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Abstract Background Although a high C-reactive protein-to-albumin ratio (CAR) is believed to increase mortality risk, the association between the physical activity (PA), CAR, and mortality among cancer survivors has not been investigated. This study aimed to examine this association among cancer survivors in the United States. Methods This cohort study used data from the National Health and Nutrition Examination Survey from 1999 to 2010. PA was self-reported using the Global Physical Activity Questionnaire, and C-reactive protein and albumin levels were obtained from laboratory data files. Mortality data were obtained by linkage of the cohort database to the National Death Index as of December 31, 2019. The analysis was conducted from November 1 to December 31, 2023. We used Cox proportional hazards multivariable regression to assess hazard ratios (HRs) and 95% confidence interval (CIs) for total and cancer-specific mortality risks attributable to PA and CAR. Results Among 2,232 cancer survivors, 325 (14.6%) reported no PA with a high CAR. During a follow-up of up to 20.75 years (median, 12.3 years; 27,453 person-years), 1,174 deaths occurred (cancer, 335; other, 839). A high CAR was observed to be consistently associated with the highest risks of total (HR, 1.59; 95% CI, 1.37–1.85) and cancer-specific (HR, 2.06; 95% CI, 1.55–2.73) mortality compared with a low CAR in a series of adjusted models. Multivariable models showed that PA was associated with a lower risk of all-cause (HR, 0.60; 95% CI, 0.52–0.69) and cancer-specific (HR, 0.64; 95% CI, 0.49–0.84) mortality compared with no PA. In the joint analyses, survivors with PA ≥ 600 metabolic equivalent min/wk and a low CAR were more likely to reduce the risk of total (HR, 0.41; 95% CI, 0.32–0.51) and cancer-specific (HR, 0.32; 95% CI, 0.20–0.50) mortality by 59% and 68% compared with those with no PA and a high CAR. Conclusion The pairing of adequate PA and a low CAR was significantly associated with reduced all-cause and cancer-related mortality risks.

Abstract Background Treatment options for correcting limb-length discrepancy after limb-salvage reconstruction for proximal tibial osteosarcoma in children have several limitations. Therefore, we aimed to evaluate the feasibility, complications, prognosis, and clinical outcomes of reconstruction using hemiarthroplasty after tumor resection in pediatric patients with proximal tibial osteosarcoma. Methods We conducted a comprehensive retrospective analysis of the data of pediatric patients with osteosarcoma of the proximal tibia who underwent surgery between December 2008 and November 2018 at our center. We enrolled 49 consecutive patients who underwent hemiarthroplasty. The cruciate ligaments of all patients were reconstructed using special spacers, and the medial and lateral collateral ligaments of the knee and joint capsule were reconstructed using a mesh. Postoperatively, if the unequal length of both lower limbs exceeded 4 cm or knee instability occurred, a second-stage surgery was performed for limb lengthening and replacing the distal femoral prosthesis. We analyzed the oncological prognosis, complications of hemiarthroplasty, postoperative stability, and postoperative function. Results The follow-up period ranged between 11 and 159 months, with a median of 84 (62, 129) months. The overall 5-year survival rate was 83.2%. Thirty-nine patients survived at the end of the follow-up period with 34 prostheses (87.2%). The overall prosthesis survival rate was 87.4% after 5 years, indicating the long-term benefits of the procedure. Limb length was measured in 28 adult patients. The average limb-length discrepancy was 33 ± 15 mm with a median of 33 mm (21, 47); the femur and tibia caused a discrepancy of 8.5 ± 9.9 mm and 24.8 ± 15.5 mm, respectively. The patients had 30–135° of knee motion, with a mean of 82 ± 24°. The femoral tibial angle was greater on the affected side than on the healthy side, with a mean difference of 4.5°±3.6°. The Musculoskeletal Tumor Society (MSTS) score was 25 ± 3. Five patients underwent second-stage distal femoral prosthesis replacement, with mean MSTS scores of 24 ± 2 and 28 ± 1 before and after second-stage surgery, respectively. Conclusions Hemiarthroplasty in children reduces limb-length discrepancy in adulthood by rebuilding cruciate ligaments, lateral collateral ligaments, and the joint capsule, thereby improving knee stability.

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.

