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Background: Hypochondroplasia (HCH) is a prevalent form of dwarfism linked to mutations in the fibroblast growth factor receptor 3 (FGFR3) gene, causing missense alterations. We previous report was the first to identify FGFR3(G382D) gain-of-function variants with a positive family history as a novel cause of HCH. However, the precise contribution of FGFR3 to the pathogenesis of HCH remains elusive. Methods: We generated an Fgfr3 (V376D) mutation mouse model using CRISPR/Cas9 technology and performed proteomic analyses to investigate the molecular mechanisms and potential therapeutic targets of HCH. Radiography and micro-computed tomography were employed to assess the bone-specific phenotype in Fgfr3 (V376D)mutant mice. Immunofluorescence, western blotting, and flow cytometry were used to systematically investigate the underlying mechanisms and therapeutic targets. Results: We observed that Fgfr3 (V376D) mutant mice exhibit a bone-specific phenotype, with symmetrically short limb bones, partially resembling the dwarfism phenotype of patients with HCH. We demonstrated that the mutant-activated FGFR3 promotes heat shock protein B 6 (HSPB6)-mediated cuproptosis by inhibiting chondrocyte autophagy both in vivo and in vitro. Additionally, we revealed that FGFR3 (G382D) mutation leads to enhanced ERK signaling, increased Drp1-mediated mitochondrial fission, and upregulated cuproptosis-related protein ferredoxin 1 (FDX1). Furthermore, genetic and pharmacological inhibition of the HSPB6-ERK-Drp1-FDX1 pathway partially alleviate the phenotypes of FGFR3 mutants. Conclusions: Our study provides the first evidence for the pathogenicity of a gain-of-function mutation in FGFR3 (G382D) using mouse and cell models, and it underscores the potential of targeting the HSPB6-ERK-Drp1-FDX1 axis as a novel therapeutic approach for HCH. Translational potential of this article: We first demonstrate that impaired autophagy and enhanced cuproptosis are pivotal in the pathogenesis of HCH. This study not only enlarged the therapeutic potential of targeting cuproptosis for treating FGFR3 mutation-related HCH but also provided a novel perspective on the role of the HSPB6-ERK-Drp1-FDX1 signaling pathway in the development of HCH. Consequently, this article provides valuable insights into the mechanisms and treatment strategies for FGFR3 mutation-related chondrodysplasia.

The interfacial bonding between graphene and Al critically influences the composite's strengthening efficiency. In this paper, nickel oxide nanoparticle-coated reduced graphene oxide (NiO@rGO) reinforcements were synthesized by alcohol-thermal and annealing process. Subsequently, NiO@rGO/Al composites were fabricated through intermittent ball milling and hot-press sintering. The presence of NiO leads to a thermite reaction during the high-temperature sintering process, forming a distinctive graded interface structure of graphene/Al2O3/Al, which boosts the interface bonding strength and enhances the load-transfer ability. Concurrently, the thermal effect generated by the Al thermal reaction would facilitate the long-distance diffusion of Ni atoms, contributing to the generation of intragranular Al3Ni, which avoids premature fracture due to stress concentration at the interface. Consequently, the composite demonstrates excellent mechanical properties. Compared to pure Al, the composite's ultimate tensile strength has increased by 66% (143.1 ± 2.3 MPa). Theoretical modeling analysis indicates that the primary enhancements in the NiO@rGO/Al composite material stem from load transfer and interface thermal mismatch.

Abstract Recent research highlights the pivotal role of N6-methyladenosine (m6A) modification and ferroptosis in the evolution of various cancers. This study aimed to establish a prognostic framework centered on genes associated with m6A and ferroptosis to enhance the accuracy of prognosis predictions for neuroblastoma (NB) patients, thereby improving targeted therapeutic strategies. Patient data, including expression profiles and clinical information from NB cases, were acquired from The Cancer Genome Atlas. Genes related to m6A modification and ferroptosis were identified, and those significant for prognosis were pinpointed using a combination of Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) regression. For further validation, the study utilized external datasets GSE62564 and GSE85047. A prognostic index was computed for each NB patient, followed by analyses of immune cell infiltration and potential drug responsiveness based on the prognostic model. Additionally, enrichment analysis was conducted on the prognostic scores. These scores showed a strong association with the tumor immune environment and the efficacy of prevalent cancer therapies. Moreover, the model’s prognostic score emerged as an independent predictive marker for NB. This research succeeded in creating and confirming a prognostic model rooted in m6A and ferroptosis-linked genes, promising to enrich the prognostic understanding and treatment approaches for NB.

Abstract Programmable metasurfaces (PMs), also called reconfigurable intelligent surfaces (RISs), are planar structures capable of dynamically manipulating electromagnetic waves in real-time. Regarded as a key enabling technology for implementing smart wireless propagation environments, PMs/RISs also serve as an ideal supporting platform for integrated sensing and communication (ISAC). Here, we propose two ISAC schemes based on a special type of PMs/RISs: space-time-coding metasurfaces (STCMs). By leveraging space-time-coding strategies, STCMs simultaneously control the propagation at the fundamental (carrier) frequency for reliable wireless communication and generate spatially distributed harmonics for sensing. The proposed schemes seamlessly integrate both communication and sensing on a shared hardware platform, eliminating the need for additional sensors. For experimental validation, we implemented an ISAC system using a 2-bit STCM operating at microwave frequencies. Experimental results align with theoretical predictions, confirming the practical viability and effectiveness of the proposed ISAC schemes for applications in communication, imaging, radar, and sensing systems.

In the present research, the nanosecond short-pulsed laser with rotary drilling method was designed to process carbon fiber-reinforced polymer (CFRP) composite plate. The hole dimension, surface morphology, heat-affected zone (HAZ), and mechanical properties were analyzed. The results reveal that the CFRP composite plate could be rapidly drilled with highly qualified processing surface by the nanosecond short-pulsed laser with rotary drilling method. The figures such as circle, square, triangle, and regular hexagon could be processed with minimum hole diameter of 0.1 mm. The changing of laser scanning speed and laser power could result in the variation in diameter of hole entrance and exit, which fluctuates in scope of 35 μm. The calculated biggest taper angle is about 0.43°, but the smallest taper angle is about 0.12°. The laser drilling on CFPR composite decreases the tensile strength by about 9%, which should be ascribed to the damage of continuous carbon fiber, but it is still acceptable. The nanosecond short-pulsed laser with rotary drilling method generates a small HAZ on hole entrance but almost no HAZ in hole exit. The surface roughness of laser processed CFRP ranges from 2.925 to 4.226 μm. Comparatively, the laser scanning speed between 800 and 1,000 mm/s and laser power around 28 W would be the optimal choice, which could realize the best balance between surface quality and efficiency.

Abstract To study the effect and mechanism of coal-rock underground impact pressure prevention and control under the influence of upper protective layer mining. In this paper, the research is carried out based on four factors, namely, the mining stress environment, the mechanical strength of coal and rock, the dynamic load disturbance effect of mining, and the energy loss space of coal and rock. Theoretical calculation and analysis, rock mechanics test, physical similar simulation test and on-site industrial experiments are adopted to study the stress distribution of the coal rock below the influence of the mining of the upper protective layer, overlying strata migration, and the law of mine pressure behavior. The results show that after the mining of the upper protective layer, the vertical stress of the coal rock body under the mined-out area increases with the depth, and the horizontal compressive stress in the shallow area gradually decreases with the increase of depth. In contrast, the horizontal tensile stress in deep areas gradually increases with the depth increase. The uniaxial compressive strength and impact energy index of the coal rock both decrease with the increase of the mining intensity of the upper protective layer. The mining of the upper protected layer will weaken the overburden structure of the mining field of the protected layer, and will reduce the breaking span and disturbance intensity of the key layer in the protected layer. The mining coal rock body in the process of upper protected mining experienced three stages of advanced stress concentration, the rapid growth of pressure relief, and the slow recovery of pressure relief, and the stress release rates all decreased with the increase of depth. The results of the study can provide an important reference value for the prevention and control of underground impact pressure and other disasters in the upper protective layer mining of closed-distance coal seam groups.

