Analytical and clinical validation of multiplex droplet digital PCR assay for detecting pathogenic fungal infection in lungs.

Pulmonary invasive fungal infection in immunocompromised hosts is difficult to diagnose, and current tools for diagnosis or monitoring of response to antifungal treatments have inherent limitations. Droplet digital PCR (ddPCR) has emerged as a promising tool for pulmonary pathogen detection with high sensitivity. This study presents a novel ddPCR panel for rapid and sensitive identification of pulmonary fungal pathogens. First, a ddPCR method for detecting three fungal genera, including Pneumocystis, Aspergillus, and Cryptococcus, was established and evaluated. Then, the clinical validation performance of ddPCR was compared with that of qPCR using 170 specimens, and the 6 specimens with inconsistent results were further verified by metagenomics next-generation sequencing, which yielded results consistent with the ddPCR findings. Finally, the area under the ROC curve (AUC) was used to evaluate the efficiency of ddPCR. While the qPCR identified 16 (9.41%) cases of Aspergillus and 6 (3.53%) cases of Pneumocystis, ddPCR detected 20 (11.76%) Aspergillus cases and 8 (4.71%) Pneumocystis cases. The AUC for Aspergillus, Cryptococcus, and Pneumocystis was 0.974, 0.998, and 0.975, respectively. These findings demonstrated that the ddPCR assay is a highly sensitive method for identifying pathogens responsible for invasive fungal pulmonary infections, and is a promising tool for early diagnosis. .

Zearalenone Decreases Food Intake by Disrupting the Gut-Liver-Hypothalamus Axis Signaling via Bile Acids.

Zearalenone (ZEN) is a mycotoxin that is harmful to humans and animals. In this study, female and male rats were exposed to ZEN, and the results showed that ZEN reduced the farnesoid X receptor (FXR) expression levels in the liver and disrupted the enterohepatic circulation of bile acids (BAs). A decrease in food intake induced by ZEN was negatively correlated with an increase in the level of total BAs. BA-targeted metabolomics revealed that ZEN increased glycochenodeoxycholic acid levels and decreased the ratio of conjugated BAs to unconjugated BAs, which further increased the hypothalamic FXR expression levels. Preventing the increase in total BA levels induced by ZEN via Lactobacillus rhamnosus GG intervention restored the appetite. In conclusion, ZEN disrupted the enterohepatic circulation of BAs to decrease the level of food intake. This study reveals a possible mechanism by which ZEN affects food intake and provides a new approach to decrease the toxic effects of ZEN.

Degradation of Photopic and Mesopic Contrast Sensitivity Function in High Myopes With Partial Posterior Vitreous Detachment.

Purpose: The purpose of this study was to evaluate the effects of posterior vitreous detachment (PVD) on visual quality in patients with high myopia, as well as investigate the associated factors of photopic and mesopic contrast sensitivity function (CSF) in high myopia. Methods: Visual quality was comprehensively assessed in patients with high myopia. Visual acuity, contrast sensitivity (CS) at four spatial frequencies (3, 6, 12, and 18 cycles per degree [c.p.d.]) under photopic and mesopic conditions, as well as the modulation transfer function cutoff value (MTFcutoff), the objective scatter index (OSI), the Strehl ratio (SR), and internal aberrations, were measured in this cross-sectional study. Results: This study included 94 eyes from 47 subjects with bilateral high myopia, including 23 eyes with complete PVD (cPVD), 21 eyes with partial PVD (pPVD), and 50 eyes without PVD (nPVD). There was no significant difference in visual quality between the cPVD group and the nPVD group. Whereas in eyes with pPVD, there was a degradation of overall photopic CSF (versus nPVD, P = 0.048), photopic CS at 3 c.p.d. (versus cPVD, P = 0.009 and versus nPVD, P = 0.032), photopic CS at 18 c.p.d. (versus nPVD, P = 0.033), overall mesopic CSF (versus nPVD, P = 0.033), and secondary astigmatism (versus cPVD, P = 0.044). Under photopic conditions, the factors affecting CSF were pPVD and SR, whereas the factors affecting mesopic CSF were pPVD, OSI, and ganglion cell-inner plexiform layer thickness. Conclusions: The pPVD impaired visual quality in patients with high myopia compared to nPVD or cPVD, and pPVD could be a factor explaining CSF at both photopic and mesopic illumination. Translational Relevance: Clinicians need to closely monitor patients with high myopia with pPVD due to the potential decline in visual quality and the development of vitreoretinal disorders.

