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Abstract Objectives This study was designed to compare the clinical data of vesicoureteral reflux (VUR) in children with and without an allergic constitution. Methods The clinical data of patients hospitalized with VUR due to a urinary tract infection (UTI) between September 1, 2019, and December 31, 2020, were retrospectively analyzed. The patients were divided into two groups: an anallergic constitution group (AC group) and a non-allergic constitution (NAC group), and their UTIs and VUR were compared at baseline and during the follow-up period. Results (1) Between September 1, 2019, and December 31, 2020, a total of 284 children were hospitalized at Shengjing Hospital Affiliated to China Medical University due to a UTI. These children included 37 cases with primary VUR and 247 cases without VUR (including 59 cases of non-VUR urinary malformation). The proportion of children with an allergic constitution was significantly higher in the patients with VUR than it was in those without VUR or with other urinary malformations (72.97% vs. 48.18% vs. 50.85%, P = 0.005, 0.032). (2) At baseline, the levels of immunoglobulin and immunoglobulin E in the AC group were significantly higher than those in the NAC group (P = 0.042, 0.017). (3) During the follow-up period, the number of recurrent UTI cases in the AC group was significantly higher than that in the NAC group (0.70 ± 0.91 vs. 0.10 ± 0.32, P= 0.005). The difference between the two groups in the VUR remission rate was not statistically significant (40% vs. 50%, P = 0.563). (4) During the follow-up period, the differences in the remission rates of recurrent UTIs and VUR in the two groups were not statistically significant. Conclusions The incidence of having an allergic constitution is high in patients with VUR, and patients with an allergic constitution present with a higher frequency of recurrent UTIs.

Abstract Food‐sourced proteins have been shown to have ameliorative effects on ulcerative colitis (UC), and studies have identified potential anti‐inflammatory activity of silkworm pupa proteins. Here, we identified and screened two novel protein‐derived peptides, PDLGLF (PD‐6) and GTEGGFPF (GT‐8), from Bombyx mori using UPLC–MS/MS and bioinformatics analysis. These peptides can serve as effective experimental drugs for colitis by modulating the gut microbiota. Treatment with peptides PD‐6 and GT‐8 inhibited colitis inflammation in UC mice, improved oxidative stress levels, and maintained intestinal epithelial barrier function. Peptides PD‐6 and GT‐8 also altered the diversity and composition of the gut microbiota in UC mice and increased the concentration of short‐chain fatty acids. In conclusion, these findings reveal the potential of the naturally derived bioactive peptides PD‐6 and GT‐8 in controlling intestinal inflammation and underscore the potential of PD‐6 and GT‐8 as promising candidates for the prevention and improvement of UC‐related inflammatory diseases.

Abstract As analogies to magnetic skyrmions, polar skyrmions in ferroelectric superlattices and multilayers have garnered widespread attention for their non-trivial topology and novel properties like negative capacitance and nonlinear optical effect. So far, they have only been theoretically predicted to be able to assemble ordered hexagonal skyrmion lattices (SkLs) in ferroelectric thin films. Here, based on phase-field simulations, we report the critical roles of flexoelectricity playing in the stabilization and transformation of polar SkLs. Different polar SkL patterns can emerge in the ferroelectric thin films, including tetragonal-SkL, and hexagonal-SkLs with diverse orientations, as summarized by phase diagrams. These emergent SkL states are attributed to the material anisotropy modified by the flexoelectric effect. Interestingly, we further found that the hexagonal-SkLs can be rotated by applying strain gradient or in-plane electric field to the films. Moreover, a nonreciprocal bending response of tetragonal-SkL is also induced by the flexoelectric effect. Our results provide useful guidelines for the implementation of polar skyrmion lattices in experiments.

Abstract Objectives To apply cardiac magnetic resonance imaging (CMR) for detailed myocardial characterization in uremic cardiomyopathy (UC), hypertensive cardiomyopathy (HTN), and hypertrophic cardiomyopathy (HCM) aiming to enrich the understanding of UC’s etiology and further support the development of therapeutic strategies. Methods A total of 152 patients (age: 49.2 ± 9.9 years; 65.8% male) underwent routine CMR from June 2016 to March 2023. Retrospectively, 53 patients with UC, 39 patients with HTN, 30 patients with HCM, and 30 healthy controls were included. Functional analysis, feature tracking of the left ventricle and left atrium, and myocardial T1, T2, and T2* mapping were performed. Statistical analysis included Pearson correlation and ROC analysis to define correlations and discriminators between groups. Results UC patients demonstrated significantly higher native T1 (p

Abstract Ovarian function suppression (OFS) benefits young women with hormone receptor (HR)-positive breast cancer but they are at risk for ovarian function breakthrough. We assessed endocrine effects of gonadotropin-releasing hormone agonist (GnRHa) treatment in a prospective cohort of patients aged ≤ 40 years with HR-positive breast cancer. Plasma estradiol (E2), estrone, and follicule-stimulating hormone (FSH) levels were measured from blood samples drawn 1 and 4 years after diagnosis. Patient characteristics, invasive breast cancer-free survival (iBCFS), and overall survival (OS) were compared between those with and without E2 > 2.72 pg/mL during GnRHa treatment. Among eligible patients, 54.7% (46/84) and 60% (15/25) had E2 > 2.72 pg/mL at 1 and 4 years, respectively. Factors associated with E2 > 2.72 pg/mL at 1 year were no prior chemotherapy (P = 0.045) and tamoxifen use (P = 0.009). After a median follow-up of 7 years, among patients with stage I-III breast cancer (N = 74), iBCFS events were seen in 6 (8.1%) with E2 > 2.72 pg/mL and 5 (6.8%) with E2 ≤ 2.72 pg/mL (P = 0.893). Among patients with de novo metastatic breast cancer (N = 12), 6 (50%) with E2 > 2.72 pg/mL and 3 (25%) with E2 ≤ 2.72 pg/mL died during follow-up (P = 0.052). Larger studies exploring the clinical implications of incomplete E2 suppression by GnRHa are needed to ensure optimal OFS treatment strategies are being employed for this population.

Abstract Objectives Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is extensively employed for the identification of filamentous fungi on MALDI Biotyper (Bruker Daltonics) and Vitek MS (biomerieux), but the performance of fungi identification on new EXS2600 (Zybio) is still unknow. Our study aims to evaluate the new EXS2600 system's (Zybio) ability to rapidly identify filamentous fungi and determine its effect on turnaround time (TAT) in our laboratory. Methods We tested 117 filamentous fungi using two pretreatment methods: the formic acid sandwich (FA-sandwich) and a commercial mold extraction kit (MEK, Zybio). All isolates were confirmed via sequence analysis. Laboratory data were extracted from our laboratory information system over two 9-month periods: pre-EXS (April to December 2022) and post-EXS (April to December 2023), respectively. Results The total correct identification (at the species, genus, or complex/group level) rate of fungi was high, FA-sandwich (95.73%, 112/117), followed by MEK (94.02%, 110/117). Excluding 6 isolates not in the database, species-level identification accuracy was 92.79% (103/111) for FA-sandwich and 91.89% (102/111) for MEK; genus-level accuracy was 97.29% (108/111) and 96.39% (107/111), respectively. Both methods attained a 100% correct identification rate for Aspergillus, Lichtheimia, Rhizopus Mucor and Talaromyces species, and were able to differentiate between Fusarium verticillioides and Fusarium proliferatum within the Fusarium fujikuroi species complex. Notably, high confidence was observed in the species-level identification of uncommon fungi such as Trichothecium roseum and Geotrichum candidum. The TAT for all positive cultures decreased from pre EXS2600 to post (108.379 VS 102.438, P

