Search

Abstract An improved method for identifying sporadic E (Es) layer properties from radio occultation (RO) electron density profiles (EDPs) is presented. The data used are sourced from COSMIC-1 RO EDPs collected between 2006 and 2019, which cover altitudes from 75 to 145 km. Initially, we evaluate the reliability of EDPs using the International Reference Ionosphere 2016 (IRI-2016) model and select only those profiles with a reliability score of 0.6 or higher (on a scale up to 1) for further analysis. Preliminary Es layer inversion results are obtained and validated against electron density data derived from ionosonde fbEs measurements, demonstrating a linear correlation with a coefficient of 0.72 and a mean absolute percentage error of 36.08%. Further verification using RO S4max data shows that this research method achieved an accuracy of 85.3% in identifying Es events. We perform a detailed analysis of Es layer relative occurrence rates, intensity, and thickness. The Es intensity is expressed by NmμEs (the layer’s maximum electron density (Nm) corresponding to the metal (μ) ion), which is estimated from the measured layer peak electron density NmEs by subtracting the ambient E region electron density NeE(hEs) at the height of the layer’s peak hEs, computed from the IRI-2016 model. Our findings reveal that Es layers predominantly occur in mid-latitude regions during summer, with average intensities between $$5\times {10}^{4 }\text{ and }8\times {10}^{4 }\text{el}/{\text{cm}}^{3}$$ 5 × 10 4 and 8 × 10 4 el / cm 3 . The most likely thickness of Es layers is approximately 1.4 km. Additionally, the present study shows that because NeE(hEs) increases during daytime, which leads to increases in NmEs, confirming that NmμEs is the proper parameter for assessing the Es layer intensity, in line with what is suggested by Haldoupis et al. (Haldoupis et al., J Atmos Sol Terr Phys 206:105327, 2020). Graphical Abstract

Abstract Purpose To apply an independent GPU-accelerated Monte Carlo (MC) dose verification for CyberKnife M6 with Iris collimator and evaluate the dose calculation accuracy of RayTracing (TPS-RT) algorithm and Monte Carlo (TPS-MC) algorithm in the Precision treatment planning system (TPS). Methods GPU-accelerated MC algorithm (ArcherQA-CK) was integrated into a commercial dose verification system, ArcherQA, to implement the patient-specific quality assurance in the CyberKnife M6 system. 30 clinical cases (10 cases in head, and 10 cases in chest, and 10 cases in abdomen) were collected in this study. For each case, three different dose calculation methods (TPS-MC, TPS-RT and ArcherQA-CK) were implemented based on the same treatment plan and compared with each other. For evaluation, the 3D global gamma analysis and dose parameters of the target volume and organs at risk (OARs) were analyzed comparatively. Results For gamma pass rates at the criterion of 2%/2 mm, the results were over 98.0% for TPS-MC vs.TPS-RT, TPS-MC vs. ArcherQA-CK and TPS-RT vs. ArcherQA-CK in head cases, 84.9% for TPS-MC vs.TPS-RT, 98.0% for TPS-MC vs. ArcherQA-CK and 83.3% for TPS-RT vs. ArcherQA-CK in chest cases, 98.2% for TPS-MC vs.TPS-RT, 99.4% for TPS-MC vs. ArcherQA-CK and 94.5% for TPS-RT vs. ArcherQA-CK in abdomen cases. For dose parameters of planning target volume (PTV) in chest cases, the deviations of TPS-RT vs. TPS-MC and ArcherQA-CK vs. TPS-MC had significant difference (P 0.05). ArcherQA-CK had less calculation time compared with TPS-MC (1.66 min vs. 65.11 min). Conclusions Our proposed MC dose engine (ArcherQA-CK) has a high degree of consistency with the Precision TPS-MC algorithm, which can quickly identify the calculation errors of TPS-RT algorithm for some chest cases. ArcherQA-CK can provide accurate patient-specific quality assurance in clinical practice.

IntroductionMajor depressive disorder is a condition involving microbiota–gut–brain axis dysfunction. Increasing research aims to improve depression through gut microbiota regulation, including interventions such as probiotics, prebiotics, and fecal microbiota transplants. However, most research focuses on exogenous depression induced by chronic stress or drugs, with less attention given to endogenous depression. Additionally, research on gut mycobiota in depression is significantly less than that on gut bacteria.MethodsIn the present study, Wistar–Kyoto rats were used as an endogenous depression and treatment-resistant depression model, while Wistar rats served as controls. Differences between the two rat strains in behavior, gut bacteria, gut mycobiota, nervous system, endocrine system, immune system, and gut barrier were evaluated. Additionally, the effects of Lactobacillus helveticus NS8 supplementation were investigated.ResultsWistar–Kyoto rats demonstrated increased depressive-like behaviors in the forced swimming test, reduced sucrose preference in the sucrose preference test, and decreased locomotor activity in the open field test. They also exhibited abnormal gut bacteria and mycobiota, characterized by higher bacterial α-diversity but lower fungal α-diversity, along with increased butyrate, L-tyrosine, and L-phenylalanine biosynthesis from bacteria. Furthermore, these rats showed dysfunction in the microbiota–gut–brain axis, evidenced by a hypo-serotonergic system, hyper-noradrenergic system, defective hypothalamic–pituitary–adrenal axis, compromised gut barrier integrity, heightened serum inflammation, and diminished gut immunity. A 1-month L. helveticus NS8 intervention increased the fecal abundance of L. helveticus; reduced the abundance of Bilophila and Debaryomycetaceae; decreased immobility time but increased climbing time in the forced swimming test; reduced hippocampal corticotropin-releasing hormone levels; decreased hypothalamic norepinephrine levels; increased hippocampal glucocorticoid receptor, brain-derived neurotrophic factor dopamine, and 5-hydroxyindoleacetic acid content; and improved the gut microbiota, serotonergic, and noradrenergic system.ConclusionThe depressive phenotype of Wistar–Kyoto rats is not only attributed to their genetic context but also closely related to their gut microbiota. Abnormal gut microbiota and a dysfunctional microbiota–gut–brain axis play important roles in endogenous depression, just as they do in exogenous depression. Supplementing with probiotics such as L. helveticus NS8 is likely a promising approach to improve endogenous depression and treatment-resistant depression.

Objective To analyze the reentry of single reagent reactive voluntary blood donors in our center, in order to provide data support and reference for the recall of single reagent reactive blood donors. Methods Collect the information of eligible blood donors from the information system of our center from January 2019 to September 2023 were collected, and the reentry were tracked and retrospectively analyzed. The demographic characteristics, active reentry rate, and re-donation rate of eligible blood donors were analyzed, and the differences between qualified reentry rates and factors affecting re-donation were compared using chi-square test. Results A total of 3 361 blood donors met the reentry criteria, with an active reentry rate of 2.7% (91/3 361) and a qualified reentry rate of 80.21% (73/91). The reentry rate of eligible blood donors showed significant differences in terms of different genders(3.3% vs 2.1%), educational background(3.7% vs 2.3%), blood donation frequency(9.3% vs 4.0% vs 1.3%), testing items(7.7% vs 2.7% vs 1.9% vs 1.3%) and blood donation types(18.1% vs 2.0%) (P

Abstract In recent years, extensive research has focused on encryption algorithms for square images, with relatively little attention given to nonsquare images. This paper introduces a novel encryption algorithm tailored for nonequal length images, integrating bit-plane chaotic mapping and Arnold transformation. To effectively implement the algorithm, the plain image is initially transformed into two equal-sized binary sequences. A new diffusion strategy is then introduced to mutually diffuse these sequences, followed by the use of a chaotic map to control the swapping of binary elements between them, enabling permutation of bits across different bitplanes. Finally, the positional information of the image is scrambled using the Arnold transform, resulting in the generation of the encrypted image. By utilizing nonequal Arnold transformation parameters and the initial value of the Lorenz chaotic map as keys, the transmission of keys is simplified, and the cryptosystem gains infinite key space to resist brute force attacks. Experimental results and security analysis confirm the effectiveness of the proposed quantum image encryption algorithm in encrypting nonsquare images, demonstrating good performance in terms of nonstatistical properties, key sensitivity, and robustness. Furthermore, simulation experiments based on Qiskit successfully validate the correctness and feasibility of the quantum image encryption algorithm.