African swine fever virus pB318L, a trans-geranylgeranyl-diphosphate synthase, negatively regulates cGAS-STING and IFNAR-JAK-STAT signaling pathways.

African swine fever (ASF) is an acute, hemorrhagic, and severe infectious disease caused by the ASF virus (ASFV). ASFV has evolved multiple strategies to escape host antiviral immune responses. Here, we reported that ASFV pB318L, a trans-geranylgeranyl-diphosphate synthase, reduced the expression of type I interferon (IFN-I) and IFN-stimulated genes (ISGs). Mechanically, pB318L not only interacted with STING to reduce the translocation of STING from the endoplasmic reticulum to the Golgi apparatus but also interacted with IFN receptors to reduce the interaction of IFNAR1/TYK2 and IFNAR2/JAK1. Of note, ASFV with interruption of B318L gene (ASFV-intB318L) infected PAMs produces more IFN-I and ISGs than that in PAMs infected with its parental ASFV HLJ/18 at the late stage of infection. Consistently, the pathogenicity of ASFV-intB318L is attenuated in piglets compared with its parental virus. Taken together, our data reveal that B318L gene may partially affect ASFV pathogenicity by reducing the production of IFN-I and ISGs. This study provides a clue to design antiviral agents or live attenuated vaccines to prevent and control ASF.

Injectable Dynamic ROS-Responsive COF-Modified Microalgae Gels for In Vivo bFGF Delivery to Treat Diabetic Wounds.

Hypoxia, chronic inflammation, and elevated reactive oxygen species (ROS) production induced by hyperglycemia pose formidable challenges to the healing of diabetic chronic wounds, often resulting in impaired recovery. Currently, sustainable and eco-friendly therapeutic approaches targeting this multifaceted problem remain uncharted. Herein, we develop a unique three-functional covalent organic framework (COF)-modified microalgae gel designed for the preparation and treatment of chronic diabetic wounds. The gel comprises an oxygen-releasing basic fibroblast growth factor (bFGF) microalgae matrix, augmented by an ROS-responsive COF. Although two of these components have been reported to be used in wound healing, the combination of all three functions represents an innovative approach to synergize the treatment of chronic diabetic wounds. Therefore, we propose a new concept of "ligand interlocking" with three functional synergistic effects. Specifically, the COF has a similar effect to the "double Excalibur", which binds bFGF to promote angiogenesis and proliferation and inhibit the inflammatory response of chronic wounds and binds live microalgae to eliminate ROS and release dissolved oxygen to alleviate the hypoxia of wounds. Moreover, in vivo experiments and RNA sequencing analyses similarly demonstrated that the COF-modified microalgae gel reduced the inflammatory cascade cycle in the wound site and promoted vascular and tissue regeneration. We posit that the COF-modified microalgae gel represents a promising strategy for the active in vivo delivery of therapeutics to the wound body in intensive care unit settings.

IL-6/STAT3 axis is hijacked by GCRV to facilitate viral replication via suppressing type â IFN signaling.

Grass carp reovirus (GCRV) infections and hemorrhagic disease (GCHD) outbreaks are typically seasonally periodic and temperature-dependent, yet the molecular mechanism remains unclear. Herein, we depicted that temperature-dependent IL-6/STAT3 axis was exploited by GCRV to facilitate viral replication via suppressing type Ⅰ IFN signaling. Combined multi-omics analysis and qPCR identified IL-6, STAT3, and IRF3 as potential effector molecules mediating GCRV infection. Deploying GCRV challenge at 18 °C and 28 °C as models of resistant and permissive infections and switched to the corresponding temperatures as temperature stress models, we illustrated that IL-6 and STAT3 expression, genome level of GCRV, and phosphorylation of STAT3 were temperature dependent and regulated by temperature stress. Further research revealed that activating IL-6/STAT3 axis enhanced GCRV replication and suppressed the expression of IFNs, whereas blocking the axis impaired viral replication. Mechanistically, grass carp STAT3 inhibited IRF3 nuclear translocation via interacting with it, thus down-regulating IFNs expression, restraining transcriptional activation of the IFN promoter, and facilitating GCRV replication. Overall, our work sheds light on an immune evasion mechanism whereby GCRV facilitates viral replication by hijacking IL-6/STAT3 axis to down-regulate IFNs expression, thus providing a valuable reference for targeted prevention and therapy of GCRV.