Objective: This study aimed to analyze the factors influencing artificial intelligence (AI) diagnostic system detection of pulmonary nodules on computed tomography (CT) scans, using a chest simulation phantom experiment with simulated lung nodules. Methods: A Toshiba (Canon) 64-slice spiral CT scanner was used. The phantom was scanned and images were reconstructed under varying scanning parameters (dose, reconstruction algorithm, and layer thickness) and non-scanning parameters (nodule size, density, and chest location). Subsequently, the AI diagnostic system performed pulmonary nodule detection on the images. Results: (1) No statistically significant difference was observed in the true positive rate of pulmonary nodules detected at different scanning doses. However, the low-dose mode produced a higher number of false positives. (2) Comparisons across the three iterative reconstruction algorithms revealed no statistically significant difference in the true positive rate of detected pulmonary nodules. However, the Strong group exhibited a higher true positive rate and a higher number of false positives. (3) The true positive rate of lung nodules detected in thin images was significantly higher than in thick images. (4) The true positive rate of pulmonary nodules located in the paramediastinum was significantly higher in the subpleural and lung parenchyma. (5) The true positive rate of nodules ≥8 mm was significantly higher than that of nodules ≤5 mm. (6) No statistically significant difference was observed in the true positive rate when detecting nodules with differing densities. Conclusion: Both CT scanning parameters (dose, reconstruction algorithm, and layer thickness) and non-scanning parameters (nodule size, density, and chest location) can influence the detection of pulmonary nodules by AI systems.

Abstract Lung cancer is the primary cause of cancer-related death worldwide, and its global incidence and mortality rates remain high. The differential expression of circular RNAs (circRNAs) can affect the development of cancer, but the mechanisms by which circRNAs regulate lung cancer progression remain unclear. In this study, we identified circSORBS1, a circRNA that has not been previously described in lung cancer and is significantly underexpressed in lung cancer tissues, blood and cell lines, and the low expression of circSORBS1 correlated with tumour grade and prognosis. In vitro and in vivo functional experiments revealed that circSORBS1 overexpression inhibited cell proliferation and migration while enhancing apoptosis. Mechanistically, circSORBS1 acts as a sponge for miR-6779-5p, indirectly inhibiting RUFY3 mRNA degradation. Simultaneously, it binds to RUFY3 mRNA to enhance its stability. This dual regulatory mechanism leads to an increase in RUFY3 protein levels, which ultimately activates the YWHAE/BAD/BCL2 apoptotic signalling pathway and suppresses lung cancer progression. Our findings not only increase the knowledge about the regulatory pattern of circRNA expression but also provide new insights into the mechanisms by which circRNAs regulate lung cancer development.

Abstract Objectives To explore the value of radiomic features derived from pericoronary adipose tissue (PCAT) obtained by coronary computed tomography angiography for prediction of coronary rapid plaque progression (RPP). Methods A total of 1233 patients from two centers were included in this multicenter retrospective study. The participants were divided into training, internal validation, and external validation cohorts. Conventional plaque characteristics and radiomic features of PCAT were extracted and analyzed. Random Forest was used to construct five models. Model 1: clinical model. Model 2: plaque characteristics model. Model 3: PCAT radiomics model. Model 4: clinical + radiomics model. Model 5: plaque characteristics + radiomics model. The evaluation of the models encompassed identification accuracy, calibration precision, and clinical applicability. Delong’ test was employed to compare the area under the curve (AUC) of different models. Results Seven radiomic features, including two shape features, three first-order features, and two textural features, were selected to build the PCAT radiomics model. In contrast to the clinical model and plaque characteristics model, the PCAT radiomics model (AUC 0.85 for training, 0.84 for internal validation, and 0.81 for external validation; p 0.05). Conclusion Radiomic feature analysis derived from PCAT significantly improves the prediction of RPP as compared to clinical and plaque characteristics. Radiomic analysis of PCAT may improve monitoring RPP over time. Critical relevance statement Our findings demonstrate PCAT radiomics model exhibited good performance in the prediction of RPP, with potential clinical value. Key Points Rapid plaque progression may be predictable with radiomics from pericoronary adipose tissue. Fibrous plaque volume, diameter stenosis, and fat attenuation index were identified as risk factors for predicting rapid plaque progression. Radiomics features of pericoronary adipose tissue can improve the predictive ability of rapid plaque progression. Graphical Abstract

With the impact of global climate change and the urbanization process, the risk of urban flooding has increased rapidly, especially in developing countries. Real-time monitoring and prediction of flooding extent and drainage system are the foundation of effective urban flood emergency management. Therefore, this paper presents a rapid nowcasting prediction method of urban flooding based on data-driven and real-time monitoring. The proposed method firstly adopts a small number of monitoring points to deduce the urban global real-time water level based on a machine learning algorithm. Then, a data-driven method is developed to achieve dynamic urban flooding nowcasting prediction with real-time monitoring data and high-accuracy precipitation prediction. The results show that the average MAE and RMSE of the urban flooding and conduit system in the deduction method for water level are 0.101 and 0.144, 0.124 and 0.162, respectively, while the flooding depth deduction is more stable compared to the conduit system by probabilistic statistical analysis. Moreover, the urban flooding nowcasting method can accurately predict the flooding depth, and the R2 are as high as 0.973 and 0.962 of testing. The urban flooding nowcasting prediction method provides technical support for emergency flood risk management. HIGHLIGHTS A rapid nowcasting prediction method of urban flood based on data-driven and real-time monitoring.; The deduction model accurately estimates the global water depth.; The proposed urban flooding nowcasting model was observed to outperform the traditional machine learning model to predict.;

IntroductionThe composition and subsets of skin cells continuously change in a dynamic manner. However, the specific microcosmic alterations of human photoaged skin, independent of chronologic aging, remain unclear and have been infrequently analyzed. This study aimed to evaluate the biological processes and mechanisms underlying cell-subgroup alterations in skin photoaging.MethodsWe utilized single-cell sequencing and biological analysis from a single case to investigate the effects of photoaging. Skin punch biopsies were taken from sun-exposed forearm skin and unexposed buttock skin from the same individual for comparative analysis.ResultsOur analysis identified 25 cell clusters and 12 skin cell types, revealing significant changes in unique gene expressions between the sun-exposed and unexposed skin samples. A comparison of cell numbers within each cluster revealed 9 dominant cell clusters in sun-exposed skin and 16 dominant cell clusters in unexposed skin. Enrichment analysis indicated that PD-L1 expression and the PD-1 checkpoint pathway were more prominent in sun-exposed skin, while MAPK, TNF-alpha, TGF-beta, and apoptosis pathways were more enriched in hair follicle cells of sun-exposed skin.DiscussionThis study reveals changes in cell components in photoaged skin from a single case and provides novel insights into cellular subpopulations and pathology during repeated UVA-induced skin damage. These findings enhance our understanding of the complex interplay between different cells in photoaged skin and offer potential targets for preventing human skin photoaging and UV-induced skin cancers.

ObjectiveThe objective of this study was to investigate the prevalence of overactive bladder (OAB) and its risk factors related to allergies among children in Northeastern China.MethodsA community survey on OAB was conducted in Northeast China from 1 April 2022 to 30 April 2022. The survey targeted children aged 5–14 years and utilized questionnaires. A total of 1,394 children were enrolled, and their parents were requested to fill out a questionnaire to provide basic information about the children. This encompassed details regarding the presence or absence of urgent urination unrelated to urinary tract infection, urinary tract infection, allergic rhinitis, asthma or cough variant asthma, atopic dermatitis, anaphylactic conjunctivitis, urticaria, constipation, and attention deficit hyperactivity disorder (ADHD). The prevalence of OAB was calculated. The chi-squared test was used to analyze OAB-related factors, which were subsequently included in the logistic regression model for multi-factor analysis.ResultsThe overall OAB prevalence was 10.7% (120 of 1,121), including 47 mild cases (39.2%), 71 moderate cases (59.1%), and 2 severe cases (1.7%). OAB prevalence decreased with age (p

The essence of fluid phase transition is the jump of physical properties distinctly induced by shock waves in the hard-sphere model. Due to the strong impact of the wave, the internal freedoms of molecules are stimulated, releasing tremendous energy that commonly triggers the phase transition. Conversely, typical thermal and dynamic jumps can be described by the Rankine–Hugoniot conditions based on the Euler equation. In the theoretical simulation, the initial density and rotational freedoms of molecules are directly regarded as the primary factors to affect processes of phase transition. However, the influence of vibrational freedom in molecules has not been discussed yet. As the increasing temperature can gradually excite the affection of vibrational freedom, it is unwise to assume that the temperature element is constant in the theory. What would be a suitable model that accurately reflects the relationship between temperature and affection from vibrational freedom? The non-limited model has been courageously attempted with the temperature range from T0 to 6T0 (T0 is unperturbed temperature). We have found that the vibrational freedom can have a great effect on properties during phase transition processes.