Abstract Background Premature ovarian insufficiency (POI) is a major cause of infertility. In this study, we aimed to investigate the effects of the combination of bone marrow mesenchymal stem cells (BMSCs) and moxibustion (BMSCs-MOX) on POI and evaluate the underlying mechanisms. Methods A POI rat model was established by injecting different doses of cyclophosphamide (Cy). The modeling of POI and the effects of the treatments were assessed by evaluating estrous cycle, serum hormone levels, ovarian weight, ovarian index, and ovarian histopathological analysis. The effects of moxibustion on BMSCs migration were evaluated by tracking DiR-labeled BMSCs and analyzing the expression of chemokines stromal cell-derived factor 1 (Sdf1) and chemokine receptor type 4 (Cxcr4). Mitochondrial function and mitophagy were assessed by measuring the levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), ATP, and the mitophagy markers (Drp1, Pink1, and Parkin). Furthermore, the mitophagy inhibitor Mdivi-1 and the mitophagy activator CCCP were used to confirm the role of mitophagy in Cy-induced ovarian injury and the underlying mechanism of combination therapy. Results A suitable rat model of POI was established using Cy injection. Compared to moxibustion or BMSCs transplantation alone, BMSCs-MOX showed improved outcomes, such as reduced estrous cycle disorders, improved ovarian weight and index, normalized serum hormone levels, increased ovarian reserve, and reduced follicle atresia. Moxibustion enhanced Sdf1 and Cxcr4 expression, promoting BMSCs migration. BMSCs-MOX reduced ROS levels; upregulated MMP and ATP levels in ovarian granulosa cells (GCs); and downregulated Drp1, Pink1, and Parkin expression in ovarian tissues. Mdivi-1 significantly mitigated mitochondrial dysfunction in ovarian GCs and improved ovarian function. CCCP inhibited the ability of BMSCs-MOX treatment to regulate mitophagy and ameliorate Cy-induced ovarian injury. Conclusions Moxibustion enhanced the migration and homing of BMSCs following transplantation and improves their ability to repair ovarian damage. The combination of BMSCs and moxibustion effectively reduced the excessive activation of mitophagy, which helped prevent mitochondrial damage, ultimately improving ovarian function. These findings provide a novel approach for the treatment of pathological ovarian aging and offer new insights into enhancing the efficacy of stem cell therapy for POI patients. Graphical abstract

Abstract Purpose Based on the quantitative and qualitative features of CT imaging, a model for predicting the invasiveness of ground-glass nodules (GGNs) was constructed, which could provide a reference value for preoperative planning of GGN patients. Materials and methods Altogether, 702 patients with GGNs (including 748 GGNs) were included in this study. The GGNs operated between September 2020 and July 2022 were classified into the training group (n = 555), and those operated between August 2022 and November 2022 were classified into the validation group (n = 193). Clinical data and the quantitative and qualitative features of CT imaging were harvested from these patients. In the training group, the quantitative and qualitative characteristics in CT imaging of GGNs were analyzed by using performing univariate and multivariate logistic regression analyses, followed by constructing a nomogram prediction model. The differentiation, calibration, and clinical practicability in both the training and validation groups were assessed by the nomogram models. Results In the training group, multivariate logistic regression analysis disclosed that the maximum diameter (OR = 4.707, 95%CI: 2.06–10.758), consolidation/tumor ratio (CTR) (OR = 1.027, 95%CI: 1.011–1.043), maximum CT value (OR = 1.025, 95%CI: 1.004–1.047), mean CT value (OR = 1.035, 95%CI: 1.008–1.063; P = 0.012), spiculation sign (OR = 2.055, 95%CI: 1.148–3.679), and vascular convergence sign (OR = 2.508, 95%CI: 1.345–4.676) were independent risk parameters for invasive adenocarcinoma. Based on these findings, we established a nomogram model for predicting the invasiveness of GGN, and the AUC was 0.910 (95%CI: 0.885–0.934) and 0.902 (95%CI: 0.859–0.944) in the training group and the validation group, respectively. The internal validation of the Bootstrap method showed an AUC value of 0.905, indicating a good differentiation of the model. Hosmer–Lemeshow goodness of fit test for the training and validation groups indicated that the model had a good fitting effect (P > 0.05). Furthermore, the calibration curve and decision analysis curve of the training and validation groups reflected that the model had a good calibration degree and clinical practicability. Conclusion Combined with the quantitative and qualitative features of CT imaging, a nomogram prediction model can be created to forecast the invasiveness of GGNs. This model has good prediction efficacy for the invasiveness of GGNs and can provide help for the clinical management and decision-making of GGNs.

Abstract Background To establish a nomogram to predict the probability of survival of patients with stage II/III gastric cancer (GC) who received incomplete peri-operative adjuvant chemotherapy (PAC). Methods The medical records of stage II/III GC patients who received curative resection and 1 to 5 cycles of PAC from two tertiary hospitals were retrospectively reviewed. Patients were randomly classified into either a training group or validation group at a ratio of 7:3. The nomogram was constructed based on various prognostic factors using Cox regression analysis in the training cohort, and was validated by the validation group. Concordance index and calibration curves were used to evaluate the discrimination and calibration of the nomogram. Additionally, decision curve analysis (DCA) was used to compare the net clinical benefits of the nomogram and eighth version of TNM staging system. Results A total of 1,070 consecutive patients were included and 749 patients were enrolled into the training group. Lower body mass index (

The construction of dams impedes energy exchange and material circulation in rivers, and the operation of hydropower stations negatively impacts the function of river ecosystems. Countries across the globe have implemented various fish protection countermeasures and conducted many associated hydraulic and ecological studies to mitigate the impact of hydropower development on fish survival, maintain the abundance and diversity of fish populations, and restore riverine and lacustrine fish migration routes and habitats. Remarkably, wild fish generally migrate in groups, whereas most contemporary studies on fish passage facilities focus on individual fish. Hence, the behavioral characteristics of fish schools are worth investigating. Given that schooling behavior is a pervasive feature of fish communities and plays an essential role in dealing with potential risks, improving self-adaptation, expanding resilience, and enhancing population sustainability, this study concentrated on investigating its effect on upstream fish migration and decoding the internal mechanism. We conducted an experiment targeting grass carp (Ctenopharyngodon idella) and silver carp (Hypophthalmichthys molitrix), two economically important freshwater fish species in China, on a non-uniform flow ground with low turbulence. The experiment quantified the impact of fish schooling on their ability to overcome flow barriers by examining the ascending sustainability and swimming performance of five-fish groups and one-fish groups at three flow velocity levels (0.25–0.50 m/s, 0.30–0.60 m/s, and 0.35–0.70 m/s) utilizing a novel index system. The new index system employed nondimensionalized ascending sustainability, first-attempt endurance, and first-attempt ascending energy consumption to indicate the fish's persistent ascending ability, ascending efficiency, and ascending energy cost, respectively. Finally, the ascending trajectory of fish was investigated simultaneously to determine the distribution of trajectory and the distribution of the hydrodynamic force factor at the trajectory points. It could be concluded that (1) the influence of schooling behavior on ascending fish behavior was related to the ascending sustainability of individual fish. Schooling behavior significantly increased the ascending sustainability while producing no specific impact on the ascending efficiency at low-level individual ascending sustainability. Inversely, schooling behavior significantly decreased the ascending efficiency while having no particular effect on high-level individual ascending sustainability. Moreover, the contribution of schooling behavior to the ascending sustainability of grass carp varied with the flow velocity, as the ascending sustainability of the five-fish groups was significantly higher (P = 0.030) and lower (P = 0.048) than the one-fish group at the velocity levels of 0.30–0.60 m/s and 0.35–0.70 m/s, respectively. In contrast, schooling behavior holistically improved the upward swimming of silver carp, significantly increasing the ascending sustainability of the five-fish groups at velocity levels of 0.30–0.60 m/s (P = 0.004) and 0.35–0.70 m/s (P < 0.001). (2) The endurance of the first attempt in the juvenile grass carp group was significantly higher than that of the single fish at the velocity levels of 0.25–0.50 m/s (P < 0.001) and 0.35–0.70 m/s (P = 0.005), while the endurance of the first attempt in the juvenile silver carp group was significantly higher than that of the single fish at the velocity levels of 0.25–0.50 m/s (P < 0.001) and 0.30–0.60 m/s (P = 0.005). The endurance of the first attempt in juvenile silver carp decreased significantly in schools (P < 0.001) solely at the velocity level of 0.35–0.70 m/s. In addition, the flow velocity generally increased the first-attempt endurance and cumulative energy consumption of individual and grouped fish. However, since the burst-coast swimming mode forced on juvenile silver carp in high-velocity conditions significantly improved ascending efficiency, the endurance of the first attempt initially increased and then decreased with the flow velocity. (3) Schooling behavior enabled grass carp to swim with less energy and significantly lowered their energy cost at the velocity level of 0.25–0.50 m/s (P < 0.001), whereas it augmented the accumulated energy consumption of five-fish groups in silver carp and significantly increased their energy cost at the velocity level of 0.25–0.50 m/s (P = 0.050). (4) Collectively, juvenile silver carp could find an ideal ascending trajectory more rapidly than juvenile grass carp. The ascending trajectory of grass carp tended to concentrate at first and then disperse with increasing velocity, whereas the trajectory of silver carp tended to concentrate with increasing velocity. In brief, schooling is an unsubstituted behavior in the upstream migration of fish migrants, motivating and inhibiting the fish's upstream movement performance with its primary effect on locomotion in terms of energy consumption, visual response, and the ability to overcome flow barriers. The findings could improve the design of fish protection measures and provide specific recommendations for the operation of fish passage facilities. For example, when silver carp migrate through a fishway, the additional light source can adequately promote schooling behavior and improve their capacity to overcome flow barriers. When grass carp migrate through a fish passage, the additional light source in the rest pond of the fishway can effectively promote schooling behavior, thereby preventing the return of fish owing to a lack of ascending sustainability. Considering that the hydrodynamic environment of natural waters and the size of fish groups are highly complex and variable, the schooling behavior characteristics of fish groups in different water flow environments should be investigated in future research to enrich the database for the planning and implementation of fish protection engineering measures.

