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Background: Pulmonary artery involvement (PAI) is not rare in Takayasu arteritis (TA). Persistently elevated pulmonary arterial pressure in TA‐PAI patients leads to pulmonary hypertension (PH), and eventually cardiac death. Thus, the early detection of right ventricular dysfunction before the onset of PH is important. Purpose: To explore the potential of right ventricular global peak longitudinal and circumferential strain (RVGLS and RVGCS, respectively) in detecting right ventricular myocardial damage in TA‐PAI patients without PH. Study Type: Retrospective. Population: One hundred and six TA patients (39.6 ± 13.9 years), of whom 52 were non‐PAI and 54 were PAI patients (36 without PH and 18 with PH), along with 58 sex‐ and age‐matched healthy volunteers (HVs) (36.7 ± 13.2 years). The involved arteries were validated by aorta magnetic resonance (MR) angiography and pulmonary artery computed tomography angiography. Field Strength/Sequence: 3 T/Cine imaging sequence with a steady‐state free precession readout. Assessment: Cardiac MRI‐derived parameters measured by two radiologists independently were compared among HVs, and TA patients with and without PAI. In addition, these indices were further compared among HVs, and TA‐PAI patients with and without PH. Statistical Tests: Student's t test, one‐way ANOVA analysis, Pearson and Spearman correlation analysis, and reproducibility analysis. A P‐value of <0.05 was considered statistically significant. Results: Although the TA‐PAI patients without PH had a similar RV ejection fraction (RVEF) with HV (P = 0.348), RVGLS (non‐PH 20.6 ± 3.7% vs. HV 24.0 ± 3.1%) was significantly lower and RVGCS (non‐PH 14.8 ± 3.9% vs. HV 13.0 ± 2.7%) higher. The TA‐PAI patients with PH had significantly poorer RVGLS (PH 13.5 ± 3.8% vs. non‐PH 20.6 ± 3.7%) and RVGCS (PH 10.9 ± 3.2% vs. non‐PH 14.8 ± 3.9%) than those without PH. Data Conclusion: Right ventricular dysfunction was detected in the TA‐PAI patients without PH. MR‐feature tracking may be an effective method for detecting early cardiac damage in the TA‐PAI patients without PH. Level of Evidence: 3 Technical Efficacy: Stage 3 [ABSTRACT FROM AUTHOR]

Targeting receptor‐interacting protein kinase 1 (RIPK1) has emerged as a promising therapeutic stratagem for neurodegenerative disorders, particularly Alzheimer's disease (AD). A positron emission tomography (PET) probe enabling brain RIPK1 imaging can provide a powerful tool to unveil the neuropathology associated with RIPK1. Herein, the development of a new PET radioligand, [11C]CNY‐10 is reported, which may enable brain RIPK1 imaging. [11C]CNY‐10 is radiosynthesized with a high radiochemical yield (41.8%) and molar activity (305 GBq/µmol). [11C]CNY‐10 is characterized by PET imaging in rodents and a non‐human primate, demonstrating good brain penetration, binding specificity, and a suitable clearance kinetic profile. It is performed autoradiography of [11C]CNY‐10 in human AD and healthy control postmortem brain tissues, which shows strong radiosignal in AD brains higher than healthy controls. Subsequently, it is conducted further characterization of RIPK1 in AD using [11C]CNY‐10‐based PET studies in combination with immunohistochemistry leveraging the 5xFAD mouse model. It is found that AD mice revealed RIPK1 brain signal significantly higher than WT control mice and that RIPK1 is closely related to amyloid plaques in the brain. The studies enable further translational studies of [11C]CNY‐10 for AD and potentially other RIPK1‐related human studies. [ABSTRACT FROM AUTHOR]

On August 11, 2022, FDA granted accelerated approval to fam-trastuzumab deruxtecan-nxki (DS-8201a, T-DXd, ENHERTU, Daiichi Sankyo) for adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating human epidermal growth factor receptor 2 (HER2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy. The approval was based on a prespecified interim analysis of DESTINY-Lung02 (Study U206), a multi-center, randomized, dose-optimization trial in patients with NSCLC harboring activating HER2 -mutations. At the approved dose of 5.4 mg/kg given intravenously every 3 weeks, the overall response rate (ORR) was 58% (95% confidence interval [CI]: 43, 71). The median duration of response was 8.7 months (95% CI: 7.1, not estimable). These results were consistent with response rates observed at the 6.4 mg/kg dose level. The most common (≥ 20%) adverse reactions were nausea, constipation, decreased appetite, vomiting, fatigue, and alopecia. The rate of interstitial lung disease (ILD) or pneumonitis was 6% at the 5.4 mg/kg dose level and 14% at the 6.4 mg/kg dose level. In the setting of similar efficacy and reduced toxicity, approval was granted for the 5.4 mg/kg dose level. The applicant conducted a randomized, dose-optimization study with guidance from the FDA Oncology Center of Excellence's Project Optimus. This is the first approval of a targeted therapy for HER2 -mutated NSCLC. [ABSTRACT FROM AUTHOR]