Abstract Our preliminary investigation has identified the potential of serum fucosylated extracellular vesicles (EVs) miR-4732-5p in the early diagnosis of lung adenocarcinoma (LUAD) by a fucose-captured strategy utilizing lentil lectin (LCA)-magnetic beads and subsequent screening of high throughput sequencing and validation of real-time quantitative polymerase chain reaction (RT-qPCR). Considering the relatively complicated procedure, expensive equipment, and stringent laboratory condition, we have constructed an electrochemical biosensor assay for the detection of miR-4732-5p. miR-4732-5p is extremely low in serum, down to the fM level, so it needs to be detected by highly sensitive electrochemical methods based on the Mg2+-dependent DNAzyme splitting nucleic acid lock (NAL) cycle and hybridization chain reaction (HCR) signal amplification. In this study, signal amplification is achieved through the dual amplification reactions using NAL cycle in combination with HCR. In addition, hybridized DNA strands bind to a large number of methylene blue (MB) molecules to enhance signaling. Based on the above strategy, we further enhance our signal amplification strategies to improve detection sensitivity and accuracy. The implementation of this assay proceeded as follows: initially, miR-4732-5p was combined with NAL, and then Mg2+-dependent DNAzyme splitted NAL to release auxiliary DNA (S1) strands, which were subsequently captured by the immobilized capture probe DNA (C1) strands on the electrode surface. Following this, abundant quantities of DNA1 (H1) and DNA2 (H2) tandems were generated by HCR, and S1 strands then hybridized with the H1 and H2 tandems through base complementary pairing. Finally, MB was bonded to the H1 and H2 tandems through π–π stacking interaction, leading to the generation of a signal current upon the detection of a potential capable of inducing a redox change of MB by the electrode. Furthermore, we evaluated the performance of our developed electrochemical biosensor assay. The results demonstrated that our assay is a reliable approach, characterized by its high sensitivity (with a detection limit of 2.6 × 10−17 M), excellent specificity, good accuracy, reproducibility, and stability. Additionally, it is cost-effective, requires simple operation, and is portable, making it suitable for the detection of serum fucosylated extracellular vesicles miR-4732-5p. Ultimately, this development has the potential to enhance the diagnostic efficiency for patients with early-stage LUAD.

Abstract The emergence of magnetic transition metal dichalcogenides has significantly advanced the development of valleytronics due to the spontaneous breaking of time-reversal symmetry and space-inversion symmetry. However, the lack of regulation methods has prevented researchers from exploring their potential applications. Herein, we propose to use strain engineering to control the spin-valley coupling in the sliding ferroelectric bilayer 2H-VX2 (X = S, Se, Te). Four multiferroic states are constructed by combining the sliding ferroelectricity and antiferromagnetism in the R-stacking bilayer VX2, where the spin and valley polarizations are coupled together from the layer-dependent spin-polarized band structures. By applying a small external strain or pressure on the out-of-plane van der Waals direction, we predicted that there is an antiferromagnetic to magnetic transition in the bilayer VX2, leading to the interesting spin-polarized and chiral circularly polarized radiation at K+ and K- valleys, similar to those found in the magnetic monolayer. To comprehend the coupling between various degrees of freedom in these multiferroic systems, we have developed an effective k·p model. This model unveils a linear relationship between the electric polarization generated by interlayer sliding and the energy difference of the valence band maximum at K+ and K- valleys. Thus, providing an alternate method to measure the electric polarization in the sliding ferroelectrics. Based on the strong coupling between the strain, spin-valley, and electric polarization, it is likely to use the strain to control the interesting emerging properties of 2H-VX2 such as the anomalous valley Hall effect.

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is on the rise globally, and past research suggests a significant association with various blood cell components. Our goal is to explore the potential correlation between whole blood cell indices and NAFLD risk using Mendelian randomization (MR). Methods We analyzed data from 4,198 participants in the 2017–2018 National Health and Nutrition Examination Survey to investigate the link between blood cell indicators and NAFLD. Using various methods like weighted quantile sum and multivariate logistic regression, we assessed the association. Additionally, two-sample Mendelian randomization were employed to infer causality for 36 blood cell indicators and NAFLD. Results Multivariate logistic regression identified 10 NAFLD risk factors. Weighted quantile sum revealed a positive correlation (p = 6.03e-07) between total blood cell indices and NAFLD, with hemoglobin and lymphocyte counts as key contributors. Restricted cubic spline analysis found five indicators with significant nonlinear correlations to NAFLD. Mendelian randomization showed a notable association between reticulocyte counts and NAFLD using the inverse-variance weighted method. Conclusions Hematological markers pose an independent NAFLD risk, with a positive causal link found for reticulocyte count. These results emphasize the importance of monitoring NAFLD and investigating specific underlying mechanisms further.

Abstract Background Aberrant fucosylation observed in cancer cells contributes to an augmented release of fucosylated exosomes into the bloodstream, where miRNAs including miR-4732-3p hold promise as potential tumor biomarkers in our pilot study. However, the mechanisms underlying the sorting of miR-4732-3p into fucosylated exosomes during lung cancer progression remain poorly understood. Methods A fucose-captured strategy based on lentil lectin-magnetic beads was utilized to isolate fucosylated exosomes and evaluate the efficiency for capturing tumor-derived exosomes using nanoparticle tracking analysis (NTA). Fluorescence in situ hybridization (FISH) and qRT-PCR were performed to determine the levels of miR-4732-3p in non-small cell lung cancer (NSCLC) tissue samples. A co-culture system was established to assess the release of miRNA via exosomes from NSCLC cells. RNA immunoprecipitation (RIP) and miRNA pull-down were applied to validate the interaction between miR-4732-3p and heterogeneous nuclear ribonucleoprotein K (hnRNPK) protein. Cell functional assays, cell derived xenograft, dual-luciferase reporter experiments, and western blot were applied to examine the effects of miR-4732-3p on MFSD12 and its downstream signaling pathways, and the impact of hnRNPK in NSCLC. Results We enriched exosomes derived from NSCLC cells using the fucose-captured strategy and detected a significant upregulation of miR-4732-3p in fucosylated exosomes present in the serum, while its expression declined in NSCLC tissues. miR-4732-3p functioned as a tumor suppressor in NSCLC by targeting 3'UTR of MFSD12, thereby inhibiting AKT/p21 signaling pathway to induce cell cycle arrest in G2/M phase. NSCLC cells preferentially released miR-4732-3p via exosomes instead of retaining them intracellularly, which was facilitated by the interaction of miR-4732-3p with hnRNPK protein for selective sorting into fucosylated exosomes. Moreover, knockdown of hnRNPK suppressed NSCLC cell proliferation, with the elevated levels of miR-4732-3p in NSCLC tissues but the decreased expression in serum fucosylated exosomes. Conclusions NSCLC cells escape suppressive effects of miR-4732-3p through hnRNPK-mediated sorting of them into fucosylated exosomes, thus supporting cell malignant properties and promoting NSCLC progression. Our study provides a promising biomarker for NSCLC and opens a novel avenue for NSCLC therapy by targeting hnRNPK to prevent the "exosome escape" of tumor-suppressive miR-4732-3p from NSCLC cells.