Changes in Corneal Epithelial Thickness in Different Areas After Femtosecond Laser-Assisted LASIK in Patients With High Astigmatism.

PURPOSE: To explore changes in corneal epithelial thickness (CET) after femtosecond laser-assisted laser in situ keratomileusis in patients with high astigmatism. METHODS: CET was measured at every intersection of the concentric circles and specific axes using AngioVue optical coherence tomography (Angio-OCT) preoperatively and 1 month postoperatively. The average thickness of corneal central, paracentral, and peripheral regions was the mean of the points within the central 2, 2 to 5, and 5 to 7 mm areas, respectively. Correlation analysis was performed to investigate the association between CET along different axes and other preoperative and postoperative parameters. RESULTS: Forty-two eyes of 28 patients were included. CET along the astigmatic (K1) and perpendicular (K2) axes in the central and paracentral areas increased (P < .001), whereas that along the K2 axis decreased in the peripheral area 1 month postoperatively (P = .001). The amount of CET change in the peripheral area between the K1 and K2 axes was significantly different (P < .001). In the central area, the change in CET along the K2 axis was positively correlated with ablation depth (r = 0.315, P = .042) and negatively with refractive power after surgery (r = -0.347, P = .024). In the peripheral area, the changes in CET along both K1 and K2 axes were negatively correlated with ablation depth (r = -0.431, P = .004; r = -0.387, P = .011, respectively). CONCLUSIONS: Epithelial modeling differed between the different astigmatism axes after refractive surgery. The compensatory response of the corneal epithelium is more pronounced along the steeper axis. [J Refract Surg. 2024;40(4):e239-e244.].

Attachment and sleep quality in adults: A multilevel meta-analysis of actor and partner effect.

Within the context of sleep, attachment is hypothesized to play a central role in regulating bedtime affect and arousal. While previous studies have suggested a link between attachment and sleep quality, a meta-analysis specifically examining this association in adults has been lacking. To address this gap, we conducted a series of multilevel meta-analyses of 28 studies on this topic. Our results indicated a correlation between attachment anxiety and an individual's own sleep quality (r = -0.16, p < 0.001), as well as their partner's sleep quality (r = -0.10, p < 0.05). There was also a negative correlation between attachment avoidance and an individual's sleep quality (r = -0.15, p < 0.001) as well as their partner's sleep quality (r = -0.16, p < 0.01). Additionally, the relationships were moderated by several variables, including age, sleep measurement, and gender. Further analysis indicated that attachment anxiety was associated with poorer subjective sleep quality (PSQI) (r = -0.23, p < 0.001), longer sleep latency (r = -0.10, p < 0.05), increased wakefulness after sleep onset (r = -0.09, p < 0.05), and greater daytime sleepiness (r = -0.20, p < 0.01). Attachment avoidance was associated with poorer self-reported sleep quality (PSQI) (r = -0.16, p < 0.001), longer time to fall asleep (r = -0.15, p < 0.05), and increased daytime sleepiness (r = -0.15, p < 0.05). In summary, the findings of the current study supported the association between attachment insecurity and poorer sleep quality in both individuals and their partners. These findings hold important implications for future interventions aimed at improving sleep quality by addressing attachment-related concerns.

Panax notoginseng saponins improve oral submucous fibrosis by inhabiting the Wnt/ß-catenin signal pathway.

OBJECTIVE: Oral submucous fibrosis (OSF) is a chronic, insidious, progressive mucosal disease that may be affected by mutations in the Wnt/ß-catenin signaling pathway. Panax notoginseng saponins (PNS) is a powerful anti-fibrosis agent; however, its effect and mechanism in treating OSF remain unclear. This study investigated the effect and mechanism of PNS treatment for OSF. STUDY DESIGN: Arecoline was used to induce OSF models in vivo and in vitro, which were then treated with PNS. Hematoxylin-eosin (HE) and Masson trichrome staining were used to observe histopathology changes; E-cadherin and ß-catenin were detected by Immunohistochemical assay, and type Ⅰ collagen (CollA1) and ß-catenin were detected by immunofluorescent staining. The Wnt/ß-catenin pathway and fibrosis signs were assessed using Western Blot and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: The expression of CollA1, Wnt1, and ß-catenin were increased, and E-cadherin, GSK-3ß, and ß-catenin expression were decreased in OSF models. PNS and inhibitor intervention increased E-cadherin, Wnt1, and ß-catenin and decreased CollA1 and GSK-3ß in a dose-dependent manner. CONCLUSION: PNS can improve OSF by inhibiting the Wnt/ß-catenin signal pathway and thus may be used as a potential medicine for the treatment of OSF.

