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The fine modeling of the lunar gravity field is a fundamental task for establishing lunar altitude references, conducting research on lunar interior structure, and other scientific endeavors. The lunar gravity field model constructed solely based on spacecraft orbit data has limited spatial resolution, making it challenging to meet the demands of fine gravity field research. The acquisition of high-resolution terrain models presents new opportunities for the study of precise lunar gravity fields. This paper reviews the current status and advancements in fine lunar gravity field modeling, including research efforts and evaluation methods for global lunar gravity field models, principles and technologies for fine gravity field modeling, as well as related research outcomes. On this basis, this paper systematically summarizes the key theoretical issues and technical challenges in the theory of lunar gravity field modeling based on high-resolution terrain models. These include data updating, error correction in high-frequency gravity field modeling, calculation efficiency, and the series divergence problem in spherical harmonic analysis. In addition, future research directions are discussed. This work will provide references for gravity field research on the Moon and other terrestrial planets.

Abstract Background Atrial Fibrillation (AF) is known to be associated with a negative emotional state. Patient-reported outcomes (PROs) are important tools for evaluating the endpoints of AF management. This study aims to examine the correlation between personality types and PROs in patients with AF. Methods All included subjects were newly diagnosed with AF fewer than one month, and their personality types were assessed using the Eysenck Personality Questionnaire (EPQ). Quality of life (QoL) was measured using the Atrial Fibrillation Effect on Quality of Life (AFEQT) questionnaire. Anxiety and depression were assessed using the General Anxiety Scale (GAD-7) and the 9-item Patient Health Questionnaire (PHQ-9), respectively. We constructed stepwise linear regression analyses for factors related to the QoL and emotional state in patients with AF. Results A total of 531 AF patients completed the survey and were categorized into four groups based on their personality types. Of these patients (mean age: 67.12 ± 10.93 years, 50.28% male), 357 (67.23%) had paroxysmal AF, and 16.95% (n = 90) had a sanguine personality. Compared to patients with other personality types, those with a sanguine personality had the highest average AFEQT scores (P

Abstract FOXO transcription factors modulate aging-related pathways and influence longevity in multiple species, but the transcriptional targets that mediate these effects remain largely unknown. Here, we identify an evolutionarily conserved FOXO target gene, Oxidative stress-responsive serine-rich protein 1 (OSER1), whose overexpression extends lifespan in silkworms, nematodes, and flies, while its depletion correspondingly shortens lifespan. In flies, overexpression of OSER1 increases resistance to oxidative stress, starvation, and heat shock, while OSER1-depleted flies are more vulnerable to these stressors. In silkworms, hydrogen peroxide both induces and is scavenged by OSER1 in vitro and in vivo. Knockdown of OSER1 in Caenorhabditis elegans leads to increased ROS production and shorter lifespan, mitochondrial fragmentation, decreased ATP production, and altered transcription of mitochondrial genes. Human proteomic analysis suggests that OSER1 plays roles in oxidative stress response, cellular senescence, and reproduction, which is consistent with the data and suggests that OSER1 could play a role in fertility in silkworms and nematodes. Human studies demonstrate that polymorphic variants in OSER1 are associated with human longevity. In summary, OSER1 is an evolutionarily conserved FOXO-regulated protein that improves resistance to oxidative stress, maintains mitochondrial functional integrity, and increases lifespan in multiple species. Additional studies will clarify the role of OSER1 as a critical effector of healthy aging.

Abstract Background Deep vein thrombosis (DVT) of lower extremity is a common complications after total knee arthroplasty (TKA). The purpose of this study was to evaluate the risk factors for DVT after TKA and analyze the expression of miR-199b-5p and nitric oxide (NO) before and after TKA, as well as their predictive value for DVT. Methods Basic clinical information of 121 patients with TKA was analyzed retrospectively. RT-qPCR was used to detect the relative expression level of miR-199b-5p in patients before and after TKA treatment. Based on the occurrence of DVT, patients were divided into DVT and non-DVT groups. Logistic regression analysis evaluated the risk factors of DVT. The receiver operating characteristic (ROC) curve assessed the predictive value of postoperative miR-199b-5p level, preoperative NO level, and their combination in DVT. The target genes of miR-199b-5p and their functions were predicted and annotated using bioinformatics analysis. Results The level of miR-199b-5p after TKA was upregulated compared with that before TKA (P

Abstract Background An mHealth-based school health education platform (EduSaltS) was promoted in real-world China to reduce salt intake among children and their families. This progress evaluation explores its implementation process and influencing factors using mixed methods. Methods The mixed-methods process evaluation employed the RE-AIM framework. Quantitative data were collected from a management website monitoring 54,435 third-grade students across two cities. Questionnaire surveys (n = 27,542) assessed pre- and post-education effectiveness. Mixed-effects models were used to control cluster effects. Qualitative interviews (23 individuals and 8 focus groups) identified program performance, facilitators, and barriers. Findings were triangulated using the RE-AIM framework. Results The program achieved 100% participation among all the third-grade classes of the 208 invited primary schools, with a 97.7% registration rate among all the 54,435 families, indicating high "Reach." Qualitative interviews revealed positive engagement from children and parents through the "small hands leading big hands" strategy. The high completion rate of 84.9% for each health cloud lesson and the significant improvement in salt reduction knowledge and behaviors scores from 75.0 (95%CI: 74.7–75.3) to 80.9 (95%CI: 80.6–81.2) out of 100 demonstrated the "Effect" of EduSaltS. The program's "Adoption" and "Implementation" were supported by attractive materials, reduced workload via auto-delivered lessons/activities and performance evaluation, and high fidelity to recommended activities, with medians 3.0 (IQR: 2.0–8.0)/class and 9.0 (IQR: 5.0–14.0)/school. Stable course completion rates (79.4%-93.4%) over one year indicated promising "Maintenance." Apart from the facilitating features praised by the interviewees, government support was the basis for the scaling up of EduSaltS. Barriers included the lack of smartphone skills among some parents and competing priorities for schools. Unhealthy off-campus environments, such as excessive use of salt in pre-packaged and restaurant foods, also hindered salt reduction efforts. The program's scalability was evident through its integration into existing health education, engagement of local governments and adaptation across various mobile devices. Conclusions The mHealth-based school health education program is scalable and effective for public salt reduction in China. Identified barriers and facilitators can inform future health program scale-ups. The program's successful implementation demonstrates its potential for broader application in public health initiatives aimed at reducing dietary salt intake.