Abstract Background It remains unclear whether the association between dyslipidemia status and triglyceride-glucose (TyG) index with myocardial damage varies in the context of type 2 diabetes mellitus (T2DM). This study aimed to determine the differential effects of dyslipidemia status and TyG index on left ventricular (LV) global function and myocardial microcirculation in patients with T2DM using cardiac magnetic resonance (CMR) imaging. Methods A total of 226 T2DM patients and 72 controls who underwent CMR examination were included. The T2DM group was further categorized into subgroups based on the presence or absence of dyslipidemia (referred to as T2DM (DysL+) and T2DM (DysL-)) or whether the TyG index exceeded 9.06. CMR-derived LV perfusion parameters, remodeling index, and global function index (GFI) were assessed and compared among groups. A multivariable linear regression model was employed to evaluate the effects of various variables on LV myocardial microcirculation, remodeling index, and GFI. Results The LV GFI sequentially decreased in controls, T2DM (DysL-), and T2DM (DysL+) groups (p

Abstract Background The cost-effectiveness of NALIRIFOX as a potential new standard of care for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) has yet to be established. Our objective was to evaluate the cost-effectiveness of NALIRIFOX vs. nab-paclitaxel and gemcitabine in this indication from the perspective of U.S. public payers. Methods A partitioned survival model was constructed from the perspective of U.S. public payers, drawing on baseline patient characteristics and vital clinical data from the NAPOLI-3 trial. Costs and utilities were sourced from publicly accessible databases and literature. A lifetime horizon was applied, with an annual discount rate of 3%. We calculated and compared cumulative costs, life years, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICER). To evaluate the model’s robustness, sensitivity analyses, scenario analyses, and subgroup analyses were carried out. Additionally, a price simulation for the costly liposomal irinotecan was conducted to inform the pricing strategy at the given willingness to pay (WTP) threshold. Results In the base-case analysis, NALIRIFOX provided an additional 0.29 QALYs with an ICER of $206,340.69 /QALY compared to nab-paclitaxel and gemcitabine, indicating it is not cost-effective at a $150,000/QALY threshold. Sensitivity analysis showed the model was most sensitive to the costs of liposomal irinotecan, capecitabine, and post-progression care. Probabilistic sensitivity analysis indicated a 17.66% probability of NALIRIFOX being cost-effective at $150,000/QALY, rising to 47.48% at $200,000/QALY. Pricing simulations suggested NALIRIFOX could become cost-effective at $150,000/QALY if the price of irinotecan liposome drops to $53.24/mg (a 14.8% reduction). Conclusions NALIRIFOX may not be cost-effective at its current price as a first-line treatment for patients with mPDAC in the long term. The cost of liposomal irinotecan has the greatest impact. It may become cost-effective only if its cost is reduced by 14.8%, with a WTP threshold of $150,000 /QALY.

Abstract Evidences illustrate that cell senescence contributes to the development of pulmonary arterial hypertension. However, the molecular mechanisms remain unclear. Since there may be different senescence subtypes between PAH patients, consistent senescence-related genes (SRGs) were utilized for consistent clustering by unsupervised clustering methods. Senescence is inextricably linked to the immune system, and the immune cells in each cluster were estimated by ssGSEA. To further screen out more important SRGs, machine learning algorithms were used for identification and their diagnostic value was assessed by ROC curves. The expression of hub genes were verified in vivo and in vitro. Transcriptome analysis was used to assess the effects of silence of hub gene on different pathways. Three senescence molecular subtypes were identified by consensus clustering. Compared with cluster A and B, most immune cells and checkpoint genes were higher in cluster C. Thus, we identified senescence cluster C as the immune subtype. The ROC curves of IGF1, HOXB7, and YWHAZ were remarkable in both datasets. The expression of these genes was increased in vitro. Western blot and immunohistochemical analyses revealed that YWHAZ expression was also increased. Our transcriptome analysis showed autophagy-related genes were significantly elevated after silence of YWHAZ. Our research provided several prospective SRGs and molecular subtypes. Silence of YWHAZ may contribute to the clearance of senescent endothelial cells by activating autophagy.