Engineering Triple-Phase Interfaces around the Anode towards Practical Alkali Metal-Air Batteries.

Alkali metal-air batteries (AMABs) promise ultrahigh gravimetric energy densities, while the inherent poor cycle stability hinders their practical application. To address this challenge, most previous efforts were devoted to advancing the air cathodes with high electrocatalytic activity. Recent studies have underlined the solid-liquid-gas triple-phase interface around the anode can play far more significant roles than previously acknowledged by the scientific community. Besides the bottlenecks of uncontrollable dendrite growth and gas evolution in conventional alkali metal batteries, the corrosive atmospheric gases, intermediate oxygen species, and redox mediators in AMABs cause more severe anode corrosion and structural collapse, posing greater challenges to the stabilization of the anode triple-phase interface. This work aims to provide a timely perspective on the anode interface engineering for durable AMABs. Taking the Li-air battery as a typical example, we have a critical review of the latest developed anode stabilization strategies, including formulating novel electrolytes to build protective interphases and alleviate corrosive attacks, fabricating advanced anodes to improve their anti-corrosion capability, and designing functional separator to shield the corrosive species. Finally, we highlight the remaining scientific and technical issues from the prospects of anode interface engineering, particularly materials system engineering, for the practical use of AMABs. This article is protected by copyright. All rights reserved.

Clinical outcomes in carriers of insertional translocation: a retrospective analysis of comprehensive chromosome screening results.

Objective: To evaluate the clinical outcomes in the carriers of insertional translocation (IT). Design: Retrospective case series. Setting: University-affiliated reproductive medical center. Patients: Twenty-three couples with ITs. Intervention: No direct interventions were involved; however, this study included patients who underwent preimplantation genetic testing for structural chromosomal rearrangements (PGT-SR). Main Outcome Measure: Outcome of preimplantation genetic testing for structural chromosomal rearrangements and percentage of blastocysts available for transfer. Results: Among 23 IT carriers, 15 were simple interchromosome ITs (type A), 3 were intrachromosome IT carriers (type B), and 5 were interchromosome IT carriers combined with other translocations (type C). A total of 190 blastocysts from 30 cycles were biopsied, 187 embryos were tested successfully, and only 57 blastocysts (30.5%) from 21 patients were available for transfer (normal or balanced). The unbalanced rearrangement rate of type C was 79.2% (42/53), and the proportion of type A was 50.0% (57/114), which was significantly higher than that of type B (5%, 1/20). In type A, the probability of embryos harboring unbalanced rearrangement in female carriers was 56.0% (51/91), which was higher than that in male carriers (26.1%, 6/23). Furthermore, the haploid autosomal length value of the inserted fragment was correlated linearly with the incidence of abnormal embryos. In type A gametes, most gametes produced by 2:2 separation without crossover, and no 3:1 separation gamete was observed. Conclusions: The chance of identifying normal or balanced and mosaic blastocysts per mature oocytes in patients with ITs are 16.6% (67/404). Greater IT complexity results in fewer transferable embryos. For simple interchromosome ITs, female carriers and those with higher haploid autosomal length values have a higher risk of producing embryos with unbalanced rearrangement.

Antimicrobial Resistance and Molecular Characterization of Salmonella Rissen Isolated in China During 2008-2019.

