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Abstract Embryonic stem cells possess the remarkable ability to self-organize into blastocyst-like structures upon induction. These stem cell-based embryo models serve as invaluable platforms for studying embryogenesis and therapeutic developments. Nevertheless, the specific intrinsic regulators that govern this potential for blastoid formation remain unknown. Here we demonstrate an intrinsic program that plays a crucial role in both blastoids and blastocysts across multiple species. We first establish metrics for grading the resemblance of blastoids to mouse blastocysts, and identify the differential activation of gene regulons involved in lineage specification among various blastoid grades. Notably, abrogation of nuclear receptor subfamily 1, group H, member 2 (Nr1h2) drastically reduces blastoid formation. Nr1h2 activation alone is sufficient to rewire conventional ESC into a distinct pluripotency state, enabling them to form blastoids with enhanced implantation capacity in the uterus and contribute to both embryonic and extraembryonic lineages in vivo. Through integrative multi-omics analyses, we uncover the broad regulatory role of Nr1h2 in the transcriptome, chromatin accessibility and epigenome, targeting genes associated with embryonic lineage and the transposable element SINE-B1. The Nr1h2-centred intrinsic program governs and drives the development of both blastoids and early embryos.

Currently, the rapid development of the industrial Internet has led to the creation of a massive number of intelligent agents that are widely and distributively applied in various edge scenarios. The work conditions in these edge scenarios are complex, uncertain, and random. Traditional manual updates or human judgments are used for task decision-making in large-scale distributive intelligent agent edge work scenarios, which lack dynamic perception and autonomous recognition capabilities for edge work conditions. This inevitably leads to low decision-making accuracy, poor reliability, and ultimately, task failure. To address this issue, this study proposes an adaptive task identification strategy based on cloud-edge collaboration. This method utilizes a cloud-edge collaborative industrial intelligent application architecture to achieve cloud-based training and encapsulation of the task model, with online calling at the edge-end. Then, edge-end intelligent agents identify edge work conditions through multi-source data fusion, enabling accurate task decision-making. Finally, the edge-end requests the cloud for task model matching. The effectiveness of the proposed method is validated in an industrial safety situation virtual detection system.

This data report presents prokaryotic metagenome-assembled genomes (MAGs) from a hot spring stream with temperatures between 64 and 100°C. The stream water was filtered and the extracted total DNA was sequenced using the Illumina HiSeq 2500 platform. Approximately 80 Gb of raw data were generated, which were subsequently assembled using MEGAHIT v1.2.9. The MAGs were generated using MetaWRAP with binning approaches of MetaBAT2, CONCOCT and MaxBin2. We constructed 25 medium-quality and 24 high-quality archaeal MAGs, and 152 medium-quality and 112 high-quality bacterial MAGs. The fasta files of these MAGs are available in the NCBI database as well as Mendeley Data. Major phyla identified include Bacteroidota, Chloroflexota, Desulfobacterota, Firmicutes, Patescibacteria, Proteobacteria, Spirochaetota, Verrucomicrobiota, Armatimonadota, Nitrospirota, Acidobacteriota, Elusimicrobiota, Planctomycetota, Candidate division WOR-3, Aquificota, Thermoproteota, and Micrarchaeota. This dataset is valuable for studies on thermophilic genomes, reconstruction of biochemical pathways and gene discovery.

Abstract As one of the most common spatial light modulators, linear micromirror arrays (MMAs) based on microelectromechanical system (MEMS) processes are currently utilized in many fields. However, two crucial challenges exist in the fabrication of such devices: the adhesion of silicon microstructures caused by anodic bonding and the destruction of the suspended silicon film due to residual stress. To solve these issues, an innovative processing method assisted by temporary anchors is presented. This approach effectively reduces the span of silicon microstructures and improves the Euler buckling limit of the silicon film. Importantly, these temporary anchors are strategically placed within the primary etching areas, enabling easy removal without additional processing steps. As a result, we successfully achieved wafer-level, high-yield manufacturing of linear MMAs with a filling factor as high as 95.1%. Demonstrating superior capabilities to those of original MMAs, our enhanced version boasts a total of 60 linear micromirror elements, each featuring a length-to-width ratio of 52.6, and the entire optical aperture measures 5 mm × 6 mm. The linear MMA exhibits an optical deflection angle of 20.4° at 110 Vdc while maintaining exceptional deflection flatness and uniformity. This study offers a viable approach for the design and fabrication of thin-film MEMS devices with high yields, and the proposed MMA is promising as a replacement for digital micromirror devices (DMDs, by TI Corp.) in fields such as spectral imaging and optical communication.

BackgroundObservational studies have indicated a potential association between autoimmune diseases and the occurrence of Osteoarthritis (OA), with an increased risk of mortality among affected patients. However, whether a causal relationship exists between the two remains unknown.MethodsIn the Mendelian randomization (MR) study, we accessed exposure Genome-wide association study (GWAS) data from both the MRC Integrative Epidemiology Unit (MRC-IEU) and the FinnGen consortium. GWAS data for OA were obtained from MRC-IEU. We employed univariable, multivariable, and reverse MR analyses to explore potential associations between autoimmune disorders and OA. Additionally, a two-step mediation MR analysis was performed to investigate indirect factors possibly influencing the relationship between autoimmune disorders and OA. Afterward, we conducted an observational analysis to further explore the relationship between autoimmune disease and occurrence as well as of OA using a real-world database (the MIMIC-IV database). Based on public gene expression sequencing data, we further explored the potential shared pathogenesis between autoimmune diseases and OA.ResultsIn our univariable MR study, we identified five autoimmune diseases that are associated with OA. These include Celiac disease (OR = 1.061, 95% CI = 1.018–1.105, p = 0.005), Crohn’s disease (OR = 1.235, 95% CI = 1.149–1.327, p = 9.44E-09), Ankylosing spondylitis (OR = 2.63, 95% CI = 1.21–5.717, p = 0.015), RA (OR = 1.082, 95% CI = 1.034–1.133, p = 0.001), and Ulcerative colitis (OR = 1.175, 95% CI = 1.068–1.294, p = 0.001). In the mediation effect analysis, it was found that there is no correlation between cytokines and autoimmune diseases and OA. Based on transcriptome data analysis, it was found that metabolism-related pathways play a key role in the co-morbidity of autoimmune diseases and OA.ConclusionOur findings revealed that genes associated with Celiac disease, Crohn’s disease, Ankylosing spondylitis, RA, and Ulcerative colitis were independently linked to the development of OA. Furthermore, we conducted an analysis of potential pathogenic genes between these diseases and OA, offering a novel approach for the simultaneous treatment of multiple conditions.