Background: The heart can be involved in immunoglobulin (Ig)-G4-related disease (IgG4-RD). This study aimed to summarize the clinical features and efficacy of treatment for IgG4-RD patients with heart involvement. Methods: We conducted a retrospective study enrolling 42 IgG4-RD patients with heart involvement from the IgG4-RD cohorts of the Peking Union Medical College Hospital and Beijing An Zhen Hospital, from 2010 to 2022. Clinical, laboratory, radiological data were collected, and treatment responses to glucocorticoids and immunosuppressants were analyzed. Results: IgG4-related cardiac involvement is a rare part of the IgG4-RD spectrum. The incidences of coronary periarteritis and pericarditis were 1.2%(13/1075) and 3.1%(33/1075), respectively in our cohort. Valvular disease possibly related to IgG4-RD was detected in two patients. None of the patients with myocardial involvement were identified. The average age was 58.2 ± 12.8 years, with a male predominance (76.7%). Coronary artery CT revealed that mass-like and diffuse wall-thickening lesions were the most frequently observed type of coronary periarteritis. Pericarditis presented as pericardial effusion, localized thickening, calcification and mass. After treatment with glucocorticoid and immunosuppressants, all patients achieved a reduced IgG4-RD responder index score and achieved radiological remission. Two patients with coronary peri-arteritis experienced clinical relapses during the maintenance period. Conclusions: Cardiac involvement in IgG4-RD is rare and easily overlooked since many patients are asymptomatic, and the diagnosis relies on imaging. Patients showed a satisfactory response to glucocorticoid based treatment. [ABSTRACT FROM AUTHOR]

Dielectric elastomers, such as thermoplastic polyurethanes (TPUs), are widely used as the dielectric layer, encapsulation layer, and substrate of flexible and stretchable devices. To construct capacitors and actuators that work stably upon deformation, it has become urgent to investigate the evolution of dielectricity under stress and strain. However, the lack of effective methods for estimating the dielectric constant of elastomers under strain poses a big challenge. This study reports a device for the in situ measurement of the dielectric constant of TPU under strain. It is found that upon stretching TPU to a strain of 400%, its dielectric constant decreases from 8.02 ± 0.01 to 2.88 ± 0.25 (at 1 MHz). In addition, combined Fourier-transform infrared spectroscopy, the X-ray scattering technique, and atomic force microscopy were utilized to characterize the evolution of the microstructure under strain. The investigation under tensile strain reveals a decreased density and average size of polarized hard domains, along with a tendency of the molecular chains to align in parallel with the tensile stress. The evolution of the microstructures results in a reduction in the measured dielectric constant in TPU. [ABSTRACT FROM AUTHOR]