ABSTRACTObjective: An association exists between immune checkpoint inhibitors and hemophagocytic lymphohistiocytosis (HLH). Therefore, the main objective of this study was to collect data on this rare but potentially life-threatening immune-related adverse reaction to identify the medications that cause it, the clinical characteristics, and effective treatments.Methods: Literature in English and Chinese on immune checkpoint inhibitors causing HLH published from August 2014 to March 2024 was analyzed. Immune checkpoint inhibitors, immunotherapy, anti-PD-1, PD-L1 inhibitors, HLH, hemophagocytic lymphohistiocytosis, hemophagocytic syndrome keywords were used to find the literature on China Knowledge Network, Wanfang, PubMed and Emabase Databases.Results and discussion: Twenty-four studies were included, with a total of 27 patients (18 males and 9 females) with a mean age of 58 years (range 26–86). The mean time to the onset of symptoms was 10.3 weeks (7 days–14 months). The main clinical characteristics were fever, cytopenia, splenomegaly, methemoglobinemia, hypofibrinogenemia, and bone marrow biopsy showed phagocytosis. Twenty-two patients improved after the treatment with steroids, cytokine blocking therapy and symptomatic treatment, four patients died, and one patient was not described.Conclusion: HLH should be not underestimated as a potentially serious adverse effect of immune checkpoint inhibitors since appropriate treatments may save the life of patients.

Excessive alcohol exposure can cause neurobehavioral deficits and structural alterations in the brain. Emerging research evidence suggests that endoplasmic reticulum (ER) stress plays an important role in alcohol-induced neurotoxicity. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an ER stress inducible protein and is responsible to maintain ER homeostasis. MANF is highly expressed in both the developing and mature brain. We have previously shown that MANF deficiency exacerbated alcohol induced neurodegeneration and ER stress in the developing brain. However, little is known regarding the role of MANF in alcohol induced neuronal damage in the adult brain. In this study, we used a neuron-specific MANF knockout (KO) mouse model to investigate the effect of MANF deficiency on acute binge alcohol exposure-induced neurobehavioral deficits and ER stress. Adult male and female MANF KO mice and littermate controls received daily alcohol gavage (5 g/kg) for 10 days and then subjected to a battery of neurobehavioral tests including rotarods, balance beam, DigiGait, open field, elevated plus maze, Barnes maze, and three-chamber sociability task. Female MANF KO animals were more susceptible to alcohol-induced body weight loss. Alcohol exposure did not affect motor function, however female but not male MANF KO mice exhibited an increased locomotor activity in open field test. Learning and memory was not significantly impaired, but it was altered by MANF deficiency in females while it was affected by alcohol treatment in males. Both alcohol-exposed male and female MANF KO mice displayed increased sociability. Alcohol induced the expression of ER chaperones GRP78 and GRP94 and altered the levels of several unfolded protein response (UPR) and neuroinflammation markers in MANF KO mice in a sex-specific manner. The expression of MANF interacting proteins neuroplastin, PDIA1, and PDIA6 was increased in MANF KO mice, and was further induced by alcohol. In conclusion, alcohol exposure and neuronal MANF deficiency interacted to alter neurobehavioral outcomes, ER homeostasis and neuroinflammation in a sex-specific manner.

ObjectivesOsteosarcoma (OS) is the primary bone tumor originating from transformed mesenchymal cells. It is unclear whether associations between specific circulating immune cells and OS are causal or due to bias. To clarify whether predicted genetically altered circulating immune cells are associated with OS development, we performed a two-sample Mendelian randomization (MR) analysis.MethodsThe genetic variants strongly associated with immune cell traits as instrumental variables (IVs) were used to perform MR analyses. The effect of specific immune cells on OS risk was measured using the summary statistics from the genome-wide association studies (GWAS).ResultsOur findings indicate that CD80 on CD62L+ myeloid dendritic cell and CD28−CD4−CD8− T-cell absolute count are positively associated with OS (CD80 on CD62L+ myeloid dendritic cell, OR: 3.41 [95% CI: 1.40 to 8.31], p = 0.007; CD28−CD4−CD8− T-cell absolute count, OR: 4.49 [95% CI: 1.29 to 15.62], p = 0.018). It is also found that CD20 has a negative effect on CD24+CD27+ B cell on OS (OR: 0.32 [95% CI: 0.14 to 0.72], p = 0.006) and a similar impact on IgD+ CD38− B cell on OS (OR: 0.19 [95% CI: 0.05 to 0.68], p = 0.011).ConclusionsThese findings illustrate that the genetic predisposition to specific immune cells can exert a causal effect on OS risk, which confirms the crucial role played by immunity in OS development. Particularly, the causal association between immune cells and OS underscores the evidence for exploring the new treatment strategy for OS in the future.

Summary: The KRAS mutation is the most common oncogenic driver in patients with non-small cell lung cancer (NSCLC). However, a detailed understanding of how self-reported race and/or ethnicity (SIRE), genetically inferred ancestry (GIA), and their interaction affect KRAS mutation is largely unknown. Here, we investigated the associations between SIRE, quantitative GIA, and KRAS mutation and its allele-specific subtypes in a multi-ethnic cohort of 3,918 patients from the Boston Lung Cancer Survival cohort and the Chinese OrigiMed cohort with an independent validation cohort of 1,450 patients with NSCLC. This comprehensive analysis included detailed covariates such as age at diagnosis, sex, clinical stage, cancer histology, and smoking status. We report that SIRE is significantly associated with KRAS mutations, modified by sex, with SIRE-Asian patients showing lower rates of KRAS mutation, transversion substitution, and the allele-specific subtype KRASG12C compared to SIRE-White patients after adjusting for potential confounders. Moreover, GIA was found to correlate with KRAS mutations, where patients with a higher proportion of European ancestry had an increased risk of KRAS mutations, especially more transition substitutions and KRASG12D. Notably, among SIRE-White patients, an increase in European ancestry was linked to a higher likelihood of KRAS mutations, whereas an increase in admixed American ancestry was associated with a reduced likelihood, suggesting that quantitative GIA offers additional information beyond SIRE. The association of SIRE, GIA, and their interplay with KRAS driver mutations in NSCLC highlights the importance of incorporating both into population-based cancer research, aiming to refine clinical decision-making processes and mitigate health disparities.

BackgroundEarlier observational studies have demonstrated a correlation between glioma and the risk of neurodegenerative diseases (NDs), but the causality and direction of their associations remain unclear. The objective of this study was to ascertain the causal link between glioma and NDs using Mendelian randomization (MR) methodology.MethodsGenome-wide association study (GWAS) data were used in a two-sample bi-directional MR analysis. From the largest meta-analysis GWAS, encompassing 18,169 controls and 12,488 cases, summary statistics data on gliomas was extracted. Summarized statistics for NDs, including Alzheimer’s disease (AD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD) were obtained from the GWAS of European ancestry. Inverse variance weighted (IVW) method was elected as the core MR approach with weighted median (WM) method and MR-Egger method as complementary methods. In addition, sensitivity analyses were performed. A Bonferroni correction was used to correct the results.ResultsGenetically predicted glioma had been related to decreased risk of AD. Specifically, for all glioma (IVW: OR = 0.93, 95% CI = 0.90–0.96, p = 4.88 × 10−6) and glioblastoma (GBM) (IVW: OR = 0.93, 95% CI = 0.91–0.95, p = 5.11 × 10−9). We also found that genetically predicted all glioma has a suggestive causative association with MS (IVW: OR = 0.90, 95% CI = 0.81–1.00, p = 0.045). There was no evidence of causal association between glioma and ALS or PD. According to the results of reverse MR analysis, no discernible causal connection of NDs was found on glioma. Sensitivity analyses validated the robustness of the above associations.ConclusionWe report evidence in support of potential causal associations of different glioma subtypes with AD and MS. More studies are required to uncover the underlying mechanisms of these findings.

