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In order to explore the weldability and widen the applicability of high entropy alloys (HEAs), dissimilar friction stir lap welding of pure copper and Al0.1CoCrFeNi alloy was investigated in this research. The results indicate that a sound dissimilar weld without tunnels and voids is produced, where a ∼20 μm thick interfacial layer is evident at the Cu-HEA interface. The lap joint is fractured at the upper Cu sheet rather than the lap surface during tensile shear test, suggesting an effective bonding of the dissimilar materials. The lap weld roughly consists of three layers along the plate thickness direction, i.e. welds of Cu, HEA and Cu-HEA interface, respectively. The interface of weld, which has experienced the most severe Cu-HEA interaction during welding, is characterized by uniformly distributed and highly recrystallized ultra-fine grains (∼0.79 μm). Meanwhile, intermetallic compounds particles (Al13Cr2 and Al13Co4) ranging in size of 150∼400 nm are generated at the fine grain boundaries. Fast diffusion of Al, Cr and Co elements and easy segregation of these elements during welding result in the formation of the particles. The sufficient DDRX and the pinning effect of particles are responsible for the formation of ultra-fine grains in the weld interface. The present study lays a theoretical foundation for the joining of conventional Cu and the multi-component HEA, which contributes to the improvement of HEA availability in the field of manufacturing industry.

ABSTRACT To adapt to various host microenvironments, the human fungal pathogen Candida albicans possesses the capacity to accumulate and store glycogen as an internal carbohydrate source. In the model yeast Saccharomyces cerevisiae, ScGlc7p and ScGac1p are the serine/threonine type 1 protein phosphatase catalytic and regulatory subunits that control glycogen synthesis by altering the phosphorylation state of the glycogen synthase Gsy2p. Despite recent delineation of the glycogen synthesis pathway in C. albicans, the molecular events driving synthase activation are currently undefined. In this study, using a combination of microbiologic and genetic techniques, we determined that the protein encoded by uncharacterized gene C1_01140C, and not the currently annotated C. albicans Gac1p, is the major regulatory subunit involved in glycogen synthesis. C1_01140Cp contains a conserved GVNK motif observed across multiple starch/glycogen-binding proteins in various species, and alanine substitution of each residue in this motif significantly impaired glycogen accumulation in C. albicans. Fluorescent protein tagging and microscopy indicated that C1_01140Cp-GFPy colocalized with CaGlc7p-tdTomato and CaGsy1p-tdTomato accordingly. Co-immunoprecipitation assays further confirmed that C1_01140Cp associates with CaGlc7p and CaGsy1p during glycogen synthesis. Lastly, c1_01140cΔ/Δ exhibited colonization defects in a murine model of vulvovaginal candidiasis. Collectively, our data indicate that uncharacterized C1_01140Cp is the functional ortholog of the PPP1R subunit ScGac1p in C. albicans.IMPORTANCEThe capacity to synthesize glycogen offers microbes metabolic flexibility, including the fungal pathogen Candida albicans. In Saccharomyces cerevisiae, dephosphorylation of glycogen synthase by the ScGlc7p-containing phosphatase is a critical rate-limiting step in glycogen synthesis. Subunits, including ScGac1p, target ScGlc7p to α-1,4-glucosyl primers for efficient ScGsy2p synthase activation. However, this process in C. albicans had not been delineated. Here, we show that the C. albicans genome encodes for two homologous phosphatase-binding subunits, annotated CaGac1p and uncharacterized C1_01140Cp, both containing a GVNK motif required for polysaccharide affinity. Surprisingly, loss of CaGac1p only moderately reduced glycogen accumulation, whereas loss of C1_01140Cp ablated it. Fluorescence microscopy and co-immunoprecipitation approaches revealed that C1_01140Cp associates with CaGlc7p and CaGsy1p during glycogen synthesis. Moreover, C1_01140Cp contributed to fungal fitness at the vaginal mucosa during murine vaginitis. Therefore, this work demonstrates that glycogen synthase regulation is conserved in C. albicans and C1_01140Cp is the functional ortholog of ScGac1p.

ABSTRACT The uridine derivatives UDP-glucose and UDP-N-acetylglucosamine are important for cell wall construction as they are the precursors for the synthesis of β-1,3-glucan and chitin, respectively. Previous studies have demonstrated attenuated virulence of uridine auxotrophs in mice, which has been attributed to insufficient uridine levels for growth in the host. We have discovered that uridine deprivation in the uridine auxotroph ura3ΔΔ disrupts cell wall architecture by increasing surface mannans, exposing β-1,3-glucan and chitin, and decreasing UDP-sugar levels. Cell wall architecture and UDP-sugars can be rescued with uridine supplementation. The cell wall architectural disruptions in the ura3ΔΔ mutant also impact immune activation since the mutant elicited greater TNFα secretion from RAW264.7 macrophages than wild type. To determine if cell wall defects contributed to decreased virulence in the ura3ΔΔ mutant, we used a murine model of systemic infection. Mice infected with the ura3ΔΔ mutant exhibited increased survival and reduced kidney fungal burden compared with mice infected with wild type. However, suppression of the immune response with cyclophosphamide did not rescue virulence in mice infected with the ura3ΔΔ mutant, indicating the attenuation in virulence of uridine auxotrophs can be attributed to decreased growth in the host but not increased exposure of β-1,3-glucan. Moreover, the ura3ΔΔ mutant is unable to grow on ex vivo kidney agar, which demonstrates its inability to colonize the kidneys due to poor growth. Thus, although uridine auxotrophy elicits changes to cell wall architecture that increase the exposure of immunogenic polymers, metabolic fitness costs more strongly drive the observed virulence attenuation.IMPORTANCECandida albicans is a common cause of bloodstream infections (candidemia). Treatment of these bloodstream infections is made difficult because of increasing antifungal resistance and drug toxicity. Thus, new tactics are needed for antifungal drug development, with immunotherapy being of particular interest. The cell wall of C. albicans is composed of highly immunogenic polymers, particularly β-1,3-glucan. However, β-1,3-glucan is naturally masked by an outer layer of mannoproteins, which hampers the detection of the fungus by the host immune system. Alteration in cell wall components has been shown to increase β-1,3-glucan exposure; however, it is unknown how the inability to synthesize precursors to cell wall components affects unmasking. Here, we demonstrate how cell wall architecture is altered in response to a deficit in precursors for cell wall synthesis and how uridine is a crucial component of these precursors.