Abstract Background Lymph node metastasis (LNM) is the primary mode of metastasis in gastric cancer (GC). However, the precise mechanisms underlying this process remain elusive. Tumor cells necessitate lipid metabolic reprogramming to facilitate metastasis, yet the role of lipoprotein lipase (LPL), a pivotal enzyme involved in exogenous lipid uptake, remains uncertain in tumor metastasis. Therefore, the aim of this study was to investigate the presence of lipid metabolic reprogramming during LNM of GC as well as the role of LPL in this process. Methods Intracellular lipid levels were quantified using oil red O staining, BODIPY 493/503 staining, and flow cytometry. Lipidomics analysis was employed to identify alterations in intracellular lipid composition following LPL knockdown. Protein expression levels were assessed through immunohistochemistry, Western blotting, and enzyme‐linked immunosorbent assays. The mouse popliteal LNM model was utilized to investigate differences in LNM. Immunoprecipitation and mass spectrometry were employed to examine protein associations. In vitro phosphorylation assays and Phos‐tag sodium dodecyl‐sulfate polyacrylamide gel electrophoresis assays were conducted to detect angiopoietin‐like protein 4 (ANGPTL4) phosphorylation. Results We identified that an elevated intracellular lipid level represents a crucial characteristic of node‐positive (N+) GC and further demonstrated that a high‐fat diet can expedite LNM. LPL was found to be significantly overexpressed in N+ GC tissues and shown to facilitate LNM by mediating dietary lipid uptake within GC cells. Leptin, an obesity‐related hormone, intercepted the effect exerted by ANGPTL4/Furin on LPL cleavage. Circulating leptin binding to the leptin receptor could induce the activation of inositol‐requiring enzyme‐1 (IRE1) kinase, leading to the phosphorylation of ANGPTL4 at the serine 30 residue and subsequently reducing its binding affinity with LPL. Moreover, our research revealed that LPL disrupted lipid homeostasis by elevating intracellular levels of arachidonic acid, which then triggered the cyclooxygenase‐2/prostaglandin E2 (PGE2) pathway, thereby promoting tumor lymphangiogenesis. Conclusions Leptin‐induced phosphorylation of ANGPTL4 facilitates LPL‐mediated lipid uptake and consequently stimulates the production of PGE2, ultimately facilitating LNM in GC.

Abstract The fate of sedimentary nitrogen during subduction is essential for understanding the origin of nitrogen in the deep Earth. Here we study the behavior of nitrogen in slab sediments during the phengite to K-hollandite transition at 10–12 GPa and 800–1100 °C. Phengite stability is extended by 1–3 GPa in the nitrogen (NH4 +)-bearing system. The phengite-fluid partition coefficient of nitrogen is 0.031 at 10 GPa, and K-hollandite-fluid partition coefficients of nitrogen range from 0.008 to 0.064, showing a positive dependence on pressure but a negative dependence on temperature. The nitrogen partitioning data suggest that K-hollandite can only preserve ~43% and ~26% of the nitrogen from phengite during the phengite to K-hollandite transition along the cold and warm slab geotherms, respectively. Combined with the slab sedimentary nitrogen influx, we find that a maximum of ~1.5 × 108 kg/y of nitrogen, representing ~20% of the initial sedimentary nitrogen influx, could be transported by K-hollandite to the lower mantle. We conclude that slab sediments may have contributed less than 15% of the lower mantle nitrogen, most of which is probably of primordial origin.

Ribonucleic acid for injection II is a clinical adjuvant cancer therapy treatment based on immunotherapy, which exerts its effects by enhancing immune function and suppressing tumor growth. However, the mechanism underlying the ameliorative effect on immunosuppressed hematopoietic dysfunction remains unclear. This study confirmed the immune-boosting and hematopoietic-promoting effects of ribonucleic acid for injection II, which has a wide distribution of molecular weights and is rich in amino acids and nucleotides. Ribonucleic acid for injection II influences the gut microbiota and serum metabolites to enhance immunity in immunosuppressed mice induced by CTX, while also mitigating bone marrow injury and increasing hematopoietic cells through mediating macrophage M1 differentiation, thereby improving hematopoietic dysfunction in mice.

Abstract Background Patients with concomitant type 2 diabetes mellitus (T2DM) and aortic regurgitation (AR) can present with right ventricular (RV) dysfunction. The current study aimed to evaluate the impact of AR on RV impairment and the importance of ventricular interdependence using cardiac magnetic resonance feature tracking (CMR‑FT) in patients with T2DM. Methods This study included 229 patients with T2DM (AR−), 88 patients with T2DM (AR+), and 122 healthy controls. The biventricular global radial strain (GRS), global circumferential strain (GCS), and global longitudinal peak strain (GLS) were calculated with CMR‑FT and compared among the healthy control, T2DM (AR−), and T2DM (AR+) groups. The RV regional strains at the basal, mid, and apical cavities between the T2DM (AR+) group and subgroups with different AR degrees were compared. Backward stepwise multivariate linear regression analyses were performed to determine the effects of AR and left ventricular (LV) strains on RV strains. Results The RV GLS, LV GRS, LV GCS, LV GLS, interventricular septal (IVS) GRS and IVS GCS were decreased gradually from the controls through the T2DM (AR−) group to the T2DM (AR+) group. The IVS GLS of the T2DM (AR−) and T2DM (AR+) groups was lower than that of the control group. AR was independently associated with LV GRS, LV GCS, LV GLS, RV GCS, and RV GLS. If AR and LV GLSs were included in the regression analyses, AR and LV GLS were independently associated with RV GLS. Conclusion AR can exacerbate RV dysfunction in patients with T2DM, which may be associated with the superimposed strain injury of the left ventricle and interventricular septum. The RV longitudinal and circumferential strains are important indicators of cardiac injury in T2DM and AR. The unfavorable LV-RV interdependence supports that while focusing on improving LV function, RV dysfunction should be monitored and treated in order to slow the progression of the disease and the onset of adverse outcomes.

Abstract Background The adverse prognostic impact of diabetes on hypertrophic cardiomyopathy (HCM) is poorly understood. We sought to explore the underlying mechanisms in terms of structural and functional remodelling in HCM patients with coexisting diabetes (HCM-DM). Methods A total of 45 HCM-DM patients were retrospectively included. Isolated HCM controls (HCM patients without diabetes) were matched to HCM-DM patients in terms of maximal wall thickness, age, and gender distribution. Left ventricular (LV) and atrial (LA) performance were evaluated using cardiac magnetic resonance feature tracking strain analyses. The associations between diabetes and LV/LA impairment were investigated by univariable and multivariable linear regression. Results Compared with the isolated HCM controls, the HCM-DM patients had smaller end-diastolic volume and stroke volume, lower ejection fraction, larger mass/volume ratio and impaired strains in all three directions (all P

Abstract Solution-processable 2D semiconductor inks based on electrochemical molecular intercalation and exfoliation of bulk layered crystals using organic cations has offered an alternative pathway to low-cost fabrication of large-area flexible and wearable electronic devices. However, the growth of large-piece bulk crystals as starting material relies on costly and prolonged high-temperature process, representing a critical roadblock towards practical and large-scale applications. Here we report a general liquid-metal-assisted approach that enables the electrochemical molecular intercalation of low-cost and readily available crystal powders. The resulted solution-processable MoS2 nanosheets are of comparable quality to those exfoliated from bulk crystals. Furthermore, this method can create a rich library of functional 2D electronic inks ( >50 types), including 2D wide-bandgap semiconductors of low electrical conductivity. Lastly, we demonstrated the all-solution-processable integration of 2D semiconductors with 2D conductors and 2D dielectrics for the fabrication of large-area thin-film transistors and memristors at a greatly reduced cost.