Background: This study aimed to provide epidemiological features of Salmonella enterica serovar Rissen, determine antimicrobial susceptibility, virulence gene profiles, and describe the potential association of S. Rissen from different sources in China. Methods: During 2008-2019, a total of non-repetitive 228 S. Rissen isolates were collected from human, animals and environment in China. The antimicrobial susceptibility test, screening of antimicrobial and virulence genes by PCR, and pulsed-field gel electrophoresis (PFGE) were performed. Results: Among the 154 isolates from human, the majority of the cases (80.5%) occurred in summer, and S. Rissen was mainly detected in people aged 21-40 (37.7%) and 41-60 (28.6%) years old, and 74 non-human source S. Rissen strains were identified, with pork being the most common source. About 93.4% isolates were resistant to at least one of the 12 tested antimicrobial agents, and high frequencies of resistance were observed for tetracyclines (91.2%), trimethoprim-sulfamethoxazole (74.1%) and ampicillin (67.5%). A total of 171 (75%) isolates were resistant to at least three categories of antimicrobials, and the most common resistance profile was Tetracycline(s)-ß-Lactams-Sulfonamides. The resistance rates to chloramphenicol, quinolones and sulfafurazole were significantly higher in strains isolated from human compared to non-human source strains. Among these isolates, the ß-Lactams resistance was mainly associated with gene blaTEM (54.7%), sulfonamide resistance with sul2 (45.7%) and sul3 (54.3%), tetracycline resistance with tetA (81.3%). All the isolates harbored virulence genes hilA, sopB, sciN, stn and ssrB, and most of them harbored ssaQ (98.7%), mgtC (98.7%) and invA (98.2%). The majority (91.7%) of S. Rissen isolates showed high similarity (>80%) with each other in PFGE patterns and came from human, animals and environment. Conclusion: The high frequencies of multidrug resistance and probable clonal dissemination in this serovar call for the necessity of systematic surveillance on S. Rissen in China.

Diagnostic performance of 18F­DCFPyL PET vs. 68Ga­PSMA PET/CT in patients with suspected prostate cancer: A systemic review and meta­analysis.

In this systematic review and meta-analysis, the diagnostic performance of 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/CT was compared with that of 18F-DCFPyL PET for patients with suspected prostate cancer (PCa). Up to September 2023, the PubMed, Embase and Web of Science databases were thoroughly searched for relevant papers. Studies examining the diagnostic performance of 18F-DCFPyL PET and 68Ga-PSMA PET/CT in patients with suspected PCa were included in the present review. The Quality Assessment of Diagnostic Performance Studies-2 tool was used to rate the diagnostic performance of each study. The diagnostic performance of 18F-DCFPyL PET and 68Ga-PSMA PET/CT for primary PCa was examined by 13 studies included, comprising 1,178 patients. The pooled sensitivity and specificity of 18F-DCFPyL PET were 0.92 (95% CI, 0.85-0.96) and 0.59 (95% CI, 0.08-0.96), respectively. For 68Ga-PSMA PET/CT, the pooled sensitivity and specificity were 0.96 (95% CI, 0.88-0.99) and 0.71 (95% CI, 0.57-0.82), respectively. 18F-DCFPyL PET and 68Ga-PSMA PET/CT both had an area under the receiver operating characteristic curve of 0.92 (95% CI, 0.89-0.94). In addition, the Fagan nomogram revealed that the post-test probabilities for 18F-DCFPyL PET and 68Ga-PSMA PET/CT could rise to 69 and 77% when the pre-test probability was set at 50%. In conclusion, a comparable diagnostic performance for patients with suspected PCa was determined for 18F-DCFPyL PET and 68Ga-PSMA PET/CT. However, it is crucial to keep in mind that the findings of the present meta-analysis come from investigations with modest sample sizes. Therefore, more extensive research is required to obtain more solid data.

Structural and functional changes of binocular corneal innervation and ocular surface function after unilateral SMILE and tPRK.

AIMS: To evaluate the bilateral changes in the sub-basal nerve plexus of the cornea and ocular surface function after unilateral small incision lenticule extraction (SMILE) and transepithelial photorefractive keratectomy (tPRK) procedures. METHODS: 34 patients were enrolled in the study and underwent unilateral SMILE (21 of 34 patients) or unilateral tPRK (13 of 34 patients). Complete ophthalmic examinations, tear film function tests and Cochet-Bonnet esthesiometry were conducted to assess the effects of the surgeries on the corneal nerves and tear function. Morphological changes were assessed using in vivo confocal microscopy to evaluate the corneal sub-basal nerve plexus and dendritic cells. ELISA was used to measure the tear neuromediators. Clinical and morphological data at each follow-up point were compared with preoperative baseline values. RESULTS: All patients who underwent unilateral SMILE or tPRK procedures exhibited bilateral corneal nerve degenerative changes, decreased corneal sensitivity, worsening of dry eye symptoms and changes in bilateral tear neuromediators. In the SMILE group, bilateral corneal sensitivity was positively correlated with corneal nerve fibre length and negatively correlated with dendritic cell area. The dry eye severity was negatively correlated with corneal sensitivity. Tear levels of substance P and nerve growth factor were positively correlated with mean dendritic cell area and dry eye severity, but negatively correlated with corneal sensitivity. In the tPRK group, bilateral corneal sensitivity was positively correlated with corneal nerve fibre density. CONCLUSIONS: Unilateral refractive surgery may bilaterally affect the morphology and function of corneal nerves and ocular surface status postoperatively.