Abstract Background Sepsis and acute kidney injury (AKI) are common severe diseases in the intensive care unit (ICU). This study aimed to estimate the attributable mortality of AKI among critically ill patients with sepsis and to assess whether AKI was an independent risk factor for 30-day mortality. Methods The information we used was derived from a multicenter prospective cohort study conducted in 18 Chinese ICUs, focusing on septic patients post ICU admission. The patients were categorized into two groups: those who developed AKI (AKI group) within seven days following a sepsis diagnosis and those who did not develop AKI (non-AKI group). Using propensity score matching (PSM), patients were matched 1:1 as AKI and non-AKI groups. We then calculated the mortality rate attributable to AKI in septic patients. Furthermore, a survival analysis was conducted comparing the matched AKI and non-AKI septic patients. The primary outcome of interest was the 30-day mortality rate following the diagnosis of sepsis. Results Out of the 2175 eligible septic patients, 61.7% developed AKI. After the application of PSM, a total of 784 septic patients who developed AKI were matched in a 1:1 ratio with 784 septic patients who did not develop AKI. The overall 30-day attributable mortality of AKI was 6.6% (95% CI 2.3 ∼ 10.9%, p = 0.002). A subgroup analysis revealed that the 30-day attributable mortality rates for stage 1, stage 2, and stage 3 AKI were 0.6% (95% CI −5.9 ∼ 7.2%, p = 0.846), 4.7% (95% CI −3.1 ∼ 12.4%, p = 0.221) and 16.8% (95% CI 8.1 ∼ 25.2%, p

Abstract The chemical transformations of methane (CH4) and carbon dioxide (CO2) greenhouse gases typically have high energy barriers. Here we present an approach of strategic coupling of CH4 oxidation and CO2 reduction in a switched microbial process governed by redox cycling of iron minerals under temperate conditions. The presence of iron minerals leads to an obvious enhancement of carbon fixation, with the minerals acting as the electron acceptor for CH4 oxidation and the electron donor for CO2 reduction, facilitated by changes in the mineral structure. The electron flow between the two functionally active microbial consortia is tracked through electrochemistry, and the energy metabolism in these consortia is predicted at the genetic level. This study offers a promising strategy for the removal of CH4 and CO2 in the natural environment and proposes an engineering technique for the utilization of major greenhouse gases.

Abstract Adoptive immunotherapy in the T cell landscape exhibits efficacy in cancer treatment. Over the past few decades, genetically modified T cells, particularly chimeric antigen receptor T cells, have enabled remarkable strides in the treatment of hematological malignancies. Besides, extensive exploration of multiple antigens for the treatment of solid tumors has led to clinical interest in the potential of T cells expressing the engineered T cell receptor (TCR). TCR-T cells possess the capacity to recognize intracellular antigen families and maintain the intrinsic properties of TCRs in terms of affinity to target epitopes and signal transduction. Recent research has provided critical insight into their capability and therapeutic targets for multiple refractory solid tumors, but also exposes some challenges for durable efficacy. In this review, we describe the screening and identification of available tumor antigens, and the acquisition and optimization of TCRs for TCR-T cell therapy. Furthermore, we summarize the complete flow from laboratory to clinical applications of TCR-T cells. Last, we emerge future prospects for improving therapeutic efficacy in cancer world with combination therapies or TCR-T derived products. In conclusion, this review depicts our current understanding of TCR-T cell therapy in solid neoplasms, and provides new perspectives for expanding its clinical applications and improving therapeutic efficacy.

Abstract Enhancement of wakefulness is a prerequisite for adaptive behaviors to cope with acute stress, but hyperarousal is associated with impaired behavioral performance. Although the neural circuitries promoting wakefulness in acute stress conditions have been extensively identified, less is known about the circuit mechanisms constraining wakefulness to prevent hyperarousal. Here, we found that chemogenetic or optogenetic activation of GAD2-positive GABAergic neurons in the midbrain dorsal raphe nucleus (DRNGAD2) decreased wakefulness, while inhibition or ablation of these neurons produced an increase in wakefulness along with hyperactivity. Surprisingly, DRNGAD2 neurons were paradoxically wakefulness-active and were further activated by acute stress. Bidirectional manipulations revealed that DRNGAD2 neurons constrained the increase of wakefulness and arousal level in a mouse model of stress. Circuit-specific investigations demonstrated that DRNGAD2 neurons constrained wakefulness via inhibition of the wakefulness-promoting paraventricular thalamus. Therefore, the present study identified a wakefulness-constraining role DRNGAD2 neurons in acute stress conditions.

Abstract Background Both sepsis and acute respiratory distress syndrome (ARDS) are common severe diseases in the intensive care unit (ICU). There is no large-scale multicenter study to clarify the attributable mortality of ARDS among septic patients. This study aimed to evaluate the excess mortality of ARDS in critically ill patients with sepsis. Methods The data were obtained from a multicenter, prospective cohort study in 18 Chinese ICUs between January 2014 and August 2015. The study population was septic patients after ICU admission. The patients were categorized into two groups: those who developed ARDS (ARDS group) within seven days following a sepsis diagnosis and those who did not develop ARDS (non-ARDS group). Applying propensity score matching (PSM), patients were matched 1:1 as ARDS and non-ARDS groups. Mortality attributed to ARDS was calculated. Subsequently, we conducted a survival analysis to estimate the impact of ARDS on mortality. The primary endpoint was 30-day mortality after sepsis diagnosis. Results 2323 septic patients were eligible, 67.8% developed ARDS. After PSM, 737 patients with ARDS were matched 1:1 with 737 non-ARDS patients. ARDS’s overall 30-day attributable mortality was 11.9% (95% CI 7.5–16.3%, p

Background: Anhedonia is a deficit of dynamic reward process, and a large proportion of schizophrenia patients continue to experience anhedonia even during the stable phase. However, few studies have examined the multiple aspects of performance in reward processing in patients with stable schizophrenia and evidence suggests that physical and cognitive effort may involve different neural mechanisms. Methods: Parallel measures of effort-based expenditure for reward tasks (EEfRT) and self-report questionnaires of pleasure were applied in 61 patients with stable schizophrenia (SSZ) and 46 healthy controls (HCs), and percentages of hard task choices (HTC%) were used to assess motivation in reward processing. Negative symptoms, neurocognitive and social function were evaluated in SSZ patients, and associations with performance in reward tasks were explored. Results: SSZ patients reported more severe consummatory and anticipatory anhedonia and social anhedonia. HTC% in reward tasks of SSZ patients were significantly lower than that of HCs, especially in cognitive-effort tasks. HTC% in cognitive tasks were correlated with motivation and pleasure dimension of negative symptoms, whereas HTC% in physical tasks were associated with expression dimension. Anticipatory anhedonia and negative symptoms were correlated with Personal and Social Performance Scale (PSP) scores. Conclusion: Patients with stable schizophrenia have social anhedonia, physically consummatory and anticipatory anhedonia and reduced reward motivation. They are less willing to make cognitive effort than physical effort for reward. The different associations of physical and cognitive effort with negative symptoms indicate physical and cognitive effort may represent disparate neuropsychological processes. Anticipatory anhedonia is closely related to social functioning.

Abstract Two‐dimensional (2D) materials with free of dangling bonds have the potential to serve as ideal channel materials for the next generation of field‐effect transistors (FETs) due to their atomic‐thin and excellent electronic properties. However, the performance of 2D materials‐based FETs is still dictated by the interface between electrodes/dielectrics and 2D materials. Several technical challenges such as improving device stability, reducing contact resistance, and advancing mobility need to be overcome. Herein, we focus on the effects of atomic‐scale interface engineering on the contact resistance and dielectric layer for 2D FETs. Universal strategies we consider to achieve ohmic contact and develop high‐quality, defect‐free dielectric layers are provided. Furthermore, advancing the performance of 2D materials‐based FETs and binding to silicon substrates are briefly analyzed.