Abstract Background Heart failure with reduced ejection fraction (HFrEF) is associated with a high rate of mortality and morbidity. Evidence has shown that sex differences may be an important contributor to phenotypic heterogeneity in patients with HFrEF. Although diabetes mellitus (DM) frequently coexists with HFrEF and results in a worse prognosis, there remains a need to identify sex-related differences in the characteristics and outcomes of this population. In this study, we aimed to investigate the between-sex differences in clinical profile, left ventricular (LV) remodeling, and cardiovascular risk factors and outcomes in patients with HFrEF concomitant with DM. Methods A total of 273 patients with HFrEF concomitant with DM who underwent cardiac MRI were included in this study. Clinical characteristics, LV remodeling as assessed by cardiac MRI, and cardiovascular risk factors and outcomes were compared between sexes. Results Women were older, leaner and prone to have anemia and hypoproteinemia but less likely to have ischemic etiology. Cardiac MRI revealed that despite similar LVEFs between the sexes, there was more LV concentric remodeling, less impaired global systolic peak strain in longitudinal and circumferential components and a decreased likelihood of late gadolinium enhancement presence in women than in men. During a median follow-up time of 34.6 months, women exhibited better overall survival than men did (log-rank P = 0.042). Multivariable Cox proportional hazards analysis indicated different risk factors for predicting outcomes between sexes, with hypertension [hazard ratio (HR) = 2.05, 95% confidence interval (CI) 1.05 to 4.85, P = 0.041] and hypoproteinemia (HR = 2.27, 95% CI 1.06 to 4.37, P = 0.039) serving as independent determinants of outcomes in women, whereas ischemic etiology (HR = 1.96, 95% CI 1.11 to 3.48, P = 0.021) and atrial fibrillation (HR = 1.86, 95% CI 1.02 to 3.41, P = 0.044) served as independent determinants of outcomes in men. Conclusions Among patients with HFrEF concomitant with DM, women displayed different LV remodeling and risk factors and had better survival than men did. Sex-based phenotypic heterogeneity in patients with HFrEF in the context of DM should be addressed in clinical practice.

Abstract Fractional flow reserve (FFR) has become the gold standard for evaluating coronary lesion-specific ischemia. However, FFR is an invasive method that may cause possible complications in the coronary artery and requires expensive equipment, which limits its use. Promising noninvasive diagnostic methods, such as computed tomography angiography–derived FFR (CT-FFR) and the quantitative flow ratio (QFR), have been proposed. In this study, we evaluated the diagnostic performance of the QFR and CT-FFR in predicting coronary lesion-specific ischemia, with the FFR serving as the reference standard. Patients with suspected or known coronary artery disease who underwent coronary CT angiography revealing 30–90% diameter stenosis in the main coronary artery (≥ 2.0 mm reference diameter) were enrolled. The FFR was measured during invasive coronary angiography (within 15 days after coronary CT angiography). An FFR ≤ 0.8 was the reference standard for coronary lesion-specific ischemia. A total of 103 vessels from 92 consecutive patients (aged 59.8 ± 9.2 years; 60.9% were men) were evaluated. The diagnostic performance of a QFR ≤ 0.80 for predicting coronary lesion-specific ischemia demonstrated good diagnostic accuracy, sensitivity, and specificity (92.2%, 87.2%, and 96.4%, respectively), with an area under the receiver operating characteristic curve (AUC) of 0.987 (P

Abstract Aerosol jet printing has the potential to fabricate fine features on various substrates due to its large stand-off distance. However, the presence of overspray and instability, particularly at high printing resolutions, has limited its widespread application. In this study, we introduce an efficient approach called annular acoustic focusing for aerosol jet printing. By determining the optimal focusing frequency (5.8 MHz) for silver nanoparticles using a particle ejection model, we achieve precise and stable printing. We also propose a modified print nozzle geometry, resulting in ultrafine traces (line width

Abstract Aging is classically associated with a decline of cognitive abilities, especially in relation to memory. While the development of potential treatments for neurodegenerative diseases has been in sharp focus, mild cognitive impairment (MCI), a form of age‐related memory loss, in the absence of severe functional impairment, a condition experienced by many healthy adults, has received relatively little attention. Advances in this space would make significant contributions to the goal of healthy aging and may also help promote cognitive performance across the wider population. The individual action of either fructooligosaccharide (FOS) or L‐theanine, both natural plant‐derived molecules, has been tentatively linked with improvements in cognition, but our understanding remains far from complete. We therefore determined the effect of different dose combinations of FOS and L‐theanine (termed MT‐01/GBL‐Memory1) in mice against FOS and L‐theanine monotherapy. FOS and L‐theanine were found to synergistically enhance murine memory in our animal tests at a dose of 100 mg/kg (coefficient of drug interaction (CDI)

Abstract Objective To investigate the accuracy and consistency of MDCT and TEE in the preoperative assessment of aortic root surgery. Methods From January 2021 to September 2022, 118 patients who underwent aortic root surgery were included in this study. All patients underwent high-quality preoperative MDCT and TEE examinations, and the examination results were independently measured and assessed by two senior radiologists or ultrasound specialists. Bland–Altman analysis and Pearson correlation testing were employed to assess the correlation and consistency between MDCT and TEE. These analyses were then compared with actual intraoperative measurement data. Results Among all the patients, 73 (61.86%) had tricuspid aortic valve (TAV), and 45 (38.14%) had bicuspid aortic valve (BAV). A comparison between the TEE and MDCT measurements showed that for the annulus diameter, the area-derived diameter had the best correlation and agreement. For the sinus of Valsalva diameter, the circumference-derived diameter was optimal. However, for the STJ diameter, the minimum cross-sectional diameter showed the best agreement with TEE. In contrast, measurements of geometric height showed a weaker correlation and agreement. Conclusion Contrast-enhanced MDCT can be a valuable tool for perioperative evaluation in aortic root surgery, with good correlation, consistency, and feasibility when compared to TEE. The choice of MDCT measurement methodology, specifically area-derived and circumference-derived diameter, proved to be more accurate than other methods. Further research is required to enhance the understanding of aortic valve repair and associated imaging techniques.

Abstract Although molecular vibronic spectra generation is pivotal for chemical analysis, tackling such exponentially complex tasks on classical computers remains inefficient. Quantum simulation, though theoretically promising, faces technological challenges in experimentally extracting vibronic spectra for molecules with multiple modes. Here, we propose a nontrivial algorithm to generate the vibronic spectra using states with zero displacements (squeezed vacuum states) coupled to a linear optical network, offering ease of experimental implementation. We also fabricate an integrated quantum photonic microprocessor chip as a versatile simulation platform containing 16 modes of single-mode squeezed vacuum states and a fully programmable interferometer network. Molecular vibronic spectra of formic acid and thymine under the Condon approximation are simulated using the quantum microprocessor chip with high reconstructed fidelity ( > 92%). Furthermore, vibronic spectra of naphthalene, phenanthrene, and benzene under the non-Condon approximation are also experimentally simulated. Such demonstrations could pave the way for solving complicated quantum chemistry problems involving vibronic spectra and computational tasks beyond the reach of classical computers.

Abstract Background Allii Macrostemonis Bulbus is also named Xiebai in China. It is an edible vegetable, and also a famous herb for treating coronary heart disease. Allium chinense G. Don (ACGD) and Allium macrostemon Bunge (AMB) are it botanical sources. The aim of this study was to explore the cardioprotective effects, and decipher the visual spatial distribution and absolute content of primary metabolites derived from these two herbs. Methods H9c2 cells were used to perform the hypoxia-reoxygenation (H/R)-induced myocardial injury model. Their protective effects were evaluated by apoptosis levels. Furthermore, matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry imaging approach (MALDI-TOF MSI) was carried out to present the spatial location of primary metabolites including fatty acids, amino acids, carotenoids, and vitamins in these two Allium herbs. Multiple analytical methods were applied to perform quantitative analysis of these primary metabolites in AMB and ACGD bulbs by liquid chromatography tandem mass spectrometry (LC–MS). Results First, AMB and ACGD extracts both could increase the cell viability in H9c2 cells, and attenuate H/R-induced injury. They markedly decreased apoptosis, accompanied by activating the BCL-2/BAX pathway. Further, MALDI-TOF MSI-based relative quantification results showed several amino acids, fatty acids, carotenoids, and vitamins were largely rich in the tunics and outside scales of fresh bulbs, while some primary metabolites were abundant in their developing flower buds. Absolute quantification results displayed total contents of amino acids in ACGD bulbs were higher than those in AMB, while total contents of fatty acids and vitamins provides opposite trends in these two Allium herbs. The total contents of carotenoids and trace elements showed no significant differences between AMB and ACGD samples. Conclusions This study would be helpful to understand the myocardial injury protection effects of these two Allium herbs, and the spatial accumulation and quantitative content levels of their main nutrients. Graphical Abstract