Abstract Strain engineering plays an important role in tuning electronic structure and improving catalytic capability of biocatalyst, but it is still challenging to modify the atomic-scale strain for specific enzyme-like reactions. Here, we systematically design Pt single atom (Pt1), several Pt atoms (Ptn) and atomically-resolved Pt clusters (Ptc) on PdAu biocatalysts to investigate the correlation between atomic strain and enzyme-like catalytic activity by experimental technology and in-depth Density Functional Theory calculations. It is found that Ptc on PdAu (Ptc-PA) with reasonable atomic strain upshifts the d-band center and exposes high potential surface, indicating the sufficient active sites to achieve superior biocatalytic performances. Besides, the Pd shell and Au core serve as storage layers providing abundant energetic charge carriers. The Ptc-PA exhibits a prominent peroxidase (POD)-like activity with the catalytic efficiency (K cat/K m) of 1.50 × 109 mM−1 min−1, about four orders of magnitude higher than natural horseradish peroxidase (HRP), while catalase (CAT)-like and superoxide dismutase (SOD)-like activities of Ptc-PA are also comparable to those of natural enzymes. Biological experiments demonstrate that the detection limit of the Ptc-PA-based catalytic detection system exceeds that of visual inspection by 132-fold in clinical cancer diagnosis. Besides, Ptc-PA can reduce multi-organ acute inflammatory damage and mitigate oxidative stress disorder.

Abstract Invasive pneumococcal disease (IPD) due to non-vaccine serotypes after the introduction of pneumococcal conjugate vaccines (PCV) remains a global concern. This study used pathogen genomics to evaluate changes in invasive pneumococcal lineages before, during and after vaccine introduction in South Africa. We included genomes (N = 3104) of IPD isolates from individuals aged

Abstract Tibetan Buddhist monasteries constitute significant cultural heritages of ethnic minorities, evolving into the Principal-Subordinate Monastery System (PSMS) with profound historical and cultural significance. This system exhibits an integrated hierarchical structure in terms of religious dominance, political administration, and cultural diffusion. Existing research primarily focuses on internal humanistic factors such as governance patterns, while there is not any research focused on its patterns and manifestations in spatial distribution. This study aims to elucidate the spatial distribution characteristics of the PSMS in Hehuang region, including the Tibetan Buddhist monasteries from all sects in the Hehuang region since the Song Dynasty It establishes a hierarchical PSMS database based on the affiliation relationships, aimed at storing spatial and property information related to PSMS. The database standardizes the naming and coding of monasteries, and classifies them through hierarchical relationships to ensure data consistency and usability. Finally, the classified and coded monastery data were analyzed by GIS tools to form the PSMS spatial distribution characterisation framework. Results reveal that (1) Monasteries demonstrate notable spatial clustering patterns from both holistic and sectarian perspectives, with density being influenced by the principal monastery’s position. (2) Almost every PSMS exhibits a spatial pattern centered around the principal monastery, with subordinate monasteries clustering within a defined range correlated with the administrative region of the principal monastery. (3) PSMS scale variations are controlled by principal monasteries, exhibiting positive correlations in hierarchical structure, control quantity, and distribution range. (4) The spatial orientation of PSMS correlates with river distribution, while the relationships among mountain ranges require further investigation. These findings provide initial insights into the spatial distribution characteristics of PSMS, confirming the spatial influence of the principal monastery. Besides, this study established an innovative spatial research framework for heritage clusters with multiple types and hierarchies. Thus, this study offers new insights into the spatial distribution of Tibetan Buddhist monastery heritage and presents a framework for further examining the spatial distribution of the Tibetan Buddhist monastery heritage in other regions, as well as other heritage clusters where connected and clustered through religious and cultural ties.