Objective: The goal of the present study was to investigate the correlation between serum 25-hydroxyvitamin D [25(OH)D] levels and disease remission in Takayasu arteritis (TAK) patients. Methods: This retrospective study included 59 patients in the study group and 80 patients in the validation cohort with TAK. After 6 months of therapy, patients were re-evaluated, and serum 25(OH)D levels were compared before and after treatment. Correlations between changes in 25(OH)D levels and changes in disease activity scores (NIH, ITAS2010, ITAS.A) were analyzed. Additionally, a predictive cut-off value for disease remission was determined. Results: After 6 months of therapy, serum 25(OH)D levels in TAK patients significantly increased compared to baseline [(18.33 ± 7.25)µg/L vs (11.77 ± 4.14) µg/L] (P < 0.001). Positive correlations were observed between the increasing changes in the 25(OH)D level and the decreasing changes in the reduced NIH, ITAS2010, and ITAS.A scores (r = 0.455, P < 0.001; r = 0.495, P < 0.001; and r = 0.352 P = 0.006, respectively). A change of 8.45 µg/L in 25(OH)D level was identified as the predictive cut-off value for TAK remission (sensitivity 54.1%, specificity 90.9%, area under the curve = 0.741). Similarly for patients with normal baseline ESR, sensitivity is 68.0%, specificity is 92.3%, and area under the curve is 0.831, and for patients with normal baseline CRP, sensitivity is 58.3%, specificity is 90.0%, and area under the curve is 0.748. Validation in an additional 80 patients demonstrated a higher remission rate in those with a 25(OH)D level change > 8.45 µg/L. Conclusion: Serum 25(OH)D levels significantly increased after treatment in TAK patients, and an increase of ≥ 8.45 µg/L was predictive of disease remission, especially in individuals with normal baseline ESR and/or CRP levels. Key Points • Following treatment, there was a significant increase in serum 25(OH)D levels among TAK patients. • The elevated changes in 25(OH)D levels before and after treatment demonstrated a positive correlation with the reduction in disease activity scores. • In patients with TAK before and after treatment, an elevation in serum 25(OH)D levels exceeding 8.45 µg/L serves as an indicator for disease remission, particularly prominent in individuals with normal baseline ESR and/or CRP levels. [ABSTRACT FROM AUTHOR]

Metastatic castration-resistant prostate cancer (CRPC) is a currently incurable disease associated with high mortality. Novel therapeutic approaches for CRPC are urgently needed to improve prognosis. In this study, we developed cross-linked, PSMA-targeted lipoic acid nanoparticles (cPLANPs), which can interact with transmembrane glycoprotein to accumulate inside prostate cancer cells, where they upregulate caspase-3, downregulate anti-apoptotic B-cell lymphoma-2 (BCL-2), and thereby induce apoptosis. The trans-cyclooctene (TCO) decoration on cPLANPs acts as a bioorthogonal handle allowing pretargeted single-photon emission computed tomography and radiotherapy, which revealed significantly enhanced tumor accumulation and minimal off-target toxicity in our experiments. The developed strategy showed a strong synergistic anti-cancer effect in vivo, with a tumor inhibition rate of up to 95.6% after 14 days of treatment. Our results suggest the potential of combining bioorthogonal pretargeted radiotherapy with suitable PSMA-targeted nanoparticles for the treatment of metastatic CRPC. [ABSTRACT FROM AUTHOR]

This study implements the least-squares inversion method for solving the exhumation history from the thermochronologic age–elevation relationship (AER) based on the linear equation among exhumation rate, age and total exhumation from the closure depth to the Earth surface. Modeling experiments suggest significant and systematic influence of initial geothermal model, the a priori exhumation rate and the time interval length on the a posteriori exhumation history. Lessons learned from the experiments include that (i) the modern geothermal gradient can be used for constraining the initial geothermal model, (ii) a relatively high a priori exhumation rate would lead to systematically lower a posteriori exhumation and vice versa, (iii) the variance of the a priori exhumation rate controls the variation in the inverted exhumation history, and (iv) the choice of time interval length should be optimized for resolving the potential temporal changes in exhumation. To mitigate the dependence of inverted erosion history on these initial parameters, we implemented a new stepwise inverse modeling method for optimizing the model parameters by comparing the observed and predicted thermochronologic data and modern geothermal gradients. Finally, method demonstration was performed using four synthetic datasets and three natural examples of different exhumation rates and histories. It is shown that the inverted rock exhumation histories from the synthetic datasets match the whole picture of the "truth", although the temporal changes in the magnitude of exhumation are underestimated. Modeling of the datasets from natural samples produces geologically reasonable exhumation histories. The code and data used in this work are available on Zenodo (10.5281/zenodo.10839275). [ABSTRACT FROM AUTHOR]

The coupling effects between the stage house and the auditorium in opera houses make the sound field very complex. In the present study, the effects of stage absorption on the primary monaural objective room acoustic parameters in the seating area of an opera house in China were investigated by means of computer simulation and scaled model measurement. In computer simulations, the absorption coefficient of the ceiling and walls of the stage house was changed across several steps, and then a series of experiments were conducted in a 1:20 scaled hall with and without curtains and wall absorption on the stage to verify the simulation results. It was found that stage absorption has a significant influence on early decay time (EDT), reverberation time (RT) and clarity (C80) in the seating area, while the effect on sound strength (G) is much smaller. The values of EDT and RT decrease with an increase in sound absorption on the stage, while C80 displays an opposite trend. In addition, when the average absorption coefficient of the stage walls and ceiling is over 0.5, the variations in these four parameters due to the increase in stage absorption can be constrained within an acceptable range. [ABSTRACT FROM AUTHOR]