Abstract Background The abnormal low-density protein cholesterol (LDL-C) level in the development of atherosclerosis is often comorbid in individuals with type 2 diabetes mellitus(T2DM). This study aimed to investigate the aggravating effect of abnormal LDL-C levels on coronary artery plaques assessed by coronary computed tomography angiography (CCTA) in T2DM. Materials and methods This study collected 3439 T2DM patients from September 2011 to February 2022. Comparative analysis of differences in coronary plaque characteristics was performed for the patients between the normal LDL-C level group and the abnormal LDL-C level group. Factors with P

Abstract Background Carotid artery stenosis (CAS) is a major cause of cerebral ischemic events (CIE). The purpose of the research was to reveal the diagnostic accuracy of long non-coding RNA hox transcript antisense intergenic RNA (HOTAIR) in asymptomatic carotid artery stenosis (ACAS) patients and its predictive significance in CIE incidence. Methods 88 patients with ACAS and 80 controls were included. Blood samples were collected and serum HOTAIR levels were detected by qRT-PCR. Logistic regression examined factors associated with the degree of carotid stenosis. The receiver operating characteristic (ROC) curve assessed the diagnostic accuracy of HOTAIR in identifying patients with ACAS. Predictive value of serum HOTAIR levels for the occurrence of CIE was assessed by Kaplan–Meier curves and Cox regression. Results Serum HOTAIR was markedly lower in ACAS patients than in controls (P

Abstract Disruptions in energy homeostasis can lead to diseases like obesity and diabetes, affecting millions of people each year. Tanycytes, the adult stem cells in the hypothalamus, play crucial roles in assisting hypothalamic neurons in maintaining energy balance. Although tanycytes have been extensively studied in rodents, our understanding of human tanycytes remains limited. In this study, we utilized single-cell transcriptomics data to explore the heterogeneity of human embryonic tanycytes, investigate their gene regulatory networks, analyze their intercellular communication, and examine their developmental trajectory. Our analysis revealed the presence of two clusters of β tanycytes and three clusters of α tanycytes in our dataset. Surprisingly, human embryonic tanycytes displayed significant similarities to mouse tanycytes in terms of marker gene expression and transcription factor activities. Trajectory analysis indicated that α tanycytes were the first to be generated, giving rise to β tanycytes in a dorsal–ventral direction along the third ventricle. Furthermore, our CellChat analyses demonstrated that tanycytes generated earlier along the developmental lineages exhibited increased intercellular communication compared to those generated later. In summary, we have thoroughly characterized the heterogeneity of human embryonic tanycytes from various angles. We are confident that our findings will serve as a foundation for future research on human tanycytes.

Herein, poly(pentanediamine terephthalamide) (PA5T) homopolymer was synthesized via a salt-forming reaction+solid state polycondensation method using bio-based 1,5-pentanediamine and terephthalic acid as the primary raw materials. To address the issue of its narrower processing window, poly(hexamethylene terephthalamide)(PA6T), which also cannot be melt processed due to the processing window is negative, was introduced into its molecular chain to synthesize poly (pentanediamine/hexanediamine terephthaloyl) (PA5T-co-6T) copolymers. The structures were investigated by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance carbon spectroscopy (13C-NMR). Furthermore, the melting temperature, crystallization temperature, thermal stability, and crystal growth mode of the polymer were tested and analyzed using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and wide-angle x-ray diffraction (WAXD), respectively. The results demonstrate that the crystal growth mode gradually changes from three-dimensional spherical growth to two-dimensional disk-like or three-dimensional spherical growth with the increase of 6T chain segment content. Simultaneously, the crystallization temperature, melting temperature, and crystallization rate of the polymer all showed a trend of decreasing first and then increasing, which was due to the combined effects of the increase in the content of 6T chain segments on the molecular-chain structure and crystal structure of the polymer. Bio-based PA5T-co-6T has excellent heat resistance and a wider processing window than PA5T and PA6T, which possesses great application prospects in the fields of automotive, electronic appliances, and LED optics.

Chemotherapy-induced cardiotoxicity with subsequent heart failure (HF) is a major cause of morbidity and mortality in cancer survivors worldwide. Chemotherapy-induced HF is exceptionally challenging as it generally manifests in patients who are typically not eligible for left ventricular device implantation or heart transplantation. To explore alternative treatment strategies for cancer survivors suffering from chemotherapy-induced HF, we developed a minimally invasive infusible cardiac stromal cell secretomes adhesive (MISA) that could be delivered locally through an endoscope-guided intrapericardial injection. To mimic the typical clinical presentation of chemotherapy-induced HF in elder patients, we established an aged rat model in which restrictive cardiomyopathy with sequential HF was induced via consecutive doxorubicin injections. In vitro, we prove that MISA not only enhanced cardiomyocytes proliferation potency and viability, but also inhibited their apoptosis. In vivo, we prove that MISA improved the ventricular contractility indexes and led to beneficial effects on histological and structural features of restrictive cardiomyopathy via promoting cardiomyocyte proliferation, angiogenesis, and mitochondrial respiration. Additionally, we also evaluated the safety and feasibility of MISA intrapericardial delivery in a healthy porcine model with an intact immune system. In general, our data indicates that MISA has a strong potential for translation into large animal models and ultimately clinical applications for chemotherapy-induced HF prior to the final option of heart transplantation.

In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.

The national independent innovation demonstration zone (NIIDZ) is an independent innovation policy that plays a crucial role in implementing strategies. Given the importance of the NIIDZ, this study uses panel data of 278 prefecture-level cities in China from 2006 to 2020 and empirically examines the effect and internal mechanism of the NIIDZ on green economic efficiency (GEE) using the difference-in-difference model (DID). The results show that the NIIDZ effectively enhances the growth of GEE, and the results remain valid through several robustness tests, such as year-by-year propensity score matching. The transmission mechanism suggests that the NIIDZ indirectly drives GEE by accelerating scientific and technological investment, promoting talent concentration, and optimizing the industrial structure. Moreover, heterogeneity analysis reveals that the promotion effect of the NIIDZ on GEE is more prominent in the eastern region and high green development level areas. The study’s findings can serve as a reference for China to further utilize the policy effectiveness of the NIIDZ and accelerate the high-quality development of the green economy in the future.

Background: The prediction of response to immunotherapy mostly depends on the programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) status, and the 22C3 pharmDx assay has been approved in esophageal squamous cell carcinoma (ESCC). However, the widespread use of the 22C3 pharmDx assay is limited due to its availability. Thus, alternative PD-L1 assays are needed. We aimed to investigate the analytical and clinical diagnostic performances of four PD-L1 assays and to compare their concordances with the 22C3 pharmDx assay. Methods: The PD-L1 22C3 pharmDx assay was performed on the Dako Autostainer Link 48 platform, three testing assays (PD-L1 E1L3N XP antibody [Ab], PD-L1 BP6099 Ab and PD-L1 CST E1L3N Ab) on the Leica BOND-MAX/III platform, and one testing assay (PD-L1 MXR006 Ab) on the Roche VENTANA Benchmark Ultra platform. A total of 218 ESCC cases from four centers were included in this retrospective study. Professionals from each center stained and read the IHC slides independently and determined the combined positive score (CPS) and the tumor proportion score (TPS). Results: Regarding analytical performance, the four testing assays demonstrated good correlations with the 22C3 pharmDx assay when evaluated by the TPS or CPS (ρ > 0.8 for all four assays). Regarding diagnostic performance (CPS ≥ 10 was used as the cutoff), the four testing assays showed moderate concordances with the 22C3 pharmDx assay (kappa > 0.7 for all four assays). The overall percent agreements between each testing assay and the 22C3 pharmDx assay was at least 87.2 %. Conclusion: This study provides insight into the potential interchangeability of the four PD-L1 assays with the 22C3 pharmDx assay.