Abstract δ-MnO2 is an important component of environmental minerals and is among the strongest sorbents and oxidants. The crystalline morphology of δ-MnO2 is one of the key factors affecting its reactivity. In this work, δ-MnO2 was initially synthesized and placed in an acidic environment to react with Mn2+ and undergo a crystalline transformation. During the transformation of crystalline δ-MnO2, kinetic sampling was conducted, followed by analyses of the structures and morphologies of the samples. The results showed that at pH 2.5 and 4, δ-MnO2 nanoflakes spontaneously self-assembled into nanoribbons via edge-to-edge assembly in the initial stage. Subsequently, these nanoribbons attached to each other to form primary nanorods through a face-to-face assembly along the c-axis. These primary nanorods then assembled along the (001) planes and lateral surfaces, achieving further growth and thickening. Since a lower pH is more favorable for the formation of vacancies in δ-MnO2, δ-MnO2 can rapidly adsorb Mn2+ directly onto the vacancies to form tunnel walls. At the same time, the rapid formation of the tunnel walls leads to a quick establishment of hydrogen bonding between adjacent nanoribbons, enabling the assembly of these nanoribbons into primary nanorods. Therefore, in a solution with the same concentration of Mn2+, the structure transformation and morphology evolution of δ-MnO2 to α-MnO2 occur faster at pH 2.5 than at pH 4. These findings provide insights into the mechanism for crystal growth from layer-based to tunnel-based nanorods and methods for efficient and controlled syntheses of nanomaterials.

Abstract Multiple synchronous lung cancers (MSLCs) constitute a unique subtype of lung cancer. To explore the genomic and immune heterogeneity across different pathological stages of MSLCs, we analyse 16 MSLCs from 8 patients using single-cell RNA-seq, single-cell TCR sequencing, and bulk whole-exome sequencing. Our investigation indicates clonally independent tumours with convergent evolution driven by shared driver mutations. However, tumours from the same individual exhibit few shared mutations, indicating independent origins. During the transition from pre-invasive to invasive adenocarcinoma, we observe a shift in T cell phenotypes characterized by increased Treg cells and exhausted CD8+ T cells, accompanied by diminished cytotoxicity. Additionally, invasive adenocarcinomas exhibit greater neoantigen abundance and a more diverse TCR repertoire, indicating heightened heterogeneity. In summary, despite having a common genetic background and environmental exposure, our study emphasizes the individuality of MSLCs at different stages, highlighting their unique genomic and immune characteristics.

Abstract Dental implant restoration shows an effective method for the rehabilitation of missing teeth. The failure rate of periodontal implants in patients with chronic periodontitis is associated with periodontal flora, inflammation, and long-term periodontal bone resorption caused by chronic periodontitis. However, the therapeutic effects of dental implant restoration on inflammation in patients with chronic periodontitis have not addressed. The purpose of this study is to evaluate the risk indicators for inflammation, bone loss and implant failure in patients with chronic periodontitis. A total of 284 patients with dental implant restoration were recruited and divided into periodontally healthy patients (n = 128) and chronic periodontitis patients (n = 156). Periodontal indices including probing depth (PD), sulcus bleeding index (SBI), plaque index (PLI), gingival bleeding (GIL) and bleeding on probing (BOP) were compared in two groups. Inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1 (IL-1), matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) levels at baseline, 6 and 12 months after surgery, and the implant survival rate at 12 months after surgery, as well as the risk factors associated with failure of dental implant were also assessed. Outcomes demonstrated that patients in the chronic periodontitis group had higher values of periodontal indices than those in the periodontally healthy group. All inflammatory parameters in the chronic periodontitis group were higher than those in the periodontally healthy group and negatively associated with the chronic periodontal index (CPI) in chronic periodontitis patients. Chronic periodontitis patients had higher the prevalence of mucositis and peri-implantitis than patients with healthy periodontium. Implant diameter, length and design was associated with the risk of implant failure for chronic periodontitis patients receiving dental implant. The cumulative implant failure rate and incidence of implant fractures for chronic periodontitis patients at 12 months after surgery were 12.10% and 7.23% (p

Due to the heterogeneity of nodes and edges, heterogeneous network embedding is a very challenging task to embed highly coupled networks into a set of low-dimensional vectors. Existing models either only learn embedding vectors for nodes or only for edges. These two methods of embedding learning are rarely performed in the same model, and they both overlook the internal correlation between nodes and edges. To solve these problems, a node and edge joint embedding model is proposed for Heterogeneous Information Networks (HINs), called NEJE. The NEJE model can better capture the latent structural and semantic information from an HIN through two joint learning strategies: type-level joint learning and element-level joint learning. Firstly, node-type-aware structure learning and edge-type-aware semantic learning are sequentially performed on the original network and its line graph to get the initial embedding of nodes and the embedding of edges. Then, to optimize performance, type-level joint learning is performed through the alternating training of node embedding on the original network and edge embedding on the line graph. Finally, a new homogeneous network is constructed from the original heterogeneous network, and the graph attention model is further used on the new network to perform element-level joint learning. Experiments on three tasks and five public datasets show that our NEJE model performance improves by about 2.83% over other models, and even improves by 6.42% on average for the node clustering task on Digital Bibliography & Library Project (DBLP) dataset.

