Demonstration of charge-hold-vent (CHV) and no-vent-fill (NVF) in a simulated propellent storage tank during tank-to-tank cryogen transfer in microgravity.

The space exploration from a low earth orbit to a high earth orbit, then to Moon, Mars, and possibly asteroids and moons of other planets is one of the biggest challenges for scientists and engineers for the new millennium. The enabling of in-space cryogenic rocket engines and the Lower-Earth-Orbit (LEO) cryogenic fuel depots for these future manned and robotic space exploration missions begins with the technology development of advanced cryogenic thermal-fluid management systems for the propellant transfer line and storage tank system. One of the key thermal-fluid management operations is the chilldown and filling of the propellant storage tank in space. As a result, highly energy efficient, breakthrough concepts for quenching heat transfer to conserve and minimize the cryogen consumption during chilldown have become the focus of engineering research and development, especially for the deep-space mission to Mars. In this paper, we introduce such thermal transport concepts and demonstrate their feasibilities in space for cryogenic propellant storage tank chilldown and filling in a simulated space microgravity condition on board an aircraft flying a parabolic trajectory. In order to maximize the storage tank chilldown thermal efficiency for the least amount of required cryogen consumption, the breakthrough quenching heat transfer concepts developed include the combination of charge-hold-vent (CHV) and no-vent-hold (NVF). The completed flight experiments successfully demonstrated the feasibility of the concepts and discovered that spray cooling combined with hold and vent is more efficient than the pure spray cooling for storage tank chilldown in microgravity. In microgravity, the data shows that the CHV thermal efficiency can reach 39.5%. The CHV efficiency in microgravity is 6.9% lower than that in terrestrial gravity. We also found that pulsing the spray can increase CHV efficiency by 6.1% in microgravity.

A novel non-invasive embryo evaluation method (NICS-Timelapse) with enhanced predictive precision and clinical impact.

The selection of the finest possible embryo in in-vitro fertilization (IVF) was crucial and revolutionary, particularly when just one embryo is transplanted to lessen the possibility of multiple pregnancies. However, practical usefulness of currently used methodologies may be constrained. Here, we established a novel non-invasive embryo evaluation method that combines non-invasive chromosomal screening (NICS) and Timelapse system along with artificial intelligence algorithms. With an area under the curve (AUC) of 0.94 and an accuracy of 0.88, the NICS-Timelapse model was able to predict blastocyst euploidy. The performance of the model was further evaluated using 75 patients in various clinical settings. The clinical pregnancy and live birth rates of embryos predicted by the NICS-Timelapse model, showing that embryos with higher euploid probabilities were associated with higher clinical pregnancy and live birth rates. These results demonstrated the NICS-Timelapse model's significantly wider application in clinical IVF due to its excellent accuracy and noninvasiveness.

The association between alcohol consumption and blood lipids in Chinese children and adolescent: findings from the China Health and Nutrition Survey.

BACKGROUND: Alcohol consumption by children and adolescents is receiving increasing attention. It may cause dyslipidemia, a risk factor for cardiovascular disease. However, the association between alcohol consumption and blood lipids in children and adolescents is unclear, and so we aimed to characterize this association. METHODS: Data from the China Health and Nutrition Survey were extracted from children and adolescents aged 7-18 years for whom information was available on alcohol consumption. The population was divided into drinking and nondrinking groups. The χ2, Student's t, or Mann-Whitney U test was used to compare groups. Univariate and multivariate linear regression and propensity score matching (PSM) analysis were used to identify the association between alcohol consumption and blood lipids. RESULTS: This study included 408 children and adolescents with 35 drinkers and 373 nondrinkers. The drinkers had significantly lower values of total cholesterol (TC) (3.8 mmol/L for nondrinkers versus 3.5 mmol/L for drinkers, p = 0.002) and high-density lipoprotein cholesterol (HDL-C) (1.3 mmol/L for nondrinkers versus 1.2 mmol/L for drinkers, p = 0.007), but not for low-density lipoprotein cholesterol (LDL-C) (2.1 mmol/L for nondrinkers versus 2.0 mmol/L for drinkers, p = 0.092) or triglyceride (TG) (0.9 mmol/L for nondrinkers versus 0.8 mmol/L for drinkers, p = 0.21). The univariate and multivariate analyses led to the same conclusions. After PSM there was still a significant negative association between alcohol consumption and TC or HDL-C. CONCLUSION: Alcohol consumption in children and adolescents exhibited significant negative associated with TC and HDL-C, but not with LDL-C or TG. These findings need to be confirmed in future prospective research, and the health effects of blood lipid changes caused by drinking in children and adolescents need to be clarified.