Abstract To evaluate the effect of recombinant human thrombopoietin (rhTPO) on platelet engraftment after autologous stem cell transplantation (ASCT) in newly diagnosed multiple myeloma (NDMM) patients. Clinical data of 40 NDMM patients who underwent high-dose melphalan conditioning and ASCT were analyzed, with 26 receiving rhTPO and 14 in the control group. The primary study endpoint was the median time to platelet engraftment. The secondary study endpoints included the median time to neutrophil engraftment, number of blood cells transfused, treatment-related adverse events, long-term hematopoietic reconstitution, and economic cost-effectiveness. The median time to neutrophil engraftment was 10.92 and 11.14 days in the rhTPO and control groups, respectively (p = 0.405). The median time to platelet engraftment (11.5 vs. 11.36 days, p = 0.776), median number of erythrocyte infusions (0.23 vs. 0 units, p = 0.326), and median number of platelet infusions (1.615 vs. 1.5 units, p = 0.721) did not significantly differ between the groups. The median hospitalization duration was 27.08 and 25.07 days in the rhTPO and control groups, respectively (p = 0.193). The median hospitalization cost was RMB 73,846 and RMB 54,136 in the rhTPO and control groups, respectively (p

Abstract Various risks often exist in metro construction and building, and how to assess the risk when metro is constructed by shield method and establish the construction risk indicator system has become a hot research topic nowadays. In this paper, HHM (hierarchical holography method) is firstly used to list the initial 26 risk indicators, and the risk list is optimized by using vague set theory to get 13 risk indicators. Then, the risk indicators are assigned by a combination of the G1 method (order-relationship hierarchy method) and the COWA method (order-weighted average operator) to determine the weights of the construction safety risk evaluation indicators of the shield construction method of metro tunnels. At the same time, to reduce the influence of the uncertainty, randomness and ambiguity of the shield construction of metro tunnels and more intuitively represent the risk weights of the indicators, and the cloud theory is used to objectively display the risk weights of the indicators. Finally, the subway tunnel shield method construction safety risk evaluation model introduced into the Tianjin Metro an interval case for risk assessment, and test of the scientific nature of the model, applicability, the evaluation results obtained, and the actual results are consistent with the validation of this paper to build the subway tunnel shield method construction safety risk evaluation model of scientific applicability and reliability, enriching the subway tunnel engineering construction safety risk evaluation method for subway tunnels. Construction safety risk evaluation provides a scientific basis for decision-making, but also for the further development of risk prevention measures, reduces the risk of construction of subway tunneling projects to provide a basis for promoting the healthy and rapid development of the construction of urban subways, and provides guidance for similar projects.

Abstract Background Enhanced recovery after surgery (ERAS) has been widely used in several surgical fields. This meta-analysis compared the clinical outcomes of the ERAS protocol and standard care (SC) in patients who underwent lumbar interbody fusion surgery. Materials and methods The PubMed, Web of Science, Cochrane Library, and Embase databases were systematically searched to identify studies reporting the effects of the ERAS protocol on clinical outcomes in patients who underwent lumbar interbody fusion surgery. Results Overall, 15 studies involving 17 865 patients were included in the final analysis. With the ERAS protocol, the length of hospitalization (SMD: − 0.47, 95% CI − 0.56 to –0.38), postoperative complications (OR = 0.62; 95% CI 0.50 to 0.77), operation time (SMD = − 0.26; 95% CI − 0.44 to –0.09), postoperative pain (SMD = − 0.35; 95% CI − 0.64 to –0.07) and duration of ambulation (SMD = − 0.80; 95% CI − 1.02 to − 0.58) were significantly reduced. The rates of readmission (OR = 0.63; 95% CI 0.38 to 1.04), estimated blood loss (SMD = − 0.31; 95% CI − 0.69 to 0.06) and hospitalization costs (SMD: − 0.56, 95% CI − 1.27 to 0.14) did not significantly differ between the ERAS and SC groups. Conclusions The present meta-analysis indicated that the ERAS protocol could be safely and feasibly implemented in the perioperative management of patients receiving lumbar interbody fusion surgery. The protocol significantly reduced the length of hospitalization, incidence of postoperative complications, operation time, duration of 1st ambulation and duration of postoperative pain. However, no differences were observed in estimated blood loss, readmission rates or hospitalization costs.

Abstract Objective This study aims to investigate the relationships between living and neighborhood environmental factors and anxiety symptoms among older adults residing in urban and rural areas of Anhui Province, China. Methods Data were collected from 5876 participants in a cross-sectional study carried out in four cities located in Anhui, China. Anxiety symptoms were evaluated via the Generalized Anxiety Disorder scale (GAD-7), and participants with scores of 5 and above were defined as having anxiety symptoms. The presence of dust and noise in the context of daily life was used to evaluate the living environment of the participants. The neighborhood environment was assessed by the availability of barrier-free facilities, proximity to facilities (supermarkets, restaurants, hospitals, and parks), and green and blue space near participants’ dwellings. Multilevel linear and logistic regression analyses were used to estimate the associations between these environmental factors and anxiety symptoms. Results The participants who lived in dusty environments had elevated GAD-7 scores and higher odds of anxiety (dust: β = 0.754, 95% CI: 0.337, 1.171; OR = 1.451, 95% CI: 1.164, 1.809). Having barrier-free facilities and the existence of a neighboring park decreased the GAD-7 scores and the likelihood of having anxiety symptoms (barrier-free facilities: β=-0.503, 95% CI: -0.992, -0.085; OR = 0.768, 95% CI: 0.656, 0.899; park: β=-0.478, 95% CI: -0.830, -0.125; OR = 0.599, 95% CI: 0.440, 0.816). However, participants residing in close proximity to the hospital presented an increased likelihood of experiencing anxiety symptoms (OR = 1.377, 95% CI: 1.162, 1.631). Conclusions Participants who lived in dusty and noisy environments were more likely to suffer from anxiety, whereas those who lived near barrier-free facilities and parks were at lower risk. The findings emphasize the need for targeted interventions to create age-friendly communities, suggesting an integrated approach that combines environmental health strategies with mental health strategies for older adults.