The copper crystal cone-shaped micro-nanostructure is used as the substrate, and the Ni–W alloy layer and Au nanolayer are plated sequentially. Instantaneous soldering with lead-free solder is realized under ultrasonic assistance at room temperature. This solves the residual stress and thermal damage caused by high melting point lead-free solder on thin chips and thermal components, and ensures the safety and reliability of electronic components. Copper-based microstructures are deposited by electrochemical methods. An amorphous Ni–W alloy layer with a thickness of 180 nm is deposited on the Cu-based microstructures by adjusting the atomic ratio of the plating solution. The Ni–W layer is further coated with a 50 nm Au layer to prevent oxidation. Solid-phase transient soldering is realized by combining the Au/Ni–W multilayer thin-film-modified Cu substructures with commercial solder (SAC305) for a holding time of 3 s at a soldering pressure of 10,000 gf (20 MPa) while ultrasonically assisted. The soldered samples are aged at 180 °C for 10 min, 30 min, and 60 min, respectively. Copper substructures with different surface modifications are subjected to destructive shear experiments with solder balls. Scanning electron microscope and X-ray fluorescence thickness gauge are used to study the microstructure, intermetallic compound (IMC) composition thickness and properties of the soldered interface and section. The cone height of the Cu-based structure is 2–4 μm, and the diameter of the bottom is 800 nm–1200 nm, which has a sharp tip and an excellent L/D ratio. The interface between the Au/Ni–W modified Cu substructure and the solder ball is almost free of holes. The average shear strength at the soldering interface is about 43.06 MPa. The fracture surface after the shear experiment basically occurs inside the solder ball matrix, which belongs to the pure toughness fracture. The interface between the Au/Ni–W-modified Cu-based structure and the solder ball is subjected to long aging treatment at 180 °C. The soldering interface showed a “bright layer”. New phases are generated on the solder side above the “bright layer”, while no new phases appear on the Cu substructure side below the “bright layer”. The copper-based microstructure is inserted into the inside of the solder ball to form an inlay and produce mechanical interlocking. Au/Ni–W alloy modification layer can effectively improve the surface hardness of copper-based structures. This creates a large hardness difference with soft solder and enables the formation of fewer holes in the insertion solder. Amorphous Ni–W alloys are prone to form dense oxide films during ultrasonication. The Au film modification prevents oxide generation and increases the average shear strength of the soldering interface. The Ni–W alloy layer retards the interdiffusion between Cu–Sn, blocks the excessive growth of Cu–Sn IMCs, and reduces the reliability problems caused by interface failure.

IntroductionInfection with SARS-CoV-2 begins in the upper respiratory tract and can trigger the production of mucosal spike-specific secretory IgA (sIgA), which provides protection against reinfection. It has been recognized that individuals with high level of nasal spike-specific IgA have a lower risk of reinfection. However, mucosal spike-specific sIgA wanes over time, and different individuals may have various level of spike-specific sIgA and descending kinetics, leading to individual differences in susceptibility to reinfection. A method for detecting spike-specific sIgA in the nasal passage would be valuable for predicting the risk of reinfection so that people at risk can have better preparedness.MethodsIn this study, we describe the development of a colloidal gold-based immunochromatographic (ICT) strip for detecting SARS-CoV-2 Omicron spike-specific sIgA in nasal mucosal lining fluids (NMLFs).ResultsThe ICT strip was designed to detect 0.125 μg or more spike-specific sIgA in 80 μL of NMLFs collected using a nasal swab. Purified nasal sIgA samples from individuals who recently recovered from an Omicron BA.5 infection were used to demonstrate that this ICT strip can specifically detect spike-specific sIgA. The signal levels positively correlated with neutralizing activities against XBB. Subsequent analysis revealed that people with low or undetectable levels of spike-specific sIgA in the nasal passage were more susceptible to SARS-CoV-2 reinfection.ConclusionsThis nasal spike-specific sIgA ICT strip provides a non-invasive, rapid, and convenient method to assess the risk of reinfection for achieving precision preparedness.

While spent mushroom substrate (SMS) has shown promise in increasing soil organic carbon (SOC) and improving soil quality, research on the interplay between SOC components and microbial community following the application of diverse SMS types remains scant. A laboratory soil incubation experiment was conducted with application of two types of SMSs from cultivation of Pleurotus eryngii (PE) and Agaricus bisporus (AB), each at three application rates (3, 5.5, and 8%). Advanced techniques, including solid-state 13C nuclear magnetic resonance (NMR) and high-throughput sequencing, were employed to investigate on SOC fractions and chemical structure, microbial community composition and functionality. Compared to SMS-AB, SMS-PE application increased the relative abundances of carbohydrate carbon and O-alkyl C in SOC. In addition, SMS-PE application increased the relative abundance of the bacterial phylum Proteobacteria and those of the fungal phyla Basidiomycota and Ascomycota. The relative abundances of cellulose-degrading bacterial (e.g., Flavisolibacter and Agromyces) and fungal genera (e.g., Myceliophthora, Thermomyces, and Conocybe) were increased as well. The application of SMS-AB increased the aromaticity index of SOC, the relative abundance of aromatic C, and the contents of humic acid and heavy fraction organic carbon. In addition, SMS-AB application significantly increased the relative abundances of the bacterial phyla Firmicutes and Actinobacteria. Notably, the genera Actinomadura, Ilumatobacter, and Bacillus, which were positively correlated with humic acid, experienced an increase in relative abundance. Functional prediction revealed that SMS-PE application elevated carbohydrate metabolism and reduced the prevalence of fungal pathogens, particularly Fusarium. The application of high-rate SMS-AB (8%) enhanced bacterial amino acid metabolism and the relative abundances of plant pathogenic fungi. Our research provides strategies for utilizing SMS to enrich soil organic carbon and fortify soil health, facilitating the achievement of sustainable soil management.

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection has many neurological manifestations, and its effects on the nervous system are increasingly recognized. There has been no systematic analysis of electroencephalography (EEG) characteristics in children exhibiting neurological symptoms of Coronavirus disease 2019 (COVID-19). The primary aim of this study was to describe the EEG characteristics caused by COVID-19 infection in children who were showing neurological symptoms and to assess the relationship between COVID-19-related EEG changes and clinical features in these children. Method: This study included 125 pediatric patients infected with SARS-CoV2 and showing neurological symptoms, and their continuous EEG was recorded. In addition, the demographic and clinical characteristics of these patients were analyzed and the correlation between the two was investigated. Results: Abnormal EEG findings were detected in 31.20% (N = 39) of the patients. Abnormal discharges (43.59%) were the most common EEG abnormalities, followed by background abnormalities (41.03%). The proportion of patients diagnosed with febrile seizure was higher in the normal EEG group than in the abnormal EEG group (P = 0.002), while the opposite was true for epilepsy and encephalitis/encephalopathy (P = 0.016 and P = 0.003, respectively). The independent associated factors of abnormal EEG were age and total length of stay (P

Abstract Organoids, three-dimensional structures cultured in vitro, can recapitulate the microenvironment, complex architecture, and cellular functions of in vivo organs or tissues. In recent decades, liver organoids have been developed rapidly, and their applications in biomedicine, such as drug screening, disease modeling, and regenerative medicine, have been widely recognized. However, the lack of repeatability and consistency, including the lack of standardized culture conditions, has been a major obstacle to the development and clinical application of liver organoids. It is time-consuming for researchers to identify an appropriate medium component scheme, and the usage of some ingredients remains controversial. In this review, we summarized and compared different methods for liver organoid cultivation that have been published in recent years, focusing on controversial medium components and discussing their advantages and drawbacks. We aimed to provide an effective reference for the development and standardization of liver organoid cultivation.

Abstract This study uses the three-cornered hat (3CH) method to estimate the observation error variances (ErrVars) of FY-3C RO refractivity, temperature, and specific humidity for the first time. The FY-3C RO data was compared to the three reference datasets including radiosonde observations and NCEP and ERA-Interim reanalyses. The ErrVars of FY-3C RO data are estimated at 18 globally distributed radiosonde stations by using the three reference datasets and are compared to corresponding gridded ErrVars estimated using only the two model datasets as references. The two types of estimates show good correlations at different heights, while the gridded estimates are generally the smaller ones, which may be attributed to the neglection of error correlations among the datasets when applying the 3CH method. Due to the lack of radiosonde data in oceanic and polar regions, the global distributions of FY-3C RO observation errors are presented based on the estimated 5° × 5° gridded ErrVars. The global distribution of the FY-3C RO fractional error standard deviations (ErrSDs) demonstrates that the observation error varies greatly at different pressure levels and latitudes. Specifically, the refractivity ErrSDs at 200 hPa and 50 hPa are significantly higher around 30°N and 30°S than in other areas. The specific humidity ErrSDs generally increase as pressure levels decrease. In addition, statistics show that the fractional ErrSDs of refractivity are generally the lowest between 45° N–75° N and 45° S–75° S at all pressure levels, and land-sea differences exist in the fractional ErrSDs for all three types of RO data.