Here we describe a cost-effective and simplified cell sorting method using tetrazine bioorthogonal chemistry. We successfully isolated SKOV3 cells from complex mixtures, demonstrating efficacy in separating mouse lymphocytes expressing interferon and HeLa cells expressing virally transduced green fluorescent protein post-infection. [ABSTRACT FROM AUTHOR]

Elsinochrome A (EA) is a naturally occurring photosensitizer with potential applications in photodynamic therapy (PDT) for various malignancies. Despite its promising therapeutic properties, the poor solubility of EA hampers its effective utilization in clinical settings. To circumvent this limitation, we engineered four distinct nano-formulations: PLGA/EA nanoparticles (NPs), CMC-PLGA/EA NPs, mPEG-PCL/EA nanomicelles (NMs), and LHP-CHOL/EA nanoliposomes (NLs), all designed to enhance the solubility of EA. A comparative evaluation of these formulations, based on metrics such as particle size, Zeta potential, drug loading efficiency, and encapsulation efficiency, identified PLGA/EA NPs and mPEG-PCL/EA NMs as the most efficacious candidates. Subsequent in vitro investigations into the drug release kinetics under varying pH conditions and the impact on cell viability and apoptosis in A549 and MCF-7 cell lines were conducted. Remarkably, the maximum drug release for PLGA/EA NPs and mPEG-PCL/EA NMs was recorded at 62.5% and 70.8% in an acidic environment (pH 5.7), respectively. Upon exposure to 460 nm light, PLGA/EA NPs induced a significant reduction in A549 cell viability to 13.8% and an apoptosis rate of 93.8%, whereas mPEG-PCL/EA NMs elicited a decrease in MCF-7 cell viability to 12.8% and an apoptosis rate of 73.0%. [ABSTRACT FROM AUTHOR]

Background: Prompt response to induction chemotherapy is a prognostic factor in pediatric acute myeloid leukemia. In this study, we aimed to evaluate the prognostic significance of multiparametric flow cytometry-minimal residual disease (MFC-MRD), assessed at the end of the first and second induction courses. Methods: MFC-MRD was performed at the end of the first induction (TP1) in 524 patients and second induction (TP2) in 467 patients who were treated according to the modified Medical Research Council (UK) acute myeloid leukemia 15 protocol. Results: Using a 0.1% cutoff level, patients with MFC-MRD at the two time points had lower event-free survival and overall survival. Only the TP2 MFC-MRD level could predict the outcome in a separate analysis of high and intermediate risks based on European LeukemiaNet risk stratification and KMT2A rearrangement. The TP2 MFC-MRD level could further differentiate the prognosis of patients into complete remission or non-complete remission based on morphological evaluation. Multivariate analysis indicated the TP2 MFC-MRD level as an independent adverse prognostic factor for event-free survival and overall survival. When comparing patients with MFC-MRD ≥ 0.1%, those who underwent hematopoietic stem cell transplant during the first complete remission had significantly higher 5-year event-free survival and overall survival and lower cumulative incidence of relapse than those who only received consolidation chemotherapy. Conclusions: The TP2 MFC-MRD level can predict the outcomes in pediatric patients with acute myeloid leukemia and help stratify post-remission treatment. [ABSTRACT FROM AUTHOR]

Platelet parameters have been recognized as important markers for disease severity in various types of diseases. The aim of our study was to investigate whether platelet count could be used as a potential predictor of refractory Takayasu arteritis (TAK). In this retrospective study, fifty-seven patients were selected as development data group to identify the associated risk factors and potential predictors of refractory TAK. Ninety-two TAK patients were included in the validation data group to verify the predictive value of platelet count for refractory TAK. Refractory TAK patients had higher levels of platelet (PLT) than non-refractory TAK patients (305.5 vs. 272.0 × 109/L, P = 0.043). For PLT, the best cut-off value was 296.5 × 109/L to predict refractory TAK. Elevated PLT (> 296.5 × 109/L) was found to be statistically related to refractory TAK (OR [95%CI] 4.000 [1.233–12.974], p = 0.021). In the validation data group, the proportion of refractory TAK in patients with elevated PLT was significantly higher than that in patients with non-elevated PLT (55.6% vs. 32.2%, P = 0.037). The 1-, 3- and 5-year cumulative incidence of refractory TAK were 37.0%, 44.4% and 55.6% in patients with elevated PLT, respectively. Elevated PLT (p = 0.035, hazard ratio (HR) 2.106) was identified as a potential predictor of refractory TAK. Clinicians should pay close attention to platelet levels in patients with TAK. For TAK patients with PLT greater than 296.5 × 109/L, closer monitoring of the disease and comprehensive assessment of disease activity are recommended to be alert to the occurrence of refractory TAK. [ABSTRACT FROM AUTHOR]