Glucose is a major energy substrate for porcine adipocytes and also serves as a regulatory signal for adipogenesis and lipid metabolism. In this study, we combined transcriptome and metabolome analyses to reveal the underlying regulatory mechanisms of high glucose (HG) on adipogenesis by comparing differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) identified in porcine adipocytes. Results showed that HG (20 mmol/L) significantly increased fat accumulation in porcine adipocytes compared to low glucose (LG, 5 mmol/L). A total of 843 DEGs and 365 DAMs were identified. Functional enrichment analyses of DEGs found that multiple pathways were related to adipogenesis, lipid metabolism, and immune-inflammatory responses. PPARγ, C/EBPα, ChREBP, and FOS were identified as the key hub genes through module 3 analysis, and PPARγ acted as a central regulator by linking genes involved in lipid metabolism and immune-inflammatory responses. Gene-metabolite networks found that PPARγ-13-HODE was the most important interaction relationship. These results revealed that PPARγ could mediate the cross-talk between adipogenesis and the immune-inflammatory response during adipocyte maturation. This work provides a comprehensive view of the regulatory mechanisms of glucose on adipogenesis in porcine adipocytes.

Abstract Background The reliance on a solitary linear reference genome has imposed a significant constraint on our comprehensive understanding of genetic variation in animals. This constraint is particularly pronounced for non-reference sequences (NRSs), which have not been extensively studied. Results In this study, we constructed a pig pangenome graph using 21 pig assemblies and identified 23,831 NRSs with a total length of 105 Mb. Our findings revealed that NRSs were more prevalent in breeds exhibiting greater genetic divergence from the reference genome. Furthermore, we observed that NRSs were rarely found within coding sequences, while NRS insertions were enriched in immune-related Gene Ontology terms. Notably, our investigation also unveiled a close association between novel genes and the immune capacity of pigs. We observed substantial differences in terms of frequencies of NRSs between Eastern and Western pigs, and the heat-resistant pigs exhibited a substantial number of NRS insertions in an 11.6 Mb interval on chromosome X. Additionally, we discovered a 665 bp insertion in the fourth intron of the TNFRSF19 gene that may be associated with the ability of heat tolerance in Southern Chinese pigs. Conclusions Our findings demonstrate the potential of a graph genome approach to reveal important functional features of NRSs in pig populations.

Abstract Objective This study aimed to investigate whether treatment with adjunct intravenous tirofiban is associated with improved outcomes following successful reperfusion in patients with intracranial atherosclerotic stroke. Methods Patients with intracranial large artery atherosclerotic (LAA) stroke and an expanded Treatment in Cerebral Ischemia angiographic score of 2b50 to 3 from the Effect of Intravenous Tirofiban versus Placebo Before Endovascular Thrombectomy on Functional Outcomes in Large Vessel Occlusion Stroke (RESCUE BT) trial were included. The primary outcome was the difference in proportion of independent functional outcome (modified Rankin score of 0–2 at 90 days). Safety outcomes included the rates of symptomatic intracranial hemorrhage (sICH) and 90‐day mortality. Results Among the 382 patients with intracranial LAA stroke and successful reperfusion, 175 patients (45.8%) were treated with intravenous tirofiban and 207 (54.2%) with placebo. The proportion of patients with independent functional outcome at 90 days was 54.3% (95 out of 175) with tirofiban and 44.0% (91 out of 207) with placebo (adjusted odds ratio [aOR], 1.58; 95% CI, 1.02–2.44; p = 0.04). Intravenous tirofiban was not significantly associated with an increased risk of sICH (12/175 [6.9%] vs. 11/207 [5.3%]; aOR, 1.41; 95% CI, 0.59–3.34; p = 0.44) or 90‐day mortality (21/175 [12.0%] vs. 34/207 [16.4%]; aOR, 0.71; 95% CI, 0.38–1.31; p = 0.27). Interpretation Among patients with acute intracranial LAA stroke and successful reperfusion following endovascular thrombectomy, adjunct intravenous tirofiban was associated with a higher rate of independent functional outcome, without higher rates of sICH or mortality. Confirmatory randomized trials in these patients are desirable.