Abstract Background Radiomics has shown promise in the diagnosis and prognosis of lung cancer. Here, we investigated the performance of computed tomography-based radiomic features, extracted from gross tumor volume (GTV), peritumoral volume (PTV), and GTV + PTV (GPTV), for predicting the pathological invasiveness of pure ground-glass nodules present in lung adenocarcinoma. Methods This was a retrospective, cross-sectional, bicentric study with data collected from January 1, 2018, to June 1, 2022. We divided the dataset into a training cohort (n = 88) from one center and an external validation cohort (n = 59) from another center. Radiomic signatures (rad-scores) were obtained after features were selected through correlation and least absolute shrinkage and selection operator analysis. Three machine learning models, a support vector machine model, a random forest model, and a generalized linear model, were then applied to build radiomic models. Results Invasive adenocarcinoma had a higher rad-score (P

The Gaoligong Mountains lie at the intersection of three global biodiversity hotspots. In recent years, with the continuous deepening of fieldwork in the region, studies have increasingly indicated that the amphibian diversity of this region remains poorly understood. During herpetological surveys in 2023, a series of Amolops specimens were collected from the Gaoligong Mountains of Yunnan Province, China. The integrated results of morphological and molecular phylogenetic analyses indicate the presence of a separate and previously unknown lineage in the A. viridimaculatus group, which we herein confirm as a new species, Amolops gudao Yu, Wu, Lu & Che, sp. nov. Our discovery increases the number of Amolops species recorded in China to 59, and the total number of Amolops species to 86. The discovery of a new species in the Gaoligong Mountains further highlights the underestimated amphibian diversity in the region, emphasizing the need for continued fieldwork and research. Furthermore, Amolops gudao Yu, Wu, Lu & Che, sp. nov. exhibits obvious intraspecific variation in color patterns, a phenomenon also reported in several species within the A. viridimaculatus group, such as A. viridimaculatus and A. kaulbacki. Future studies on the taxonomy of A. viridimaculatus group should be careful with the use of color patterns as a diagnostic characteristic.

The chest X-ray (CXR) imaging has been the most frequently performed radiographic examination for decades, and its demand continues to grow due to their critical role in diagnosing various diseases. However, the image quality of CXR has long been a factor limiting their diagnostic accuracy. As a post-processing procedure, image enhancement can cost-effectively improve image quality. Recently, the successful application of deep learning (DL) algorithms in medical image analysis has prompted researchers to propose and design DL-based CXR image enhancement algorithms. This review examines advancements in CXR image enhancement methods from 2018 to 2023, categorizing them into four groups: bone suppression, image denoising, super-resolution reconstruction, and contrast enhancement. For each group, the unique approaches, strengths, and challenges are analyzed. The review concludes by discussing shared challenges across these methods and proposing directions for future research.

During operation, wind turbine systems are affected by external wind speed disturbances and the dynamic coupling of the system, which can lead to significant resonance phenomena within certain frequency ranges. Resonance causes a dramatic increase in the system’s dynamic response at specific frequencies, resulting in unstable power output and exacerbating the accumulation of fatigue loads, posing a threat to the safety and operational reliability of the wind turbine. To address this issue, this study proposes a multi-objective H $_{\mathrm {\infty }}$ /generalized H2 additional damping control method, which improves control precision by minimizing the integral of time-weighted absolute error of state variables, effectively suppressing the resonance peaks at critical frequencies and reducing the resulting power and load fluctuations. Experimental results show that, compared to reference open-source controller tuning, the proposed strategy reduces the standard deviations of output power, tower-top fore-aft displacement, and tower base roll moment by 19.97%, 18.90%, and 30.13%, respectively. This approach significantly enhances the power stability of the wind turbine system and effectively reduces load fluctuations, providing an efficient solution for improving the operational reliability and lifespan of wind turbines.

Epigenetic regulation is critical to multiple physiological and pathological processes. However, little is known regarding the epigenetic changes during neonatal skin development and skin aging, and in response to ultraviolet (UV) exposure. The transcriptomes of human skin samples from different ages or irradiated with different types and doses of UV light were analyzed using R (version 4.0.3) software. The epigenetic landscape of the skin, including histone modifications, genetic imprinting and m6A modification, which are mainly involved in collagen formation, extracellular matrix organization, immune function and keratinization, underwent significant changes during neonatal to adult development. Epigenetic effectors such as IGF2BP2, GATA2, GATA3, CPA4 and CDK1 were significantly correlated with extracellular matrix organization, and VEGFA, CDK1 and PRKCB with skin immune function. The m6A readers such as IGF2BP2, IGF2BP3, HNRNPA2B1 and EIF3G showed significant correlation with extracellular matrix organization, metabolism, or antigen processing and presentation. Small doses of UV exposure only induced changes in the expression levels of some epigenetic effectors, without any significant effect on the overall epigenetic landscape. However, the minimal erythema dose of UV exposure altered multiple epigenetic effectors regulating extracellular matrix organization, cell-matrix adhesion, innate immune response, mitochondrial function and mRNA processing. In addition, epigenetic changes following UV exposure were more pronounced in the elderly skin compared to the younger skin. In conclusion, histone modifications, genetic imprinting and m6A modification play critical roles during skin development, and a large dose of UV exposure can significantly change the expression of multiple epigenetic effectors.

Abstract Background Insulin resistance (IR) plays a pivotal role in the interplay between metabolic disorders and heart failure with preserved ejection fraction (HFpEF). Various non-insulin-based indices emerge as reliable surrogate markers for assessing IR, including the triglyceride-glucose (TyG) index, the TyG index with body mass index (TyG-BMI), atherogenic index of plasma (AIP), and the metabolic score for insulin resistance (METS-IR). However, the ability of different IR indices to predict outcome in HFpEF patients has not been extensively explored. Methods Patients having HFpEF were recruited from January 2012 and December 2023. The outcome was defined as major adverse cardiovascular event (MACE), encompassing all-cause mortality and rehospitalization for heart failure. The potential linear relationship was visualized by the restricted cubic spline (RCS) curve. Both univariable and multivariable Cox proportional hazards models were employed to examine the association between the IR indexes and MACE. Furthermore, to assess the incremental prognostic value of the TyG index, we conducted comprehensive analyses using area under the curve (AUC), the continuous net reclassification index (cNRI), and the integrated discrimination index (IDI). Results A total of 8693 patients met the inclusion criteria and were included in the final analysis. The mean age of the patients was 70.59 ± 10.6 years, with 5045 (58.04%) being male. The Kaplan-Meier survival analysis revealed that higher degree of the four IR indexes was associated with higher risk of MACE (all log-rank P

Abstract Background The C-repeat binding factor (CBF)/dehydration-responsive element binding (DREB1) belongs to a subfamily of the AP2/ERF (APETALA2/ethylene-responsive factor) superfamily, which can regulate many physiological and biochemical processes in plants, such as plant growth and development, hormone signal transduction and response to abiotic stress. Although the CBF/DREB1 family has been identified in many plants, studies of the CBF/DREB1 family in alfalfa are insufficient. Results In this study, 25 MsCBF genes were identified in the genome of alfalfa (“Zhongmu No. 4”). These genes were distributed on chromosomes 1, 5, 6 and unassembled scaffolds. Phylogenetics divided the CBF members of Medicago sativa, Arabidopsis thaliana, and Medicago truncatula into six groups, of which group VI had the most MsCBFs members, reaching 52% (13/25). Gene duplication analysis showed that 64% (16/25) of MsCBFs formed tandem duplications, and 32% (8/25) formed segment duplications. The expression pattern of MsCBF9 under different hormone treatments was verified by RT-qPCR, and it was found that MsCBF9 responded to GA3, IAA, SA, and MeJA. Overexpression of MsCBF9 in Arabidopsis significantly delayed the flowering time of Arabidopsis. In contrast, the flowering time of the cbfs mutant was earlier, and overexpression of MsCBF9 also increased the number and size of Arabidopsis rosette leaves. Conclusion In this study, the CBF/DREB1 family of alfalfa was comprehensively identified and analyzed, and the function of MsCBF9 in regulating flowering time was studied. This study laid a foundation for further analysis of the function of the CBF family in alfalfa. Clinical trial number Not applicable.