Abstract Background Stress hyperglycemia occurs frequently in patients following acute myocardial infarction (AMI) and may aggravate myocardial stiffness, but relevant evidence is still lacking. Accordingly, this study aimed to examine the impact of admission stress hyperglycemia on left ventricular (LV) myocardial deformation in patients following AMI. Methods A total of 171 patients with first AMI (96 with normoglycemia and 75 with hyperglycemia) underwent cardiac magnetic resonance (CMR) examination were included. AMI patients were classified according to admission blood glucose level (aBGL): < 7.8 mmol/L (n = 96), 7.8–11.1 mmol/L (n = 41) and ≥ 11.1 mmol/L (n = 34). LV strains, including global radial/circumferential/longitudinal peak strain (PS)/peak systolic strain rate (PSSR)/peak diastolic strain rate (PDSR), were measured and compared between groups. Further, subgroup analyses were separately conducted for AMI patients with and without diabetes. Multivariate analysis was employed to assess the independent association between aBGL and LV global PS in AMI patients. Results LV global PS, PSSR and PDSR were decreased in radial, circumferential and longitudinal directions in hyperglycemic AMI patients compared with normoglycemic AMI patients (all P

Abstract Background Leaf morphology plays a crucial role in photosynthetic efficiency and yield potential in crops. Cigar tobacco plants, which are derived from common tobacco (Nicotiana tabacum L.), possess special leaf characteristics including thin and delicate leaves with few visible veins, making it a good system for studying the genetic basis of leaf morphological characters. Results In this study, GWAS and QTL mapping were simultaneously performed using a natural population containing 185 accessions collected worldwide and an F2 population consisting of 240 individuals, respectively. A total of 26 QTLs related to leaf morphological traits were mapped in the F2 population at three different developmental stages, and some QTL intervals were repeatedly detected for different traits and at different developmental stages. Among the 206 significant SNPs identified in the natural population using GWAS, several associated with the leaf thickness phenotype were co-mapped via QTL mapping. By analyzing linkage disequilibrium and transcriptome data from different tissues combined with gene functional annotations, 7 candidate genes from the co-mapped region were identified as the potential causative genes associated with leaf thickness. Conclusions These results presented a valuable cigar tobacco resource showing the genetic diversity regarding its leaf morphological traits at different developmental stages. It also provides valuable information for novel genes and molecular markers that will be useful for further functional verification and for molecular breeding of leaf morphological traits in crops in the future.

Background: The relationship between obesity, sexual behavior, and prostate cancer (PCa) has been widely debated, contributing to a lack of understanding of its potential mechanisms and hindering the development of effective prevention measures. Purpose: The aim of this study was to examine the causal effect of body mass index (BMI), age at first sexual intercourse (AFS), and bioavailable testosterone levels on PCa while also quantifying the potential roles of mediators. Method: We conducted a Mendelian randomization (MR) study using summary statistics from genome-wide associations of BMI (152,893 European males), AFS (182,791 European males), bioavailable testosterone (184,205 European males), and PCa (79,148 cases, 61,106 controls, European ancestry). Inverse-variance weighted method, weighted median method, MR-Egger regression, Least Absolute Shrinkage and Selection Operator (LASSO), and outlier test were used for MR analyses. Reverse MR and mediation analysis were performed. Data analyses were conducted from December 2022 to July 2023. Results: The results showed that genetic liability to BMI was protective of PCa (OR, 0.82; 95% CI: 0.74-0.91; P = 3.29 × 10−4). Genetic liability to later AFS (OR, 1.28; 95% CI: 1.08-1.53; P = 5.64 × 10−3) and higher bioavailable testosterone levels (OR = 1.11, 95% CI: 1.01–1.24, P = 0.04) were associated with an increased risk of PCa. All of these potential causal effects could only be forwarded and were not affected by prostate specific antigen (PSA) screening. After controlling for bioavailable testosterone levels, the causal impact of BMI and AFS on PCa was no longer significant. The mediation analysis suggested that the causal influence of AFS/BMI on PCa relied on bioavailable testosterone levels. Conclusion: In conclusion, the difference between the univariable and multivariable MR results suggested that the causal influence of BMI and AFS on PCa relied on bioavailable testosterone levels. Further work is needed to identify other risk factors and to elucidate the specific mechanisms that underlie this causal pathway.

Abstract The precise calculation and evaluation of the in-situ rock stress tensor is a crucial factor in addressing the major challenges related to subsurface engineering applications and earth science research. To improve the accuracy of in-situ stress measurement and prediction, an improved overcoring technique involving a measurement circuit, temperature compensation, and calculation method is presented for accurately measuring the in-situ rock stress tensor. Furthermore, an embedded grey BP neural network (GM–BPNN) model is established for predicting in-situ rock stress values. The results indicate that the improved overcoring technique has significantly improved the stress measurement accuracy, and a large number of valuable stress data obtained from many mines have proved the testing performance of this technique. Moreover, the mean relative errors of the prediction results of GM(0, 1) for the three principal stresses all reach 6–30%, and the accuracy of the model fails to meet the requirements. The average relative errors of the prediction results of the BPNN model are all less than 10%, and the model accuracy meets the requirements and has sufficient credibility. Compared with the GM and BPNN models, the embedded GM–BPNN model produces the best results, with mean relative errors of 0.0001–4.8338%. The embedded GM–BPNN model fully utilizes the characteristics of grey theory and BP neural network, which require a small sample size, weaken the randomness of the original data, and gradually approach the accuracy of the model, making it particularly suitable for situations with limited stress data.

Abstract Background Gasless transaxillary endoscopic thyroidectomy (GTET) and endoscopic thyroidectomy via the areola approach (ETA) have emerged as minimally invasive surgical techniques for managing papillary thyroid carcinoma (PTC). This study aimed to assess the surgical efficacy of endoscopic thyroidectomy (ET) as compared to conventional open thyroidectomy (COT) in PTC patients. Methods Between 2020 and 2022, 571 PTC patients underwent unilateral thyroidectomy accompanied by ipsilateral central lymph node dissection. This cohort comprised 72 patients who underwent GTET, 105 ETA, and 394 COT. The analysis encompassed a comprehensive examination of patient clinicopathologic characteristics and postoperative complaints. Furthermore, the learning curve of GTET was evaluated using the cumulative summation (CUSUM) method. Results Patients in the ET group exhibited a lower mean age and a higher proportion of female individuals. Operation time in the ET group was significantly longer. No significant differences were observed in the incidence of postoperative complications among the three groups. With regard to postoperative complaints reported three months after surgery, GTET demonstrated superior alleviation of anterior chest discomfort and swallowing difficulties. Patients who underwent ET reported significantly higher cosmetic satisfaction levels. Additionally, the learning curve of GTET was 27 cases, and the operation time during the mature phase of the learning curve exhibited a significant reduction when compared to ETA. Conclusions The findings of this study affirm the safety and feasibility of employing GTET and ETA for the surgical management of PTC. GTET presents an attractive surgical option, particularly for patients with unilateral PTC who place a premium on cosmetic outcomes.