Structural mechanism of voltage-gated sodium channel slow inactivation.

Voltage-gated sodium (NaV) channels mediate a plethora of electrical activities. NaV channels govern cellular excitability in response to depolarizing stimuli. Inactivation is an intrinsic property of NaV channels that regulates cellular excitability by controlling the channel availability. The fast inactivation, mediated by the Ile-Phe-Met (IFM) motif and the N-terminal helix (N-helix), has been well-characterized. However, the molecular mechanism underlying NaV channel slow inactivation remains elusive. Here, we demonstrate that the removal of the N-helix of NaVEh (NaVEhΔN) results in a slow-inactivated channel, and present cryo-EM structure of NaVEhΔN in a potential slow-inactivated state. The structure features a closed activation gate and a dilated selectivity filter (SF), indicating that the upper SF and the inner gate could serve as a gate for slow inactivation. In comparison to the NaVEh structure, NaVEhΔN undergoes marked conformational shifts on the intracellular side. Together, our results provide important mechanistic insights into NaV channel slow inactivation.

A Novel "Microscrew With Tie-Down Sutures" Technique for FGG Anchorage: A Case Report.

The most challenging and time-consuming step in the free gingival graft (FGG) for keratinized mucosa augmentation is the compression suture anchoring the FGG to the periosteum. This article proposed a novel "microscrew with tie-down sutures" technique to anchor the FGG to the recipient site without the traditional trans-periosteum suture. This patient's keratinized mucosa width (KMW) around the healing abutments of teeth #29 and #30 was less than 1 mm. After an apically positioned flap (AFP) was prepared, 2 microscrews were placed at the buccal plate of the alveolar ridge bone, which is the coronal margin of the AFP. Then, the sutures winded between the microscrews and the healing abutments to anchor the FGG. In conclusion, the "microscrew with tie-down sutures" technique offers a feasible and straightforward alternative for the trans-periosteum compression suture, mainly when the periosteum is fragile, thin, or injured.

Design and sample size determination for multiple-dose randomized phase II trials for dose optimization.

The U.S. Food and Drug Administration (FDA) has launched Project Optimus to shift dose selection from the maximum tolerated dose (MTD) to the dose that produces the optimal risk-benefit tradeoff. One approach highlighted in the FDA's guidance involves conducting a randomized phase II trial following the completion of a phase I trial, where multiple doses (typically including the MTD and one or two doses lower than the MTD) are compared to identify the optimal dose that maximizes the benefit-risk tradeoff. This article focuses on the design of such a multiple-dose randomized trial, specifically the determination of the sample size. We generalized the standard definitions of type I error and power to accommodate the unique characteristics of dose optimization and derived a decision rule along with an algorithm to determine the optimal sample size. The resulting design is referred to as MERIT (Multiple-dosE RandomIzed Trial design for dose optimization based on toxicity and efficacy). Simulation studies demonstrate that MERIT has desirable operating characteristics, and a sample size between 20 and 40 per dosage arm often offers reasonable power and type I errors to ensure patient safety and benefit. To facilitate the implementation of the MERIT design, we provide software, available at https://www.trialdesign.org.

Ultra-flat bands at large twist angles in group-V twisted bilayer materials.