Abstract This study investigates the role of flavonoid Icaritin (ICT) in estrogen-deficient ovariectomized (OVX) female mice by activating the Estrogen receptor (ER)/ Phosphatidylinositol 3-kinase (PI3K)/Protein kinase B (Akt) signaling pathway, potentially delaying Parkinson’s disease (PD) progression post-castration. Seventy-five 8-week-old C57BL/6J female mice underwent ovariectomy, followed by MPTP (20 mg/kg) injection for 7 days. ICT (20 mg/kg) was administered for 14 days, and motor function was assessed using various behavioral tests. Serum estradiol, FSH, LH levels were measured by ELISA, and the expression of PI3K/Akt signaling and apoptosis proteins was analyzed by Western blot. Bone mineral density was assessed via dual-energy X-ray absorption, and histology of the uterus and femur was performed. Results showed that ICT alleviated MPTP-induced motor deficits, increased serum estradiol, and improved uterine atrophy. At the molecular level, ICT activated the PI3K/Akt pathway, reduced apoptosis, and mitigated PD symptoms and osteoporosis induced by OVX. These findings suggest ICT may offer therapeutic potential in managing OVX-induced motor dysfunction and PD.

Abstract Background Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy, and current postoperative prognostic assessment methods remain unsatisfactory, underlining the urgent to develop a reliable approach for precision medicine. Given the similarities with gametogenesis, cancer/testis genes (CTGs) are acknowledged for regulation unrestrained multiplication and immune microenvironment during oncogenic processes. These processes are associated with advanced disease and poorer prognosis, indicating that CTGs could serve as ideal prognostic biomarkers in ESCC. The purpose of this study is to develop a novel clinically prognostic prediction system to facilitate the individualized postoperative care. Methods We conducted LASSO regression analysis of protein-coding CTGs and clinical characteristics from 119 pathologically confirmed ESCC patients to recognize powerful predictive variables. We employed nine supervised machine learning classifiers and integrated best predictive machine learning classifiers by weighted voting method to construct an ensemble model called PPMESCC. Additionally, functional assay was conducted to examine the potential effect of top-ranking CTG HENMT1 in ESCC. Results LASSO regression identified five CTGs and TNM stage as optimized prognostic features. Six machine learning classifiers were integrated to construct an ensemble model, PPMESCC, which exhibited outstanding performance in ESCC prediction. The AUC for PPMESCC was 0.9828 (95% confidence interval: 0.9608 to 0.9926), with an accuracy of 98.32% (95% CI: 96.64–99.16%) in the discovery cohort and 0.9057 (95% CI: 0.8897 to 0.9583) of AUC with an accuracy of 90% (95% CI: 89.08–93.28%) in validation cohort. In addition, the top-ranking CTG HENMT1 encodes 2’-O-methyltransferase of piRNAs that was confirmed positively correlated with the proliferation capacity of ESCC cells. Then we systematically screen piRNAs associated with esophageal carcinoma based on GWAS, eQTL-piRNA, and i2OM databases, and successfully discovered 8 piRNAs potentially regulated by HENMT1. Conclusion The study highlights the clinical utility of PPMESCC algorithm in prognostic prediction that may facilitate to establish the personalized screening and management strategies for postoperative ESCC patients.

Abstract Background Primary healthcare (PHC) plays a key role in hyperlipidemia (HL) management yet lacks adequate monitoring and feedback. This study aims at identifying pragmatic measures out from routinely collected electronic records to enable automatic monitoring and inform continuous optimization of HL-management at PHC settings. Methods The study used randomly selected electronic records of PHC (from the province-wide data center of Anhui-province, China) as the main data source and generated both procedure-based and encounter-based measures for assessing HL-management. The procedure-based measures were derived from specific quality-facts of 21 stages/procedures (e.g., lipid lowering medication prescription) using self-designed algorithms. While the encounter-based measures included number or rate of visits for HL, currently-noticed hyperlipidemia (CNHL, or HL noticed during the current consultation), and ever-diagnosed hyperlipidemia (EDHL). Analysis of these measures employed mainly simple descriptives and linear regression modeling. Results The study revealed interesting findings including: low and varied rates of visits for HL(from 0.01 to 1.43%) and visits by patients with EDHL/CNHL(from 0.13 to 20.54% or from 0.02 to 2.99%) between regions; large differences (5.14 to 22.20 times) between the mean or cumulative proportions of visits by patients with EDHL versus CNHL among clinician groups; consistent increase in the ratio of visits for HL in all cause visits over the study period (from 0.087 to 1.000%) accompanied with relatively stable proportions of patients with CNHL/EDHL; Relatively low scores in the procedure-based measures (ranged from 0.00 to 36.08% for specific procedures by seasons). Conclusions The measures identified are not only feasible from real-world PHC records but also give some useful metrics about how well current HL-management is going and what future actions are needed.

Abstract Photoimmunotherapy, which combines phototherapy with immunotherapy, exhibits significantly improved therapeutic effects compared with mono-treatment regimens. However, its use is associated with drawbacks, such as insufficient reactive oxygen species (ROS) production and uneven photosensitizer distribution. To address these issues, we developed a controllable, targeted nanosystem that enhances oxidative stress through multiple pathways, achieving synergistic photothermal, photodynamic, and immunotherapy effects for tumor treatment. These nanoparticles (D/I@HST NPs) accurately target overexpressed transferrin receptors (TfRs) on the surface of tumor cells through surface-modified transferrin (Tf). After endocytosis, D/I@HST NPs generate ROS under 808-nm laser irradiation, breaking the ROS-responsive crosslinking agent and increasing drug release and utilization. Tf also carries Fe3+, which is reduced to Fe2+ by iron reductase in the acidic tumor microenvironment (TME). Consequently, the endoperoxide bridge structure in dihydroartemisinin is cleaved, causing additional ROS generation. Furthermore, the released IR-780 exerts both photodynamic and photothermal effects, enhancing tumor cell death. This multi-pathway oxidative stress amplification and photothermal effect can trigger immunogenic cell death in tumors, promoting the release of relevant antigens and damage-associated molecular patterns, thereby increasing dendritic cell maturation and sensitivity of tumor cells to immunotherapy. Mature dendritic cells transmit signals to T cells, increasing T cells infiltration and activation, facilitating tumor growth inhibition and the suppression of lung metastasis. Furthermore, the myeloid-derived suppressor cells in the tumor decreases significantly after treatment. In summary, this multi-pathway oxidative stress-amplified targeted nanosystem effectively inhibits tumors, reverses the immunosuppressive tumor microenvironment, and provides new insights into tumor immunotherapy combined with phototherapy.

Abstract Background Achieving viral suppression through effective treatment adherence is critical for adolescents with HIV; however, the role of treatment adherence self-efficacy—an individual’s confidence in their ability to consistently follow antiretroviral therapy (ART) regimens—remains under-explored among Chinese adolescents. This gap is particularly concerning given the United Nations’ “95-95-95” targets to end the AIDS epidemic by 2030. Objective The aim of this study is to investigate the treatment adherence self-efficacy levels of Yi ethnic adolescents with HIV in a county in Liangshan Prefecture, and to explore the association between self-acceptance, emotion regulation, and treatment adherence self-efficacy. Methods A cross-sectional study was conducted in a county of Liangshan Prefecture from November 2023 to March 2024. A convenience sampling method was used to select 205 participants. Multiple linear regression models were employed to examine the relationships between demographic variables, self-acceptance, emotion regulation and treatment adherence self-efficacy. A p-value