The TianQin program is an independently proposed space-borne detection initiative from China. The inertial sensor, as a crucial component, is susceptible to disturbances from temperature fluctuations, the impact of which on acceleration measurements remains elusive. Therefore, a comprehensive analysis on the influence of temperature disturbance is necessary to avoid errors in acceleration measurement. In this study, we proposed a complete scheme for calculating the level of acceleration noise. Based on the traditional temperature control scheme of using a heat pipe, we developed a systematic heat transfer simulation model to obtain the temperature signals. These signals can then be converted into the frequency domain and used to calculate the acceleration noise level within the target bandwidth. Our results indicate that, with a temperature control of 0.13 K/Hz1/2@1 mHz, the largest contributions to acceleration noise come from the outgassing effect, radiometer effect, and radiative pressure effect, in descending order. The total noise peak is 3.6×10−12 m/(s2⋅Hz1/2) at 1 mHz, which is more than three orders of magnitude higher than the TianQin target of 10−15 m/(s2⋅Hz1/2). This study provides new avenues for evaluating measurement errors and solutions for the TianQin program.

Adaptive response to physiological oxygen levels (physO2; 5% O2) enables embryonic survival in a low-oxygen developmental environment. However, the mechanism underlying the role of physO2 in supporting preimplantation development, remains elusive. Here, we systematically studied oxygen responses of hallmark events in preimplantation development. Focusing on impeded transcriptional upregulation under atmospheric oxygen levels (atmosO2; 20% O2) during the 2-cell stage, we functionally identified a novel role of HIF-1α in promoting major zygotic genome activation by serving as an oxygen-sensitive transcription factor. Moreover, during blastocyst formation, atmosO2 impeded H3K4me3 and H3K27me3 deposition by deregulating histone-lysine methyltransferases, thus impairing X-chromosome inactivation in blastocysts. In addition, we found atmosO2 impedes metabolic shift to glycolysis before blastocyst formation, thus resulting a low-level histone lactylation deposition. Notably, we also reported an increased sex-dimorphic oxygen response of embryos upon preimplantation development. Together, focusing on genetic and epigenetic events that are essential for embryonic survival and development, the present study advances current knowledge of embryonic adaptive responses to physO2, and provides novel insight into mechanism underlying irreversibly impaired developmental potential due to a short-term atmosO2 exposure.

Abstract Hairy cell leukemia (HCL) is a B-lymphoma induced by BRAF(V600E) mutation. However, introducing BRAF(V600E) in B-lymphocytes fails to induce hematological malignancy, suggesting that BRAF(V600E) needs concurrent mutations to drive HCL ontogeny. To resolve this issue, here we surveyed human HCL genomic sequencing data. Together with previous reports, we speculated that the tumor suppressor TP53, P27, or PTEN restrict the oncogenicity of BRAF(V600E) in B-lymphocytes, and therefore that their loss-of-function facilitates BRAF(V600E)-driven HCL ontogeny. Using genetically modified mouse models, we demonstrate that indeed BRAF(V600E)KI together with Trp53KO or pTENKO in B-lymphocytes induces chronic lymphoma with pathological features of human HCL. To further understand the cellular programs essential for HCL ontogeny, we profiled the gene expression of leukemic cells isolated from BRAF(V600E)KI and Trp53KO or pTENKO mice, and found that they had similar but different gene expression signatures that resemble that of M2 or M1 macrophages. In addition, we examined the expression signature of transcription factors/regulators required for germinal center reaction and memory B cell versus plasma cell differentiation in these leukemic cells and found that most transcription factors/regulators essential for these programs were severely inhibited, illustrating why hairy cells are arrested at a transitional stage between activated B cells and memory B cells. Together, our study has uncovered concurrent mutations required for HCL ontogeny, revealed the B cell origin of hairy cells and investigated the molecular basis underlying the unique pathological features of the disease, with important implications for HCL research and treatment.

Thymic stromal lymphopoietin is a key cytokine involved in the pathogenesis of asthma and other allergic diseases. Targeting TSLP and its signaling pathways is increasingly recognized as an effective strategy for asthma treatment. This study focused on enhancing the affinity of the T6 antibody, which specifically targets TSLP, by integrating computational and experimental methods. The initial affinity of the T6 antibody for TSLP was lower than the benchmark antibody AMG157. To improve this, we utilized alanine scanning, molecular docking, and computational tools including mCSM-PPI2 and GEO-PPI to identify critical amino acid residues for site-directed mutagenesis. Subsequent mutations and experimental validations resulted in an antibody with significantly enhanced blocking capacity against TSLP. Our findings demonstrate the potential of computer-assisted techniques in expediting antibody affinity maturation, thereby reducing both the time and cost of experiments. The integration of computational methods with experimental approaches holds great promise for the development of targeted therapeutic antibodies for TSLP-related diseases.

Abstract Keratins are an integral part of cell structure and function. Here, it is shown that ectopic expression of a truncated isoform of keratin 81 (tKRT81) in breast cancer is upregulated in metastatic lesions compared to primary tumors and patient‐derived circulating tumor cells, and is associated with more aggressive subtypes. tKRT81 physically interacts with keratin 18 (KRT18) and leads to changes in the cytosolic keratin intermediate filament network and desmosomal plaque formation. These structural changes are associated with a softer, more elastically deformable cancer cell with enhanced adhesion and clustering ability leading to greater in vivo lung metastatic burden. This work describes a novel biomechanical mechanism by which tKRT81 promotes metastasis, highlighting the importance of the biophysical characteristics of tumor cells.