Flat bands in 2D twisted materials are key to the realization of correlation-related exotic phenomena. However, a flat band often was achieved in the large system with a very small twist angle, which enormously increases the computational and experimental complexity. In this work, we proposed group-V twisted bilayer materials, including P, As, and Sb in the ß phase with large twist angles. The band structure of twisted bilayer materials up to 2524 atoms has been investigated by a deep learning method DeepH, which significantly reduces the computational time. Our results show that the bandgap and the flat bandwidth of twisted bilayer ß-P, ß-As, and ß-Sb reduce gradually with the decreasing of twist angle, and the ultra-flat band with bandwidth approaching 0 eV is achieved. Interestingly, we found that a twist angle of 9.43° is sufficient to achieve the band flatness for ß-As comparable to that of twist bilayer graphene at the magic angle of 1.08°. Moreover, we also find that the bandgap reduces with decreasing interlayer distance while the flat band is still preserved, which suggests interlayer distance as an effective routine to tune the bandgap of flat band systems. Our research provides a feasible platform for exploring physical phenomena related to flat bands in twisted layered 2D materials.

Multi-omics reveal disturbance of glucose homeostasis in pregnant rats exposed to short-chain perfluorobutanesulfonic acid.

Perfluorobutanesulfonic acid (PFBS), a short-chain alternative to perfluorooctanesulfonic acid (PFOS), is widely used in various products and is increasingly present in environmental media and human bodies. Recent epidemiological findings have raised concerns about its potential adverse health effects, although the specific toxic mechanism remains unclear. This study aimed to investigate the metabolic toxicity of gestational PFBS exposure in maternal rats. Pregnant Sprague Dawley (SD) rats were randomly assigned to three groups and administered either 3% starch gel (control), 5, or 50 mg/kg bw·d PFBS. Oral glucose tolerance tests (OGTT) and lipid profiles were measured, and integrated omics analysis (transcriptomics and non-targeted metabolomics) was employed to identify changes in genes and metabolites and their relationships with metabolic phenotypes. The results revealed that rats exposed to 50 mg/kg bw·d PFBS exhibited a significant decrease in 1-h glucose levels and the area under the curve (AUC) of OGTT compared with the starch group. Transcriptomics analysis indicated significant alterations in gene expression related to cytochrome P450 exogenous metabolism, glutathione metabolism, bile acid secretion, tumor pathways, and retinol metabolism. Differentially expressed metabolites (DEMs) were enriched in pathways such as pyruvate metabolism, the glucagon signaling pathway, central carbon metabolism in cancer, and the citric acid cycle. Co-enrichment analysis and pairwise correlation analysis among genes, metabolites, and outcomes identified several differentially expressed genes (DEGs), including Gstm1, Kit, Adcy1, Gck, Ppp1r3c, Ppp1r3d, and DEMs such as fumaric acid, L-lactic acid, 4-hydroxynonenal, and acetylvalerenolic acid. These DEGs and DEMs may play a role in the modulation of glucolipid metabolic pathways. In conclusion, our results suggest that gestational exposure to PFBS may induce molecular perturbations in glucose homeostasis. These findings provide insights into the potential mechanisms contributing to the heightened risk of abnormal glucose tolerance associated with PFBS exposure.

Enhancing clinical utility: deep learning-based embryo scoring model for non-invasive aneuploidy prediction.