Abstract Background A significant number of primiparous women lack awareness of labor epidural analgesia, resulting in lower acceptance of labor epidural analgesia. Additional prenatal education may help primiparas understand labor epidural analgesia and increase labor epidural analgesia rates. This randomized controlled trial (RCT) will evaluate the effects of an online and offline prenatal labor epidural analgesia education program for primiparas to improve their labor epidural analgesia rate and to reduce their misunderstanding of labor epidural analgesia and fear of birth. Methods A single-blinded, randomized, controlled, parallel-design trial will be conducted. Based on the Theory of Planned Behavior, online and offline prenatal labor epidural analgesia education program has five modules: (a)elementary knowledge, (b)attitude, (c)subjective norm, (d) perceived behavioral control and (e)behavioral intention. Primiparous women will be recruited in the obstetrics department or midwife clinic of a tertiary hospital in Shenzhen, China. The participants (N = 196) will be randomly allocated to the intervention group (N = 98) that receives routine prenatal education and access to the online and offline prenatal labor epidural analgesia education program and the control group (N = 98) that receives routine prenatal education. Labor epidural analgesia rate will be extracted from the electronic medical record; misunderstanding and intention of labor epidural analgesia and fear of birth will be measured at baseline and immediately after the intervention. The study was ethically approved in November 2023. Discussion If the online and offline prenatal labor epidural analgesia education program has positive outcomes, it may offer an effective intervention program to decrease misperceptions of labor epidural analgesia and fear of birth and to improve the labor epidural analgesia rate for Chinese primiparas. As the first RCT study to evaluate the effect of the online and offline prenatal labor epidural analgesia education program with a strict research design and a theoretical framework, this research will provide evidence on prenatal labor analgesia health education for clinical practice in China. Trial Registration Registered at the Chinese Clinical Trials.gov on January 11th, 2024. Trial Registration Number: ChiCTR2400079767.

Tenosynovial giant cell tumor (TGCT) is a rare mesenchymal tumor that clinically presents as nodular-type or diffuse-type (D-TGCT). D-TGCT is more aggressive, has a higher surgical recurrence rate, and can potentially lead to severe joint destruction. The traditional treatment is primarily through surgical intervention. Recent advancements in understanding the molecular mechanisms of the disease and the development of new drugs have significantly changed TGCT treatment strategies. Drug therapy and active surveillance have become important treatment options for unresectable or high-recurrence-risk TGCT. Imaging examinations and patient-reported outcome tools play a crucial role in evaluating efficacy and guiding treatment decisions. Comprehensive management by a multidisciplinary team and utilizing individualized treatment plans can significantly improve the quality of life and treatment outcomes of patients. Future research should explore the molecular mechanisms of TGCT, enhance multidisciplinary collaboration, and emphasize long-term management to improve treatment efficacy and patient prognosis.

Narrative medicine emphasizes the social, relational, and psychological dimensions of patient care, fostering students’ development in areas such as empathy, humanistic values, self-reflection, psychological resilience, moral beliefs, professional integrity, and the ability to build harmonious interpersonal relationships. Through literature review, it reveals that the integration of narrative medicine in geriatrics education remains limited. This article reflects on the unique characteristics of geriatrics education and examines the potential role of narrative medicine in enhancing its teaching methods. Through this exploration, we aim to provide insights and guidance for developing more effective educational approaches in geriatrics using narrative medicine.

Abstract Biometallic ions play a crucial role in regulating the immune system. In recent years, cancer immunotherapy has become a breakthrough in cancer treatment, achieving good efficacy in a wide range of cancers with its specificity and durability advantages. However, existing therapies still face challenges, such as immune tolerance and immune escape. Biometallic ions (e.g. zinc, copper, magnesium, manganese, etc.) can assist in enhancing the efficacy of immunotherapy through the activation of immune cells, enhancement of tumor antigen presentation, and improvement of the tumor microenvironment. In addition, biometallic ions and derivatives can directly inhibit tumor cell progression and offer the possibility of effectively overcoming the limitations of current cancer immunotherapy by promoting immune responses and reducing immunosuppressive signals. This review explores the role and potential application prospects of biometallic ions in cancer immunotherapy, providing new ideas for future clinical application of metal ions as part of cancer immunotherapy and helping to guide the development of more effective and safe therapeutic regimens.

Abstract The ubiquitous use of rare earth elements (REEs) in modern living environments raised concern about their impact on human health. With the detrimental and beneficial effects of REEs reported by different studies, the genuine role of REEs in the human body remains a mystery. This study explored the association between REEs and genetic mutations in patients with lung adenocarcinoma (LUAD). A cohort of 53 LUAD patients underwent tumor DNA sequencing (1123 cancer-related genes) and plasma REE (lanthanum (La), cerium (Ce), praseodymium (Pr), neodymium (Nd), and yttrium (Y)) quantification. We found divergent relationships between plasma REE levels and mutation load between sexes. Specifically, Ce levels and mutation load were positively correlated in males but negatively correlated in females, while La exposure exhibited opposite associations in the two sexes. This observation was validated using the Bayesian Kernel Machine Regression (BKMR) model. Additionally, plasma REE levels was associated with specific mutation types and variant allele frequencies (VAFs) of particular genes in a sex-dependent manner. Mutational signature analysis revealed sex-specific associations of La with indel signatures. These findings highlight the intricate interplay between plasma REE levels and genetic mutations in LUAD, emphasizing the need for a personalized, sex-oriented approach to understand and treat this disease.

Abstract Background and objectives Accurate classification of lymphadenopathy is essential for determining the pathological nature of lymph nodes (LNs), which plays a crucial role in treatment selection. The biopsy method is invasive and carries the risk of sampling failure, while the utilization of non-invasive approaches such as ultrasound can minimize the probability of iatrogenic injury and infection. With the advancement of artificial intelligence (AI) and machine learning, the diagnostic efficiency of LNs is further enhanced. This study evaluates the performance of ultrasound-based AI applications in the classification of benign and malignant LNs. Methods The literature research was conducted using the PubMed, EMBASE, and Cochrane Library databases as of June 2024. The quality of the included studies was evaluated using the QUADAS-2 tool. The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated to assess the diagnostic efficacy of ultrasound-based AI in classifying benign and malignant LNs. Subgroup analyses were also conducted to identify potential sources of heterogeneity. Results A total of 1,355 studies were identified and reviewed. Among these studies, 19 studies met the inclusion criteria, and 2,354 cases were included in the analysis. The pooled sensitivity, specificity, and DOR of ultrasound-based machine learning in classifying benign and malignant LNs were 0.836 (95% CI [0.805, 0.863]), 0.850 (95% CI [0.805, 0.886]), and 33.331 (95% CI [22.873, 48.57]), respectively, indicating no publication bias (p = 0.12). Subgroup analyses may suggest that the location of lymph nodes, validation methods, and type of primary tumor are the sources of heterogeneity. Conclusion AI can accurately differentiate benign from malignant LNs. Given the widespread use of ultrasonography in diagnosing malignant LNs in cancer patients, there is significant potential for integrating AI-based decision support systems into clinical practice to enhance the diagnostic accuracy.

Abstract Background Numerous noncontrast computed tomography (NCCT) markers have been reported and validated as effective predictors of hematoma expansion (HE). Our objective was to develop and validate a score based on NCCT markers and clinical characteristics to predict risk of HE in acute intracerebral hemorrhage (ICH) patients. Methods We prospectively collected spontaneous ICH patients at the First Affiliated Hospital of Chongqing Medical University to form the development cohort (n = 395) and at the Third Affiliated Hospital of Chongqing Medical University to establish the validation cohort (n = 139). We adopted a revised HE definition, incorporating the standard definition of HE (> 6 mL or > 33%) and intraventricular hemorrhage (IVH) expansion (any new IVH or IVH expansion ≥ 1 ml). The predictive score was formulated based on the parameter estimates derived from the multivariable logistic regression analysis. Result The Glasgow Coma Scale, island sign, ventricular hemorrhage and time elapsed from onset to NCCT scan (GIVE) score was created as a total of individual points (0–6) based on Glasgow Coma Scale (2 points for ≤ 11), island sign (1 point for presence), ventricular hemorrhage (1 point for presence), and time elapsed from onset to NCCT scan (2 points for ≤ 2.5 h). The c statistic was 0.72(95% confidence interval [CI], 0.66–0.78) and 0.73(95% CI, 0.63–0.82) in the development and validation cohorts, respectively. Conclusion A six-point scoring algorithm has been developed and validated to assess the risk of HE in patients with ICH. This scoring system facilitates the rapid and accurate identification of patients at increased risk for HE.