TGF-ß1/SMAD3-driven GLI2 isoform expression contributes to aggressive phenotypes of hepatocellular carcinoma.

Hedgehog signaling is activated in response to liver injury, and modulates organogenesis. However, the role of non-canonical hedgehog activation via TGF-ß1/SMAD3 in hepatic carcinogenesis is poorly understood. TGF-ß1/SMAD3-mediated non-canonical activation was found in approximately half of GLI2-positive hepatocellular carcinoma (HCC), and two new GLI2 isoforms with transactivating activity were identified. Phospho-SMAD3 interacted with active GLI2 isoforms to transactivate downstream genes in modulation of stemness, epithelial-mesenchymal transition, chemo-resistance and metastasis in poorly-differentiated hepatoma cells. Non-canonical activation of hedgehog signaling was confirmed in a transgenic HBV-associated HCC mouse model. Inhibition of TGF-ß/SMAD3 signaling reduced lung metastasis in a mouse in situ hepatic xenograft model. In another cohort of 55 HCC patients, subjects with high GLI2 expression had a shorter disease-free survival than those with low expression. Moreover, co-positivity of GLI2 with SMAD3 was observed in 87.5% of relapsed HCC patients with high GLI2 expression, indicating an increased risk of post-resection recurrence of HCC. The findings underscore that suppressing the non-canonical hedgehog signaling pathway may confer a potential strategy in the treatment of HCC.

Predictors of Very Poor Outcome After Mechanical Thrombectomy in Older Patients with Acute Ischemic Stroke.

BACKGROUND: Mechanical thrombectomy (MT) is an effective treatment for patients with acute ischemic stroke due to large vessel occlusion. However, some elderly patients with recanalization have a very poor outcome, including vegetative state and mortality. This study evaluated predictors of very poor outcome at 3 months in older patients with stroke undergoing MT treatment. METHODS: We retrospectively collected data from consecutive stroke patients ≥80 years old undergoing MT between April 2018 and January 2021. A very poor outcome was defined as a modified Rankin Scale (mRS) score of 5 or 6 at 3-month follow-up. Multiple logistic regression analysis was performed to identify the predictors of very poor outcome at 3 months. RESULTS: The study enrolled 62 patients with a median age of 85.5 years (interquartile range: 82.0-89.0). Of patients, 35 (56.5%) had a very poor outcome at 3-month follow-up. Multiple logistic regression analysis identified female sex (odds ratio = 3.592, 95% confidence interval 1.047-12.319, P = 0.042) and stroke-associated pneumonia (odds ratio = 6.103, 95% CI 1.541-24.174, P = 0.010) as independent predictors of very poor outcome. CONCLUSIONS: In elderly stroke patients undergoing MT treatment, female sex and stroke-associated pneumonia were independent predictors of very poor outcome at 3 months.

Freezing Shrinkage Dynamics and Surface Dendritic Growth of Floating Refractory Alloy Droplets in Outer Space.

The freezing shrinkage and dendritic growth are of great importance for various alloys solidified from high-temperature liquids to solids since they dominate microstructure patterns and follow-up processing. However, the microgravity freezing shrinkage dynamics is scarcely explored on the ground as it is hard to suppress the strong natural convection inside liquid alloys. Here, a series of in-orbit solidification experiments is conducted aboard the China Space Station with a long-term stable 10-5 g0 microgravity condition. The highest temperature up to 2265 K together with substantial liquid undercoolings far from a thermodynamically stable state are attained for both Nb82.7Si17.3 and Zr64V36 refractory alloys. Furthermore, the solidification under microgravity of a droplet is simulated to reveal the liquid-solid interface migration, temperature gradient, and flow field. The microgravity solidification process leads to freezing shrinkage cavities and distinctive surface dendritic microstructure patterns. The combined effects of shrinkage dynamics and liquid surface flow in outer space result in the dendrites growing not only along the tangential direction but also along the normal direction to the droplet surface. These space experimental results contribute to a further understanding of the solidification behavior of liquid alloys under a weaker convection condition, which is often masked by gravity on the ground.