Current antimicrobial susceptibility testing (AST) requires 16-24 hours, delaying initiation of appropriate antibiotics. Hence, there is a need for rapid AST. This study aims to develop and evaluate the feasibility of a rapid flow cytometric AST assay to determine minimum inhibitory concentration (MIC) for carbapenem-resistant Acinetobacter baumannii (CRAB). Antibiotic exposure causes increased intracellular reactive oxygen species (ROS) in bacteria. We hypothesized that ROS can be used as a marker to determine MIC. We assessed three CRAB clinical isolates across fifteen antibiotics at various concentrations in a customized 96-well microtiter plate. The antibiotics assessed include amikacin, beta-lactams (ampicillin/sulbactam, aztreonam, cefepime, ceftolozane/tazobactam, doripenem, imipenem, meropenem, and piperacillin/tazobactam), levofloxacin, polymyxin B, rifampicin, trimethoprim/sulfamethoxazole, and tetracyclines (tigecycline and minocycline). These clinical CRAB isolates were assessed for ROS after antibiotic treatment. Increased ROS levels indicated by increased RedoxSensorTM Green (RSG) fluorescence intensity was assessed using flow cytometry (FCM). MIC was set as the lowest antibiotic concentration that gives a ≥1.5-fold increase in mode RSG fluorescence intensity (MICRSG). Accuracy of MICRSG was determined by comparing against microtiter broth dilution method performed under CLSI guidelines. ROS was deemed accurate in determining the MICs for β-lactams (83.3% accuracy) and trimethoprim/sulfamethoxazole (100% accuracy). In contrast, ROS is less accurate in determining MICs for levofloxacin (33.3% accuracy), rifampicin (0% accuracy), amikacin (33.3% accuracy), and tetracyclines (33.3% accuracy). Collectively, this study described an FCM-AST assay to determine antibiotic susceptibility of CRAB isolates within 5 hours, reducing turnaround time up to 19 hours.

We consider a risk model perturbed by a Brownian motion, where the individual claim sizes are dependent on the inter-claim times. We study the Gerber–Shiu functions when ruin is due to a claim or the jump-diffusion process. Integro-differential equations and Laplace transforms satisfied by the Gerber–Shiu functions are obtained. Then, it is shown that the expected discounted penalty functions satisfy defective renewal equations. Explicit expressions can be obtained for exponential claim sizes. Finally, a numerical example is provided to measure the impact of the various dependence parameters in the risk model on the ruin probabilities.

Antibiotic resistance is a global health crisis. Notably, carbapenem-resistant Enterobacterales (CRE) pose a significant clinical challenge due to the limited effective treatment options. This problem is exacerbated by persisters that develop upon antibiotic exposure. Bacteria persisters can tolerate high antibiotic doses and can cause recalcitrant infections, potentially developing further antibiotic resistance. Iron is a critical micronutrient for survival. We aimed to evaluate the utility of iron chelators, alone and in combination with antibiotics, in managing persisters. We hypothesized that iron chelators eradicate CRE persisters in vitro, when administered in combination with antibiotics. Our screening revealed three clinical isolates with bacteria persisters that resuscitated upon antibiotic removal. These isolates were treated with both meropenem and an iron chelator (deferoxamine mesylate, deferiprone or dexrazoxane) over 24 h. Against our hypothesis, bacteria persisters survived and resuscitated upon withdrawing both the antibiotic and iron chelator. Pursuing our aim, we next hypothesized that iron chelation is feasible as a post-antibiotic treatment in managing and suppressing persisters’ resuscitation. We exposed bacteria persisters to an iron chelator without antibiotics. Flow cytometric assessments revealed that iron chelators are inconsistent in suppressing persister resuscitation. Collectively, these results suggest that the iron chelation strategy may not be useful as an antibiotic adjunct to target planktonic bacteria persisters.

We study genuine tripartite entanglement and multipartite entanglement in arbitrary n-partite quantum systems based on complete orthogonal basis (COB). While the usual Bloch representation of a density matrix uses three types of generators, the density matrix with COB operators has one uniformed type of generators which may simplify related computations. We take the advantage of this simplicity to derive useful and operational criteria to detect genuine tripartite entanglement and multipartite entanglement. We first convert the general states to simpler forms by using the relationship between general symmetric informationally complete measurements and COB. Then we derive an operational criteria to detect genuine tripartite entanglement. We study multipartite entanglement in arbitrary dimensional multipartite systems. By providing detailed examples, we demonstrate that our criteria can detect more genuine entangled and multipartite entangled states than the previously existing criteria.

Background: The objective of this study was to estimate the effectiveness of early biologics compared to conventional treatment in the management of Crohn's disease among pediatric and adolescent patients. Methods: A comprehensive literature search was conducted in four electronic databases to identify relevant studies published from inception to 2023. The inclusion criteria comprised randomized controlled trials (RCTs) and cohort studies that reported on the efficacy and clinical outcomes of early biologic therapy compared to late/conventional therapy in children with Crohn's disease. The quality of the studies was assessed using the Cochrane Risk of Bias tool and the Newcastle Ottawa scale. Results: A total of 13 studies (2 RCTs and 11 cohort studies), involving 861 patients, were included in the meta-analysis. The results demonstrated that early biologic therapy was associated with a significantly higher rate of clinical remission (risk ratio [RR] 1.30, 95% confidence interval [CI] 1.10–1.54), lower relapse rates (RR 0.33, 95% CI 0.21–0.53), and improved mucosal healing (RR 1.47, 95% CI 1.10–1.97) compared to late/conventional therapy. However, it should be noted that there was evidence of publication bias among studies reporting clinical remission. Conclusion: In conclusion, early biologic therapy is significantly more effective in achieving clinical remission (within two years of diagnosis), promoting mucosal healing, and reducing relapse rates in pediatric and adolescent patients with Crohn's disease, compared to late/conventional therapy. These findings emphasize the importance of initiating biological therapy early in the treatment of Crohn's disease in this patient population.