Abstract Gravitational echoes can be used to probe the structure of spacetime. In this paper, we investigate the gravitational echoes in different braneworld models in five-dimensional spacetime. We derive the gravitational perturbation equations of these models, and obtain the time-dependent evolution equations of the extra-dimensional and radial components. Using a Gaussian wave packet as initial data, we study the time evolution of the gravitational perturbation. By monitoring the evolution of the Gaussian wave packet, the gravitational echoes are observed whether the wave packet is generated from inside or outside the braneworld. Furthermore, we can restrict the parameters of the braneworld by calculating the strength of the first gravitational echo and using the current gravitational wave data.

Abstract Polycystic ovary syndrome (PCOS) is a common endocrine disorder with various contributing factors. Shear wave elastography (SWE) is a contemporary noninvasive imaging technique that reports on the elasticity of tissues. This study aimed to evaluate ovarian stiffness in patients with PCOS using transvaginal SWE, and investigate the potential biological mechanisms underlying increased ovarian stiffness. Patients with PCOS and healthy controls underwent transvaginal 2D ultrasound and SWE to measure the number of follicles, ovarian volume, and ovarian elasticity. Multivariate logistic regression analysis was conducted to identify risk factors for PCOS. A rat model of PCOS was established to further investigate the biological basis of increased ovarian stiffness. Histological analysis, enzyme-linked immunosorbent assay, quantitative reverse transcription-polymerase chain reaction, western blotting, transcriptomics, and proteomics were performed to assess alterations in fibrosis and basement membrane (BM) gene expression. The results demonstrated that patients with PCOS (n = 59) showed an increased number of follicles, ovarian volume, and SWE (mean and max) compared with controls (n = 56; P

Urban functional structures and daily rhythms significantly impact population mobility. Detecting and quantifying thematic activity changes in the short-term aggregated inflow and outflow of urban population mobility (referred to as black holes and volcanoes, respectively) contribute to the economy and public services. Current research is focused on the changes in intensity of single-region population activity, but it overlooks the daily rhythms of the aggregated flows and latent thematic activity changes in urban populations. Here, we propose an Aggregated Inflow-Outflow Thematic Detection (AIOTD) method. It can detect thematic activity changes in population inflows and outflows from a spatiotemporal aggregation perspective by leveraging traffic flow theory and semantic models. Considering the stationary of flow sequences within the same time periods and the spatial continuity of flows, we designed a spatial aggregation method based on the relative ratios of population flows in spatiotemporal units. This method enables a quantitative depiction of the spatiotemporal evolution of black holes and volcanoes. Furthermore, due to the spatial proximity of land features and category imbalances, we utilized the SMOTETomek-Place2vec model to construct a spatial context information dataset at the grid level, enhancing the accuracy of capturing thematic activities. Results demonstrate that our method outperforms existing approaches in capturing the number of spatiotemporal units for black hole and volcano clusters at both the 500 m grid and 1000 m grid scales, in terms of both semantics and spatiotemporal dimensions. It reveals the spatiotemporal complementarity and thematic cross-symmetry of urban population mobility between black holes and volcanoes. By applying this method to daytime and nighttime economies and public services, we quantified changes in the fine-grained functional service vitality and the distribution of functional facilities in commuting zones. These findings offer guidance for urban services and insights into the behavioral preferences of residents.

Deep learning has been successfully applied to solve the synthetic aperture radar (SAR) imaging problem, which shows superior imaging performance to compressive sensing (CS)-based methods under sparse sampling conditions. However, due to the computation of the large-scale matrix, the optimal searching in an iterative manner will involve tremendous computational complexity with slow convergence, which will prevent deep learning algorithms from being efficiently applied for SAR imaging. To address this problem, an efficient network is proposed for SAR imaging under sparse sampling conditions, which can be designed by an improved conjugate gradient (CG) optimization strategy. First, the large-scale matrix in the CG algorithm can be approximately decomposed by introducing a matched filtering (MF)-based operator, which will facilitate the gradient computation with high efficiency during the optimization process. Second, the strategy utilizes the advantages of CG optimization to precisely eliminate the error component with conjugate searching in each iteration to achieve fast convergence. By incorporating the improved CG into the convolutional neural network (CNN), the network can be developed to automatically learn the prior information and parameters from the training data, based on which the efficiency of the designed network can be increased dramatically to achieve high imaging performance for SAR applications, especially in the cases of wide-scene and high-resolution imaging. Experimental results show that the proposed network exhibits excellent imaging performance and high computational efficiency in SAR imaging of point targets, surface targets, and different types of real scenes.

Abstract The oral-gut microbiota axis plays a crucial role in cardiometabolic health. This review explores the interactions between these microbiomes through enteric, hematogenous, and immune pathways, resulting in disruptions in microbial balance and metabolic processes. These disruptions contribute to systemic inflammation, metabolic disorders, and endothelial dysfunction, which are closely associated with cardiometabolic diseases. Understanding these interactions provides insights for innovative therapeutic strategies to prevent and manage cardiometabolic diseases.

Abstract Non-small cell lung adenocarcinoma (LUAD) is a markedly heterogeneous disease, with its underlying molecular mechanisms and prognosis prediction presenting ongoing challenges. In this study, we integrated data from multiple public datasets, including TCGA, GSE31210, and GSE13213, encompassing a total of 867 tumor samples. By employing Mendelian randomization (MR) analysis, machine learning techniques, and comprehensive bioinformatics approaches, we conducted an in-depth investigation into the molecular characteristics, prognostic markers, and potential therapeutic targets of LUAD. Our analysis identified 321 genes significantly associated with LUAD, with CENP-A, MCM7, and DLGAP5 emerging as highly connected nodes in network analyses. By performing correlation analysis and Cox regression analysis, we identified 26 prognostic genes and classified LUAD samples into two molecular subtypes with significantly distinct survival outcomes. The Random Survival Forest (RSF) model exhibited robust prognostic predictive capabilities across multiple independent cohorts (AUC > 0.75). Beyond merely predicting patient outcomes, this model also captures key features of the tumor immune microenvironment and potential therapeutic responses. Functional enrichment analysis revealed the complex interplay of cell cycle regulation, DNA repair, immune response, and metabolic reprogramming in the progression of LUAD. Furthermore, we observed a strong correlation between risk scores and the expression of specific cytokines, such as CCL17, CCR2, and CCL20, suggesting novel avenues for developing cytokine network-based therapeutic strategies. This study offers fresh insights into the molecular subtyping, prognostic prediction, and personalized therapeutic decision-making in LUAD, laying a critical foundation for future clinical applications and targeted therapy research.