There are some bottleneck problems in the pressure relief and antireflection technology of submerged water jet in a downward hole, such as weak impact force, low coal breaking efficiency, less coal cutting and poor adaptability. In this study, the idea and principle of coal breaking and antireflection of self-excited pulsed water jet in downward hole strengthened by the annular fluid were put forward in order to break the pressure holding effect at the bottom of the hole and the drag increase effect of water cushion, and improve the impact force and coal breaking efficiency of the submerged water jet. The high-efficiency modulation and coal-breaking characteristics of self-excited pulsed water jet enhanced by annular fluid were studied by using large eddy simulation, impact force test and impact kettle coal breaking experiment. Firstly, the physical model of an annular fluid-enhanced self-excited pulse nozzle suitable for the anti-reflection of downward holes in coal mines was established, and the nozzle structure parameters were optimized. Then a high-frequency impact force test system of a submerged pulsed jet and annular fluid-enhanced self-excited pulsed water jet nozzle was developed, and the impact force and flow field characteristics of the annular fluid-enhanced self-excited pulsed nozzle in the submerged environment were quantitatively analyzed. Finally, the coal breaking experiment system of submerged water jet was developed, and the coal breaking experiment of submerged water jet was carried out, which revealed the coal breaking characteristics of the annular fluid-enhanced self-excited pulsed water jet. The results show that under the engineering condition of a down-hole in the coal mines, the self-excited pulse water jet enhanced by annulus fluid can be effectively generated by the self-excited pulse nozzle with self-priming Helmholtz resonance cavity structure on both sides. The optimal nozzle structure parameters are as follows: the diameter of the upper nozzle d1=3 mm, the angle of collapse wall α=120°, the diameter of the lower nozzle d2=3.6 mm, the length of the oscillation cavity L=10.5 mm, the diameter of the oscillation cavity D=27 mm, the diameter of the inlet port d3 =4.2 mm. When the pump pressure is 10 MPa, the maximum amount of entrainment annulus water is 0.28 L/s, with an average of 0.19 L/s. When the pump pressure is the same, the dominant frequency of the annular fluid-enhanced self-excited pulsed water jet is close to that of the self-excited pulsed water jet. The dominant frequency range of the annular fluid-enhanced self-excited pulsed water jet is 253−285 Hz, while that of the self-excited pulsed water jet is 251−282 Hz. The peak impact force of the annular fluid-enhanced self-excited pulsed water jet is 1.05−1.08 times and 1.63−1.89 times higher than that of the self-excited pulsed water jet and the continuous jet, respectively. The average impact force is 1.09−1.16 times higher than that of the self-excited pulsed water jet, which reflects that the annular fluid-enhanced self-excited pulsed water jet can continuously generate a large impact force in the submerged state and has good pulsed jet characteristics. Under the condition of the same pump pressure and target distance, the damaging effect of annular fluid enhanced self-excited pulsed water jet is stronger than that of self-excited pulsed water jet and continuous water jet on coal samples. The annular fluid enhanced self-excited pulsed water jet has a good erosion effect on coal body, and about 88.65% of the coal slag particle size is below 8 mm. When the pump pressure is 10 MPa, the target distance is 10d1, and the erosion time is 10 s, the jet has the best erosion effect on coal samples, with an erosion depth of 47.32 mm and the erosion volume of 15.7 cm3. The research results can not only solve the bottleneck problem of a downward hole water jet in the coal mines, but also have the advantages of less excavation and cost saving. It is expected to replace and exceed the pressure relief and permeability enhancement of the upward hole water jet. It has broad application prospects in the gas disaster prevention and coalbed methane development of coal mines.

Abstract Background Natural and artificial selection for more than 9000 years have led to a variety of domestic pig breeds. Accurate identification of pig breeds is important for breed conservation, sustainable breeding, pork traceability, and local resource registration. Results We evaluated the performance of four selectors and six classifiers for breed identification using a wide range of pig breeds (N = 91). The internal cross-validation and external independent testing showed that partial least squares regression (PLSR) was the most effective selector and partial least squares-discriminant analysis (PLS-DA) was the most powerful classifier for breed identification among many breeds. Five-fold cross-validation indicated that using PLSR as the selector and PLS-DA as the classifier to discriminate 91 pig breeds yielded 98.4% accuracy with only 3K single nucleotide polymorphisms (SNPs). We also constructed a reference dataset with 124 pig breeds and used it to develop the web tool iDIGs ( http://alphaindex.zju.edu.cn/iDIGs_en/ ) as a comprehensive application for global pig breed identification. iDIGs allows users to (1) identify pig breeds without a reference population and (2) design small panels to discriminate several specific pig breeds. Conclusions In this study, we proved that breed identification among a wide range of pig breeds is feasible and we developed a web tool for such pig breed identification.