Accurate location of the fault section in distribution networks is essential in ensuring power supply reliability and self-healing. Based on the extraction and analysis of fault feature information of automatic monitoring devices， this paper constructs the switching function and fitness function suitable for multi-state and different distributed power sources. It introduces additional fault criteria to improve the traditional fitness function. Moreover， it proposes an improved whale optimization algorithm based on multiple strategies. It uses the Sobol sequence to obtain a uniformly distributed initial population and uses differential variation perturbation factor and adaptive weight to improve the optimization accuracy and convergence speed. The simulation on an example shows that the improved whale optimization algorithm used in fault location is characterized by its strong fault tolerance， high fault identification rate， and optimization stability； Moreover， the algorithm can enhance the solution efficiency of fault location.

Silicon-based optical switch is one of the key components for on-chip optical interconnect systems, and mode division multiplexing technology has been employed to boost optical switches’ channel capacity. However, the majority of the proven multimode optical switches have a switching time in the microsecond range, which is insufficient for some applications. In this paper, we design and experimentally demonstrate a high-speed dual-mode 4 × 4 optical switch based on a mode-diversity scheme, composed of four pairs of mode multiplexers and de-multiplexers, and two optimized single-mode 4 × 4 optical switches. Fast switching is enabled based on the carrier dispersion effect. At the same time, we improve the performances of the optical switch by reducing the number of optical switch units used in the 4 × 4 Spanke–Beneš architecture. Its power consumptions are reduced by ∼17%. Its insertion losses are within 8.8 dB in the wavelength range of 1525–1565 nm in the both sates of “through” and “all-cross”, while the optical signal-to-noise ratios are larger than 12.8 dB. Also, 50 Gbps data transmission experiments verify the device’s data transmission functionality.

Abstract Background Compared with the stomach of ruminant cattle, the stomach of horse is small and mainly for chemical digestion, but the microorganisms in the stomach play an important role in maintaining the homeostasis of the internal environment. Due to the complexity of the microbes in the stomach, little is known about the diversity and structure of bacteria in the equine stomach. Grains are the main energy source for plant-eating livestock and energy is derived through enzymatic hydrolysis of grains into glucose or their microbial fermentation into Volatile fatty acids (VFA). However, the mechanism through which these ingested grains are chemically digested as well as the effect of these grains on the stomach remains elusive. This study explored the effects of feeding different grains (corn, oats, and barley) on bacterial diversity, structure, and composition in the foal’s stomach content. Furthermore, the effects of different grains on the vitality of starch digestion-related stomach enzymes were investigated. Results No significant differences were observed (P > 0.05) in the bacterial rarefaction curves of Operational Taxonomic Units (OTUs) and diversity of the stomach microbiota in all foals. This study also revealed the statistical differences for Firmicutes, Cyanobacteria, Actinobacteria, Fibrobacteres, Lactobacillaceae, Streptococcaceae, Unidentified_Clostridiales, Prevotellaceae, Lactobacillus, Streptococcus, Unidentified_Cyanobacteria, Unidentified_Clostridiales, Lactococcus, Sphingomonas, Lactobacillus_hayakitensis, Lactobacillus_equigenerosi, and Clostridium_perfringens. The linear discriminant analysis effect size analysis revealed 9 bacteria at each classification level. The functional analysis of species information by using FAPROTAX software was able to predict 35 functions, and the top 5 functions were chemoheterotrophy, fermentation, animal_parasites_or_symbionts, nitrate_reduction, and aerobic_chemoheterotrophy. The study also revealed statistical differences for pH, glucose concentration, β-amylase, maltase, and amylase. Conclusions The different grains had no significant effect on the microbial diversity of the stomach content of the foal. However, the relative bacterial abundances differed significantly in response to different diets. Particularly, oats fed to the foals significantly increased the relative abundance of Firmicutes, Lactobacillaceae, Lactobacillus, and Lactobacillus_hayakitensis. The grain had no significant effect on the pH of the stomach content, glucose concentration, and enzyme viability in the foal.

Background: This study assessed the potential cost-effectiveness of high (80–100%) vs low (21–35%) fraction of inspired oxygen (FiO2) at preventing surgical site infections (SSIs) after abdominal surgery in Nigeria, India, and South Africa. Methods: Decision-analytic models were constructed using best available evidence sourced from unbundled data of an ongoing pilot trial assessing the effectiveness of high FiO2, published literature, and a cost survey in Nigeria, India, and South Africa. Effectiveness was measured as percentage of SSIs at 30 days after surgery, a healthcare perspective was adopted, and costs were reported in US dollars ($). Results: High FiO2 may be cost-effective (cheaper and effective). In Nigeria, the average cost for high FiO2 was $216 compared with $222 for low FiO2 leading to a −$6 (95% confidence interval [CI]: −$13 to −$1) difference in costs. In India, the average cost for high FiO2 was $184 compared with $195 for low FiO2 leading to a −$11 (95% CI: −$15 to −$6) difference in costs. In South Africa, the average cost for high FiO2 was $1164 compared with $1257 for low FiO2 leading to a −$93 (95% CI: −$132 to −$65) difference in costs. The high FiO2 arm had few SSIs, 7.33% compared with 8.38% for low FiO2, leading to a −1.05 (95% CI: −1.14 to −0.90) percentage point reduction in SSIs. Conclusion: High FiO2 could be cost-effective at preventing SSIs in the three countries but further data from large clinical trials are required to confirm this.

In order to obtain bright aluminum alloy wires and eliminate the environmental and human hazards of traditional chemical polishing, the H _3 PO _4 -H _2 SO _4 system chemical polishing process was developed for SAL5087, and the surface roughness was measured by laser confocal microscopy and the surface morphology was observed by sweeping electron microscopy as the evaluation index of the polishing quality. The process optimization was carried out by orthogonal experiments and the role of each component was analyzed. The experiments showed that phosphoric acid dominates the polishing process, which can effectively enhance the polishing effect under the synergistic effect with various additives. The surface roughness of the polished wire was reduced to 0.257 μm in the optimum process, and the surface was free of defects such as burrs and scratches.