BackgroundLEOPARD syndrome (LS) is a rare genetic disorder presenting various clinical manifestations from childhood, complicating its diagnosis. In this study, we aim to refine the imaging presentation of LS and emphasize the importance of multimodality imaging in enhancing diagnostic accuracy and preventing serious cardiovascular events.CaseA 41-year-old woman was admitted to hospital with a suspected apical tumor detected by a transthoracic echocardiogram (TTE), which was later identified as apical myocardial hypertrophy through cardiac magnetic resonance imaging (CMR). She had abnormal electrocardiograms from the age of 2 years and freckles around the age of 4 years. In recent years, she has been experiencing exertional dyspnea. Supplemental coronary computer tomography angiography (CCTA) revealed diffuse coronary dilatation. Both multimodality imaging and clinical manifestations led to a suspicion of LS, which was confirmed by subsequent genetic testing. The patient declined further treatment. A 3-month follow-up CMR showed no significant change in the lesion.ConclusionThis report elucidates the diagnostic transition from an initial suspicion of an apical tumor by TTE to a definitive diagnosis of left ventricular apical hypertrophy by CMR in a 41-year-old woman with LS. It underscores the value of multimodality imaging (TTE, CCTA, CMR) in unraveling unusual cardiac manifestations in rare genetic disorders such as LS.

With the popularization of electronic products, visual fatigue is inevitably frequent. The causes of visual fatigue are varied, but from the perspective of physiological mechanisms, it is mainly closely related to retinal function or structural damage, especially the light source from various mobile devices and office equipments nowadays, which induces oxidative stress damage in the retina and exacerbates the degree of visual fatigue, resulting in the inability to use the eyes for a long period of time, pain in the eyes and periorbital area, blurred vision, dry eyes, tearing, and other discomforts. Food ingredients derived from natural plants have greater application in relieving visual fatigue. Therefore, this paper presents a detailed compilation of six plants that are widely used for their visual fatigue-relieving function, in the hope of providing more raw material choices for the development of products with visual fatigue-relieving functions in the future.

Purpose Compared with older women diagnosed with breast cancer, younger women are more likely to die of breast cancer and more likely to suffer psychosocially in both the short-term and long term. The Young Women’s Breast Cancer Study (YWS) is a multisite prospective cohort study established to address gaps in our knowledge about this vulnerable and understudied population.Participants The YWS enrolled 1302 women newly diagnosed with stages 0–IV breast cancer at age 40 years or younger at 13 academic and community sites in North America between 2006 and 2016. Longitudinal patient-reported outcome data are complemented by clinical data abstraction and biospecimen collection at multiple timepoints.Findings to date Key findings related to fertility include that nearly 40% of participants were interested in pregnancy following diagnosis; of those who reported interest, 10% pursued fertility preservation. Overall, approximately 10% of YWS participants became pregnant in the first 5 years after diagnosis; follow-up is ongoing for pregnancies after 5 years. Studies focused on psychosocial outcomes have characterised quality of life, post-traumatic stress and fear of recurrence, with findings detailing the factors associated with the substantial psychosocial burden many young women face during and following active treatment. Multiple studies have leveraged YWS biospecimens, including whole-exome sequencing of tumour analyses that revealed that select somatic alterations occur at different frequencies in young (age≤35) versus older women with luminal A breast cancer, and a study that explored clonal hematopoiesis of indeterminate potential found it to be rare in young survivors.Future plans With a median follow-up of approximately 10 years, the cohort is just maturing for many relevant long-term outcomes and provides outstanding opportunities to further study and build collaborations to address gaps in our knowledge, with the ultimate objective to improve care and outcomes for young women with breast cancer.Trial registration number NCT01468246.

BackgroundMetachronous second primary lung cancer (MSPLC) is not that rare but is seldom studied. ObjectiveWe aim to compare real-world survival outcomes between different surgery strategies and radiotherapy for MSPLC. MethodsThis retrospective study analyzed data collected from patients with MSPLC between 1988 and 2012 in the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) analyses and machine learning were performed to compare variables between patients with MSPLC. Survival curves were plotted using the Kaplan-Meier method and were compared using log-rank tests. ResultsA total of 2451 MSPLC patients were categorized into the following treatment groups: 864 (35.3%) received radiotherapy, 759 (31%) underwent surgery, 89 (3.6%) had surgery plus radiotherapy, and 739 (30.2%) had neither treatment. After PSM, 470 pairs each for radiotherapy and surgery were generated. The surgery group had significantly better survival than the radiotherapy group (P

A plethora of studies have indicated that protein or peptides derived from food sources possess potential anti-inflammatory activity. In our previous research, we discovered peptides from silkworm pupae (Bombyx mori) exhibited promising anti-inflammatory effects in mice. However, the anti-inflammatory activity of silkworm pupae protein peptides (SPP) has yet to be validated at the cellular level, and its underlying anti-inflammatory mechanisms remain unclear. Therefore, the aim of this study was to explore the anti-inflammatory potential of SPP in lipopolysaccharide (LPS)-induced RAW264.7 inflammation model. Our research findings demonstrated that SPP significantly reduced LPS-induced inflammation in RAW264.7 cells in a dose-dependent manner, including decreased levels of inflammatory mediators (NO, MCP-1, and PEG2) and cytokines (TNF-α, IL-6, and IL-1β). Furthermore, we observed significant downregulation of mRNA and protein expression of iNOS and COX-2 by SPP (p

Abstract Cysteine protease inhibitor 1 (CST1) is a cystatin superfamily protein that inhibits cysteine protease activity and is reported to be involved in the development of many malignancies. Mitochondrial oxidative phosphorylation (OXPHOS) also plays an important role in cancer cell growth regulation. However, the relationship and roles of CST1 and OXPHOS in esophageal squamous cell carcinoma (ESCC) remains unclear. In our pilot study, CST1 was shown the potential of promoting ESCC migration and invasion by the activation of MEK/ERK pathway. Transcriptome sequencing analysis revealed that CST1 is closely associated with OXPHOS. Based on a real-time ATP rate assay, mitochondrial complex I enzyme activity assay, immunofluorescence, co-immunoprecipitation, and addition of the OXPHOS inhibitor Rotenone and MEK/ERK inhibitor PD98059, we determined that CST1 affects mitochondrial complex I enzyme activity by interacting with the GRIM19 protein to elevate OXPHOS levels, and a reciprocal regulatory relationship exists between OXPHOS and the MEK/ERK pathway in ESCC cells. Finally, an in vivo study demonstrated the potential of CST1 in ESCC metastasis through regulation of the OXPHOS and MEK/ERK pathways. This study is the first to reveal the oncogenic role of CST1 in ESCC development by enhancing mitochondrial respiratory chain complex I activity to activate the OXPHOS/MEK/ERK axis, and then promote ESCC metastasis, suggesting that CST1/OXPHOS is a promising target for ESCC treatment.

Abstract Background Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphologic features, and PCOS is associated with infertility. PH domain Leucine-rich repeat Protein Phosphatase 1 (PHLPP1) has been shown to regulate AKT. The aim of present study is to investigate the role of PHLPP1 in PCOS. Methods The expression levels of PHLPP1 in dihydrotestosterone (DHT)-treated human ovarian granular KGN cells were determined by qRT-PCR and Western blot. PHLPP1 was silenced or overexpressed using lentivirus. Cell proliferation was detected by CCK-8. Apoptosis and ROS generation were analyzed by flow cytometry. Glycolysis was analyzed by measuring extracellular acidification rate (ECAR). Results DHT treatment suppressed proliferation, promoted apoptosis, enhanced ROS, and inhibited glycolysis in KGN cells. PHLPP1 silencing alleviated the DHT-induced suppression of proliferation and glycolysis, and promotion of apoptosis and ROS in KGN cells. PHLPP1 regulated cell proliferation and glycolysis in human KGN cells via the AKT signaling pathway. Conclusions Our results showed that PHLPP1 mediates the proliferation and aerobic glycolysis activity of human ovarian granular cells through regulating AKT signaling.