Introduction: Enlarged perivascular spaces (EPVS) are considered early manifestations of impaired clearance mechanisms in the brain; however, it is unclear whether EPVS they are associated with the development of malignant cerebral edema (MCE) after large hemispheric infarction (LHI). Therefore, we investigated the predictive value of EPVS in predicting MCE in LHI. Methods: Patients suffering from acute LHI were consecutively enrolled. EPVS were rated after the stroke with validated rating scales from magnetic resonance imagess. Patients were divided into two groups according to the occurrence of MCE. Logistic regression was used to analyze the relationship between EPVS and MCE in the basal ganglia (BG) and centrum semiovale (CS) regions. Receiver operating characteristic (ROC) curves assessed the ability of EPVS individually and with other factors in predicting MCE. Results: We included a total of 255 patients, of whom 98 were MCE patients (58 [59.2%] males, aged 70 [range=61.75-78] years) and found that atrial fibrillation, National Institutes of Health Stroke Scale score, infarct volume, neutrophil-lymphocyte ratio, and moderate-to-severe CS-EPVS were positively associated with MCE. After adjusting for confounds, moderate-to-severe CS-EPVS remained independent risk factor of MCE (odds ratio=16.212, p＜0.001). According to the ROC analysis, MCE was highly suspected when CS-EPVS > 14 (sensitivity=0.82, specificity=0.48), and the guiding value were higher when CS-EPVS combined with other MCE predictors (area under the curve=0.90, sensitivity=0.74, specificity=0.90). Conclusion: CS-EPVS were important risk factor for MEC in patients with acute LHI and can help identify patients at risk for MCE.

Abstract There are many nanoscale pores in deep low permeability coal seams. The flow of coalbed methane (gas) in nanoscale pores belongs to the gas flow in porous media with medium and high Knudsen numbers. Its flow mechanism is one of the key unsolved scientific problems. In order to explore the gas transport law in nanopores of coal, a gas transport model based on microscopic boundary restriction was adopted to describe the gas flow law, and its rationality was verified by experimental data. The Field Emission Scanning Electron Microscope was used to scan the nanopores of customized anodized aluminum membrane. Then, the Maximally Stable Extremal Regions (MSER) algorithm of MATLAB and binarization algorithm were employed to quantify the pore structure parameters (equivalent pore size and porosity) of the membrane nanoscale pores. Finally, PMI micro-flow permeability tester was used to carry out different rarefied degree gas penetration experiments through anodized aluminum membranes, and the adopted gas transport model was verified. The results show that the binarization method is more accurate to characterize sample whose theoretical pore sizes are 20–35 nm, while MSER characterizes samples whose theoretical pore sizes are 110–150 nm and 200–300 nm more accurately. In other words, binarization method is more accurate for characterizing mesopores, while MSER algorithm is more accurate for macropores. The results have important reference value for more accurate extraction of nanopore parameters of porous media. Compared with traditional gas transport model, the adopted model considering the microscopic boundary restriction in this paper is closer to the experimental results. Moreover, it is suitable for describing the gas flow law in multiscale nanopores. The study provided important guiding significance for ascertaining the gas migration law in low permeability coal seam, improving the prediction accuracy of gas extraction and taking effective measures to increase production. The research results can further enrich the theoretical system of gas transport in coal, which is conducive to the efficient gas extraction, and is of great significance to promote the realization of carbon peak and carbon neutrality.

ABSTRACT The polymorphic fungus Candida albicans remains a leading cause of both invasive and superficial mycoses, including vulvovaginal candidiasis (VVC). Metabolic plasticity, including carbohydrate catabolism, confers fitness advantages at anatomical site-specific host niches. C. albicans possesses the capacity to accumulate and store carbohydrates as glycogen and can consume intracellular glycogen stores when nutrients become limited. In the vaginal environment, estrogen promotes epithelial glycogen accumulation and C. albicans colonization. However, whether these factors are mechanistically linked is unexplored. Here, we characterized the glycogen metabolism pathways in C. albicans and investigated whether these impact the long-term survival of C. albicans, both in vitro and in vivo during murine VVC, or virulence during systemic infection. SC5314 and 6 clinical isolates demonstrated impaired growth when glycogen was used as the sole carbon source, suggesting that environmental glycogen acquisition is limited. The genetic deletion and complementation of key genes involved in glycogen metabolism in Saccharomyces cerevisiae confirmed that GSY1 and GLC3, as well as GPH1 and GDB1, are essential for glycogen synthesis and catabolism in C. albicans, respectively. Potential compensatory roles for a glucoamylase encoded by SGA1 were also explored. Competitive survival assays revealed that gsy1Δ/Δ, gph1Δ/Δ, and gph1Δ/Δ sga1Δ/Δ mutants exhibited long-term survival defects in vitro under starvation conditions and in vivo during vaginal colonization. A complete inability to catabolize glycogen (gph1Δ/Δ sga1Δ/Δ) also rendered C. albicans significantly less virulent during disseminated infections. This is the first study fully validating the glycogen metabolism pathways in C. albicans, and the results further suggest that intracellular glycogen catabolism positively impacts the long-term fitness of C. albicans in nutrient deficient environments and is important for full virulence. IMPORTANCE Glycogen is a highly branched polymer of glucose and is used across the tree of life as an efficient and compact form of energy storage. Whereas glycogen metabolism pathways have been studied in model yeasts, they have not been extensively explored in pathogenic fungi. Using a combination of microbiologic, molecular genetic, and biochemical approaches, we reveal orthologous functions of glycogen metabolism genes in the fungal pathogen Candida albicans. We also provide evidence that extracellular glycogen poorly supports growth across the Candida species and clinical isolates. Competitive fitness assays reveal that the loss of glycogen synthesis or catabolism significantly impacts survival during both in vitro starvation and the colonization of the mouse vagina. Moreover, a global glycogen catabolism mutant is rendered less virulent during murine invasive candidiasis. Therefore, this work demonstrates that glycogen metabolism in C. albicans contributes to survival and virulence in the mammalian host and may be a novel antifungal target.