With the increasing demand for natural interactions, people have realized that an intuitive Computer-Aided Design (CAD) interaction mode can reduce the complexity of CAD operation and improve the design experience. Although interaction modes like gaze and gesture are compatible with some complex CAD manipulations, they still require people to express their design intentions physically. The brain contains design intentions implicitly and controls the corresponding body parts that execute the task. Therefore, building an end-to-end channel between the brain and computer as an auxiliary mode for CAD manipulation will allow people to send design intentions mentally and make their interaction more intuitive. This work focuses on the 1-D translation scene and studies a spatial visual imagery (SVI) paradigm to provide theoretical support for building an electroencephalograph (EEG)-based brain–computer interface (BCI) for CAD manipulation. Based on the analysis of three spatial EEG features related to SVI (e.g., common spatial patterns, cross-correlation, and coherence), a multi-feature fusion-based discrimination model was built for SVI. The average accuracy of the intent discrimination of 10 subjects was 86%, and the highest accuracy was 93%. The method proposed was verified to be feasible for discriminating the intentions of CAD object translation with good classification performance. This work further proves the potential of BCI in natural CAD manipulation.

Abstract Background Sudden cardiac arrest with or without sudden cardiac death (SCD) represents a heterogeneous spectrum of underlying etiology but is often a catastrophic event. Despite improvements in pre‐hospital response and post‐resuscitation care, outcomes remain grim. Thus, we aim to evaluate the predictors of survival in out‐of‐hospital cardiac arrests (OHCAs) and describe autopsy findings of those with the uncertain cause of death (COD). Methods This is a subgroup analysis of the Singapore cohort from the Pan Asian Resuscitation Outcome Study which studied 933 OHCAs admitted to two Singapore tertiary hospitals from April 2010 to May 2012. Results Of the patients analysed, 30.2% (n = 282) had an initial return of spontaneous circulation (ROSC) at the emergency department, 18.0% (n = 168) had sustained ROSC with subsequent admission and 3.4% (n = 32) had survival to discharge. On multivariate analysis, an initial shockable rhythm, a witnessed event, prehospital defibrillation, and shorter time to hospital predicted ROSC as well as survival to discharge. A total of 163 (17.5%) autopsies were performed of which a cardiac etiology of SCD was noted in 92.1% (n = 151). Ischemic heart disease accounted for 54.3% (n = 89) of the autopsy cohort, with acute myocardial infarction (26.9%, n = 44) and myocarditis (3.7%, n = 6) rounding out the top three causes of demise. Conclusion OHCA remains a clinical presentation that portends a poor prognosis. Of those with uncertain COD, cardiac etiology appears to predominate from autopsy study. Identification of prognostic factors will play an important role in improving individual‐level and systemic‐level variables to further optimize outcomes.

A simple and efficient vortex-assisted matrix solid phase dispersion with a ultra-high-performance liquid chromatography-triple quadrupole mass spectrometer (VA-MSPD-UHPLC-MS/MS) was applied for simultaneous extraction and determination of seven alkaloids and three organic acids from Uncariae Ramulas Cum Unicis. The optimal extraction conditions of the target components were obtained by Box-Behnken design (BBD) combined with response surface methodology (RSM). The results of the method validation showed that this analytical method displayed good linearity with a correlation coefficient (r) no lower than 0.9990. The recoveries of ten active ingredients from Uncariae Ramulas Cum Unicis ranged from 95.9% to 103% (RSD ≤ 2.77%). The RSDs of intra-day and inter-day precisions were all below 2.97%. The present method exhibited not only lower solvent and sample usage, but also shorter sample processing and analysis time. Consequently, the developed VA-MSPD-UHPLC-MS/MS method could be successfully and effectively used for the extraction and analysis of ten active components from Uncariae Ramulas Cum Unicis.

Background: The coronavirus disease-2019 (COVID-19) pandemic significantly affected management of cardiovascular disease around the world. The effect of the pandemic on volume of cardiovascular diagnostic procedures is not known. Objectives: This study sought to evaluate the effects of the early phase of the COVID-19 pandemic on cardiovascular diagnostic procedures and safety practices in Asia. Methods: The International Atomic Energy Agency conducted a worldwide survey to assess changes in cardiovascular procedure volume and safety practices caused by COVID-19. Testing volumes were reported for March 2020 and April 2020 and were compared to those from March 2019. Data from 180 centers across 33 Asian countries were grouped into 4 subregions for comparison. Results: Procedure volumes decreased by 47% from March 2019 to March 2020, showing recovery from March 2020 to April 2020 in Eastern Asia, particularly in China. The majority of centers cancelled outpatient activities and increased time per study. Practice changes included implementing physical distancing and restricting visitors. Although COVID testing was not commonly performed, it was conducted in one-third of facilities in Eastern Asia. The most severe reductions in procedure volumes were observed in lower-income countries, where volumes decreased 81% from March 2019 to April 2020. Conclusions: The COVID-19 pandemic in Asia caused significant reductions in cardiovascular diagnostic procedures, particularly in low-income countries. Further studies on effects of COVID-19 on cardiovascular outcomes and changes in care delivery are warranted.

Abstract The impact of organic anion‐transporting polypeptide (OATP) inhibition on systemic and liver exposures of three OATP substrates was investigated in cynomolgus monkeys. A monkey physiologically‐based pharmacokinetic (PBPK) model was constructed to describe the exposure changes followed by OATP functional attenuation. Rosuvastatin, bromfenac, and carotegrast were administered as a single intravenous cassette dose (0.5 mg/kg each) in monkeys with and without predosing with rifampin (RIF; 20 mg/kg) orally. The plasma exposure of rosuvastatin, bromfenac, carotegrast, and OATP biomarkers, coproporphyrin I (CP‐I) and CP‐III were increased 2.3, 2.1, 9.1, 5.4, and 8.8‐fold, respectively, when compared to the vehicle group. The liver to plasma ratios of rosuvastatin and bromfenac were reduced but the liver concentration of the drugs remained unchanged by RIF treatment. The liver concentrations of carotegrast, CP‐I, and CP‐III were unchanged at 1 h but increased at 6 h in the RIF‐treated group. The passive permeability, active uptake, and biliary excretion were characterized in suspended and sandwich‐cultured monkey hepatocytes and then incorporated into the monkey PBPK model. As demonstrated by the PBPK model, the plasma exposure is increased through OATP inhibition while liver exposure is maintained by passive permeability driven from an elevated plasma level. Liver exposure is sensitive to the changes of metabolism and biliary clearances. The model further suggested the involvement of additional mechanisms for hepatic uptakes of rosuvastatin and bromfenac, and of the inhibition of biliary excretion for carotegrast, CP‐I, and CP‐III by RIF. Collectively, impaired OATP function would not reduce the liver exposure of its substrates in monkeys.