Objective: Takayasu arteritis (TAK) is an inflammatory disease of blood vessels, and its pathogenesis is not clear at present. In this study, we explored the immunological characteristics of T cell receptor (TCR) α‐chain complementarity‐determining region 3 (CDR3) in patients with TAK. Methods: Five untreated patients with TAK were collected from June 2019 to December 2019. Four healthy blood samples were matched as the control group. The blood mononuclear cells were separated, and RNA was extracted for reverse transcription to obtain complementary DNA. Then high‐throughput sequencing was performed. The quality of samples was evaluated by principal component analysis. We compared the diversity and expression of TCR α‐chain between TAK group and control group. R software was used for statistical analysis and drawing, and Mann–Whitney U test was used to analyze the differences between the two groups. Results: The results showed that there was a significant difference in the diversity of TCR α‐chain CDR3 between the two groups. Three V region genes expression significantly higher in the TAK patients than in the control group. A total of 196 VJ rearrangement genes are significantly different between the two groups, of which 149 rearrangement genes in the TAK group are lower than those in the control group, and 47 rearrangement genes in the TAK group are higher than those in the control group. Conclusion: Patients with TAK have a unique TCR α‐chain CDR3 library. These characteristic genes may be a marker for early diagnosis and provide a new theoretical basis for treating TAK. [ABSTRACT FROM AUTHOR]

In multivariate regression analysis, a coefficient matrix is used to relate multiple response variables to regressor variables in a noisy linear system from given data. Optimization is a natural approach to find such coefficient matrix with few nonzero rows. However, the relationship of most group sparse optimization models with cardinality penalty or cardinality constraints is not clear. In this paper, we give a comprehensive description of the relationship between three widely used group sparse optimization problems with cardinality terms: (i) the number of nonzero rows is minimized subject to an error tolerance for regression; (ii) the error for regression is minimized subject to a row cardinality constraint; (iii) the sum of the number of nonzero rows and error for regression is minimized. The first two problems have convex constraints and cardinality constraints respectively, while the third one is an unconstrained optimization problem with a cardinality penalty. We provide sufficient conditions under which the three optimization problems have the same global minimizers. Moreover, we analyze the relationship of stationary points and local minimizers of the three problems. Finally, we use two examples to illustrate our theoretical results for finding solutions of constrained optimization problems involving cardinality terms by unconstrained optimization problems with penalty functions. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is a highly heterogeneous cancer with major challenges in both prevention and therapy. Metformin, adenosine monophosphate‐activated protein kinase (AMPK) activator, has been suggested to reduce the incidence of HCC when used for patients with diabetes in preclinical and clinical studies. However, the possible effects of metformin and their mechanisms of action in non‐diabetic HCC have not been adequately investigated. Methods: Fah−/− mice were used to construct a liver‐injury‐induced non‐diabetic HCC model for exploring hepatocarcinogenesis and therapeutic potential of metformin. Changes in relevant tumour and biochemical indicators were measured. Bulk and single‐cell RNA‐sequencing analyses were performed to validate the crucial role of proinflammatory/pro‐tumour CD8+ T cells. In vitro and in vivo experiments were performed to confirm Cyp26a1‐related antitumour mechanisms of metformin. Results: RNA‐sequencing analysis showed that chronic liver injury led to significant changes in AMPK‐, glucose‐ and retinol metabolism‐related pathways in Fah−/− mice. Metformin prevented the formation of non‐diabetic HCC in Fah−/− mice with chronic liver injury. Cyp26a1 ddexpression in hepatocytes was significantly suppressed after metformin treatment. Moreover, downregulation of Cyp26a1 occurred in conjunction with increased levels of all‐trans‐retinoic acid (atRA), which is involved in the activation of metformin‐suppressed hepatocarcinogenesis in Fah−/− mice. In contrast, both CD8+ T‐cell infiltration and proinflammatory/pro‐tumour cytokines in the liver were significantly upregulated in Fah−/− mice during chronic liver injury, which was notably reversed by either metformin or atRA treatment. Regarding mechanisms, metformin regulated the decrease in Cyp26a1 enzyme expression and increased atRA expression via the AMPK/STAT3/Gadd45β/JNK/c‐Jun pathway. Conclusions: Metformin inhibits non‐diabetic HCC by upregulating atRA levels and downregulating CD8+ T cells. This is the first reporting that the traditional drug metformin regulates the metabolite atRA via the Cyp26a1‐involved pathway. The present study provides a potential application of metformin and atRA in non‐diabetic HCC. [ABSTRACT FROM AUTHOR]