Abstract Background The formation of a tree’s heartwood gives the wood properties such as natural decay resistance and aesthetic color, and often directly determines the value of wood products. Regulating the quantity and quality of heartwood is of great importance to the use of wood. However, the mechanism of heartwood formation has been poorly understood. Results Using Dalbergia odorifera as the study species, the number of starch grains, the morphology of the nuclei, the changes in the content of water and secondary metabolites were observed continuously in the radial direction of the xylem. The results show that from the outer toward inner sapwood, the starch grains are abundant, the length to diameter ratio of the nuclei is decreasing, and the morphology changes from elongated elliptical and then to round. In the outer transition zone, the starch grains begin to decrease abruptly and the nuclei shrink at a slower rate, with a radial width of approximately 2 mm. In the inner transition zone, the heartwood color begins to appear, the starch grains disappear and a few nuclei with reduced fluorescence are present, with a radial width of approximately 1 mm. Heartwood formation after complete disappearance of the nuclei. The moisture content of the heartwood is higher than that of the sapwood, and the inner transition zone is where the content rises. The secondary metabolites of the heartwood begin to accumulate in large quantities in the inner transition zone. Conclusion Based on the physiological changes of parenchyma cells in the xylem, the radial width of the transition zone of Dalbergia odorifera is clearly defined as approximately 3 mm. Both the water and secondary metabolite abrupt changes occur at the final stage of programmed cell death, and neither is a direct cause of programmed cell death in parenchyma cells.

Rotating machinery is widely used in modern industrial systems, and its health status can directly impact the operation of the entire system. Timely and accurate diagnosis of rotating machinery faults is crucial for ensuring production safety, reducing economic losses, and improving efficiency. Traditional deep learning methods can only extract features from the vertices of the input data, thereby overlooking the information contained in the relationships between vertices. This paper proposes a Legendre graph convolutional network (LGCN) integrated with a self-attention graph pooling method, which is applied to fault diagnosis of rotating machinery. The SA-LGCN model converts vibration signals from Euclidean space into graph signals in non-Euclidean space, employing a fast local spectral filter based on Legendre polynomials and a self-attention graph pooling method, significantly improving the model’s stability and computational efficiency. By applying the proposed method to 10 different planetary gearbox fault tasks, we verify that it offers significant advantages in fault diagnosis accuracy and load adaptability under various working conditions.

Background: The decline in muscle strength and function with aging is well recognized, but remains poorly characterized at the molecular level. Here, we report the epigenetic relationship between genome-wide DNA methylation and handgrip strength (HGS) among Chinese monozygotic (MZ) twins.Methods: DNA methylation (DNAm) profiling was conducted in whole blood samples through Reduced Representation Bisulfite Sequencing method. Generalized estimating equation was applied to regress the DNAm of each CpG with HGS. The Genomic Regions Enrichment of Annotations Tool was used to perform enrichment analysis. Differentially methylated regions (DMRs) were detected using comb-p. Causal inference was performed using Inference about Causation through Examination of Familial Confounding method. Finally, we validated candidate CpGs in community residents.Results: We identified 25 CpGs reaching genome-wide significance level. These CpGs located in 9 genes, especially FBLN1, RXRA, and ABHD14B. Many enriched terms highlighted calcium channels, neuromuscular junctions, and skeletal muscle organ development. We identified 21 DMRs of HGS, with several DMRs within FBLN1, SLC30A8, CST3, and SOCS3. Causal inference indicated that the DNAm of 16 top CpGs within FBLN1, RXRA, ABHD14B, MFSD6, and TYW1B might influence HGS, while HGS influenced DNAm at two CpGs within FBLN1 and RXRA. In validation analysis, methylation levels of six CpGs mapped to FLBN1 and one CpG mapped to ABHD14B were negatively associated with HGS weakness in community population.Conclusion: Our study identified multiple DNAm variants potentially related to HGS, especially CpGs within FBLN1 and ABHD14B. These findings provide new clues to the epigenetic modification underlying muscle strength decline.

PurposeAlcohol consumption increases the risk of breast cancer and promotes cancer progression. Alcohol exposure could affect both processes of the mammary carcinogenesis, namely, the cell transformation and onset of tumorigenesis as well as cancer aggressiveness including metastasis and drug resistance/recurrence. However, the cellular and molecular mechanisms underlying alcohol tumor promotion remain unclear. There are four members of the mammalian p38 mitogen-activated protein kinase (MAPK) family, namely, p38α, p38β, p38γ and p38δ. We have previously demonstrated alcohol exposure selectively activated p38γ MAPK in breast cancer cells in vitro and in vivo. Pirfenidone (PFD), an antifibrotic compound approved for the treatment of idiopathic pulmonary fibrosis, is also a pharmacological inhibitor of p38γ MAPK. This study aimed to determine whether PFD is useful to inhibit alcohol-induced promotion of breast cancer.MethodsFemale adolescent (5 weeks) MMTV-Wnt1 mice were exposed to alcohol with a liquid diet containing 6.7% ethanol. Some mice received intraperitoneal (IP) injection of PFD (100 mg/kg) every other day. After that, the effects of alcohol and PFD on mammary tumorigenesis and metastasis were examined.ResultsAlcohol promoted the progression of mammary tumors in adolescent MMTV-Wnt1 mice. Treatment of PFD blocked tumor growth and alcohol-promoted metastasis. It also significantly inhibited alcohol-induced tumorsphere formation and cancer stem cell (CSC) population.ConclusionPFD inhibited mammary tumor growth and alcohol-promoted metastasis. Since PFD is an FDA-approved drug, the current findings may be helpful to re-purpose its application in treating aggressive breast cancer and alcohol-promoted mammary tumor progression.

Abstract Background The success of neuroimaging in revealing neural correlates of obsessive-compulsive disorder (OCD) has raised hopes of using magnetic resonance imaging (MRI) indices to discriminate patients with OCD and the healthy. The aim of this study was to explore MRI based OCD diagnosis using machine learning methods. Methods Fifty patients with OCD and fifty healthy subjects were allocated into training and testing set by eight to two. Functional MRI (fMRI) indices, including amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), degree of centrality (DC), and structural MRI (sMRI) indices, including volume of gray matter, cortical thickness and sulcal depth, were extracted in each brain region as features. The features were reduced using least absolute shrinkage and selection operator regression on training set. Diagnosis models based on single MRI index / combined MRI indices were established on training set using support vector machine (SVM), logistic regression and random forest, and validated on testing set. Results SVM model based on combined fMRI indices, including ALFF, fALFF, ReHo and DC, achieved the optimal performance, with a cross-validation accuracy of 94%; on testing set, the area under the receiver operating characteristic curve was 0.90 and the validation accuracy was 85%. The selected features were located both within and outside the cortico-striato-thalamo-cortical (CSTC) circuit of OCD. Models based on single MRI index / combined fMRI and sMRI indices underperformed on the classification, with a largest validation accuracy of 75% from SVM model of ALFF on testing set. Conclusion SVM model of combined fMRI indices has the greatest potential to discriminate patients with OCD and the healthy, suggesting a complementary effect of fMRI indices on the classification; the features were located within and outside the CSTC circuit, indicating an importance of including various brain regions in the model.

Abstract Oral tongue squamous cell carcinoma (OTSCC) is a malignant tumor. Recently, studies have found that adenylate cyclase 6 (ADCY6) plays a pivotal role in many lethal tumors formation processes. The role of ADCY6 in OTSCC remains unknown. The expression of ADCY6 in OTSCC tissue samples was detected. The clinical significance of ADCY6 in OTSCC was analyzed by statistical methods. OTSCC cell lines were selected to analyze the biological function of ADCY6. Meanwhile, the effect of ADCY6 on the growth of OTSCC in vivo was explored using subcutaneous tumorigenesis assay. WB assay was used to detect the underlying signaling pathway. Cell function recovery test used to investigate the mechanism of ADCY6‐promoting OTSCC malignant biological behavior via Hippo signaling pathway. We report that ADCY6 was obviously downregulated in OTSCC tissue samples and cell lines. Importantly, lower expression of ADCY6 indicates a poorer prognosis in patients with OTSCC, and its expression is significantly correlated with TNM stage and tumor size. Functionally, forced expression of ADCY6 can significantly inhibit the proliferation, migration, invasion, and promote apoptosis of OTSCC cells. Mechanistically, we demonstrated that ADCY6 upregulation impaired Hippo signaling pathway to reduce the malignant biological behavior of OTSCC. Generally, our findings suggest that ADCY6 suppressed Hippo signaling pathway to regulate malignant biological behavior in OTSCC, which provide new cues for further exploring the mechanism of occurrence and development of OTSCC.