Tumor vaccine, a promising modality of tumor immunotherapy, needs to go through the process of tumor antigen generation and loading, antigen drainage to lymph nodes (LNs), antigen internalization by dendritic cells (DCs), DC maturation, and antigen cross-presentation to activate T-cells. However, tumor vaccines are often unable to satisfy all the steps, leading to the limitation of their application and efficacy. Herein, based on a smart nanogel system, an in situ nano-vaccine (CpG@Man-P/Tra/Gel) targeting LNs was constructed to induce potent anti-tumor immune effects and inhibit the recurrence and metastasis of ovarian cancer. The CpG@Man-P/Tra/Gel exhibited MMP-2-sensitive release of trametinib (Tra) and nano-adjuvant CPG@Man-P, which generated abundant in situ depot of whole-cell tumor antigens and formed in situ nano-vaccines with CpG@Man-P. Benefiting from mannose (Man) modification, the nano-vaccines targeted to LNs, promoted the uptake of antigens by DCs, further inducing the maturation of DCs and activation of T cells. Moreover, CpG@Man-P with different particle sizes were prepared and the effective size was selected to evaluate the antitumor effect and immune response in vivo. Notably, combined with PD-1 blocking, the vaccine effectively inhibited primary tumor growth and induced tumor-specific immune response against tumor recurrence and metastasis of ovarian cancer.

This study examines market and future-level sentiment in the Chinese agricultural futures market, distinguishing between contagious and idiosyncratic sentiment. Our analysis reveals that agricultural future-level sentiment is significantly affected by market-level sentiment and domestic stock market sentiment, particularly during bullish market conditions, while global stock market sentiment has minimal impact. Furthermore, we find that both market and future-level sentiment strongly and positively influence futures returns, with contagious and idiosyncratic sentiment exerting favorable influences, particularly in bullish markets. Our findings provide clear evidence of sentiment's impact on agricultural futures returns, offering valuable insights for regulators to identify potential market bubbles and implement effective sentiment regulation measures.

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 Type 2 diabetes mellitus (T2DM) and metabolic-associated fatty liver disease (MAFLD) are both metabolic disorders that negatively impact the cardiovascular system. This study comprehensively analyzed the additive effect of MAFLD on left ventricular function and global strain in T2DM patients by cardiac magnetic resonance (CMR). Methods Data of 261 T2DM patients, including 109 with and 152 without MAFLD, as well as 73 matched normal controls from our medical center between June 2015 and March 2022 were retrospectively analyzed. CMR-derived parameters, including LV function and global strain parameters, were compared among different groups. Univariate and multivariate linear regression analyses were conducted to investigate the impact of various factors on LV function and global strain. Results Our investigation revealed a progressive deterioration in LV functional parameters across three groups: control subjects, T2DM patients without MAFLD, and T2DM patients with MAFLD. Statistically significant increases in left ventricular end-diastolic volume index (LVEDVI), left ventricular end-systolic volume index (LVESVI), left ventricular mass index (LVMI) were observed, along with decreases in left ventricular ejection fraction (LVEF) and left ventricular global function index (LVGFI). Among these three groups, significant reductions were also noted in the absolute values of LV global radial, circumferential, and longitudinal peak strains (GRPS, GCPS, and GLPS), as well as in peak systolic (PSSR) and peak diastolic strain rates (PDSR). MAFLD was identified as an independent predictor of LVEF, LVMI, LVGFI, GRPS, GCPS, and GLPS in multivariate linear analysis. Besides, the incidence of late gadolinium enhancement was higher in MAFLD patients than in non-MAFLD patients (50/109 [45.9%] vs. 42/152 [27.6%], p = 0.003). Furthermore, escalating MAFLD severity was associated with a numerical deterioration in both LV function parameters and global strain values. Conclusions This study thoroughly compared CMR parameters in T2DM patients with and without MAFLD, uncovering MAFLD’s adverse impact on LV function and deformation in T2DM patients. These findings highlight the critical need for early detection and comprehensive management of cardiac function in T2DM patients with MAFLD.