BACKGROUND: The best method for selecting embryos ploidy is preimplantation genetic testing for aneuploidies (PGT-A). However, it takes more labour, money, and experience. As such, more approachable, non- invasive techniques were still needed. Analyses driven by artificial intelligence have been presented recently to automate and objectify picture assessments. METHODS: In present retrospective study, a total of 3448 biopsied blastocysts from 979 Time-lapse (TL)-PGT cycles were retrospectively analyzed. The "intelligent data analysis (iDA) Score" as a deep learning algorithm was used in TL incubators and assigned each blastocyst with a score between 1.0 and 9.9. RESULTS: Significant differences were observed in iDAScore among blastocysts with different ploidy. Additionally, multivariate logistic regression analysis showed that higher scores were significantly correlated with euploidy (p < 0.001). The Area Under the Curve (AUC) of iDAScore alone for predicting euploidy embryo is 0.612, but rose to 0.688 by adding clinical and embryonic characteristics. CONCLUSIONS: This study provided additional information to strengthen the clinical applicability of iDAScore. This may provide a non-invasive and inexpensive alternative for patients who have no available blastocyst for biopsy or who are economically disadvantaged. However, the accuracy of embryo ploidy is still dependent on the results of next-generation sequencing technology (NGS) analysis.

MAPKAP1 orchestrates macrophage polarization and lipid metabolism in fatty liver-enhanced colorectal cancer.

Various factors, including fatty liver and macrophage alterations, influence colorectal cancer (CRC). This study explores the mechanistic role of fatty liver in CRC progression, focusing on macrophage polarization and lipid metabolism. A murine fatty liver model was created with a high-fat diet (HFD), and CRC was induced using AOM and DSS. Single-cell transcriptome sequencing (scRNA-seq) identified MAPKAP1 as a critical gene promoting CRC via M2 macrophage polarization and lipid metabolism reprogramming. Prognosis analysis on the TCGA-CRC dataset confirmed MAPKAP1's significance. In vitro and in vivo experiments demonstrated that EVs from fatty liver cells enhanced MAPKAP1 expression, accelerating CRC development and metastasis. HFD exacerbated CRC, but fatty acid inhibitors delayed progression. Fatty liver upregulates MAPKAP1, driving M2 macrophage polarization and lipid metabolism changes, worsening CRC. These findings suggest potential therapeutic strategies for CRC, particularly targeting lipid metabolism and macrophage-mediated tumor promotion.

Biosynthetic Pathways of Tryptophan Metabolites in Saccharomyces cerevisiae Strain: Insights and Implications.

Tryptophan metabolites, such as 5-hydroxytryptophan (5-HTP), serotonin, and melatonin, hold significant promise as supplements for managing various mood-related disorders, including depression and insomnia. However, their chemical production via chemical synthesis and phytochemical extraction presents drawbacks, such as the generation of toxic byproducts and low yields. In this study, we explore an alternative approach utilizing S. cerevisiae STG S101 for biosynthesis. Through a series of eleven experiments employing different combinations of tryptophan supplementation, Tween 20, and HEPES buffer, we investigated the production of these indolamines. The tryptophan metabolites were analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Notably, setups replacing peptone in the YPD media with tryptophan (Run 3) and incorporating tryptophan along with 25 mM HEPES buffer (Run 4) demonstrated successful biosynthesis of 5-HTP and serotonin. The highest 5-HTP and serotonin concentrations were 58.9 ± 16.0 mg L-1 and 0.0650 ± 0.00211 mg L-1, respectively. Melatonin concentrations were undetected in all the setups. These findings underscore the potential of using probiotic yeast strains as a safer and conceivably more cost-effective alternative for indolamine synthesis. The utilization of probiotic strains presents a promising avenue, potentially offering scalability, sustainability, reduced environmental impact, and feasibility for large-scale production.

Unveiling species diversity within the family Conidiobolaceae (Entomophthorales) in China: Descriptions of two new species and reassessment of the taxonomic position of Conidioboluspolyspermus.