Abstract Background In China, patients with somatoform disorders (SFD) often seek medical treatment repeatedly in outpatient clinics of general hospitals, which increases unreasonable medical expenses. It is imperative to provide early screening to these patients and specialized treatment to reduce the unnecessary cost. This study aimed to screen patients with SFD in general hospitals using a new Chinese questionnaire and explore the characteristics and economic burden of these patients. Methods Patients (n = 1497) from the outpatient department of neurology, cardiology and gastroenterology of three large general hospitals were included. Participants were screened using a newly developed questionnaire, the Self-screening Questionnaire for Somatic Symptoms (SQSS), to identify the patients with SFD (total SQSS score ≥ 29 points). We compared the demographics and clinical information of patients with and without SFD. Logistic regression was used to explore potential factors related to medical expenses, visits to doctors and sick leave days taken. Results The frequency of detection of patients with SFD was 17.03%. There were significant differences in employment, doctor visits, symptom duration, medical expenses, sick leave days, PHQ-15 scores, and PHQ-9 scores between patients with SFD and without SFD. General nonspecific somatic symptoms were frequently present in patients with SFD. Several potential factors were associated with higher medical expenses, repeated doctor visits, and sick leave days taken in the regression analysis. Conclusion The findings indicate that patients with SFD are common in general hospitals, and their direct and indirect economic burden is higher than that of non-SFD patients, which indicates that more screening effort should be made to this group to early identify their problems. Certain characteristics were identified among patients with SFD and several factors were associated with negative consequences of SFD, all of which might be prevented by developing a preventive intervention program to reduce the economic burden of the patients.

The timing of potato tuberization is affected by potato ripeness, environmental factors, and polygene regulation. The accurate control of the transition to tuberization has both scientific and practical production value, but the key factors regulating this transition remain unclear. This study grafted an early-maturing potato variety (Favorita) scion to the late-maturing Qingshu 9 variety and demonstrated that a heterologous early-maturing scion can induce early potato formation on a late-maturing rootstock. The transcriptome of functional leaves and stolons of grafted plants was comprehensively analyzed and 593 differentially expressed genes (DEGs) were identified, including 38 transcription factors. Based on gene molecular function analysis and previous reports, we propose that PIF5, bHLH93, CBF3, ERF109, TCP19, and YABBY1 are the key DEGs that induce tuber formation in early- and late-maturing potatoes. The YABBY1 gene was subjected to functional verification. The leaf area of StYABBY1-overexpressing plants was smaller than the wild type and no potato tubercles were formed, while an RNA interference plant line showed no change in leaf area and formed tubers, indicating that StYABBY1 has a role in leaf size regulation and tuber formation.

Two-dimensional van der Waals heterostructures have good application prospects in solar energy conversion due to their excellent optoelectronic performance. In this work, the electronic structures of Sc2CF2/Sc2CCl2, Sc2CF2/Sc2CBr2, and Sc2CCl2/Sc2CBr2 heterostructures, as well as their properties in photocatalysis and photovoltaics, have been comprehensively studied using the first-principles method. Firstly, both of the three thermodynamically and dynamically stable heterostructures are found to have type-II band alignment with band gap values of 0.58 eV, 0.78 eV, and 1.35 eV. Meanwhile, the photogenerated carriers in Sc2CF2/Sc2CCl2 and Sc2CF2/Sc2CBr2 heterostructures are predicated to follow the direct Z-scheme path, enabling their abilities for water splitting. As for the Sc2CCl2/Sc2CBr2 heterostructure, its photovoltaic conversion efficiency is estimated to be 20.78%. Significantly, the light absorption coefficients of Sc2CF2/Sc2CCl2, Sc2CF2/Sc2CBr2, and Sc2CCl2/Sc2CBr2 heterostructures are enhanced more than those of the corresponding monolayers. Moreover, biaxial strains have been observed to considerably tune the aforementioned properties of heterostructures. All the theoretical results presented in this work demonstrate the application potential of Sc2CX2/Sc2CY2 (X, Y = F, Cl, Br) heterostructures in photocatalysis and photovoltaics.

The structural, electronic, and magnetic properties of a novel two-dimensional monolayer material, TaF4, are investigated using first-principles calculations. The dynamical and thermal stabilities of two-dimensional monolayer TaF4 were confirmed using its phonon dispersion spectrum and molecular dynamics calculations. The band structure obtained via the high-accuracy HSE06 (Heyd–Scuseria–Ernzerhof 2006) functional theory revealed that monolayer two-dimensional TaF4 is an indirect bandgap semiconductor with a bandgap width of 2.58 eV. By extracting the exchange interaction intensities and magnetocrystalline anisotropy energy in a J1-J2-J3-K Heisenberg model, it was found that two-dimensional monolayer TaF4 possesses a Néel-type antiferromagnetic ground state and has a relatively high Néel temperature (208 K) and strong magnetocrystalline anisotropy energy (2.06 meV). These results are verified via the magnon spectrum.

Abstract Background Osteoporosis, characterized by reduced bone mass and deterioration of bone quality, is a significant health concern for postmenopausal women. Considering that the specific role of circRNAs in osteoporosis and osteoclast differentiation remains poorly understood, this study aims to shed light on their involvement in these processes to enhance our understanding and potentially contribute to improved treatment strategies for osteoporosis. Methods An osteoporotic model was constructed in vivo in ovariectomized mouse. In vitro, we induced osteoclast formation in bone marrow-derived macrophages (BMDMs) using M-CSF + RANKL. To assess osteoporosis in mice, we conducted HE staining. We used MTT and TRAP staining to measure cell viability and osteoclast formation, respectively, and also evaluated their mRNA and protein expression levels. In addition, RNA pull-down, RIP and luciferase reporter assays were performed to investigate interactions, and ChIP assay was used to examine the impact of circZNF367 knockdown on the binding between FUS and CRY2. Results We observed increased expression of CircZNF367, FUS and CRY2 in osteoporotic mice and M-CSF + RANKL-induced BMDMs. Functionally, knocking down circZNF367 inhibited osteoporosis in vivo. Furthermore, interference with circZNF367 suppressed osteoclast proliferation and the expression of TRAP, NFATc1, and c-FOS. Mechanistically, circZNF367 interacted with FUS to maintain CRY2 mRNA stability. Additionally, knocking down CRY2 rescued M-CSF + RANKL-induced osteoclast differentiation in BMDMs promoted by circZNF367 and FUS. Conclusion This study reveals that the circZNF367/FUS axis may accelerate osteoclasts differentiation by upregulating CRY2 in osteoporosis and suggests that targeting circZNF367 may have potential therapeutic effects on osteoporosis.

Abstract Background With the in-depth research on the tumor microenvironment, the tumor stroma is considered to play a leading role in malignant tumor behavior, and PD-L1 is also related to the tumor stroma. The tumor–stroma ratio (TSR) has been regarded as a novel prognostic factor in many cancers. Our study aims to assess the TSR and PD-L1 clinical value in hepatocellular carcinoma (HCC) patients. Methods Ninety-five patients who were diagnosed with HCC were included in our study. TSR was estimated on HCC specimen hematoxylin–eosin staining (HE) sections, and the optimal TSR cut-off value was determined by receiver operating characteristic (ROC) curves. The correlation between the TSR and clinicopathologic features was also calculated. Immunohistochemistry (IHC) staining was also carried out to analyze the PD-L1 expression level in HCCs. Results The optimal TSR cut-off value was 0.525. The median OS of the stroma-high and stroma-low groups was 27 and 36 months, respectively. The median RFS of the stroma-high and stroma-low groups was 14.5 and 27 months, respectively. In the Cox multivariate analysis, the TSR was an independent prognostic factor for HCC overall survival (OS) and recurrence-free survival (RFS) in patients who underwent liver resection. IHC staining revealed TSR-high HCC samples with high PD-L1-positive cell expression. Conclusions Our results suggest that the TSR can predict the prognosis of HCC patients who underwent liver resection. The TSR is related to PD-L1 expression and may be a therapeutic target that can dramatically improve HCC patients’ clinical outcomes.

NUT carcinoma is a rare subcategory of squamous cell carcinoma. The latter is primarily characterized by the fusion of the coding sequence NUTM1 on chromosome 15q14 with BRD4 or BRD3, both of which are acetyl-histone binding bromodomains. This tumor is often misdiagnosed due to its rarity and its histological similarity with other squamous cell carcinomas. It typically presents as a poorly differentiated squamous cell carcinoma in the head, neck, and mediastinal region, and has no distinct clinical characteristics that set it apart from other malignancies. Although uncommon, other NUT carcinomas have been reported in the literature outside of the midline region. Through next-generation sequencing, we were able to correctly diagnose our patient with the first-documented case of NUT carcinoma of hepatic-only origin.

We present the first known case of a patient with BRD2::NUTM1-driven NUT carcinoma. A 59-year-old woman presented with poorly differentiated squamous cell lung cancer metastatic to the pleura. Eventually, a positive NUT immunohistochemistry, NUT fluorescence in situ hybridization, and RNA next-generation sequencing with a BRD2::NUTM1 fusion led to the diagnosis of NUT carcinoma. She received multiple lines of chemotherapy with response and is still alive at 2 years postdiagnosis. This report expands on the known fusions in NUT carcinoma and highlights potential differences in patient prognosis on the basis of gene fusion partners.