Abstract A 1 millisecond (1‐ms) vision system that guarantees high efficiency and timely response for tomato defect detection is essential for factory automation. Because of various defect appearances, recently many existing researches focus on CNN based defect detection, but few of them attempt to reach high processing speed to adapt to the factorial assembly line. This paper proposes a global to multi‐scale local based parallel architecture with hardwired CNN for tomato defect detection. This architecture breaks down image‐wise detection into pixel‐wise localization and block‐wise classification. The pixel‐wise localization utilizes tomato‐aware information as constraints for localization performance. The block‐wise classification uses a fully pipelined network structure to obtain the classification result for each block as the pixel stream moves through the network. The classification network has a six‐layer lightweight network structure with quantization for hardwired type implementation on FPGA. The experiment results show that the proposed architecture processes 1000 FPS images with 0.9476 ms/frame delay. And for detection performance, this architecture keeps f1−score at 80.18%, only 1.31% lower than ResNet50 based detection system.

Balancing mechanical and corrosion performance is a decisive factor in the use of high entropy and medium entropy alloys (H & MEAs) as advanced engineering structural materials. This study investigates the microstructure of Fe77.3-xMnxSi9.1Cr9.8C3.8 (x = 14, 23.2) HEAs by combining experiments and first-principles calculations to elucidate the effects of adjusting Mn content on the mechanical and corrosion properties of FCC and FCC + HCP phases. The results demonstrate that HEAs with low Mn content exhibit a single FCC phase, whereas increasing Mn content not only precipitates the HCP phase but also refines the grain size. The yield strength, compressive fracture strength, work hardening index, and plasticity of Fe77.3-xMnxSi9.1Cr9.8C3.8 (x = 14, 23.2 at.%) HEAs are 1300 and 1526 MPa, 2380 and 2332 MPa, 0.42 and 0.36, 16.7% and 16%, respectively. Both HEAs exhibit superior electrochemical and salt spray corrosion performance compared to 304 stainless steels, with the Fe63.3Mn14Si9.1Cr9.8C3.8 alloy performing the best, exhibiting a self-corrosion potential of −0.523V and a self-corrosion current density of 2.605 × 10−6 A cm−2. The excellent corrosion resistance of Fe63.3Mn14Si9.1Cr9.8C3.8 can be attributed to the moderate grain size, resulting in excellent passivation film characteristics, and the lower Mn content, leading to a higher Cr2O3 content in the passivation film. First-principles calculations reveal that Fe63.3Mn14Si9.1Cr9.8C3.8 has a lower density of states number at the Fermi level (i.e., Fe63.3Mn14Si9.1Cr9.8C3.8 is 214.145eV, Fe54.1Mn23.2Si9.1Cr9.8C3.8 is 337.077eV), a wider pseudogap width, higher work function (5.700ev, 5.189ev), and better stability. Additionally, there exists a strong trade-off between corrosion and mechanical properties due to the influence of the HCP phase and grain size.

Abstract The dysregulation of pro- and anti-inflammatory processes in the brain has been linked to the pathogenesis of major depressive disorder (MDD), although the precise mechanisms remain unclear. In this study, we discovered that microglial conditional knockout of Pdcd4 conferred protection against LPS-induced hyperactivation of microglia and depressive-like behavior in mice. Mechanically, microglial Pdcd4 plays a role in promoting neuroinflammatory responses triggered by LPS by inhibiting Daxx-mediated PPARγ nucleus translocation, leading to the suppression of anti-inflammatory cytokine IL-10 expression. Finally, the antidepressant effect of microglial Pdcd4 knockout under LPS-challenged conditions was abolished by intracerebroventricular injection of the IL-10 neutralizing antibody IL-10Rα. Our study elucidates the distinct involvement of microglial Pdcd4 in neuroinflammation, suggesting its potential as a therapeutic target for neuroinflammation-related depression.

Abstract Background Periodontitis is strongly associated with type 2 diabetes (T2D) that results in serious complications and mortality. However, the pathogenic role of periodontitis in the development of T2D and the underlain mechanism have not been fully elucidated. Methods A Mendelian randomization (MR) was performed to estimate the causality between two diseases. Bioinformatics tools, including gene ontology and pathway enrichment analyses, were employed to analyze the common differentially expressed genes (DEGs) in periodontitis and T2D. MR and colocalization analyses were then utilized to investigate the causal associations between potential pathogenic gene expression and the risk of T2D. Single cell-type expression analysis was further performed to detect the cellular localization of these genes. Results Genetically predicted periodontitis was associated with a higher risk of T2D (OR, 1.469; 95% CI, 1.117–1.930; P = 0.006) and insulin resistance (OR 1.034; 95%CI 1.001–1.068; P = 0.041). 79 common DEGs associated with periodontitis and T2D were then identified and demonstrated enrichment mainly in CXC receptor chemokine receptor binding and interleutin-17 signaling pathway. The integration of GWAS with the expression quantitative trait locis of these genes from the peripheral blood genetically prioritized 6 candidate genes, including 2 risk genes (RAP2A, MCUR1) and 4 protective genes (WNK1, NFIX, FOS, PANX1) in periodontitis-related T2D. Enriched in natural killer cells, RAP2A (OR 4.909; 95% CI 1.849–13.039; P = 0.001) demonstrated high risk influence on T2D, and exhibited strong genetic evidence of colocalization (coloc.abf-PPH4 = 0.632). Conclusions This study used a multi-omics integration method to explore causality between periodontitis and T2D, and revealed molecular mechanisms using bioinformatics tools. Periodontitis was associated with a higher risk of T2D. MCUR1, RAP2A, FOS, PANX1, NFIX and WNK1 may play important roles in the pathogenesis of periodontitis-related T2D, shedding light on the development of potential drug targets.

Abstract Introduction To determine risk factors associated with postoperative cerebrospinal fluid leaks (CSFLs) after intrathecal drug delivery system (IDDS) and external pump implantation. Methods The clinical data of 248 patients with advanced cancer who underwent IDDS implantation from January 2021 to December 2022 at the Department of Pain Medicine at the Hunan Cancer Hospital were retrospectively reviewed. Information regarding age, gender, height, weight, body mass index (BMI), tumour type, albumin levels, haemoglobin levels, history of diabetes and pre- and postoperative anti-tumour therapy was collected and analysed. Results Postoperative CSFLs occurred in 7 of 231 patients (3.30%). Statistical analysis indicated that gender, age, height, weight, BMI, tumour type, albumin levels, haemoglobin levels, history of diabetes, pre- and postoperative chemotherapy, pre- and postoperative radiotherapy, preoperative immunotherapy and postoperative targeted therapy were not independent factors for CSFLs. Preoperative targeted therapy [odds ratio (OR): 16.64; 95% confidence interval (CI): 1.42, 195.56; P = 0.01] and postoperative immunotherapy (OR: 13.38; 95% CI: 1.60, 111.65; P = 0.017) were factors associated with an increased postoperative CSFL rate. Of the two locations where CSFLs can occur, the back (puncture site of catheter, n = 4) and the hypochondriac region (location of infusion port implanted, n = 3), back CSFLs occurred earlier than in the hypochondriac region (18.25 ± 6.45 vs 115 ± 62.02 days, P = 0.032). Conclusion Based on the data from our study, the timing of preoperative targeted therapy and postoperative immunotherapy should be considered to prevent the occurrence of CSFLs in cancer pain patients who have an IDDS and external pump.