Background Current stroke guidelines recommend advanced imaging (computed tomography [CT] perfusion or magnetic resonance imaging) prior to endovascular therapy (EVT) in patients with late presentation of large vessel occlusion. Adherence to guidelines may be constrained by resources or timely access to imaging. We sought to understand the factors which influence late window imaging selection for EVT candidates with large vessel occlusion. Methods We conducted an international survey from January to May 2022. The questions aimed to identify advanced imaging and treatment decisions based on access to imaging, time delays, and simulated patient scenarios. Results There were 3000 invited participants and 1506 respondents, the majority (89.6%) from comprehensive stroke centers in high‐income countries. Neurointerventionalists comprised 31.8% and noninterventionalists 68.2% of respondents. Overall, 70.7% reported routine use of advanced imaging for late EVT selection, and 63.6% reported its usage in every case. There was greater availability of advanced imaging in comprehensive stroke centers versus primary stroke centers (67.0% versus 33.7%; P

Nociceptors are kinds of sensory neurons that send warning information to the central nervous system in response to noxious stimuli. Thermal nociception happens as the thermal stimulus exceeds 45 °C as this temperature is perceived to be potentially harmful. Simulating this function is of great significance to developing bioinspired electronic skins and humanoid robots, which thus creates more demands for electronic devices that can simulate thermal nociception. Herein, an artificial thermal nociceptor (ATN) is fabricated by integrating a temperature sensor and a synaptic transistor, which can simulate the thermal pain threshold of the human body and operates in a very similar way as the transient receptor potential vanilloid 1 (TRPV1). For this ATN, the function of temperature sensing is realized by a graphite–polydimethylsiloxane (Gr–PDMS) composite temperature sensor, and the synaptic functions, as well as nociceptor features, are emulated through a synaptic transistor using xanthan gum polysaccharide electrolyte as gate dielectric, providing energy‐efficient building blocks for brain‐inspired computation systems. In a word, the ATN proposed can help to open a new avenue and provides more possibilities in the design of artificial sensory systems with the functions of temperature perception and thermal feedback.

In order to reveal the process and mechanism of gas flow in a low-permeability coal seam, a new multiple-relaxation-time lattice Boltzmann method (MRT-LBM) model of gas migration in coal micro/nanopores based on Langmuir monolayer adsorption theory, the slip boundary scheme and Bosanquet effective viscosity was established. The software MATLAB was used to carry out the simulation study of uniform pore gas flow based on the MRT-LBM model, and the results were compared and verified with the porous anodic alumina membrane gas flow experimental results. On this basis, the gas flow in coal pores with different micro/nanopore sizes considering adsorption was simulated. The results show that the dimensionless permeability coefficient increases with decreasing pore size under the same pressure, which reflects the subsequent enhancement of the microboundary constraint effect and reveals that the pore system becomes the main controlling factor of coal seam permeability within the coal matrix in the middle and late stages of coal seam gas extraction, while the role of the microboundary constraint effect needs to be considered. The gas adsorption layer weakens the pore gas flow capacity, but for pores with a radius greater than 16 nm, the apparent change in permeability caused by the adsorption layer is less than 5%, and the adsorption effect can be ignored. N2, CH4, and CO2 enter the transition flow regime under different pressure conditions; with gas extraction, the gas pressure decreases, and the difference in the gas flow characteristics of the three gases increases.

Background and PurposeOptimal blood pressure management of patients with basilar artery occlusion (BAO) remains uncertain. This study aimed to investigate the relationship between admission blood pressure and clinical outcomes following acute BAO.Materials and MethodsWe analyzed data from a prospective, nationwide cohort study of 829 patients with acute BAO and posterior circulation stroke. Baseline systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded on admission. The primary outcome was neurological functional disability based on the modified Rankin Scale (mRS) score at 90 days. Secondary outcomes included successful reperfusion, mortality within 90 days, and National Institutes of Health Stroke Scale (NIHSS) score change. Multivariable logistic regression was used to assess the associations of SBP and DBP with outcomes.ResultsWe include 829 patients with posterior circulation stroke and BAO between January 2014 and May 2019. Multivariate logistic regression showed high SBP and DBP correlated with unfavorable outcomes. The favorable prognosis (mRS ≤ 3) rates of the low-to-normal and the hypertension groups were 34.8 and 23.9%, respectively. After adjusting for covariates, multivariate regression analysis demonstrated that an SBP > 140 mm Hg was associated with a poor functional outcome [adjusted OR (aOR), 1.509; 95% CI, 1.130–2.015] and mortality at 90 days (aOR, 1.447; 95% CI, 1.055–1.985), and predicted a lower probability of successful reperfusion (aOR, 0.550; 95% CI, 0.389–0.778). The risk of symptomatic intracranial hemorrhage and the NIHSS score at 24 h were not significantly different between the high SBP group and the low-to-normal blood pressure group. And the results for DBP were similar.ConclusionAmong patients with acute BAO, higher systolic or DBP at admission was associated with poor stroke outcomes and had a lower probability of successful reperfusion, with an increased risk of mortality. Trail Registration: [http://www.chictr.org.cn], [ChiCTR1800014759].