Abstract Lysosomes is a well-recognized oncogenic driver and chemoresistance across variable cancer types, and has been associated with tumor invasiveness, metastasis, and poor prognosis. However, the significance of lysosomes in hepatocellular carcinoma (HCC) is not well understood. Lysosomes-related genes (LRGs) were downloaded from Genome Enrichment Analysis (GSEA) databases. Lysosome-related risk score (LRRS), including eight LRGs, was constructed via expression difference analysis (DEGs), univariate and LASSO-penalized Cox regression algorithm based on the TCGA cohort, while the ICGC cohort was obtained for signature validation. Based on GSE149614 Single-cell RNA sequencing data, model gene expression and liver tumor niche were further analyzed. Moreover, the functional enrichments, tumor microenvironment (TME), and genomic variation landscape between LRRSlow/LRRShigh subgroup were systematically investigated. A total of 15 Lysosomes-related differentially expressed genes (DELRGs) in HCC were detected, and then 10 prognosis DELRGs were screened out. Finally, the 8 optimal DELRGs (CLN3, GBA, CTSA, BSG, APLN, SORT1, ANXA2, and LAPTM4B) were selected to construct the LRRS prognosis signature of HCC. LRRS was considered as an independent prognostic factor and was associated with advanced clinicopathological features. LRRS also proved to be a potential marker for HCC diagnosis, especially for early-stage HCC. Then, a nomogram integrating the LRRS and clinical parameters was set up displaying great prognostic predictive performance. Moreover, patients with high LRRS showed higher tumor stemness, higher heterogeneity, and higher genomic alteration status than those in the low LRRS group and enriched in metabolism-related pathways, suggesting its underlying role in the progression and development of liver cancer. Meanwhile, the LRRS can affect the proportion of immunosuppressive cell infiltration, making it a vital immunosuppressive factor in the tumor microenvironment. Additionally, HCC patients with low LRRS were more sensitive to immunotherapy, while patients in the high LRRS group responded better to chemotherapy. Upon single-cell RNA sequencing, CLN3, GBA, and LAPTM4B were found to be specially expressed in hepatocytes, where they promoted cell progression. Finally, RT-qPCR and external datasets confirmed the mRNA expression levels of model genes. This study provided a direct links between LRRS signature and clinical characteristics, tumor microenvironment, and clinical drug-response, highlighting the critical role of lysosome in the development and treatment resistance of liver cancer, providing valuable insights into the prognosis prediction and treatment response of HCC, thereby providing valuable insights into prognostic prediction, early diagnosis, and therapeutic response of HCC.

Objective To evaluate the therapeutic efficacy of a combination of compound middle-layer acid and 30% supramolecular salicylic acid for melasma. Methods Five female patients with melasma who were admitted to our hospital from May 2022 to December 2022 were enrolled in this study. A self-parallel controlled study was carried out. The patients' treated side was treated with compound middle-layer acid while the control side was treated with 30% supramolecular salicylic acid at weeks 0 and 4. On week 8, the treated side and control side were treated with 30% supramolecular salicylic acid and compound middle-layer acid, respectively. We compared the area score of facial lesions, skin color, sebum, water content and the severity of melasma-related psychological stress between the two sides. Results The combination therapy significantly decreased the area scores on the forehead, cheek and chin (P0.10). Moreover, the combination therapy decreased both SAS (from 21.62±5.99 to 20.86±6.44, P

In recent years, the mechanisms of repeated ultraviolet light (UV) radiation-induced spatial and temporal changes in the immune microenvironment and the imbalance are the hot research topic in the fields of skin, immunity, tumor and aging. Chronic UV radiation (UVR) can induce cellular phenotypic and functional changes in the skin microenvironment, and directly and indirectly alter the skin immune microenvironment. UVR induces immunosuppression, including activation of regulatory T cells and alterations in the number and function of antigen-presenting cells. The interactions among B cells, T cells, Langerhans cells and mast cells play an important role in UVR-induced immunosuppression. In addition, the effects of UVR on T cell co-inhibitory and co-stimulatory signals have been increasingly appreciated. In this paper, we review the recent progress in the imbalance of the immune microenvironment in the chronically photodamaged skin.

Background: Some COVID-19 patients deteriorate to severe cases with relatively higher case-fatality rates, which increases the medical burden. This necessitates identification of patients at risk of severe disease. Early assessment plays a crucial role in identifying patients at risk of severe disease. This study is to assess the effectiveness of SUPER score as a predictor of severe COVID-19 cases. Methods: We consecutively enrolled COVID-19 patients admitted to a comprehensive medical center in Wuhan, China, and recorded clinical characteristics and laboratory indexes. The SUPER score was calculated using parameters including oxygen saturation, urine volume, pulse, emotional state, and respiratory rate. In addition, the area under the receiver operating characteristic curve (AUC), specificity, and sensitivity of the SUPER score for the diagnosis of severe COVID-19 were calculated and compared with the National Early Warning Score 2 (NEWS2). Results: The SUPER score at admission, with a threshold of 4, exhibited good predictive performance for early identification of severe COVID-19 cases, yielding an AUC of 0.985 (95% confidence interval [CI] 0.897–1.000), sensitivity of 1.00 (95% CI 0.715–1.000), and specificity of 0.92 (95% CI 0.775–0.982), similar to NEWS2 (AUC 0.984; 95% CI 0.895–1.000, sensitivity 0.91; 95% CI 0.587–0.998, specificity 0.97; 95% CI 0.858–0.999). Compared with patients with a SUPER score

Abstract Background Patients’ attitudes toward medication have been shown to be a predictor of nonadherence to antipsychotic treatment. However, most previous studies that explored this relationship used a cross-sectional design. It is important to explore the association of attitudes toward drugs with discontinuation at different time points during antipsychotic treatment. In this study, we investigated the association of attitudes toward drugs (measured by the Drug Attitude Inventory (DAI-10)) with adherence at seven time points (baseline, 4 weeks, 8 weeks, 12 weeks, 26 weeks, 39 weeks, and 52 weeks) during 1 year of treatment. Factors that were potentially associated with attitudes toward drugs at the time point of interest were also studied. Methods Demographic characteristics, psychopathology, social functioning, and attitudes toward drugs (measured by the DAI-10) were collected at baseline, 4 weeks, 8 weeks, 12 weeks, 26 weeks, 39 weeks and 52 weeks. The association of attitudes toward drugs (measured by DAI-10) with adherence at the seven time points was calculated using the Mann‒Whitney U test. The optimal cutoff point for the DAI-10 was then determined using receiver operating characteristic (ROC) analysis. Cox regression analysis was conducted to further investigate the association of DAI-10 scores with discontinuation, controlling for potential confounding variables. We used multiple regression analysis to identify the factors associated with DAI-10 scores. Results Among the six time points, only baseline DAI-10 total scores were significantly different between the completed and discontinued groups (p = 0.004). Female sex and a baseline DAI-10 total score greater than − 1 were found to be independent protective factors against discontinuation of antipsychotic drug treatments during the 1-year follow-up. At baseline, the severity of the disease (CGI-s) and insight regarding the disease were shown to be associated with DAI-10 total scores. Conclusion Attitudes toward antipsychotic drugs at baseline were shown to play a crucial role in predicting treatment discontinuation. Trial registration The data were collected from a clinical trial and the clinical trials.gov ID of the study is NCT01057849.

ABSTRACTIn order to find a green and safe solution as the base solution for the quantitative detection of glucose, the neutral solution Na2S2O3 was selected as the base solution. A three-electrode electrochemical system was designed. In this system, the working electrode was copper sheet, the counter electrode was platinum electrode, and the reference electrode was saturated KCl calomel solution electrode. Cyclic voltammetry (CV) and chronoamperometry(i-t) methods were used for the experiment. CV scanning results showed that glucose could produce the oxidation-reduction reaction on the surface of the copper electrode, and the parameters of i-t were adjusted. According to the results of i-t scanning, the quantitative detection model of glucose was established. The model was [Formula: see text]. The regression parameter R2 was 0.99672. Glucose was tested with different base solutions. Results showed that Na2S2O3 solution was a good base solution. The i-t control experiments showed that the proposed method were effective in Na2S2O3 solution.