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

The fibroblast growth factor receptor (FGFR) is a crucial receptor tyrosine kinase involved in essential biological processes, including growth, development, and tissue repair. However, FGFR gene mutations, including amplification, fusion, and mutation, can disrupt epigenetics, transcriptional regulation, and tumor microenvironment interactions, leading to cancer development. Targeting these kinase mutations with small molecule drugs or antibodies has shown clinical benefits. For example, erdafitinib is approved for treating locally advanced or metastatic urothelial cancer patients with FGFR2/FGFR3 mutations, and pemigatinib is approved for treating cholangiocarcinoma with FGFR2 fusion/rearrangement. Effective screening of FGFR variant patients is crucial for the clinical application of FGFR inhibitors. Various detection methods, such as polymerase chain reaction, next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry, are available, and their selection should be based on diagnostic and treatment decision-making needs. Our developed expert consensus aims to standardize the diagnosis and treatment process for FGFR gene mutations and facilitate the practical application of FGFR inhibitors in clinical practice.

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.

Inclusion clusters with a size of several tens of micrometers were found to be inclined to early crack initiation, resulting in an abnormally reduced fatigue life. Fatigue tests were conducted to elucidate crack initiation behaviors of inclusion clusters in nickel-based powder metallurgy (P/M) FGH96 superalloy. The inclusion clusters with varying sizes and shapes located at grain boundaries are composed of Al2O3, MgO and ZrO2 particles. The inclusion cluster with large size within 25–35 μm, small average particle distance within 0–4 μm and large orientation relative to loading direction within 35–66° will be more likely to cause crack initiation. In particular, the inclusion clusters with large size and high aggregation degree experience extruding during processing and subsequent heat-treatments due to the difference in thermal expansion coefficient with the matrix behave multiple cracking before fatigue loading, thereby facilitating crack initiation in the surrounding matrix grains. Moreover, as the main cracking part of inclusion clusters, the Al2O3 particles exhibit self-cracking and interface debonding, owing to higher hardness and poorer deformation coordination degree with matrix compared to other component inclusion particles.

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 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.

Hetaoyu well field has large production capacity and stable distribution of coal seam， The thick sandstone aquifer of Luohe Formation in the roof of coal seam is the main water-filling aquifer which will result in coal seam roof water damage and threatening the safety of mine production with the deepening of mining degree when the water-conducting fissure zone leads to the water-rich area of the overlying aquife. It is necessary for the safety mining of coal mine to find out the law of water-rich distribution of aquifer, because water richness evaluation of coal seam roof aquifer is the basis of water hazard prevention and control. In order to evaluate the water richness of Luohe Formation aquifer in the first mining area of the Hetaoyu well field, six indexes including aquifer thickness, collecting rate of drill core, thickness ratio of brittle-plasticity, washing liquid consumption, permeability coefficient, unit water inflow were selected as evaluation factors by analyzing borehole data and other well field data in the study area. Combination Weighting Method is used to carry out the index weight comprehensively based on Analytic Hierarchy Process (AHP) and CRITIC method，and the comprehensive weights of each index were 0.1707, 0.2078, 0.0976, 0.1171, 0.1465 and 0.2603, respectively. Using the FDAHP-Independent weight coefficient method, the weights of the four main controlling factors, such as aquifer thickness, core extraction rate, thickness ratio of brittle plastic rock and wash fluid consumption, are 0.1675, 0.312, 0.2575 and 0.263, respectively. A method of aquifer water-richness evaluation index model based on the combination weighting method was proposed, and zonation of water-richness zoning was made for seam roof Luohe Formation aquifer. The results show that the water richness distribution of the Luohe Formation aquifer in the roof of coal seam in the first mining area of Hetaoyu is uneven，which is obviously different from the distribution of each single index. The relatively weak and relatively weak water-rich areas are located in the eastern part of the study area, the middle part has medium water-rich water, and the strong water-rich areas are located in the central and western parts of the study area respectively. There are large areas of relatively strong water-richness in the central and western areas. It is necessary to pay attention to the strong water-richness in the western areas and local strong water richness points and do well in water exploration and release in advance.

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.