Abstract The Maisotsenko cycle-based coolers have gained increasing attention in recent years due to their advantages of low energy consumption and environmental friendliness. Optimizing the model structure and operating conditions is the primary approach for enhancing the cooling performance of dew-point evaporation systems. In this paper, a novel mathematical model of the perforated dew-point evaporative cooler was developed to investigate its cooling performance. The key findings that emerged from this investigation were: (1) Both perforated and non-perforated dew-point evaporative cooling systems exhibited similar trends in relation to the impact of model size and inlet air parameters. (2) The performance of the dew-point evaporative cooler could be enhanced by implementing the perforation method when the total supply air ratio is below 0.5, and optimal performance was achieved with a single-perforation design. (3) The outlet temperature of the dry channel initially showed a downward trend when the supply air ratio was 0.3, and subsequently gradually increased with an elevated supply air ratio. It is worth noting that within the range of 0.5 to 0.6 for the supply air ratio, the minimum outlet air temperature was achieved.

Abstract Background Metabolic syndrome associated with glucose metabolism plays a pivotal role in tumorigenesis, potentially elevating the risk of endometrial cancer (EC). This study sought to establish a glucose metabolism-related gene (GMRG) signature linked to EC. Methods Differential analysis was conducted to identify differentially expressed genes (DEGs) between EC and normal samples from the TCGA-EC dataset. Glucose metabolism-related DEGs (GMR-DEGs) were then derived by intersecting these DEGs with GMRGs. A prognostic signature for EC was developed through the Least Absolute Shrinkage and Selection Operator (LASSO) regression and univariate Cox analysis. Additionally, immune profiling and immunotherapy responsiveness were evaluated across two distinct risk subgroups, accompanied by a single-cell analysis of prognostic genes. The expression levels of these prognostic genes were quantified at both transcriptional and translational stages using reverse transcription quantitative PCR (RT-qPCR) and immunohistochemistry (IHC) in clinical samples. Furthermore, the functional significance of key genes was explored through in vitro assays. Results 2,912 DEGs and 202 GMR-DEGs were identified between the EC and normal groups. Subsequently, six prognostic genes were derived, including ASRGL1, SLC38A3, SLC2A1, ALDH1B1, GAD1, and GLYATL1. EC patients were classified into high and low-risk subgroups based on the six genes. Independent prognostic analysis indicated that risk score and disease stage were significant independent prognostic factors. Single-cell analysis revealed that the six prognostic genes were highly expressed in ciliated and epithelial cells. Immune cell infiltration was generally lower in the high-risk group, where tumor purity was elevated. The expression levels of SLC38A3, SLC2A1, and ASRGL1 are higher in tumor samples by RT-qPCR, with IHC confirming increased SLC38A3 expression. Finally, SLC38A3 may function as oncogenes in EC, as revealed by the results of in vitro experiments. Conclusions In this study, we developed six novel prognostic genes in EC based on glycolysis, and corresponding prognostic models were developed. Notably, we identified SLC38A3 as the key gene, which offers valuable insights for further research into EC.

Abstract Background To detect the differences in physical symptoms between depressed and undepressed patients with breast cancer (BC), including common symptoms, co-occurring symptoms, and symptom clusters based on texts derived from social media and expressive writing. Methods A total of 1830 texts from social media and expressive writing were collected. The Chi-square test was used to compare the frequency of physical symptoms between depressed and undepressed patients with BC. Symptom lexicon of BC and K-medoids Clustering were used for mining physical symptoms and cluster analysis. Results The common physical symptoms reported by texts included general pains (59.38%), fatigue (26.60%), vomiting (24.82%), swelling of limbs (21.69%), difficulty sleeping (21.56%), nausea (16.78%), alopecia (15.14%), loss of appetite (13.78%), dizziness (11.60%), and concentration problems (11.19%). The frequency of difficulty sleeping (depressed 28.40%; undepressed 18.16%; P = 0.002) in depressed patients was higher than undepressed patients with BC. High co-occurrence was observed in both commonly mentioned symptoms and those less commonly mentioned but frequently co-occurring with them. There were 5 symptom clusters identified in depressed patients and 6 symptom clusters in undepressed patients. Pain-related symptom cluster and gastrointestinal symptom cluster were both identified in the depressed and undepressed patients. The novel immune system impairment symptom cluster consisting of bleeding and fever was found in the undepressed patients. Conclusions This study found that difficulty sleeping was reported more frequently, and identified difficulty sleeping-pain symptom cluster in depressed patients. The novel immune system impairment symptom cluster in undepressed patients was detected. Healthcare providers can provide targeted care to depressed and undepressed patients based on these differences. These findings demonstrate that social media can provide new perspectives on symptom experiences. The combination of digital tools and traditional clinical tools for symptom management in follow-up has great potential in the future. Clinical trial number Not applicable.

Abstract Catheter-based pulmonary artery denervation (PADN) has achieved promising outcomes to treat pulmonary hypertension (PH). We herein present stereotactic body radiotherapy (SBRT) as a novel noninvasive approach for PADN. A single fraction of 15 Gy, 20 Gy or 25 Gy was delivered for PADN in a thromboxane A2 (TxA2) - induced acute PH swine model. We demonstrated that PADN by 20-Gy SBRT reduced mean pulmonary artery (PA) pressure during the TxA2 challenge. All SBRT dosages led to a deeper denervation area compared with radiofrequency ablation (RFA) and reduced sympathetic neural norepinephrine synthesis in the ablation zone. Probable radiation related side effects were mostly found in animals treated with 25-Gy. In subsequent monocrotaline-induced chronic PH animals, PADN by 20-Gy SBRT resulted in more significant improvement in pulmonary hemodynamics and PA remodeling in comparison to RFA. In summary, our findings suggest that appropriate SBRT scheme could balance the efficacy and safety for PADN, potentiating to be a novel strategy to treat PH.

Abstract Background We investigated the consistency and accuracy of the Index of Consciousness (IoC) and the Bispectral Index (BIS) in monitoring the sedative effect of ciprofol during the induction of general anesthesia. There is extensive literature that reports good consistency and correlations between the IoC1 and the BIS in reflecting the sedation levels induced by propofol and sevoflurane but not by ciprofol. Objective The aim was to compare the consistency and accuracy of the IoC and BIS in monitoring the sedative effect of ciprofol during the induction of general anesthesia. Methods We conducted a prospective observational study. A total of 130 patients aged 18 to 65 years who underwent noncardiac or noncranial elective surgery under general anesthesia were included. All patients were diligently monitored for both the BIS and IoC. IoC1 and BIS values were recorded at eight specific time points (T1 to T8) during the induction of general anesthesia. Bland‒Altman analysis was conducted to assess the consistency between the IoC1 and BIS, including the calculation of mean differences and 95% limits of agreement (LOAs). Receiver operating characteristic (ROC) curves were utilized to evaluate the predictive accuracy of the IoC1 for loss of responsiveness. Results The mean difference in the BIS and IoC1 values from T1 to T8 between the two measurement methods was − 0.4308 (95% LOA ranging from − 19.47 to 18.61). There was no significant difference between the IoC1 and BIS (P = 0.6664). The areas under the curve (AUCs) for the IoC1 and BIS in predicting loss of responsiveness were 0.9821 (95% CI 0.9741 to 0.9900) and 0.9855 (95% CI 0.9789 to 0.9922), respectively. The optimal threshold values were 91.5 (sensitivity 94.6%, specificity 96.0%) and 82.5 (sensitivity 99.2%, specificity 93.7%). Conclusion The IoC1 is highly consistent with the BIS in the assessment of the sedative effects of ciprofol during general anesthesia induction. The IoC is effective in monitoring the sedative effects of ciprofol when responsiveness disappears. The IoC is an effective monitoring tool for monitoring the sedative effects of ciprofol-induced general anesthesia. Trial registration ChiCTR2400086320.