ABSTRACT: Objectives: To investigate the gene mutations associated with ceftriaxone (CRO) resistance among gonococcal isolates, and to determine the effects of the mutated genes on CRO minimum inhibitory concentrations (MICs) with transformation assays and antisense peptide nucleic acids (asPNAs). Methods: Ceftriaxone-resistant (CROR) and ceftriaxone-susceptible (CROS) isolates were identified using EUCAST and paired according to similarity in their MICs to other antimicrobials. The two groups of gonococci were sequenced and analysed. Mutated genes that showed a statistical difference between the two groups were transformed into gonococcal reference strains to determine their functions. AsPNAs were designed and transformed into the former transformant to further confirm the effects of the mutated genes. Results: Twenty-two paired CROR and CROS isolates were obtained. The incidence of the penA-A501T and penA-G542S mutations individually, as well as combined mutations (penA-A501T and ftsX-R251H, penA-G542S and ftsX R251H), was statistically different between the two groups. The MIC of ATCC43069 (A43) increased 2 times following transformation with penA-A501T, and the MICs of A43 and ATCC49226 (A49) increased 32 times and 2 times following transformation with penA-A501T and ftsX-R251H, respectively. Antisense PNA-P3 reduced the MIC of the A43 transformant most significantly when transformed individually. PNA-P3 and PNA-F1 (asPNAs of the penA and ftsX) restored CRO susceptibility. Conclusions: PenA-A501T and penA-G542S mutations are important in CRO resistance among gonococci isolates. The ftsX-R251H mutation is also related to CRO resistance, and combined mutations of ftsX-R251H and penA-A501T comediate a significant reduction in CRO susceptibility. The combined application of PNA-P3 and PNA-F1 could effectively reverse the resistance to CRO in N. gonorrhoeae.

ABSTRACTThe migrasomes formation is mediated by the assembly of micron-scale tetraspanin macrodomains and the recruitment of tetraspanin 4 (TSPAN4). However, the physiological functions of TSPAN4 on migrasomes are less known. The TSPAN4 expression in macrophages in single-cell sequencing data, GEO datasets and TCGA database were determined. TSPAN4 expression was highly associated with atherosclerosis regression-related macrophages, intraplaque hemorrhage and ruptured plaques. TSPAN4 expression was upregulated in spontaneous MI and inducible MI mice model. Besides, TSPAN4 expression was highly correlated with tumor-associated macrophages. The study provided a critical role of TSPAN4 aberrant expression in the progression of atherosclerosis and pan-cancer, and the intervention of TSPAN4 and migrasomes may save dying patients’ lives and improve their prognosis.

Thermal errors affect machining accuracy in high-speed precision machining. The variability of machine tool operating conditions poses a challenge to the modeling of thermal errors. In this paper, a thermal error model based on transfer temperature feature fusion is proposed. Firstly, the temperature information fusion features are built as inputs to the model, which is based on a self-attention mechanism to assign weights to the temperature information and fuse the features. Secondly, an improved direct normalization-based adaptive matrix approach is proposed, updating the background matrix using an autoencoder and reconstructing the adaptive matrix to realize domain self-adaptation. In addition, for the improved adaptive matrix, a criterion for determining whether the working conditions are transferrable to each other is proposed. The proposed method shows high prediction accuracy while ensuring training efficiency. Finally, thermal error experiments are performed on a VCM850 CNC machine tool.

Chrysanthemums and wild chrysanthemums are herbs with high application value. As edible plants of the Asteraceae family, they have good antioxidant, anti-inflammatory and hepatoprotective properties. Chrysanthemums and wild chrysanthemums contain a wide variety of volatile organic compounds, and these volatile components are the main factors contributing to the flavor differences. Therefore, in this study, we investigated the volatile components of holland chrysanthemum from Bozhou, Anhui Province, Chu-chrysanthemum from Chuzhou, Anhui Province, Gong-chrysanthemums from Huangshan, Anhui Province, Huai-chrysanthemums from Jiaozuo, Henan Province, Hang-chrysanthemum from Hangzhou, Zhejiang Province, and wild chrysanthemum from Dabie Mountain by headspace–gas chromatography–ion mobility spectrometry (HS-GC-IMS) coupled with principal component analysis (PCA). The results showed that Chrysanthemum and wild chrysanthemum contain alcohols, esters, hydrocarbons, ketones, aldehydes, acids, camphor, pyrazines and furans. Among them, alcohols, esters and hydrocarbons accounted for more than 15%. It was hypothesized that 2-methyl-1-propanol, 2-methylbutanol, 1-hexanol in alcohols and hexyl acetate, 3-methylbutyl acetate and ethyl 2-methylpropanoate in esters might be the main reasons for the alcoholic and sweet flavors of chrysanthemum and chrysanthemum officinale. Based on the principal component analysis, cluster analysis with the Euclidean distance and similarity analysis of fingerprints, it was found that there were significant differences in the volatile components in chrysanthemums from different origins, among which the differences between Chu-chrysanthemum and Hang-chrysanthemum were the most significant. In addition, as a genus of wild chrysanthemum with the same species, it contains a richer variety of volatile organic compounds, and the content of hydrocarbons and alcohols is significantly higher than that of chrysanthemum.

Alpha-fetoprotein (AFP) serves as a crucial diagnostic marker for primary hepatocellular carcinoma (HCC) and germ cell tumors (GCTs), with rare instances of significantly elevated levels in other diseases. In this study, we present a case of an elderly patient who was diagnosed with AFP-producing gastric cancer (AFPGC) following an elevated AFP result during physical examination. In investigating liver cancer at an early stage, the diagnosis was missed because of failure in detecting the lesion, resulting in delayed treatment initiation. AFPGC is a rare aggressive tumor that demands heightened awareness among clinicians to foster early detection, diagnosis, and treatment for improved prognosis.

Abstract BiFeO3 is a rare single‐phase multiferroic which shows coupled ferroelectricity, ferroelasticity and antiferromagnetism at room temperature. Many fantastic properties of BiFeO3 are regulated by its domain structure. While (001) rhombohedral BiFeO3 thin films can possibly develop up‐to eight degenerate states of two‐variant 71° ferroelastic domain stripes, complete selective control of all possible switching paths between these states has not yet been achieved. Here, combining phase field simulations and scanning probe microscopy experiments, we demonstrated such a complete selective control. The tip bias and the built‐in field were shown to affect the volume fraction of the 71°, 109° and 180° switched domains in rhombohedral BiFeO3 thin films under single‐point loading. Meanwhile, tip scanning further broke the symmetry of the nucleated domains, leading to different switched domain patterns. We then grew BiFeO3 thin films with a specific two‐variant 71° ferroelastic domain state and showed that such a state could be deterministically switched into the other seven two‐variant domain states by collaborative controlling tip scanning and tip bias in scanning probe microscopy experiments. These results should deepen our current understanding on the domain switching kinetics in BiFeO3 thin films and indicate they are promising platforms for developing configurable electronic and spintronic devices.

Summary: Allergic asthma is a chronic non-communicable disease characterized by lung tissue inflammation. Current treatments can alleviate the clinical symptoms to some extent, but there is still no cure. Recently, the transplantation of mesenchymal stem cells (MSCs) has emerged as a potential approach for treating allergic asthma. Gingival-derived mesenchymal stem cells (GMSCs), a type of MSC recently studied, have shown significant therapeutic effects in various experimental models of autoimmune diseases. However, their application in allergic diseases has yet to be fully elucidated. In this study, using an OVA-induced allergic asthma model, we demonstrated that GMSCs decrease CD11b+CD11c+ proinflammatory dendritic cells (DCs), reduce Th2 cells differentiation, and thus effectively diminish eosinophils infiltration. We also identified that the core functional factor, hepatocyte growth factor (HGF) secreted by GMSCs, mediated its effects in relieving airway inflammation. Taken together, our findings indicate GMSCs as a potential therapy for allergic asthma and other related diseases.