Introduction: COVID-19 challenged a graduate medical student Emergency Medicine Clinical Clerkship to transform a 160-hour face-to-face clinical syllabus to a remotely delivered e-learning programme comprising of live streamed lectures, case-based discussions, and telesimulation experiences. This paper outlines the evaluation of the telesimulation component of a programme that was designed as a solution to COVID-19 restriction. Methods: A mixed methods approach was used to evaluate the telesimulation educational activities. Via a post-course online survey student were asked to rate the pre-simulation preparation, level of engagement, confidence in recognising and responding to the four clinical presentations and to evaluate telesimulation as a tool to prepare for working in the clinical environment. Students responded to open-ended questions describing their experience in greater depth. Results: Forty-two (72.4%) out of 58 students responded. 97.62% agreed that participating in the simulation was interesting and useful and 90.48% felt that this will provide a good grounding prior to clinical work. Four key themes were identified: Fidelity, Realism, Engagement and Knowledge, Skills and Attitudes Outcomes. Limitations of telesimulation included the inability to examine patients, perform procedures and experience non-verbal cues of team members and patients; but this emphasised importance of non-verbal cues and close looped communication. Additionally, designing the telesimulation according to defined objectives and scheduling it after the theory teaching contributed to successful execution. Conclusion: Telesimulation is an effective alternative when in-person teaching is not possible and if used correctly, can sharpen non-tactile aspects of clinical care such as history taking, executing treatment algorithms and team communication.

Introduction: Singapore experienced the COVID-19 outbreak from January 2020 and Emergency Departments (ED) were at the forefront of healthcare activity during this time. Medical students who were attached to the EDs had their clinical training affected. Methods: We surveyed teaching faculty in a tertiary teaching hospital in Singapore to assess if they would consider delivering clinical teaching to medical students during the outbreak and conducted a thematic analysis of their responses. Results: 53.6% felt that medical students should not undergo clinical teaching in the ED and 60.7% did not wish to teach medical students during the outbreak. Three themes arose during the analysis of the data - Cognitive Overload of Clinical Teachers, Prioritisation of Clinical Staff Welfare versus Medical Students, and Risk of Viral Exposure versus Clinical Education. Conclusion(s): During a pandemic, a balance needs to be sought between clinical service and education, and faculty attitudes towards teaching in high-risk environments can shift their priorities in favour of providing the former over the latter.

Calcium carbonate (CaCO3) is difficult to deliver in food matrices due to its poor solubility. In this work, CaCO3 powders were encapsulated into Solid-in-Oil-in-Water (S/O/W) emulsions to fabricate delivery systems. The impact of the concentrations of propylene glycol alginate and Xanthan gum (PGA-XG) complexes on the physical stability and structural characteristics of S/O/W calcium-lipid emulsions microspheres were studied. The S/O/W calcium-lipid emulsions were characterized by the particle size, zeta potential, physical stability, and apparent viscosity. The S/O/W calcium-lipid emulsion has higher physical stability (including 6-week storage at 4°C), smaller mean particle size (7.60 ± 1.10 μm), and higher negative zeta-potential (45.91 ± 0.97 mV) when the concentration of PGA-XG complexes was 0.8 wt%. Moreover, Confocal laser scanning microscopy (CLSM) images confirmed that the CaCO3 powders were encapsulated in the O phase. Transmission electron microscopy (TEM) showed that S/O/W calcium-lipid emulsion was spherical. The X-ray diffraction (XRD) analysis further confirmed that CaCO3 was loaded in the S/O/W calcium-lipid emulsion as an amorphous state. The formation mechanism of S/O/W calcium-lipid microspheres was studied by Fourier transform infrared spectroscopy (FTIR) and Raman spectrum analysis. This study provided new ideas that accelerate the creation of a novel type of calcium preparation with higher quality utilization.

This study aims to investigate the effects of commercial probiotic supplementation in water on the performance parameters, carcass traits, immune function, and antioxidant capacity of broiler chicks. In the experiment, 120 Arbor Acres (AA) broilers (60 male and 60 female) were randomly allocated into four groups (G) – G1: basal diet and G2, G3, and G4: basal diet with 1% Lactobacillus casei, 1% L. acidophilus, and 1% Bifidobacterium in the water, lasting 42 days. The experimental results revealed that probiotic additives produced positive impacts on body weight, average daily feed intake (ADFI), and average daily weight gain for female chicks, whereas these probiotics significantly reduced ADFI and the feed conversion ratio of male chicks (P < 0.05). Probiotics efficiently improved eviscerated yield and breast yield while reducing the abdominal fat (P < 0.05) for the male broiler chicks. A marked increase was observed in the weight of the spleen, bursa of Fabricius, and thymus in the treatment group (P < 0.05). Besides, probiotics produced a significant effect on the concentrations of immune-related proteins (P < 0.05) and markedly increased the concentrations of antioxidase and digestive enzymes when compared with the control (P < 0.05). The addition of probiotics dramatically reduced the total counts of Escherichia coli and Salmonella and increased the quantity of Lactobacilli (P < 0.05). The results of the present study demonstrated an increase in growth performance, carcass traits, immune function, gut microbial population, and antioxidant capacity by supplementing 1% probiotics (L. casei, L. acidophilus, and Bifidobacterium) in the water for broilers.