Abstract A knowledge graph can effectively showcase the essential characteristics of data and is increasingly emerging as a significant means of integrating information in the field of artificial intelligence. Coronary artery plaque represents a significant etiology of cardiovascular events, posing a diagnostic challenge for clinicians who are confronted with a multitude of nonspecific symptoms. To visualize the hierarchical relationship network graph of the molecular mechanisms underlying plaque properties and symptom phenotypes, patient symptomatology was extracted from electronic health record data from real-world clinical settings. Phenotypic networks were constructed utilizing clinical data and protein‒protein interaction networks. Machine learning techniques, including convolutional neural networks, Dijkstra's algorithm, and gene ontology semantic similarity, were employed to quantify clinical and biological features within the network. The resulting features were then utilized to train a K-nearest neighbor model, yielding 23 symptoms, 41 association rules, and 61 hub genes across the three types of plaques studied, achieving an area under the curve of 92.5%. Weighted correlation network analysis and pathway enrichment were subsequently utilized to identify lipid status-related genes and inflammation-associated pathways that could help explain the differences in plaque properties. To confirm the validity of the network graph model, we conducted coexpression analysis of the hub genes to evaluate their potential diagnostic value. Additionally, we investigated immune cell infiltration, examined the correlations between hub genes and immune cells, and validated the reliability of the identified biological pathways. By integrating clinical data and molecular network information, this biomedical knowledge graph model effectively elucidated the potential molecular mechanisms that collude symptoms, diseases, and molecules.

Abstract Colorectal cancer (CRC) arises via the progressive accumulation of dysregulation in key genes including oncogenes and tumor-suppressor genes. Prostaglandin-endoperoxide synthase 2 (PTGS2, also called COX2) acts as an oncogenic driver in CRC. Here, we explored the upstream transcription factors (TFs) responsible for elevating PTGS2 expression in CRC cells. The results showed that PTGS2 silencing repressed cell growth, migration and invasion in HCT116 and SW480 CRC cells. The two fragments (499–981 bp) and (1053–1434 bp) were confirmed as the core TF binding profiles of the PTGS2 promoter. PTGS2 expression positively correlated with RUNX1 level in colon adenocarcinoma (COAD) samples using the TCGA-COAD dataset. Furthermore, RUNX1 acted as a positive regulator of PTGS2 expression by promoting transcriptional activation of the PTGS2 promoter via the 1086–1096 bp binding motif. In conclusion, our study demonstrates that PTGS2 upregulation induced by the TF RUNX1 promotes CRC cell growth, migration and invasion, providing an increased rationale for the use of PTGS2 inhibitors in CRC prevention and treatment.

Abstract Background The gut microbiota and their hosts profoundly affect each other’s physiology and evolution. Identifying host-selected traits is crucial to understanding the processes that govern the evolving interactions between animals and symbiotic microbes. Current experimental approaches mainly focus on the model bacteria, like hypermutating Escherichia coli or the evolutionary changes of wild stains by host transmissions. A method called atmospheric and room temperature plasma (ARTP) may overcome the bottleneck of low spontaneous mutation rates while maintaining mild conditions for the gut bacteria. Results We established an experimental symbiotic system with gnotobiotic bee models to unravel the molecular mechanisms promoting host colonization. By in vivo serial passage, we tracked the genetic changes of ARTP-treated Snodgrassella strains from Bombus terrestris in the non-native honeybee host. We observed that passaged isolates showing genetic changes in the mutual gliding locus have a competitive advantage in the non-native host. Specifically, alleles in the orphan mglB, the GTPase activating protein, promoted colonization potentially by altering the type IV pili-dependent motility of the cells. Finally, competition assays confirmed that the mutations out-competed the ancestral strain in the non-native honeybee gut but not in the native host. Conclusions Using the ARTP mutagenesis to generate a mutation library of gut symbionts, we explored the potential genetic mechanisms for improved gut colonization in non-native hosts. Our findings demonstrate the implication of the cell mutual-gliding motility in host association and provide an experimental system for future study on host-microbe interactions. Video Abstract

Abstract Backgrounds Intraplacental choriocarcinoma (IC) is an extremely rare subtype of gestational choriocarcinoma. The long-term follow-up and reproductive outcomes of IC patients remain unclear. Here, we report a series of 14 cases and conduct a literature review to assess the fertility and recurrence results of this rare disease. Results Fourteen patients with pathologically confirmed IC treated in Peking Union Medical College Hospital between January 2002 and July 2022 were included in this study. Half of them had metastatic IC and were treated by chemotherapy with or without surgery. Only 1 patient had chemoresistant disease, but she achieved complete remission after immunotherapy. The median follow-up time was 45.5 months (range 4-192), and no recurrence occurred. One metastatic IC patient who achieved remission after chemotherapy had a full-term delivery. Among the 5 patients with fertility demands, 3 abandoned their pursuit of pregnancy because of “fear and worry about choriocarcinoma recurrence”. We reviewed a total of 89 cases of IC in English and Chinese literature from 1963 to 2022, and only 5 cases with subsequent pregnancy were reported, all of them were nonmetastatic IC cases. Conclusions IC is sensitive to chemotherapy and has good long-term remission and a low recurrence rate. Patients with metastatic or nonmetastatic IC can have good pregnancy results after treatment. Doctors should pay more attention to the psychology of these patients. Clinical trial registration N/A.

Abstract Sodium (Na) metal is a competitive anode for next‐generation energy storage applications in view of its low cost and high‐energy density. However, the uncontrolled side reactions, unstable solid electrolyte interphase (SEI) and dendrite growth at the electrode/electrolyte interfaces impede the practical application of Na metal as anode. Herein, a heterogeneous Na‐based alloys interfacial protective layer is constructed in situ on the surface of Na foil by self‐diffusion of liquid metal at room temperature, named “HAIP Na.” The interfacial Na‐based alloys layer with good electrolyte wettability and strong sodiophilicity, and assisted in the construction of NaF‐rich SEI. By means of direct visualization and theoretical simulation, we verify that the interfacial Na‐based alloys layer enabling uniform Na+ flux deposition and suppressing the dendrite growth. As a result, in the carbonate‐based electrolyte, the HAIP Na||HAIP Na symmetric cells exhibit a remarkably enhanced cycling life for more than 650 h with a capacity of 1 mAh cm−2 at a current density of 1 mA cm−2. When the HAIP Na anode is paired with sulfurized polyacrylonitrile (SPAN) cathode, the SPAN||HAIP Na full cells demonstrate excellent rate performance and cycling stability.

Abstract Background Premature infants commonly encounter difficulties with oral feeding, a complication that extends hospital stays, affects infants’ quality of life, and imposes substantial burdens on families and society. Enhancing preterm infants’ oral feeding skills and facilitating their transition from parenteral or nasal feeding to full oral feeding pose challenges for neonatal intensive care unit (NICU) healthcare professionals. Research indicates that oral motor interventions (OMIs) can enhance preterm infants’ oral feeding capabilities and expedite the transition from feeding initiation to full oral feeding. Nonetheless, the most suitable timing for commencing these interventions remains uncertain. Methods This is a single-blind, randomized controlled trial. Preterm with a gestational age between 29+0 to 34+6 weeks will be eligible for the study. These infants will be randomized and allocated to one of two groups, both of which will receive the OMIs. The intervention commences once the infant begins milk intake during the early OMIs. Additionally, in the late OMIs group, the intervention will initiate 48 h after discontinuing nasal continuous positive airway pressure. Discussion OMIs encompass non-nutritive sucking and artificial oral stimulation techniques. These techniques target the lips, jaw, muscles, or tongue of premature infants, aiming to facilitate the shift from tube feeding to oral feeding. The primary objective is to determine the ideal intervention timing that fosters the development of oral feeding skills and ensures a seamless transition from parenteral or nasal feeding to full oral feeding among preterm infants. Furthermore, this study might yield insights into the long-term effects of OMIs on the growth and neurodevelopmental outcomes of preterm infants. Such insights could bear substantial significance for the quality of survival among preterm infants and the societal burden imposed by preterm birth. Trial registration chictr.org.cn ChiCTR2300076721. Registered on October 17, 2023.