ABSTRACT As increasing evidence emerges that interstrain genetic diversity among Candida albicans clinical isolates underpins phenotypic variation compared to the reference isolate SC5314, new genetic tools are required to interrogate gene function across strain backgrounds. Here, the SAT1-flipper plasmid was reengineered to contain a C. albicans codon optimized hygromycin B resistance gene (CaHygB). Cassettes were PCR-amplified from both SAT1-flipper and CaHygB-flipper plasmids using primers with homologous sequences flanking target genes of interest to serve as repair templates. Ribonucleoprotein (RNP) complexes containing proprietary CRISPR RNAs (crRNAs), universal transactivating CRISPR RNA (tracrRNA), and Cas9 protein were assembled in vitro and transformed, along with both repair templates, by electroporation into C. albicans. Homozygous deletion of the ADE2 gene results in red-pigmented colonies and this gene was used to validate our approach. Both in SC5314 and a variety of clinical isolates (529L, JS15, SJCA1, TW1), homozygous gene targeting was nearly 100% when plating on media containing nourseothricin and hygromycin B with transformation efficiencies exceeding 104 homozygous deletion mutants per μg of DNA. A gene reversion system was also employed with plasmids pDUP3 and pDIS3 engineered to contain the ADH1 terminator and an overlap extension PCR-mediated approach combined with CRISPR-Cas9 targeting at the NEUT5 neutral locus. A variety of single or compound mutants (Δ/Δals3, Δ/Δcph1 Δ/Δefg1, Δ/Δece1) and their revertant strains were constructed and phenotypically validated by a variety of assays, including biofilm formation, hyphal growth, and macrophage IL-1β response. Thus, we have established a cloning-free, modular system for highly efficient homozygous gene deletion and reversion in diverse isolates. IMPORTANCE Recently, phenotypic heterogeneity in Candida albicans isolates has been recognized as an underappreciated factor contributing to gene diversification and broadly impacts strain-to-strain antifungal resistance, fitness, and pathogenicity. We have designed a cloning-free genetic system for rapid gene deletion and reversion in C. albicans clinical isolates that interlaces established recyclable genetic systems with CRISPR-Cas9 technology. The SAT1-flipper was reengineered to contain CaHygB encoding resistance to hygromycin B. Using a modular PCR-mediated approach coupled with in vitro ribonucleoprotein assembly with commercial reagents, both SAT1- and CaHygB-flipper cassettes were simultaneously integrated at loci with high efficiency (104 transformants per μg DNA) and upward of 99% homozygous gene targeting across a collection of diverse isolates of various anatomical origin. Revertant strains were constructed by overlap extension PCR with CRISPR-Cas9 targeted integration at the NEUT5 locus. Thus, this facile system will aid in unraveling the genetic factors contributing to the complexity of intraspecies diversity.

As the prevalence of Staphylococcus aureus infections is of worldwide concern, phenotype and genotype in prevalent MRSA strains require longitudinal investigation. In this study, the antibiotic resistance, virulence gene acquisition, and molecular type were determined on a large scale of nosocomial S. aureus strains in Southern China during 2009–2015. Bacterial identification and antimicrobial susceptibility to 10 antibiotics were tested by Vitek-2. Virulence genes encoding staphylococcal enterotoxins (SEA, SEB, SEC, SED, and SEE), exfoliative toxins (ETA and ETB), Panton–Valentine leukocidin (PVL), and toxic shock syndrome toxin (TSST) were detected by PCR, with SCCmec typing also conducted by multiplex PCR strategy. Genotypes were discriminated by MLST and spaA typing. MLST was performed by amplification of the internal region of seven housekeeping genes. PCR amplification targeting the spa gene was performed for spa typing. No resistance to vancomycin, linezolid, or quinupristin and increase in the resistance to trimethoprim/sulfamethoxazole (55.5%) were identified. A total of nine SCCmec types and subtypes, thirteen STs clustered into thirteen spa types were identified, with ST239-SCCmec III-t037 presenting the predominant methicillin-resistant S. aureus (MRSA) clone. Typically, SCCmec type IX and ST546 were emergent types in China. Isolates positive for both pvl and tsst genes and for both eta and etb genes were also identified. Important findings in this study include: firstly, we have provided comprehensive knowledge on the molecular epidemiology of MRSA in Southern China which fills the gap since 2006 or 2010 from previous studies. Secondly, we have presented the correlation between virulence factors (four major groups) and genotypes (SCCmec, ST and spa types). Thirdly, we have shown evidence for earliest emergence of type I SCCmec from 2012, type VI from 2009 and type XI from 2012 in MRSA from Southern China.

Pre conditioning injury or environmental enrichment have been shown to promote axon regeneration. Here the authors show that environmental enrichment, combined with preconditioning injury promotes regeneration via a redox signalling dependent mechanism.