Although lithofacies routinely is featured by distinct logging responses from each other, many types of lithofacies in practical cases show similar measuring characteristics on logs, and then to achieve a desirable solution from logging‐based lithofacies prediction actually is challengeable. Since the mathematical essence of lithofacies prediction can be explained as an issue of pattern recognition, a light gradient boosting machine, a state‐of‐the‐art ensemble learning, specifically developed to address supervised classification, could be a potential solver. Nonetheless, due to an incompatibility of inherent exclusive feature bundling algorithm for logs and usage of a great deal of hyper‐parameters, a raw light gradient boosting machine might not be suitable or functional to predict lithofacies. Thus, continuous restricted Boltzmann machine and Bayesian optimization, respectively, employed to process original logging data and optimize hyper‐parameters, are adopted as technical assistants for the light gradient boosting machine, and accordingly a new ensemble learning‐based predictor called continuous restricted Boltzmann machine – Bayesian optimization – the light gradient boosting machine, is proposed for lithofacies. To validate classifying capability and robust nature of new predictor, three experiments are designed purposefully based on the application of a dataset collected from the wells located within pre‐salt lacustrine carbonate reservoirs of the Santos Basin. Simultaneously, to highlight validating effect, other three sophisticated classifiers are introduced as competitors in all experiments, including supper vector machine, random forest and extreme gradient boosting. According to the analysis and comparison of all experimental results, overall four points are verified: (1) the integration of continuous restricted Boltzmann machine and Bayesian optimization indeed is beneficial for the light gradient boosting machine in data preprocess and modelling stage; (2) the light gradient boosting machine cored predictor shows more capability of producing reliable predicted lithofacies information compared to other three competitors; (3) training more learning samples is a simple and effective approach to enhance computing capability of any validated predictor, and under this circumstance the light gradient boosting machine cored predictor still performs relatively better; (4) the light gradient boosting machine cored predictor is characterized with a better robustness as its predicting outcomes, even derived from a sparse‐condition dataset, are also proved more qualified. Consequently, the new proposed predictor is demonstrated as a high‐efficient and robust solver for the prediction of lithofacies and deserves a widespread application in the geological, geophysical and petrophysical research. [ABSTRACT FROM AUTHOR]

This study implements the least-squares inversion method for solving the exhumation history from thermochornologic age-elevation relationship (AER) based on the linear equation among exhumation rate, thermochronologic age and total exhumation from the closure depth to the Earth surface. Modelling experiments demonstrate the significant and systematic influence of initial geothermal model, the a priori exhumation rate and the time interval length on the a posterior exhumation history. Lessons learned from the experiments include that (i) the modern geothermal gradient can be used for constraining the initial geothermal model, (ii) a relatively higher a priori exhumation rate would lead to systematically lower inversion results, and vice versa , (iii) the variance of the a priori exhumation rate controls the variation of the inverted exhumation history, (iv) the choice of time interval length should be optimized for resolving the potential temporal changes in exhumation. Putting together these findings, we propose a new stepwise inversion modeling strategy for optimizing the model parameters to mitigate the model dependencies on the initial parameters. Finally, we use three examples of different exhumation rates and histories for method demonstration. It is shown that our new modelling strategy produces geologically reasonable exhumation histories and geothermal gradients that are consistent with both the observed AER and modern geothermal data. The code and data used in this work is available in GitHub (https://github.com/yuntao-github/code4modelAER). [ABSTRACT FROM AUTHOR]