The properties of fluid phase transition can be distinctly induced by shock-waves in the hard-sphere model. Typical thermal and dynamic characteristics of the fluid have been described by conditions in the Rankine–Hugoniot (RH) theory based on Euler equations. Due to the strong impact from shock-waves, states of excitation or even phase transition can be detected. However, various factors can influence the jump in the fluid, such as degrees of freedom in molecules. The simple hard-sphere model typically assumes three degrees, neglecting internal freedoms of particles. However, the effect of molecular rotation often plays a significant role under general conditions, influencing fluid phase transition. So, the rotational freedom of molecules has been taken into the thermal equations in this work. The excited state or phase transition of the fluid has been substantiated by using the RH theory, and we have found that internal freedoms of the fluid can have a dramatic effect on the physical properties during phase transition processes.

ChatGPT (OpenAI), a cutting-edge natural language processing model, holds immense promise for revolutionizing medical education. With its remarkable performance in language-related tasks, ChatGPT offers personalized and efficient learning experiences for medical students and doctors. Through training, it enhances clinical reasoning and decision-making skills, leading to improved case analysis and diagnosis. The model facilitates simulated dialogues, intelligent tutoring, and automated question-answering, enabling the practical application of medical knowledge. However, integrating ChatGPT into medical education raises ethical and legal concerns. Safeguarding patient data and adhering to data protection regulations are critical. Transparent communication with students, physicians, and patients is essential to ensure their understanding of the technology’s purpose and implications, as well as the potential risks and benefits. Maintaining a balance between personalized learning and face-to-face interactions is crucial to avoid hindering critical thinking and communication skills. Despite challenges, ChatGPT offers transformative opportunities. Integrating it with problem-based learning, team-based learning, and case-based learning methodologies can further enhance medical education. With proper regulation and supervision, ChatGPT can contribute to a well-rounded learning environment, nurturing skilled and knowledgeable medical professionals ready to tackle health care challenges. By emphasizing ethical considerations and human-centric approaches, ChatGPT’s potential can be fully harnessed in medical education, benefiting both students and patients alike.

BackgroundDifferences in border zone contribute to different outcomes post-infarction, such as left ventricular aneurysm (LVA) and myocardial infarction (MI). LVA usually forms within 24 h of the onset of MI and may cause heart rupture; however, LVA surgery is best performed 3 months after MI. Few studies have investigated the LVA model, the differences in border zones between LVA and MI, and the mechanism in the border zone.MethodsThe LVA, MI, and SHAM mouse models were used. Echocardiography, Masson’s trichrome staining, and immunofluorescence staining were performed, and RNA sequencing of the border zone was conducted. The adipocyte-conditioned medium-treated hypoxic macrophage cell line and LVA and MI mouse models were employed to determine the effects of the hub gene, adiponectin (ADPN), on macrophages. Quantitative polymerase chain reaction (qPCR), Western blot analysis, transmission electron microscopy, and chromatin immunoprecipitation (ChIP) assays were conducted to elucidate the mechanism in the border zone. Human subepicardial adipose tissue and blood samples were collected to validate the effects of ADPN.ResultsA novel, simple, consistent, and low-cost LVA mouse model was constructed. LVA caused a greater reduction in contractile functions than MI owing to reduced wall thickness and edema in the border zone. ADPN impeded cardiac edema and promoted lymphangiogenesis by increasing macrophage infiltration post-infarction. Adipocyte-derived ADPN promoted M2 polarization and sustained mitochondrial quality via the ADPN/AdipoR2/HMGB1 axis. Mechanistically, ADPN impeded macrophage HMGB1 inflammation and decreased interleukin-6 (IL6) and HMGB1 secretion. The secretion of IL6 and HMGB1 increased ADPN expression via STAT3 and the co-transcription factor, YAP, in adipocytes. Based on ChIP and Dual-Glo luciferase experiments, STAT3 promoted ADPN transcription by binding to its promoter in adipocytes. In vivo, ADPN promoted lymphangiogenesis and decreased myocardial injury after MI. These phenotypes were rescued by macrophage depletion or HMGB1 knockdown in macrophages. Supplying adipocytes overexpressing STAT3 decreased collagen disposition, increased lymphangiogenesis, and impaired myocardial injury. However, these effects were rescued after HMGB1 knockdown in macrophages. Overall, the IL6/ADPN/HMGB1 axis was validated using human subepicardial tissue and blood samples. This axis could serve as an independent factor in overweight MI patients who need coronary artery bypass grafting (CABG) treatment.ConclusionThe IL6/ADPN/HMGB1 loop between adipocytes and macrophages in the border zone contributes to different clinical outcomes post-infarction. Thus, targeting the IL6/ADPN/HMGB1 loop may be a novel therapeutic approach for cardiac lymphatic regulation and reduction of cell senescence post-infarction.

Background Effective discrimination of lung adenocarcinoma (LUAD) in situ (AIS) from benign pulmonary nodules (BPN) is critical for the early diagnosis of AIS. Our pilot study in a small cohort of 90 serum samples has shown that serum interleukin 6 (IL-6) detection can distinguish AIS from BPN and health controls (HC). In this study, we intend to comprehensively define the diagnostic value of individual and combined detection of serum IL-6 related to the traditional tumor markers carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1) for AIS. Methods The diagnostic performance of serum IL-6 along with CEA and CYFRA21-1 were evaluated in a large cohort of 300 serum samples by a chemiluminescence immunoassay and an electrochemiluminescence immunoassay. A training set comprised of 65 AIS, 65 BPN, and 65 HC samples was used to develop the predictive model for AIS. Data obtained from an independent validation set was applied to evaluate and validate the predictive model. Results In the training set, the levels of serum IL-6 and CEA in the AIS group were significantly higher than those in the BPN/HC group (P < 0.05). There was no significant difference in serum CYFRA21-1 levels between the AIS group and the BPN/HC group (P> 0.05). Serum IL-6 and CEA levels for AIS patients showed an area under the curve (AUC) of 0.622 with 23.1% sensitivity at 90.7% specificity, and an AUC of 0.672 with 24.6% sensitivity at 97.6% specificity, respectively. The combination of serum IL-6 and CEA presented an AUC of 0.739, with 60.0% sensitivity at 95.4% specificity. The combination of serum IL-6 and CEA showed an AUC of 0.767 for AIS patients, with 57.1% sensitivity at 91.4% specificity in the validation set. Conclusions IL-6 shows potential as a prospective serum biomarker for the diagnosis of AIS, and the combination of serum IL-6 with CEA may contribute to increased accuracy in AIS diagnosis. However, it is worth noting that further research is still necessary to validate and optimize the diagnostic efficacy of these biomarkers and to address potential sensitivity limitations.

Abstract With the large-scale vaccination of lipid nanoparticles (LNP)-based COVID-19 mRNA vaccines, elucidating the potential polyethylene glycol (PEG)-associated immune responses triggered by clinically relevant LNP has become imminent. However, inconsistent findings were observed across very limited population-based studies. Herein we initiated a study using LNP carrier of Comirnaty® as a representative, and simulated real-world clinical practice covering a series of time points and various doses correlated with approved LNP-delivered drugs in a rat model. We demonstrated the time- and dose-dependency of LNP-induced anti-PEG antibodies in rats. As a thymus-independent antigen, LNP unexpectedly induced isotype switch and immune memory, leading to rapid enhancement and longer lasting time of anti-PEG IgM and IgG upon re-injection in rats. Importantly, initial LNP injection accelerated the blood clearance of subsequent dosing in rats. These findings refine our understandings on LNP and possibly other PEG derivatives, and may promote optimization of related premarket guidelines and clinical protocols.