Abstract Esophageal squamous cell carcinoma (ESCC) is one of most prevalent cancers worldwide, especially in China. Lacking in depth mechanism study, effective targets and therapeutics are desperately needed in the clinic. RNA-binding proteins (RBPs) mediate the localization, stability, and translation of the target transcripts and fine-tune the physiological functions of the proteins encoded. Bioinformatics analysis revealed that IGF2BPs were highly expressed in ESCC tissues and at least participated in the regulation of cell proliferation of ESCC cells. Biological researches demonstrated that IGF2BP2 promoted the cell proliferation, migration and invasion of ESCC KYSE30 and KYSE450 cells. IGF2BP2 could bind to EIF4A1 mRNA by recognition of m6A sites and enhanced translation of EIF4A1. IGF2BPs, as m6A reader, IGF2BPs were oncogenic genes in ESCC by regulating the expression of EIF4A1 through m6A sites. IGF2BP2, EIF4A1 and their targets could serve as potential biomarkers and therapeutic targets for ESCC, offering promising novel approaches for the diagnosis and treatment of ESCC.

To improve the performance of PcBN composites prepared under high temperature and high pressure, mixed cBN particle sizes ranging from 0 to 0.5 μm and 0.5 to 1.0 μm were used as the raw material, Al-Ti-Al2O3 was used as the binder and the carbon nanotubes with different contents were added. The PcBN composites were prepared by sintering under high temperature and high pressure conditions. The effect of carbon nanotube content on the structure and properties of PcBN composites was investigated. The results show that there is no chemical reaction between PcBN and carbon nanotubes after the addition of carbon nanotubes, and the carbon nanotubes exist in the form of reinforcement inside the composite. The composite material is relatively dense, and the relative density of PcBN increases first and then decreases with the addition of carbon nanotubes. When the mass fraction of carbon nanotubes added is 1.5%, the relative density of PcBN reaches its maximum value of 97.9%, while PcBN has the maximum microhardness and fracture toughness of 3 892 HV and 6.82 MPa·m1/2, respectively. When the mass fraction of carbon nanotubes added is 1.0%, PcBN has the maximum bending strength and wear ratio, which are 584 MPa and 6 873 MPa, respectively. The pull-out and bridging effects of carbon nanotubes improve the mechanical properties of PcBN composites.

The monolithic PcBN composite tool materials were prepared at 5.5 GPa and 1450 ℃ with different contents of Ti3AlC2 as the binder phase. The effects of different mass fractions of Ti3AlC2 on the phase composition, microstructure, and mechanical properties of PcBN tool materials were studied. The results show that Ti3AlC2 can decompose completely to form TiC and Al-Ti alloys under high temperature and high pressure, and reacts with cBN to form AlN, TiB2, and TiC0.7N0.3 phases. TiC, AlN, TiB2, and TiC0.7N0.3 are uniformly distributed around the cBN and tightly bonded to the cBN, thereby improving the mechanical properties of PcBN. When the mass fraction of Ti3AlC2 is 25 %, the relative density, bending strength, fracture toughness, and wear ratio of PcBN reach the maximum values, which are 98.9%, 592 MPa, 6.87 MPa·m1/2and 7 350, respectively. When the mass fraction of Ti3AlC2 is 20%, the microhardness of PcBN reaches the maximum value of 4 786.7 HV.

Abstract Background Glycemic control, as measured by glycosylated hemoglobin (HbA1c), is an important biomarker to evaluate diabetes severity and is believed to be associated with heart failure development. Type 2 diabetes mellitus (T2DM) and heart failure with reduced ejection fraction (HFrEF) commonly coexist, and the combination of these two diseases indicates a considerably poorer outcome than either disease alone. Therefore, glycemic control should be carefully managed. The present study aimed to explore the association between glycemic control and clinical outcomes, and to determine the optimal glycemic target in this specific population. Methods A total of 262 patients who underwent cardiac MRI were included and were split by HbA1c levels [HbA1c 7.5% (poor control)]. The biventricular volume and function, as well as left ventricular (LV) systolic strains in patients in different HbA1c categories, were measured and compared. The primary and secondary outcomes were recorded. The association of different HbA1c levels with adverse outcomes was assessed. Results Despite similar biventricular ejection fractions, both patients with intensive and poor glycemic control exhibited prominent deterioration of LV systolic strain in the longitudinal component (P = 0.004). After a median follow-up of 35.0 months, 55 patients (21.0%) experienced at least one confirmed endpoint event. Cox multivariable analysis indicated that both patients in the lowest and highest HbA1c categories exhibited a more than 2-fold increase in the risk for primary outcomes [HbA1c 7.5%: HR = 2.24, 95% CI = 1.01–4.99; P = 0.038] and secondary outcomes (HbA1c 7.5%: HR = 2.65, 95% CI = 1.08–6.50; P = 0.038) compared with those in the middle HbA1c category. Conclusions We showed a U-shaped association of glycemic control with clinical outcomes in patients with T2DM and HFrEF, with the lowest risk of adverse outcomes among patients with modest glycemic control. HbA1c between 6.5% and 7.5% may be served as the optimal hypoglycemic target in this specific population.

Abstract Background Metabolic syndrome (MetS) can increase the risk of morbidity and mortality of cardiovascular disease and obstructive coronary artery disease (OCAD), which usually have a poor prognosis. This study aimed to explore the impact of MetS on left ventricular (LV) deformation and function in OCAD patients and investigate the independent factors of impaired LV function and deformation. Materials and methods A total of 121 patients with OCAD and 52 sex- and age-matched controls who underwent cardiac magnetic resonance scanning were enrolled in the study. All OCAD patients were divided into two groups: OCAD with MetS [OCAD(MetS+), n = 83] and OCAD without MetS [OCAD(MetS−), n = 38]. LV functional and global strain parameters were measured and compared among the three groups. Multivariable linear regression analyses were constructed to investigate the independent factors of LV impairment in OCAD patients. Logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed to test the prediction efficiency of MetS for LV impairment. Results From controls to the OCAD(MetS−) group to the OCAD(MetS+) group, LV mass (LVM) increased, and LV global function index (LVGFI) and LV global longitudinal peak strain (GLPS) decreased (all p

Abstract Micro RNAs (miRs) have been implicated in various tumorigenic processes. Osteosarcoma (OS) is a primary bone malignancy seen in adolescents. However, the mechanism of miRs in OS has not been fully demonstrated yet. Here, miR-134-5p was found to inhibit OS progression and was also expressed at significantly lower levels in OS tissues and cells relative to normal controls. miR-134-5p was found to reduce vasculogenic mimicry, proliferation, invasion, and migration of OS cells, with miR-134-5p knockdown having the opposite effects. Mechanistically, miR-134-5p inhibited expression of the ITGB1/MMP2/PI3K/Akt axis, thus reducing the malignant features of OS cells. In summary, miR-134-5p reduced OS tumorigenesis by modulation of the ITGB1/MMP2/PI3K/Akt axis, suggesting the potential for using miR-134-5p as a target for treating OS.