The temporal protein signature analyses of developing human deciduous molar tooth germ.

The tooth serves as an exemplary model for developmental studies, encompassing epithelial-mesenchymal transition and cell differentiation. The essential factors and pathways identified in tooth development will help understand the natural development process and the malformations of mineralized tissues such as skeleton. The time-dependent proteomic changes were investigated through the proteomics of healthy human molars during embryonic stages, ranging from the cap-to-early bell stage. A comprehensive analysis revealed 713 differentially expressed proteins (DEPs) exhibiting five distinct temporal expression patterns. Through the application of weighted gene co-expression network analysis (WGCNA), 24 potential driver proteins of tooth development were screened, including CHID1, RAP1GDS1, HAPLN3, AKAP12, WLS, GSS, DDAH1, CLSTN1, AFM, RBP1, AGO1, SET, HMGB2, HMGB1, ANP32A, SPON1, FREM1, C8B, PRPS2, FCHO2, PPP1R12A, GPALPP1, U2AF2, and RCC2. Then, the proteomics and transcriptomics expression patterns of these proteins were further compared, complemented by single-cell RNA-sequencing (scRNA-seq). In summary, this study not only offers a wealth of information regarding the molecular intricacies of human embryonic epithelial and mesenchymal cell differentiation but also serves as an invaluable resource for future mechanistic inquiries into tooth development.

Prenatal diagnosis, pregnancy determination and follow up of sex chromosome aneuploidy screened by non-invasive prenatal testing from 122 453 unselected singleton pregnancies: A retrospective analysis of 7-year experience.

The phenotype of SCA patients are diversities, make prenatal counseling and parental decision-making following the prenatal diagnosis of SCA more complicated and challenging. NIPT has higher sensitivity and specificity in screening trisomy 21 syndrome, but the effectiveness of NIPT in detecting SCA is still controversial. This study is a large-scale retrospective cohort of positive SCA screened from unselected singleton pregnancies by non-invasive prenatal testing (NIPT) from a single prenatal center of a tertiary hospital. Clinical information, indications, diagnostic results, ultrasound findings, pregnancy determinations, and follow-up were reviewed and analyzed. 596 cases of SCA positive were screened out of 122 453, giving a positive detection rate of 0.49%. 510 cases (85.6%) conducted with amniocentesis to detect fetal chromosome, of which 236 were confirmed as true positive of SCA with PPV of 46.3% (236/510). Of the 236 cases confirmed as true positive SCA, 114 cases (48.3%)chose to terminate the pregnancy (93.0%, 65.3%, 15.4% and 10.9% for 45,X, 47,XXY, 47,XXX and 47,XYY, respectively), 122 cases (51.7%) elected to continue the pregnancy. In conclusions, NIPT as a first-tier routine method for screening autosomal aneuploidies, also could play an important role in screening SCA. Low-risk pregnant women are the main indication for the detection of SCA as NIPT test provides to non-selective population. For 47,XXX and 47,XYY with mild phenotype, couples would like to continue the pregnancy. But for 45,X and 47,XXY, parents apt to terminate pregnancy no matter ultrasound abnormalities were found or not.

Metastable Liquid Properties and Surface Flow Patterns of Ultrahigh Temperature Alloys Explored in Outer Space.

The metastable liquid properties and chemical bonds beyond 2000 K remain a huge challenge for ground-based research on liquid materials chemistry. We show the strong undercooling capability, metastable liquid properties and surface wave patterns of refractory Nb-Si and Zr-V binary alloys explored in space environment. The floating droplet of Nb82.7Si17.3 eutectic alloy superheated up to 2338 K exhibited an extreme undercooling of 437 K, approaching the 0.2TE threshold for homogeneous nucleation of liquid-solid reaction. The microgravity state endowed alloy droplets with nearly perfect sphericity and thus ensured the high accuracy to determine metastable undercooled liquid properties. A special kind of swirling flow was induced for liquid alloy owing to Marangoni convection, which resulted in the spiral microstructures on Zr64V36 alloy surface during liquid-solid phase transition. The coupled impacts of surface nucleation and surface flow brought in a novel olivary shape for these binary alloys. Furthermore, the chemical bonds and atomic structures of high temperature liquids were revealed to understand the liquid properties in outer space circumstances.