Abstract The design of micropolarizer array (MPA) patterns in Fourier domain provides an efficient approach to reconstruct and investigate the polarization information. Inspired by Alenin’s works, in this paper, we propose an improved design model to cover both 2 × N MPAs and other original MPAs, by which an entirely new class of MPA patterns is suggested. The performance of the new patterns is evaluated through Fourier domain analysis and numerical simulations compared with the existing MPAs. Particularly, we analyze the reconstruction accuracy of the first three Stokes parameters and degree of linear polarization (DoLP) in detail. The experimental results confirm that the 2 × 2 × 2 MPA provides the highest reconstruction quality of s 0, s 1, s 2 and DoLP in terms of quantitative measures and visual quality, while the 3 × 3 diagonal MPA achieves the state-of-the-art best results in case of single-snapshot systems. The guidance of this extended model and new diagonal MPAs show its massive potential for the division of focal plane (DoFP) polarization imaging applications.

Nitrogen deficiency is a major factor that affects the yield and quality of horticultural crops. Differentially expressed proteins were identified in cucumber fruit under nitrogen deficiency treatment, and are expected to be highly useful for dissecting carbon, nitrogen and ascorbate metabolism in cucumber and for improving nitrogen fertilizer utilization. Cucumber plants grown hydroponically in Hoagland solution were transferred to nitrogen-free conditions for 3 or 5 d after the blossom of female flowers. Fruit proteome profiles were assessed using two-dimensional electrophoresis. The relative expression of the genes encoding 50 selected differentially expressed proteins and 4 key enzymes in carbon metabolism was analyzed by qRT-PCR. Resulted showed that most of the identified differentially expressed proteins were mainly associated with carbon metabolism, amino acid biosynthesis, ascorbate metabolism, and proteasomes. Glucose phosphorylation was enhanced, while the pentose phosphate pathway was inhibited. Carbon metabolism and the synthesis of most amino acids was affected significantly, and ascorbate might be accumulated under nitrogen deficiency in cucumber fruit.

In recent years, much attention has been paid to the application of high-speed centrifugal pumps; still, the development of this pump faces several challenges. In order to obtain a more comprehensive understanding of the high-speed centrifugal pump, this paper reviewed the engineering application, technical challenges, and feasible solutions of this pump from the aspects of hydraulic design, including cavitation, hydraulic excitation, efficiency issue at an ultra-low specific speed, and the solution to these problems. The current state of the structural design of the high-speed centrifugal pump was briefly described in addition. For the faults in the existing high-speed centrifugal pump, some research studies on pump monitoring were presented. Finally, the status and shortcomings of the design of the pump were simply analyzed and summarized. It is hoped that this study can provide some references for the design and practical usage of high-speed centrifugal pumps.

In this study, carboxymethyl cellulose (CMC) was added to soybean protein isolate (SPI)-stabilized rice bran oil (RBO) emulsion to improve its physicochemical stability and free fatty acid (FFA) release characteristics. RBO emulsions stabilized by SPI and various contents of CMC were prepared and assessed by measuring zeta potential, particle size, transmission, and microstructure, the rheological properties were analyzed by dynamic shear rheometer. In addition, its chemical stability was characterized by a storage experiment, and the FFA release was explored by a simulated gastrointestinal tract (GIT) model. It showed that the negative charge of the droplets of RBO emulsion was increased with increasing CMC content. The decrease in transmission of SPI-stabilized RBO emulsion with increasing CMC content was due to the droplets not being free to move by the special network interaction and an increase in the viscosity. According to the determination of the reactive substances of lipid hydroperoxide and thiobarbituric acid during 30 days storage at 37°C, the chemical stability of the emulsion added with CMC was enhanced compared with the SPI-stabilized RBO emulsion. In-vitro digestion studies not only evaluated the structural changes of RBO emulsions at different stages, but also found that RBO emulsion with CMC showed a higher level of free fatty acids release in comparison with that without CMC. It indicated that the utilization of CMC can improve the bioavailability of RBO emulsions.

Objective: Delivery of chemotherapeutic drugs to the brain has remained a major obstacle in the treatment of glioma, owing to the presence of the blood-brain barrier and the activity of P-gp, which pumps its substrate back into the systemic circulation. The aim of the present study was to develop an intravenous formulation of HM30181A (HM) to inhibit P-gp in the brain to effectively deliver paclitaxel (PTX) for the treatment of malignant glioma. Methods: Two formulations of solubilized HM were designed on the basis of different solid dispersion strategies: i) spray-drying [polyvinlypyrrolidone (PVP)-HM] and ii) solvent evaporation [HP-β-cyclodextrin (cyclodextrin)-HM]. The P-gp inhibition of these 2 formulations was assessed on the basis of rhodamine 123 uptake in cancer cells. Blood and brain pharmacokinetic parameters were also determined, and the antitumor effect of cyclodextrin-HM with PTX was evaluated in an orthotopic glioma xenograft mouse model. Results: Although both PVP-HM and cyclodextrin-HM formulations showed promising P-gp inhibition activity in vitro, cyclodextrin-HM had a higher maximum tolerated dose in mice than did PVP-HM. Pharmacokinetic study of cyclodextrin-HM revealed a plasma concentration plateau at 20 mg/kg, and the mice began to lose weight at doses above this level. Cyclodextrin-HM (10 mg/kg) administered with PTX at 10 mg/kg showed optimal antitumor activity in a mouse model, according to both tumor volume measurement and survival time (P < 0.05). Conclusions: In a mouse orthotopic brain tumor model, the intravenous co-administration of cyclodextrin-HM with PTX showed potent antitumor effects and therefore may have potential for glioma therapy in humans.

Abstract Background Blueberry (Vaccinium spp.) is a small berry with high economic value. Although cold storage can extend the storage time of blueberry to more than 60 days, it leads to chilling injury (CI) displaying as pedicle pits; and the samples of 0 °C-30 days was the critical point of CI. However, little is known about the mechanism and the molecular basis response to cold stress in blueberry have not been explained definitely. To comprehensively reveal the CI mechanisms in response to cold stress, we performed high-throughput RNA Seq analysis to investigate the gene regulation network in 0d (control) and 30d chilled blueberry. At the same time, the pitting and decay rate, electrolyte leakage (EL), malondialdehyde (MDA) proline content and GSH content were measured. Results Two cDNA libraries from 0d (control) and 30d chilled samples were constructed and sequenced, generating a total of 35,060 unigenes with an N50 length of 1348 bp. Of these, 1852 were differentially expressed, with 1167 upregulated and 685 downregulated. Forty-five cold-induced transcription factor (TF) families containing 1023 TFs were identified. The DEGs indicated biological processes such as stress responses; cell wall metabolism; abscisic acid, gibberellin, membrane lipid, energy metabolism, cellular components, and molecular functions were significantly responsed to cold storage. The transcriptional level of 40 DEGs were verified by qRT-PCR. Conclusions The postharvest cold storage leads serious CI in blueberry, which substantially decreases the quality, storability and consumer acceptance. The MDA content, proline content, EL increased and the GSH content decreased in this chilled process. The biological processes such as stress responses, hormone metabolic processes were significantly affected by CI. Overall, the results obtained here are valuable for preventing CI under cold storage and could help to perfect the lack of the genetic information of non-model plant species.