In the present study, two new Conidiobolus s.s. species were described relying on the morphological studies and phylogenetic analysis utilizing nuclear large subunit of rDNA (nucLSU), mitochondrial small subunit of rDNA (mtSSU), and elongation-factor-like gene (EFL) sequences. Conidiobolusjiangxiensissp. nov. is distinguished by its short primary conidiophores, a feature not commonly observed in other Conidiobolus s.s. species. Conversely, Conidiobolusmarcoconidiussp. nov. is characterized by larger primary conidia and the emergence of 2-5 secondary conidia from each branched secondary conidiophores. Additionally, the taxonomic reassessment of C.polyspermus confirms its distinct status within the genus Conidiobolus s.s. Moreover, molecular analyses, incorporating the nucLSU, mtSSU, and EFL sequences, provide robust support for the phylogenetic placement of the two newly described species and the taxonomic identity of C.polyspermus. This investigation contributes valuable insights into the species diversity of Conidiobolaceae in China, enhancing our understanding of the taxonomy within this fungal family.

Hindrance or facilitator? The economic consequences of national demonstration eco-industrial parks in China.

Many countries attach great importance to the green, low-carbon, and circular development of industrial parks. China is one of them and has entered an exploration journey of national demonstration eco-industrial parks (NDEIPs). However, the impact of the transformation of industrial parks into NDEIPs on local economic development still remains a mystery. To address this issue, we develop an empirical study using a combination of the multi-period difference-in-differences method and the propensity score matching method based on the panel data for 266 cities in China from 2001 to 2021. The results show that industrial parks becoming NDEIPs promotes cities' economic development. This conclusion still holds after a series of robustness tests, such as the reverse causality test and the placebo test. Moreover, the park heterogeneity tests show that the economic consequences vary according to differences in levels, industry types, life cycle phases, and the degree of foreign firm agglomeration. The city heterogeneity tests show that the economic consequences differ based on administrative levels, innovation capabilities, technology industrialization, and environmental friendliness. The spatial heterogeneity tests show that the economic consequences differ according to geographical location and whether situated in the Yangtze River Economic Belt. The policy upgrading heterogeneity tests show that the economic consequences differ during the process of policy upgrading and transformation. In addition, the mechanism tests reveal that green innovation, human capital level, and firm attractiveness mediate the relationship between industrial parks becoming NDEIPs and cities' economic development. This study provides a new perspective for understanding the economic effects of the transformation of industrial parks into NDEIPs, and provides a reference for the government on how to maximize these economic effects.

Simple Isopropanol-Assisted Direct Soft Imprint Lithography for Residue-Free Microstructure Patterning.

A direct soft imprint lithography was proposed to realize the direct fabrication of residue-free, well-shaped functional patterns through a single step. This imprint method requires only a simply prepared isopropanol-treated polydimethylsiloxane (PDMS) stamp without any additional resists. Residue-free Ag patterns were successfully fabricated on different substrates by directly imprinting the Ag ink with the isopropanol-treated PDMS stamp. Furthermore, the coffee-ring effect of the imprinting Ag patterns can be eliminated by optimizing the imprinting time, isopropanol-treating time, and imprinting temperatures. Studies show that the residual Ag ink in the contact region can be absorbed by the isopropanol-treated PDMS stamp due to the "like dissolves like" principle. Finally, this method was employed to fabricate the Ag electrodes for the thin-film transistors, attaining a mobility of ∼8 cm2 V-1 s-1, which is comparable to those with vacuum-processed electrodes. This process provides a simple, low-cost, residue-free, coffee-ring-free, and fast patterning method in the field of microelectronics.

The joint effect of long-term exposure to multiple air pollutants on non-accidental and cause-specific mortality: A longitudinal cohort study.

The long-term joint impacts of fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) on mortality are inconclusive. To bridge this research gap, we included 283,568 adults from the Taiwan MJ cohort between 2005 and 2016 and linked with the mortality data until 31 May 2019. Participants' annual average exposures to PM2.5, NO2, and O3 were estimated using satellite-based spatial-temporal models. We applied elastic net-regularised Cox models to construct a weighted environmental risk score (WERS) for the joint effects of three pollutants on non-accidental, cardiovascular, and cancer mortality and evaluated the contribution of each pollutant. The three pollutants jointly raised non-accidental mortality risk with a WERS hazard ratio (HR) of 1.186 (95% CI: 1.118-1.259) per standard deviation increase in each pollutant and weights of 72.8%, 15.2%, and 12.0% for PM2.5, NO2, and O3, respectively. The WERS increased cardiovascular death risk [HR: 1.248 (1.042-1.496)], with PM2.5 as the first contributor and O3 as the second. The WERS also elevated the cancer death risk [HR: 1.173 (1.083-1.270)], where PM2.5 played the dominant role and NO2 ranked second. Coordinated control of these three pollutants can optimise the health benefits of air quality improvements.