Generative artificial intelligence (GAI) shocked the world with its unprecedented ability and raised significant tensions in the education field. Educators inevitably transition to an educational future that embraces GAI rather than shuns it. Understanding the mechanism between students interacting with GAI tools and their achievement is important for educators and schools, but relevant empirical evidence is relatively lacking. Due to the characteristics of personalization and real-time interactivity of GAI tools, we propose that the students–GAI interaction would affect their learning achievement through serial mediators of self-efficacy and cognitive engagement. Based on questionnaire surveys that include 389 participants as the objective, this study finds that: (1) in total, there is a significantly positive relationship between student–GAI interaction and learning achievement. (2) This positive relationship is mediated by self-efficacy, with a significant mediation effect value of 0.015. (3) Cognitive engagement also acts as a mediator in the mechanism between the student–GAI interaction and learning achievement, evidenced by a significant and relatively strong mediating effect value of 0.046. (4) Self-efficacy and cognitive engagement in series mediate this positive association, with a serial mediating effect value of 0.011, which is relatively small in comparison but also shows significance. In addition, the propensity score matching (PSM) method is applied to alleviate self-selection bias, reinforcing the validity of the results. The findings offer empirical evidence for the incorporation of GAI in teaching and learning.

With growing concerns over global warming, cultivating heat-tolerant crops has become paramount to prepare for the anticipated warmer climate. Cassava (Manihot esculenta Crantz), a vital tropical crop, demonstrates exceptional growth and productivity under high-temperature (HT) conditions. Yet, studies elucidating HT resistance mechanisms in cassava, particularly within vascular tissues, are rare. We dissected the leaf mid-vein from leaf, and did the comparative transcriptome profiling between mid-vein and leaf to figure out the cassava vasculature HT resistance molecular mechanism. Anatomical microscopy revealed that cassava leaf veins predominantly consisted of vasculature. A thermal imaging analysis indicated that cassava experienced elevated temperatures, coinciding with a reduction in photosynthesis. Transcriptome sequencing produced clean reads in total of 89.17G. Using Venn enrichment, there were 65 differentially expressed genes (DEGs) and 93 DEGs had been found highly specifically expressed in leaf and mid-vein. Further investigation disclosed that leaves enhanced pyruvate synthesis as a strategy to withstand high temperatures, while mid-veins fortified themselves by bolstering lignin synthesis by comprehensive GO and KEGG analysis of DEGs. The identified genes in these metabolic pathways were corroborated through quantity PCR (QPCR), with results aligning with the transcriptomic data. To verify the expression localization of DEGs, we used in situ hybridization experiments to identify the expression of MeCCoAMT(caffeoyl-coenzyme A-3-O-methyltransferase) in the lignin synthesis pathway in cassava leaf veins xylem. These findings unravel the disparate thermotolerance mechanisms exhibited by cassava leaves and mid-veins, offering insights that could potentially inform strategies for enhancing thermotolerance in other crops.

The COVID-19 infodemic, characterized by the rapid spread of misinformation and unverified claims related to the pandemic, presents a significant challenge. This paper presents a comparative analysis of the COVID-19 infodemic in the English and Chinese languages, utilizing textual data extracted from social media platforms. To ensure a balanced representation, two infodemic datasets were created by augmenting previously collected social media textual data. Through word frequency analysis, the 30 most frequently occurring infodemic words are identified, shedding light on prevalent discussions surrounding the infodemic. Moreover, topic clustering analysis uncovers thematic structures and provides a deeper understanding of primary topics within each language context. Additionally, sentiment analysis enables comprehension of the emotional tone associated with COVID-19 information on social media platforms in English and Chinese. This research contributes to a better understanding of the COVID-19 infodemic phenomenon and can guide the development of strategies to combat misinformation during public health crises across different languages.

Abstract We developed a continuous learning system (CLS) based on deep learning and optimization and ensemble approach, and conducted a retrospective data simulated prospective study using ultrasound images of breast masses for precise diagnoses. We extracted 629 breast masses and 2235 images from 561 cases in the institution to train the model in six stages to diagnose benign and malignant tumors, pathological types, and diseases. We randomly selected 180 out of 3098 cases from two external institutions. The CLS was tested with seven independent datasets and compared with 21 physicians, and the system’s diagnostic ability exceeded 20 physicians by training stage six. The optimal integrated method we developed is expected accurately diagnose breast masses. This method can also be extended to the intelligent diagnosis of masses in other organs. Overall, our findings have potential value in further promoting the application of AI diagnosis in precision medicine.

Based on the hourly surface ozone (O3) observations and meteorological data from Zhuzhou in 2021, the pollution characteristics and influencing factors of O3 in Zhuzhou were investigated in the study. In addition, the Potential Source Contribution Function (PSCF) and Concentration Weighted Trajectory (CWT) analysis methods were employed to analyze the transmission paths and potential pollution sources of O3 pollution in Zhuzhou. The results showed that the total number of days with O3 exceeding the standard at all monitoring stations in Zhuzhou was 142 days in 2021. The overall air quality was less affected by SO2, NO2, and CO, and the trend of O3 pollution was still increasing. The concentrations of O3, CO, and NO2 varied significantly in different months, and the variation of O3 exhibited a “double-peak” pattern, with the peak value occurring in September. The O3 concentration in urban areas was significantly higher than that in suburban areas. Meteorological conditions had a significant impact on the degree of O3 pollution in Zhuzhou. The average wind speed in Zhuzhou throughout the year was 1.7 m/s, and the prevailing wind direction in summer was southeast, with a frequency of 16%. O3 pollution was mainly transported by short-distance airflow during the over-standard periods in 2021, accounting for 37.64%. The main source of O3 pollutant was from Jiangxi Province in the east, with the shortest distance of regional transport and the highest O3 concentration. In addition, transportation from central Guangdong Province, western Jiangxi Province, and central Hubei Province also had a significant impact.

MAX phases have great research value and application prospects, but it is challenging to synthesize the MAX phases containing Cd and Sb for the time being. In this paper, we confirmed the existence of the 312 MAX phases of Zr3CdC2 and Zr3SbC2, both from theoretical calculations and experimental synthesis. The Zr3AC2 (A = Cd, Sb) phase was predicted by the first-principles calculations, and the two MAX phases were confirmed to meet the requests of thermal, thermodynamic, and mechanical stabilities using formation energy, phonon dispersion, and the Born–Huang criteria. Their theoretical mechanical properties were also systematically investigated. It was found that the elastic moduli of Zr3CdC2 and Zr3SbC2 were 162.8 GPa and 164.3 GPa, respectively. Then, differences in the mechanical properties of Zr3AC2 (A = Cd, In, Sn, and Sb) were explained using bond layouts and charge transfers. The low theoretical Vickers hardness of the Zr3CdC2 (5.4 GPa) and Zr3SbC2 (4.3 GPa) phases exhibited excellent machinability. Subsequently, through spark plasma sintering, composites containing Zr3CdC2 and Zr3SbC2 phases were successfully synthesized at the temperatures of 850 °C and 1300 °C, respectively. The optimal molar ratio of Zr:Cd/Sb:C was determined as 3:1.5:1.5. SEM and the EDS results analysis confirmed the typical layered microstructure of Zr3CdC2 and Zr3SbC2 grains.

The gravity wave (GW) potential energy (Ep) in the lower stratosphere (LS) of the altitude range between 20 and 30 km over the Indian region (60°E–100°E, 0°–30°N) is retrieved using the dry temperature profiles from the Constellation Observing System for Meteorology Ionosphere and Climate-2 (COSMIC-2) radio occultation (RO) mission from December 2019 to November 2021. Through correlation analysis and dominance analysis (DA) methods, the impacts of multiple influencing factors on the local LS GW activity are quantified and compared. The results demonstrate that in the central and northern part of Indian region, the three factors, including the convective activity (using outgoing long-wave radiation as the proxy) mainly caused by the Indian summer monsoon, the mean zonal wind speed between 15 and 17 km, the height range where the maximum tropical easterly jet (TEJ) wind speed appears, and the mean zonal wind speed between 20 and 30 km, have the greatest impacts on the LS GW activity. In the southern part of the Indian Peninsula and over the Indian Ocean, the mean zonal wind shear between 20 and 30 km plays a dominant role in the LS GW activity, which is due to the fact that the GW energy can be attenuated by large background wind shears. It can be concluded that the LS GW activity in the Indian region is mainly influenced by the Indian summer monsoon, the TEJ, and the wind activity in the LS, while over different local areas, differences exist in which factors are the dominant ones.