Anti-idiotypic antibody technology has been widely developed. Here, we prepared the F(ab’)2 fragments of the Cry1F toxin polyclonal antibody as Ab1and screened an anti-idiotype nanobody (VHH) for Bt Cry1F toxin from the camelid naive antibody phage display library. After three cycles of panning, six clones were isolated and subjected to indirect competitive enzyme-linked immunosorbent assay (IC-ELISA) for the detection of the Cry1F toxin. A competition inhibition rate of 47.00% exists between the anti-idiotype nanobody with the highest activity (5B) and Cry1F toxin for F(ab’)2 fragments. The binding abilities between the anti-idiotypic nanobody 5B and brush border membrane vesicles (BBMV) of Ostrinia furnacalis (Guenée) are also good. The anti-idiotypic nanobody 5B expressed through the prokaryotic system has the same activity as in phage form, and mortality compared to controls could reach 23.3% (P

We tested both real and model branches of four local tree species in a wind tunnel, for wind speeds up to 20 m/s. The model branches were same-size replicas of the real branches obtained via photogrammetry and 3D-printed or CNC-machined. Real leaves were attached to the models in approximately similar configuration. After comparing the streamwise force, drag coefficient (based on initial frontal area) and streamwise deflection, we found that the models exhibited similar trends to that of the real branches. Although not identical in value, the measurements for the model branches were similar in magnitude to the real branches. In particular, the drag coefficients appeared to approach very similar plateaus. We believe the differences in streamwise force and deflection to be due to the plastic used for the models, as well as perhaps how the leaves were attached to the models. We thus consider these physical models to be generally feasible for studying tree branches.

This article investigates the causal effect between the stock market and the real economy. Based on the data of China’s A-share market from 1998 to 2017, this article uses the fixed-effect model and other methods to find the causal effect from the perspective of the impact of illiquidity at the individual stock level on enterprise investment decision-making. Empirical results show that stock illiquidity significantly decreases enterprise investment. Information asymmetry is one of the important channels between the stock market and the real economy. The financial constraints and agency conflicts caused by information asymmetry significantly affect the causal effect. Macroeconomic policies to alleviate market information asymmetry can effectively act on the real economy through the stock market. From the microperspective of studying the causal effect, this study controls the time effect and individual effect and further explores the influence mechanism between the stock market and the real economy. Research shows that macroeconomic policies can effectively affect the real economy through the stock market and provides decision-making references for future macropolicy formulation.

Objective: This study aims to investigate the quality of life of children with primary nephrotic syndrome (PNS), assess their parents' disease awareness, and provide a basis for the comprehensive management of children with PNS.Methods: A total of 231 children with PNS who were hospitalized in the Department of Pediatric Renal Rheumatology and Immunology in the ShengJing Hospital of the China Medical University from March 2019 to October 2020 were selected as the study subjects. The subjects and their parents were surveyed via a disease education and communication WeChat group and online questionnaire to investigate the children's quality of life, the needs of the parents, and their knowledge related to the disease.Results: In 93.51% of cases, the child's quality of life was affected, with mild to moderate effects being the most frequent (90.47%). The lowest overall quality of life scores were recorded for children who had been diagnosed 1–3 year prior to inclusion in the study, and the scores plateaued thereafter. On the physical functioning scale, the longer the illness, the greater the physical impact, with children typically experiencing pain and fatigue. The children generally scored low on the emotional functioning scale, exhibiting sleep disturbances for up to 5 years and worrying about accidents. The children's average score on the social functioning scale was high, with males achieving significantly higher scores (69.61 ± 25.42) than females (62.30 ± 27.51), and more than one-third of the children experiencing problems getting along with other teenagers and making friends. The primary problems expressed by parents were anxiety (59%), sadness (44%), fear (43%), and depression (40%), and several parents indicated that they struggled with issues of self-blame.Conclusion: PNS impacts the physical and psychological wellbeing of children suffering from the condition, significantly reduces their quality of life, and negatively impacts the psychological wellbeing of their parents. Therefore, children with PNS and their families need integrated management by doctors, nurses, dieticians, psychotherapists, educational institutions, and social stakeholders to improve their quality of life.

In the process of continuing to investigate ultraviolet b (UVB) irradiation protective constituents from Oplopanax elatus stems, nine new sesquiterpenes, named as eurylosesquiterpenosides A–D (1–4), eurylosesquiterpenols E–I (5–9), and ten known ones (10–19) were gained. Their structures were established by analysis of their NMR spectroscopic data, and electronic circular dichroism calculations were applied to define their absolute configurations. In addition, UVB induced HaCaT cells were used to study their anti-photoaging activities and mechanism. The results consolidated that compounds 7, 11, and 14 could improve the survival rate of HaCaT cells in concentration dependent manner at 10, 25, and 50 μM. Furthermore, western blot assay suggested that all of them could inhibit the expression of matrix metalloproteinase-1 (MMP-1), and increase the level of type I collagen markedly. Compounds 11 and 14 could reduce the phosphorylation of extracellular signal-regulated kinase and p38, respectively. Besides, compounds 7, 11, and 14 could significantly down-regulate the expression of inflammation related protein, such as tumor necrosis factor-α and cyclooxygenase-2, which indicated that they played anti-photoaging activities by reducing MMP-1 expression via down-regulating the production of inflammatory mediators and cytokines in UVB-induced HaCaT cells.