Focal adhesion kinase-YAP signaling axis drives drug-tolerant persister cells and residual disease in lung cancer.

Targeted therapy is effective in many tumor types including lung cancer, the leading cause of cancer mortality. Paradigm defining examples are targeted therapies directed against non-small cell lung cancer (NSCLC) subtypes with oncogenic alterations in EGFR, ALK and KRAS. The success of targeted therapy is limited by drug-tolerant persister cells (DTPs) which withstand and adapt to treatment and comprise the residual disease state that is typical during treatment with clinical targeted therapies. Here, we integrate studies in patient-derived and immunocompetent lung cancer models and clinical specimens obtained from patients on targeted therapy to uncover a focal adhesion kinase (FAK)-YAP signaling axis that promotes residual disease during oncogenic EGFR-, ALK-, and KRAS-targeted therapies. FAK-YAP signaling inhibition combined with the primary targeted therapy suppressed residual drug-tolerant cells and enhanced tumor responses. This study unveils a FAK-YAP signaling module that promotes residual disease in lung cancer and mechanism-based therapeutic strategies to improve tumor response.

Terrestrial locomotion characteristics of climbing perch (Anabas testudineus).

The evolution and utilization of limbs facilitated terrestrial vertebrate movement on land, but little is known about how other lateral structures enhance terrestrial locomotion in amphibian fishes without terrestrialized limb structures. Climbing perch (Anabas testudineus) exhibit sustained terrestrial locomotion using uniaxial rotating gill covers instead of appendages. To investigate the role of such simple lateral structures in terrestrial locomotion and the motion-generating mechanism of the corresponding locomotor structure configuration (gill covers and body undulation), we measured the terrestrial kinematics of climbing perch and quantitatively analysed its motion characteristics. The digitized locomotor kinematics showed a unique body postural adjustment ability that enables the regulation of the posture of the caudal peduncle for converting lateral bending force into propulsion. An analysis of the coordination characteristics demonstrated that the motion of the gill cover is kinematically independent of axial undulation, suggesting that the gill cover functions as an anchored simple support pole while axial undulation actively mediates body posture and produces propulsive force. The two identified feature shapes explained more than 87% of the complex lateral undulation in multistage locomotion. The kinematic characteristics enhance our understanding of the underlying coordinating mechanism corresponding to locomotor configurations. Our work provides quantitative insight into the terrestrial locomotor adaptation of climbing perch and sheds light on terrestrial motion potential of locomotor configurations containing a typical aquatic body and restricted lateral structure.

Nonvolatile Modulation of Bi2O2Se/Pb(Zr,Ti)O3 Heteroepitaxy.

The pursuit of high-performance electronic devices has driven the research focus toward 2D semiconductors with high electron mobility and suitable band gaps. Previous studies have demonstrated that quasi-2D Bi2O2Se (BOSe) has remarkable physical properties and is a promising candidate for further exploration. Building upon this foundation, the present work introduces a novel concept for achieving nonvolatile and reversible control of BOSe's electronic properties. The approach involves the epitaxial integration of a ferroelectric PbZr0.2Ti0.8O3 (PZT) layer to modify BOSe's band alignment. Within the BOSe/PZT heteroepitaxy, through two opposite ferroelectric polarization states of the PZT layer, we can tune the Fermi level in the BOSe layer. Consequently, this controlled modulation of the electronic structure provides a pathway to manipulate the electrical properties of the BOSe layer and the corresponding devices.