Abstract Long-term potentiation (LTP) and long-term depression (LTD) are widely used to study synaptic plasticity. However, whether proteins regulating LTP and LTD are altered in cognitive disorders and contribute to disease onset remains to be determined. Herein, we induced LTP and LTD in the hippocampal CA3-CA1 Schaffer collateral pathway, respectively, and then performed proteomic analysis of the CA1 region. We identified 20 differentially expressed proteins (DEPs) shared by the LTP and the LTD processes. Among them, we found that HtrA serine peptidase 2 (HTRA2) was mainly expressed in neurons and that HTRA2 levels were increased in both the LTP and the LTD processes in C57BL/6 mice. HTRA2 downregulation impaired synapses and reduced ATP production in cultured primary neurons. Furthermore, adeno-associated virus (AAV)-mediated HTRA2 downregulation in the hippocampus impaired synaptic plasticity and cognitive function in C57BL/6 mice. Moreover, we found that HTRA2 expression decreased in the brains of Alzheimer’s disease patients, frontotemporal lobar degeneration with ubiquitin inclusions patients, and tauopathy model mice. Finally, we showed that lentivirus-mediated HTRA2 overexpression in the hippocampus rescued PP2B reduction, alleviated tau hyperphosphorylation, and partially attenuated synaptic plasticity and cognitive deficits in the PS19 tauopathy model mice. Our study not only indicates that HTRA2 in neurons plays an important role in regulating synaptic plasticity under both physiological and pathological conditions, but also provides a novel, electrophysiology-based strategy to identify proteins regulating synaptic plasticity systematically.

Abstract Polyploidy is a common outcome of chemotherapies, but there is conflicting evidence as to whether polyploidy is an adverse, benign or even favourable outcome. We show Aurora B kinase inhibitors efficiently promote polyploidy in many cell types, resulting in the cell cycle exit in RB and p53 functional cells, but hyper-polyploidy in cells with loss of RB and p53 function. These hyper-polyploid cells (>8n DNA content) are viable but have lost long-term proliferative potential in vitro and fail to form tumours in vivo. Investigation of mitosis in these cells revealed high numbers of centrosomes that were capable of supporting functional mitotic spindle poles, but these failed to progress to anaphase/telophase structures even when AURKB inhibitor was removed after 2–3 days. However, when AURKB inhibitor was removed after 1 day and cells had failed a single cytokinesis to become tetraploid, they retained colony forming ability and long-term proliferative potential. Mathematical modelling of the potential for polyploid cells to produce viable daughter cells demonstrated that cells with >8n DNA and >4 functional spindle poles approach zero probability of a viable daughter, supporting our experimental observations. These findings demonstrate that tetraploidy is tolerated by tumour cells, but higher ploidy states are incompatible with long-term proliferative potential. Model for AURKBi driven hyper-polyploid cells formation and fate. Aurora B inhibitor (AURKBi) treatment of RB+p53 defective cells efficiently promotes failed cell division. One failed cell division produces three possible outcomes, continued proliferation of the tetraploid daughter, cell death, or if AURKBi is continued, high polyploid states. Once cell have failed cell division >twice and have >8n DNA content they will continue to undergo rounds of endomitosis even in the absence of AURKBi to either become viable hyper-polyploid or die. The hyper-polyploid cells have no long-term proliferative potential.

Abstract Background Hearing loss significantly affects children’s lives; however, the health-related quality of life (QoL) of children with this disability is not well measured. We sought to develop a reliable and valid measure of health-related QoL in children with hearing loss. Methods We constructed a conceptual framework to assess the QoL of children with hearing loss based on the Pediatric Quality of Life Inventory™ Version 4.0 child quality of life scale and World Health Organization Quality of Life Brief Version disability general version. The item pool was generated through two rounds of the Delphi method and subsequent group discussions. Subsequently, both a pre-survey and a formal survey were administered across eight hospitals and nine special education schools located in Shanxi and Hebei Province, China. The process of selecting items was grounded in classical test theory and item response theory. Ultimately, we assessed the reliability and validity of the QoL Scale designed for children with hearing loss in China.x` Results The final health-related QoL scale for children with hearing loss (HRQOL-CHL) included 37 items, 6 domains, and 8 subdomains. Reliability assessment encompassed Cronbach’s alpha coefficient, split-half reliability, and retest reliability measures. Specifically, for the entire scale, Cronbach’s alpha yielded a coefficient of 0.755, binary reliability of 0.796, and retest reliability of 0. 931. The validity findings indicated that the scale performed as anticipated. Both exploratory factor analysis and confirmatory factor analysis demonstrated that this multidimensional scale was well-suited for assessing children with hearing loss, demonstrating a superior fit. Conclusions The HRQOL-CHL exhibits positive reliability, validity, and feasibility, which makes it an efficient QoL assessment tool for children with hearing loss in China.

In this study, a novel (α+β) dual-phase Ti–19Nb–0.6O was developed and processed via additive manufacturing, featuring ultra-low Young’s modulus of 42 GPa approximating that of human bone, coupled with high strength (919 MPa), and 15% elongation. By utilizing post-heat treatment to adjust the distribution and content of the precipitated α phase, the elemental distribution of Nb and O between α and β phase was effectively manipulated, meanwhile, the β matrix stability was regulated, enabling the attainment of lower modulus and higher strength. These findings advance the development of biomedical titanium alloys produced using additive manufacturing, characterized by excellent mechanical performance.

Gaze tracking technology in HMDs (Head-Mounted Displays) suffers from decreased accuracy due to highlight reflection noise from users' glasses. To address this, we present a denoising method which directly pinpoints the noisy regions through advanced segmentation models and then fills the flawed regions through advanced image inpainting algorithms. In segmentation stage, we introduce a novel model based on the recently proposed segmentation large model SAM (Segment Anything Model), called SF-SAM-Adapter (Spatial and Frequency aware SAM Adapter). It injects prior knowledge regarding the strip-like shaped in spatial and high-frequency in frequency of reflection noise into SAM by integrating specially designed trainable adapter modules into the original structure, while retaining the expressive power of the large model and better adapting to the downstream task. We achieved segmentation metrics of IoU (Intersection over Union) = 0.749 and Dice = 0.853 at a memory size of 13.9 MB, outperforming recent techniques, including UNet, UNet++, BATFormer, FANet, MSA, and SAM2-Adapter. In inpainting, we employ the advanced inpainting algorithm LAMA (Large Mask inpainting), resulting in significant improvements in gaze tracking accuracy by 0.502°, 0.182°, and 0.319° across three algorithms. The code and datasets used in current study are available in the repository: https://github.com/leiting5297/SF-SAM-Adapter.git.

Our earth is immersed in the near-earth space plasma environment, which plays a vital role in protecting our planet against the solar-wind impact and influencing space activities. It is significant to investigate the physical processes dominating the environment, for deepening our scientific understanding of it and improving the ability to forecast the space weather. As a crucial part of the National Major Scientific and Technological Infrastructure–Space Environment Simulation Research Infrastructure (SESRI) in Harbin, the Space Plasma Environment Research Facility (SPERF) builds a system to replicate the near-earth space plasma environment in the laboratory. The system aims to simulate the three-dimensional (3-D) structure and processes of the terrestrial magnetosphere for the first time in the world, providing a unique platform to reveal the physics of the 3-D asymmetric magnetic reconnection relevant to the earth's magnetopause, wave–particle interaction in the earth's radiation belt, particles' dynamics during the geomagnetic storm, etc. The paper will present the engineering design and construction of the near-earth space plasma simulation system of the SPERF, with a focus on the critical technologies that have been resolved to achieve the scientific goals. Meanwhile, the possible physical issues that can be studied based on the apparatus are sketched briefly. The earth-based system is of great value in understanding the space plasma environment and supporting space exploration. [ABSTRACT FROM AUTHOR]