPx, CAT, nuclear factor erythroid 2-related factor 2 (Nrf2), IL-1ß, IL-2, and TNF-α. Results showed that on day 14 an elevated temperature reduced (p < 0.05) the level of GPx, T-SOD, T-AOC, and IgG, whereas significantly increased (p < 0.05) CAT, MDA, IgA, and TNF-α levels. Gene expressions of SOD1 and GPx were down-regulated (p < 0.05). On day 28, ITNC group significantly decreased (p < 0.05) CAT, GPx, T-SOD, T-AOC, IgG, and IL-2 levels and increased (p < 0.05) MDA, IL-1, and TNF-α levels, accompanying by the reducing or increasing (p < 0.05) of their relative gene expression apart from CAT and IL-1ß gene (p > 0.10). In addition, in ITNC and OTNC groups, the level of CAT, T-SOD, T-AOC, IgG, IgM, and IL-2 and the expression of CAT, SOD2, and IL-2 reduced (p < 0.05), whereas IL-1 and TNF-α levels and IL-1ß expression increased (p < 0.05) on day 28 compared with day 14. In ITC group, the level of IgA, IL-1, and TNF-α and the expression of IL-1ß and TNF-α increased (p < 0.05), while the content of IgG and IgM reduced (p < 0.05) on day 28 compared with day 14. These results indicated that heat stress negatively affected the antioxidant status and immune response of lambs, and the negative effects of heat stress are not only related to the stress duration but also associated with the stress severity.

Deep Anomaly Detection for CNC Machine Cutting Tool Using Spindle Current Signals.

In recent years, industrial production has become more and more automated. Machine cutting tool as an important part of industrial production have a large impact on the production efficiency and costs of products. In a real manufacturing process, tool breakage often occurs in an instant without warning, which results a extremely unbalanced ratio of the tool breakage samples to the normal ones. In this case, the traditional supervised learning model can not fit the sample of tool breakage well, which results to inaccurate prediction of tool breakage. In this paper, we use the high precision Hall sensor to collect spindle current data of computer numerical control (CNC). Combining the anomaly detection and deep learning methods, we propose a simple and novel method called CNN-AD to solve the class-imbalance problem in tool breakage prediction. Compared with other prediction algorithms, the proposed method can converge faster and has better accuracy.

The less weight loss due to modest food restriction drove more fat accumulation in striped hamsters refed with high-fat diet.

Food restriction (FR) has been commonly used to decrease body fat, reducing the risk of overweight in humans and animals. However, the lost weight has been shown to be followed by overweight when food restriction ends. It remains uncertain whether the weight loss drives the overweight, or not. In the present study, striped hamsters were restricted by 15%, 30% and 40% of ad libitum food intake for 2 weeks, followed by high-fat refeeding for 6 weeks (FR15%-Re, FR30%-Re and FR40%-Re). The hamsters in FR15%, FR30% and FR40% groups decreased by 21.1%, 37.8% and 50.0% in fat mass (P < 0.01), and 16.8%, 42.8% and 53.4% in leptin levels (P < 0.01) compared with the hamsters fed ad libitum. The FR15%-Re, FR30%-Re and FR40%-Re groups showed 77.0%, 37.2% and 23.7% more body fat than ad libitum group (P < 0.01). The FR15%-Re group showed considerable decreases in gene expression of arcuate nucleus co-expressing proopiomelanocortin (POMC), cocaine - and amphetamineregulated transcript (CART) and the long isoform of leptin receptor (LepRb) in the hypothalamus and of several genes associated with fatty acid transport to mitochondria and ß-oxidation in brown adipose tissue and liver. It suggests that less weight loss is likely to drive more fat accumulation when food restriction ends, in which the impaired function of LepRb, POMC and CART in the brain and fatty acid oxidation in brown adipose tissue and liver may be involved.

Fluorescence lifetime-based pH sensing by platinum nanoclusters.

In this work, we report for the first time the application of ultrasmall Pt nanoclusters (Pt NCs) as a fluorescence-lifetime-based pH sensor. The fluorescence properties of our prepared Pt NCs show strong pH dependence, due to the change of the surface states of Pt NCs under alkaline/acidic conditions. Interestingly, both the fluorescence intensity and the fluorescence lifetime of Pt NCs exhibit a good linear relationship in the physiologically relevant pH range of 6.02-7.54. Our Pt NC-based pH sensor possesses many important features as an attractive sensor, including high anti-jamming capability, excellent stability and good reversibility. Moreover, the use of fluorescence lifetime as the optical readout signal rather than the intensity makes the present pH sensor more reliable in practical applications because the fluorescence lifetime is invariant to the probe concentration or changes in excitation conditions. Application of the Pt NC-based system for pH detection in real water samples and simulated intracellular environment samples has also been successfully demonstrated.

pH-Sensitive DOX-Loaded PAA-PF127-PAA Micelles Combined with Cryotherapy for Treating Walker 256 Carcinosarcoma in a Rat Model.