Abstract Background Body size traits as one of the main breeding selection criteria was widely used to monitor cattle growth and to evaluate the selection response. In this study, body size was defined as body height (BH), body length (BL), hip height (HH), heart size (HS), abdominal size (AS), and cannon bone size (CS). We performed genome-wide association studies (GWAS) of these traits over the course of three growth stages (6, 12 and 18 months after birth) using three statistical models, single-trait GWAS, multi-trait GWAS and LONG-GWAS. The Illumina Bovine HD 770 K BeadChip was used to identify genomic single nucleotide polymorphisms (SNPs) in 1217 individuals. Results In total, 19, 29, and 10 significant SNPs were identified by the three models, respectively. Among these, 21 genes were promising candidate genes, including SOX2, SNRPD1, RASGEF1B, EFNA5, PTBP1, SNX9, SV2C, PKDCC, SYNDIG1, AKR1E2, and PRIM2 identified by single-trait analysis; SLC37A1, LAP3, PCDH7, MANEA, and LHCGR identified by multi-trait analysis; and P2RY1, MPZL1, LINGO2, CMIP, and WSCD1 identified by LONG-GWAS. Conclusions Multiple association analysis was performed for six growth traits at each growth stage. These findings offer valuable insights for the further investigation of potential genetic mechanism of growth traits in Simmental beef cattle.

Vulvovaginal candidiasis (VVC), caused primarily by the human fungal pathogen Candida albicans, results in significant quality-of-life issues for women worldwide. Candidalysin, a toxin derived from a polypeptide (Ece1p) encoded by the ECE1 gene, plays a crucial role in driving immunopathology at the vaginal mucosa. This study aimed to determine if expression and/or processing of Ece1p differs across C. albicans isolates and whether this partly underlies differential pathogenicity observed clinically. Using a targeted sequencing approach, we determined that isolate 529L harbors a similarly expressed, yet distinct Ece1p isoform variant that encodes for a predicted functional candidalysin; this isoform was conserved amongst a collection of clinical isolates. Expression of the ECE1 open reading frame (ORF) from 529L in an SC5314-derived ece1Δ/Δ strain resulted in significantly reduced vaginopathogenicity as compared to an isogenic control expressing a wild-type (WT) ECE1 allele. However, in vitro challenge of vaginal epithelial cells with synthetic candidalysin demonstrated similar toxigenic activity amongst SC5314 and 529L isoforms. Creation of an isogenic panel of chimeric strains harboring swapped Ece1p peptides or HiBiT tags revealed reduced secretion with the ORF from 529L that was associated with reduced virulence. A genetic survey of 78 clinical isolates demonstrated a conserved pattern between Ece1p P2 and P3 sequences, suggesting that substrate specificity around Kex2p-mediated KR cleavage sites involved in protein processing may contribute to differential pathogenicity amongst clinical isolates. Therefore, we present a new mechanism for attenuation of C. albicans virulence at the ECE1 locus.

Machine learning (ML) is perhaps the most useful tool for the interpretation of large genomic datasets. However, the performance of a single machine learning method in genomic selection (GS) is currently unsatisfactory. To improve the genomic predictions, we constructed a stacking ensemble learning framework (SELF), integrating three machine learning methods, to predict genomic estimated breeding values (GEBVs). The present study evaluated the prediction ability of SELF by analyzing three real datasets, with different genetic architecture; comparing the prediction accuracy of SELF, base learners, genomic best linear unbiased prediction (GBLUP) and BayesB. For each trait, SELF performed better than base learners, which included support vector regression (SVR), kernel ridge regression (KRR) and elastic net (ENET). The prediction accuracy of SELF was, on average, 7.70% higher than GBLUP in three datasets. Except for the milk fat percentage (MFP) traits, of the German Holstein dairy cattle dataset, SELF was more robust than BayesB in all remaining traits. Therefore, we believed that SEFL has the potential to be promoted to estimate GEBVs in other animals and plants.

Non-small cell lung cancer (NSCLC) is the most deadly cancer in the world due to its often delayed diagnosis. Identification of biomarkers with high sensitivity, specificity, and accessibility for early detection, such as circulating microRNAs, is therefore of utmost importance. In the present study, we identified a significantly higher expression of miR-146a-5p in the serum and tissue samples of NSCLC patients than that of the healthy controls. In parallel, miR-146a-5p was also highly expressed in three human NSCLC adenocarcinoma-cell lines (A549, H1299, and H1975) compared to the human bronchial epithelium cell line (HBE). By dual-luciferase reporter assay and manipulation of the expressions of miR-146a-5p and its target gene, tumor necrosis factor receptor-associated factor 6 (TRAF6), we showed that the functional effects of miR-146a-5p on NSCLC cell survival and migration were mediated by direct binding to and suppression of TRAF6. Overexpression of TRAF6 sufficiently reversed miR-146a-5p-induced cancer cell proliferation, migration, and apoptosis resistance. Our data implied that miR-146a-5p/TRAF6/NF-κB-p65 axis could be a promising diagnostic marker and a therapeutic target for NSCLC.

Chinese Simmental beef cattle are the most economically important cattle breed in China. Estimated breeding values for growth, carcass, and meat quality traits are commonly used as selection criteria in animal breeding. The objective of this study was to evaluate the accuracy of alternative statistical methods for the estimation of genomic breeding values. Analyses of the accuracy of genomic best linear unbiased prediction (GBLUP), BayesB, and elastic net (EN) were performed with an Illumina BovineHD BeadChip on 1,217 animals by applying 5-fold cross-validation. Overall, the accuracies ranged from 0.17 to 0.296 for ten traits, and the heritability estimates ranged from 0.36 to 0.63. The EN (alpha = 0.001) model provided the most accurate prediction, which was also slightly higher (0.2-2%) than that of GBLUP for most traits, such as average daily weight gain (ADG) and carcass weight (CW). BayesB was less accurate for each trait than were EN (alpha = 0.001) and GBLUP. These findings indicate the importance of using an appropriate variable selection method for the genomic selection of traits and suggest the influence of the genetic architecture of the traits we analyzed.