Abstract Sensorineural hearing loss (SNHL) is a common otologic condition caused by damage to hair cells and spiral ganglion neurons that affects transmission pathways. Most of these cells cannot be regenerated, and there has been no breakthrough in regeneration techniques for inner ear cells. SNHL has a high incidence rate and can cause a variety of clinical symptoms, greatly impacting people's daily lives. With limited clinical treatments, the search for critical targets is urgent. Studies have shown that inflammation is prevalent in the pathogenesis of SNHL and plays a significant role in it. Inflammation is a normal body defense response, and a systemic anti‐inflammatory approach is undesirable. It is crucial for us to identify potential targets of inflammation in SNHL and take measures specifically targeting those targets with minimal systemic impact. This paper firstly describes the role of inflammation in various types of SNHL and then provides an overview of the interactions between inflammation and cochlear immunity, cochlear microcirculation, vascular spasm, and glutamate metabolism and finally comprehensively examines the feasibility of targets in these interactions. This paper is expected to facilitate the development of targeted anti‐inflammation for SNHL and provide strategies and approaches for treating clinical SNHL.

With the gradual expansion of the protected vegetable planting area, dense planting stubbles and increasing labor cost, the treatment of vegetable residues has become an urgent problem to be solved. Soil bacterial community structure plays an important role in vegetable residue return and is susceptible to environmental changes. Therefore, understanding the influences of different soil water holding capacities on plant residue decomposition and soil bacterial communities is important for biodegradation. During the whole incubation period, the weight loss ratio of plant residue with 100% water holding capacity was 69.60 to 75.27%, which was significantly higher than that with 60% water holding capacity in clay and sandy soil, indicating that high water holding capacity promoted the decomposition of plant residue. The degradation of lignin and cellulose was also promoted within 14 days. Furthermore, with the increase in soil water holding capacity, the contents of NH4+ increased to 5.36 and 4.54 times the initial value in the clay and sandy soil, respectively. The increase in napA and nrfA resulted in the conversion of NO3– into NH4+. The increase in water holding capacity made the bacterial network structure more compact and changed the keystone bacteria. The increase in water holding capacity also increased the relative abundance of Firmicutes at the phylum level and Symbiobacterium, Clostridium at the genus level, which are all involved in lignin and cellulose degradation and might promote their degradation. Overall, these findings provide new insight into the effects of different soil water holding capacities on the degradation of plant residues in situ and the corresponding bacterial mechanisms.

Background: The Pilot Plan of National Centralized Volume-Based Procurement (NCVBP) was adopted to cope with the rapid increase in drug expenditures. This research aimed to quantitatively evaluate the impact of the NCVBP on antiviral medications for the hepatitis B virus.Methods: Data on nucleoside analogs (NAs) medications of hepatitis B virus monthly procurement records in the pilot cities from January 2018 to December 2019 were extracted from the China Drug Supply Information Platform (CDSIP). The impacts of the NCVBP on purchased volumes, expenditures, and pre-defined daily dose costs were evaluated by interrupted time-series (ITS) analysis using Stata 16.0. We constructed two segments with one interruptive point (March 2019).Results: Compared to the same period between pre-and post-intervention, the purchased volume of NAs medications were increased by 92.85%, and selected medications were increased by 119.09%. Analysis of changes in the level of NAs medication followed a decrease in purchased expenditure (coefficient: 5364.88, p < 0.001), meanwhile, the purchased volume was increased with statistical significance (coefficient:605.49, p < 0.001). The Defined Daily Dose cost (DDDc) of NAs medication followed a decrease (coefficient: 8.90, p < 0.001). The NCVBP reform was followed by an increase of 618.41 ten thousand Defined Daily Dose (DDD) (p < 0.001) in purchased volume and a reduction of 5273.84 ten thousand Chinese Yuan (CNY) (p < 0.001) in the purchased expenditure of selected medications in the level. The DDDc of selected medications decreased in the level (coefficient: 9.87, p < 0.001), while the DDDc of alternative medications increased in the slope (coefficient:0.07, p = 0.030). The purchased volume and expenditure of bid-winning products increased by 964.08 ten thousand DDD and 637.36 ten thousand CNY in the level (p < 0.001). An increase of 633.46 ten thousand DDD (p < 0.001) in purchased volume and a reduction of 4285.32 ten thousand CNY (p < 0.001) in the purchased expenditure of generic drugs in the level was observed.Conclusion: The NCVBP reduced the DDDc of NAs medication, improved the utilization of the selected medications, and promoted the usage of generic products.

Cross-modal hashing retrieval has attracted extensive attention due to its low storage requirements as well as high retrieval efficiency. In particular, how to more fully exploit the correlation of different modality data and generate a more distinguished representation is the key to improving the performance of this method. Moreover, Transformer-based models have been widely used in various fields, including natural language processing, due to their powerful contextual information processing capabilities. Based on these motivations, we propose a Transformer-based Distinguishing Strong Representation Deep Hashing (TDSRDH). For text modality, since the sequential relations between words imply semantic relations that are not independent relations, we thoughtfully encode them using a transformer-based encoder to obtain a strong representation. In addition, we propose a triple-supervised loss based on the commonly used pairwise loss and quantization loss. The latter two ensure the learned features and hash-codes can preserve the similarity of the original data during the learning process. The former ensures that the distance between similar instances is closer and the distance between dissimilar instances is farther. So that TDSRDH can generate more discriminative representations while preserving the similarity between modalities. Finally, experiments on the three datasets MIRFLICKR-25K, IAPR TC-12, and NUS-WIDE demonstrated the superiority of TDSRDH over the other baselines. Moreover, the effectiveness of the proposed idea was demonstrated by ablation experiments.

Highlights Oxygen-respirable sponge was constructed by carbon dots-assisted synthesis strategy. The hydrophilicity and aerophilicity of Co@C–O–Cs active sites boost oxygen diffusion and the bifunctional oxygen reduction reaction and oxygen evolution reaction activities. Co@C–O–Cs-based Zn-air battery (ZAB) displays excellent specific capacity and stability, and the all-solid-state Co@C–O–Cs-based ZAB exhibits excellent flexibility.

Prostate cancer (PCa) is the most common malignant tumor in men. Chemotherapy with docetaxel (DTX) and novel hormonal agents such as enzalutamide (EZL) and abiraterone are the preferred first-line therapeutic regimens. Prostate-specific membrane antigen (PSMA) is overexpressed on the surface of PCa cells. This study aimed to prepare a PSMA targeted (Glutamate-Urea-Lysine, GUL ligand modified), glutathione (GSH)-sensitive (Cystamine, SS), DTX and EZL co-loaded nanoparticles (GUL-SS DTX/EZL-NPs) to treat PCa. Polyethylene glycol (PEG) was conjugated with oleic acid (OA) using a GSH-sensitive ligand: cystamine (PEG-SS-OA). GUL was covalently coupled to PEG-SS-OA to achieve GUL-PEG-SS-OA. GUL-PEG-SS-OA was used to prepare GUL-SS DTX/EZL-NPs. To evaluate the in vitro and in vivo efficiency of the system, human prostate cancer cell lines and PCa cells bearing mice were applied. Single drug-loaded nanoparticle and free drugs systems were utilized for the comparison of the anticancer ability. GUL-SS DTX/EZL-NPs showed a size of 143.7 ± 4.1 nm, with a PDI of 0.162 ± 0.037 and a zeta potential of +29.1 ± 2.4 mV. GUL-SS DTX/EZL-NPs showed high cancer cell uptake of about 70%, as well as higher cell growth inhibition efficiency (a maximum 79% of cells were inhibited after treatment) than single drug-loaded NPs and free drugs. GUL-SS DTX/EZL-NPs showed the most prominent tumor inhibition ability and less systemic toxicity. The novel GUL-SS DTX/EZL-NPs could be used as a promising system for PCa therapy.

African swine fever virus (ASFV), a large and complex cytoplasmic double-stranded DNA virus, has developed multiple strategies to evade the antiviral innate immune responses. Cytosolic DNA arising from invading ASFV is mainly detected by the cyclic GMP-AMP synthase (cGAS) and then triggers a series of innate immune responses to prevent virus invasion. However, the immune escape mechanism of ASFV remains to be fully clarified. The pS273R of ASFV is a member of the SUMO-1-specific protease family and is crucial for valid virus replication. In this study, we identified pS273R as a suppressor of cGAS-STING pathway mediated type I interferon (IFN) production by ASFV genomic open reading frame screening. The pS273R was further confirmed as an inhibitor of IFN production as well as its downstream antiviral genes in cGAS-STING pathway. Mechanistically, pS273R greatly decreased the cGAS-STING signaling by targeting IKKε but not TBK1, and pS273R was found to disturb the interaction between IKKε and STING through its interaction with IKKε. Further, mutational analyses revealed that pS273R antagonized the cGAS-STING pathway by enzyme catalytic activity, which might affect the IKKε sumoylation state required for the interaction with STING. In summary, our results revealed for the first time that pS273R acts as an obvious negative regulator of cGAS-STING pathway by targeting IKKε via its enzymatic activity, which shows a new immune evasion mechanism of ASFV.