In this work, a novel combination of drug therapy and cryotherapy for tumor treatment was developed. Pluronic F127 modified with poly(acrylic acid) at two terminals (denoted as PAA-PF127-PAA) was used as carriers for doxorubicin (DOX) delivery. Due to the pH-sensitive property endowed by PAA, the DOX-loaded PAA-PF127-PAA micelles released DOX faster in the slightly acidic physiological environment of the tumor site than that in the neutral physiological environment. Three-group rats bearing Walker 256 carcinosarcoma were respectively treated with cryotherapy, combination of DOX-loaded micelles and cryotherapy, and saline injection to investigate the effect of the combined therapy. The apoptosis rate of TdT-mediated dUTP nick-end labeling (TUNEL) slices indicated that compared with cryotherapy alone, the DOX-loaded PAA-PF127-PAA micelles combining with cryotherapy showed increased apoptosis. Thus, the combination of drug therapy and cryotherapy can be used as an effective technique for tumor treatment.

The roles of metabolic thermogenesis in body fat regulation in striped hamsters fed high-fat diet at different temperatures.

The metabolic thermogenesis plays important roles in thermoregulation, and it may be also involved in body fat regulation. The thermogenesis of brown adipose tissue (BAT) is largely affected by ambient temperature, but it is unclear if the roles in body fat regulation are dependent on the temperature. In the present study, uncoupling protein 1 (ucp1)-based BAT thermogenesis, energy budget and body fat content were examined in the striped hamsters fed high fat diet (HF) at cold (5°C) and warm (30°C) temperatures. The effect of 2, 4-dinitrophenol (DNP), a chemical uncoupler, on body fat was also examined. The striped hamsters showed a notable increase in body fat following the HF feeding at 21°C. The increased body fat was markedly elevated at 30°C, but was significantly attenuated at 5°C compared to that at 21°C. The hamsters significantly increased energy intake at 5°C, but consumed less food at 30°C relative to those at 21°C. Metabolic thermogenesis, indicated by basal metabolic rate, UCP1 expression and/or serum triiodothyronine levels, significantly increased at 5°C, but decreased at 30°C compared to that at 21°C. A significant decrease in body fat content was observed in DNP-treated hamsters relative to the controls. These findings suggest that the roles of metabolic thermogenesis in body fat regulation largely depend on ambient temperature. The cold-induced enhancement of BAT thermogenesis may contribute the decreased body fat, resulting in a lean mass. Instead, the attenuation of BAT thermogenesis at the warm may result in notable obesity.

Effective improvement of the activity of membrane-bound alcohol dehydrogenase by overexpression of adhS in Gluconobacter oxydans.

OBJECTIVES: To investigate the roles of adhS, which encodes the AdhS subunit of membrane-bound alcohol dehydrogenase (mADH) in Gluconobacter oxydans DSM2003, and to rationally improve mADH activity. RESULTS: adhS was identified and overexpressed in G. oxydans DSM2003. Its overexpression promoted the AdhA subunit which serves as the primary dehydrogenase transfer from the periplasmic space to the periplasmic surface of the membrane thereby increasing the amount of active mADH and thus enhancing mADH activity up to 1.96-fold. The increased mADH activity significantly altered product selectivity (glyceric acid/dihydroxyacetone) during glycerol oxidation and increased the glyceric acid production by 7.6-fold. By comparison, overexpression of adhS and adhABS was equally effective in increasing the mADH activity and glyceric acid production. CONCLUSIONS: adhS overexpression effectively improved mADH activity, indicating that for mADH, adhS might be a limiting component. The findings provide a guide for the efficient application of Gluconobacter spp. in hydroxy acid production.

The increase in fat content in the warm-acclimated striped hamsters is associated with the down-regulated metabolic thermogenesis.

It has been well known that metabolic thermogenesis plays an important role in the thermoregulation of small mammals under different temperatures, while its role in fat accumulation is far from clear. In the present study, several physiological, hormonal, and biochemical measures indicative of metabolic thermogenesis were measured in the weaning striped hamsters after acclimated to a warm condition (30°C) for 1, 3 and 4months. The warm-acclimated groups significantly decreased energy intake, and simultaneously decreased nonshivering thermogenesis compared to those housed at 21°C. Body fat content increased by 29.9%, 22.1% and 19.6% in the hamsters acclimated to 1, 3 or 4months, respectively relative to their counterparts maintain at 21°C (P<0.05). The cytochrome c oxidase (COX) activity of brain, liver, heart and skeletal muscle, and the ratio of serum tri-iodothyronine to thyroxine significantly decreased in warm-acclimated groups compared with 21°C group. COX activity and uncoupling protein 1 (UCP1) mRNA expression of brown adipose tissue (BAT) were significantly down-regulated under the warm conditions. COX activity of BAT, liver, heart and muscle were significantly negatively correlated with body fat content, and the correlation between UCP1 expression and body fat content tended to be negative. These findings suggest that the decrease in the energy spent on metabolic thermogenesis plays an important role in the fat accumulation. The attenuation of COX and UCP1-based BAT activity may be involved in body fat accumulation in animals under warm conditions.