Individualized positive end-expiratory pressure (PEEP) combined with recruitment maneuvers improves intraoperative oxygenation in individuals undergoing robot-assisted prostatectomy. However, whether electrical impedance tomography (EIT)-guided individualized PEEP without recruitment maneuvers can also improve intraoperative oxygenation is unknown. To test this, fifty-six male patients undergoing elective robot-assisted laparoscopic prostatectomy were randomly assigned to either individualized PEEP (Group PEEPIND, n = 28) or a control with a fixed PEEP of 5 cm H2O (Group PEEP5, n = 28). Individualized PEEP was guided by EIT after placing the patients in the Trendelenburg position and performing intraperitoneal insufflation. Patients in Group PEEPIND maintained individualized PEEP without intermittent recruitment maneuvers, and those in Group PEEP5 maintained a PEEP of 5 cm H2O intraoperatively. Both groups were extubated in a semi-sitting position once the extubation criteria were met. The primary outcome was arterial oxygen partial pressure (PaO2)/inspiratory oxygen fraction (FiO2) prior to extubation. Other outcomes included intraoperative driving pressure, plateau pressure and dynamic, respiratory system compliance, and the incidence of postoperative hypoxemia in the post-operative care unit (PACU). Our results showed that the intraoperative median for PEEPIND was 16 cm H2O (ranging from 12 to 18 cm H2O). EIT-guided PEEPIND was associated with higher PaO2/FiO2 before extubation compared to PEEP5 (71.6 ± 10.7 vs. 56.8 ± 14.1 kPa, p = 0.003). Improved oxygenation extended into the PACU with a lower incidence of postoperative hypoxemia (3.8% vs. 26.9%, p = 0.021). Additionally, PEEPIND was associated with lower driving pressures (12.0 ± 3.0 vs. 15.0 ± 4.4 cm H2O, p = 0.044) and better compliance (44.5 ± 12.8 vs. 33.6 ± 9.1 mL/cm H2O, p = 0.017). Our data indicated that individualized PEEP guided by EIT without intraoperative recruitment maneuvers also improved perioperative oxygenation in patients undergoing robot-assisted laparoscopic radical prostatectomy, which could benefit patients with the risk of intraoperative hemodynamic instability caused by recruitment maneuvers. Trial registration: China Clinical Trial Registration Center Identifier: ChiCTR2100053839. This study was registered on 1 December 2021. The first patient was recruited on 15 December 2021. [ABSTRACT FROM AUTHOR]

Developing high‐efficient photocatalysts for H2 production is still the focus of current research. A series of CoSx/Zn0.3Cd0.7S (CoSx/ZCS) samples with different mass ratios were successfully synthesized for H2 production by the oxidation of p‐chlorobenzyl alcohol (Cl‐PhCH2OH). Herein, Zn0.3Cd0.7S (ZCS) solid‐solution nanoparticles are distributed on the surface of CoSx polyhedron, and CoSx is obtained from ZIF‐67, composed of Co1−xS and CoS2. The photocatalytic H2 production was performed by Cl‐PhCH2OH oxidation in N,N‐Dimethylformamide (DMF) solution under visible light irradiation, and 5% CoSx/ZCS sample showed the best photocatalytic activity, with the H2 generated rate high to 2.80 mmol g−1 h−1. Meanwhile, the selectivity of Cl‐PhCH2OH oxidation to p‐chlorobenzaldehyde (Cl‐PhCHO) is 97.6%, and the rate is 2.95 mmol g−1 h−1. Moreover, the reasons for the excellent photocatalytic performance of CoSx/ZCS samples were deeply analyzed by experimental and theoretical results, such as trapping agents, photoelectrochemistry test, electron paramagnetic resonance (EPR), specific surface area, and density functional theory (DFT) calculation. This work provides a new theoretical guidance and experimental experience for the application of H2 application and design of novel photocatalysts. [ABSTRACT FROM AUTHOR]

Background Accurate evaluation of the activity stage in Takayasu arteritis (TA) is important for the revascularization of TA with coronary artery involvement (TA-CAD). Here, we report the case of a patient with a mismatch of systemic and local inflammatory activity, leading to 13 times the need for recurrent coronary revascularization. Case summary A 31-year-old woman with a family history of coronary artery disease underwent percutaneous coronary intervention (PCI) for critical ostial lesions. This patient was identified with Numano Type V TA and she underwent optimal medical therapy and PCIs. Her clinical inflammatory markers were quickly normalized. However, in-stent restenosis events recurred every 3 months. Virtual-histology intravascular ultrasound (VH-IVUS) and 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) confirmed local vascular inflammation. A coronary artery bypass graft (CABG) was also conducted. Before this procedure, both the CABG grafts and the anastomotic areas were accurately assessed with 18FDG-PET/CT. Eventually, this patient remained both angina- and event-free for 2 years post-CABG. Discussion The persistence of TA activity despite normal clinical inflammatory markers is uncommon as is the need for recurrent revascularization after appropriate PCI management. Intracoronary imaging and 18FDG-PET/CT play a critical role in assessing TA activity as well as precisely guiding CABG grafts and anastomosis sites to prevent graft failure. [ABSTRACT FROM AUTHOR]