Metro barrier-detection has been one of the most popular research fields. How to detect obstacles quickly and accurately during metro operation is the key issue in the study of automatic train operation. Intelligent monitoring systems based on computer vision not only complete safeguarding tasks efficiently but also save a great deal of human labor. Deep convolutional neural networks (DCNNs) are the most state-of-the-art technology in computer vision tasks. In this paper, we evaluated the effectiveness in classifying the common facility images in metro tunnels based on Google’s Inception V3 DCNN. The model requires fewer computational resources. The number of parameters and the computational complexity are much smaller than similar DCNNs. We changed its architecture (the last softmax layer and the auxiliary classifier) and used transfer learning technology to retrain the common facility images in the metro tunnel. We use mean average precision (mAP) as the metric for performance evaluation. The results indicate that our recognition model achieved 90.81% mAP. Compared with the existing method, this method is a considerable improvement.

BACKGROUND: The occurrence and prevalence of integrons in clinical microorganisms and their role played in antimicrobial resistance have been well studied recently. As screening and detection of integrons are concerned, current diagnostic methodologies are restricted by significant drawbacks and novel methods are required for integrons detection. RESULTS: In this study, three loop-mediated isothermal amplification (LAMP) assays targeting on class 1, 2 and 3 integrons were implemented and evaluated. Optimization of these detection assays were performed, including studing on the reaction temperature, volume, time, sensitivity and specificity (both primers and targets). Application of the established LAMP assays were further verified on a total of 1082 isolates (previously identified to be 397 integron-positive and 685 integron-negative strains). According to the results, the indispensability of each primer had been confirmed and the optimal reaction temperature, volume and time were found to be 65°C, 45 min and 25 µL, respectively. As application was concerned, 361, 28 and 8 isolates carrying intI1, intI2 and intI3 yielded positive amplicons, respectively. Other 685 integron-negative bacteria were negative for the integron-screening LAMP assays, totaling the detection rate and specificity to be 100%. CONCLUSIONS: The intI1-, intI2- and intI3-LAMP assays established in this study were demonstrated to be the valid and rapid detection methodologies for the screening of bacterial integrons.

Improving mental well-being is essential for social workers. Self-care services are often facilitated to enhance it, but there is limited research exploring their characteristics and effectiveness. We conducted a systematic review of self-care interventions targeting the mental well-being of social workers. A comprehensive search of four English and one Chinese databases yielded 2969 studies for initial screening. Fourteen eligible studies were finally included and reviewed. The results underscored mindfulness as prevalent and effective, with social work students being the main service recipients. Although with limitations, the findings inform future research and self-care services for social workers. [ABSTRACT FROM AUTHOR]

Self-care has been widely used in the field of social work as an effective practice for improving social workers' well-being. However, its interventional implementation in China is still unknown. A scoping review was employed to examine the self-care interventions for improving social workers' mental health and well-being and their effectiveness in Mainland China. While 2233 relevant studies from English and Chinese databases were retrieved, no study was determined to be ineligible because no interventional practices were conducted. The current state of research calls for widespread dissemination and efforts in addressing and implementing self-care interventions for Chinese social workers to enhance their mental well-being. [ABSTRACT FROM AUTHOR]

Background: Previous trials confirmed the benefit of endovascular treatment (EVT) in acute large core stroke, but the effect of EVT on outcomes in these patients based on noncontrast computed tomography (NCCT) in real-world clinical practice was unclear. The aim of this study was to explore the effect of EVT versus standard medical treatment (SMT) in patients with large ischemic core stroke defined as Alberta Stroke Program Early CT Score (ASPECTS) =5 based on NCCT alone. Materials and methods: Patients with acute large core stroke at 38 Chinese centers between November 2021 and February 2023 were reviewed from a prospectively maintained database. The primary outcome was favorable functional outcome [modified Rankin Scale score (mRS), 0-3] at 90 days. Safety outcomes included 48 h symptomatic intracerebral hemorrhage (sICH) and 90-day mortality. Results: Of 745 eligible patients recruited at 38 stroke centers between November 2021 and February 2023, 490 were treated with EVT+SMT and 255 with SMT alone. One hundred and eighty-one (36.9%) in the EVT group achieved favorable functional independence versus 48 (18.8%) treated with SMT only [adjusted risk ratio (RR), 1.86; 95% CI: 1.43-2.42, P<0.001; adjusted risk difference (RD), 13.77; 95% CI: 7.40-20.15, P <0.001]. The proportion of sICH was significantly higher in patients undergoing EVT (13.3 vs. 2.4%; adjusted RR, 5.17; 95% CI: 2.17-12.32, P<0.001; adjusted RD, 10.10; 95% CI: 6.12-14.09, P<0.001). No significant difference of mortality between the groups was observed (41.8 vs. 49.0%; adjusted RR, 0.91; 95% CI: 0.77-1.07, P =0.24; adjusted RD, - 5.91; 95% CI: - 12.91-1.09, P=0.1). Conclusion: Among patients with acute large core stroke based on NCCT in real-world, EVT is associated with better functional outcomes at 90 days despite of higher risk of sICH. Rates of procedure-related complications were relatively higher in the EVT+SMT group. [ABSTRACT FROM AUTHOR]