Classical local anesthetics are unsuitable to treat regional pain lasting several days due to their limited duration and systemic toxicity. Self-delivery nano systems without excipients were designed for long-term sensory blocks. 1a self-assembled into different vehicles with different fractions of intermolecular π–π stacking, transported itself into nerve cells, and released single molecules slowly to achieve long-term duration for rats' sciatic nerve block for 11.6 h in water, 12.1 h in water with CO2 and 3.4 h in NS (normal saline). After the counter ions were changed to SO42−, 1e can self-assemble into vesicles and prolong the duration to 43.2 h, which was much longer than the 3.8 h led by (s)-bupivacaine hydrocloride (0.75%). This was mainly caused by the enhancement of self-release and counter ion exchange inside nerve cells, which were affected by the gemini surfactant structure, pKa of the counter ions and π–π stacking interactions. [ABSTRACT FROM AUTHOR]

Boron neutron capture therapy (BNCT) is a promising therapy for refractory cancer based on the cytotoxic reaction of 10B (n, α) 7Li. Although two BNCT agents are clinically available, they are quickly metabolized and show modest enrichment in tumor sites, partially limiting BNCT widespread application. Consequently, novel agents that perform active targeting and show good biocompatibility have to be developed. Herein, boronophenylalanine‐containing polydopamine (B‐PDA) nanoparticles are easily fabricated by encapsulating boronophenylalanine (BPA) in polydopamine via nitrogen‐boronate coordination. In this study, B‐PDA achieves increased tumor accumulation and prolonged retention effects in the tumor site and superior antitumor activity post neutron irradiation in the orthotopic xenograft glioma model. In brief, this study offers a novel strategy for BPA delivery and may broaden the perspective on nanomedicine design for BNCT. [ABSTRACT FROM AUTHOR]

Stretchable magnetic materials are highly desirable for developing flexible high‐performance magnetoelectronic devices. However, it is still challenge to fabricate stretchable magnetic films with high growth temperature. In this work, metamagnetic FeRh films are grown on mica substrates at high temperature and then transferred onto the prestrained polydimethylsiloxane (PDMS). Due to the large modulus mismatch between FeRh films and PDMS, FeRh films with periodic wrinkle pattern is formed after releasing the prestrain, enabling a controllable stretchability up to a few tens of percent. Moreover, the meta‐magnetic phase transition temperature can be effectively controlled by the prestrain, with an increase of ≈4 K for every 10% increase in the prestrain. In case of the applied tensile strain less than the prestrain, the obtained flexible FeRh films can maintain stable performance after thousands of stretches, making it promising for applications in flexible magnetoelectronic devices. [ABSTRACT FROM AUTHOR]

With the merits of high sensitivity, high stability, high flexibility, low cost, and simple manufacturing, flexible magnetic field sensors have potential applications in various fields such as geomagnetosensitive E-Skins, magnetoelectric compass, and non-contact interactive platforms. Based on the principles of various magnetic field sensors, this paper introduces the research progress of flexible magnetic field sensors, including the preparation, performance, related applications, etc. In addition, the prospects of flexible magnetic field sensors and their challenges are presented. [ABSTRACT FROM AUTHOR]

Rare-earth and transition-metal (RE-TM) alloys have been studied extensively due to their unique optical and magneto-transport properties for advanced magnetic memory devices. Recent studies reveal an extra hump in the anomalous Hall effect in ferrimagnetic CoxGd100−x alloys with x ≈ 78, yet its origin is still ambiguous. In this article, the magnetic properties and Hall effect have been studied in CoxGd100−x alloys with varying Co concentrations in the range of 39 ≤ x ≤ 73. Complex anomalous Hall effect, including temperature-dependent polarity reversal and the appearance of an extra hump, has been found in a certain range of Co concentration. These characteristics were explained by the combined effect of magnetic domain evolution and spin-flop behavior. These results are helpful for understanding the complex transport properties in the RE-TM ferrimagnetic alloys. [ABSTRACT FROM AUTHOR]

Lidocaine salts self-assembled into different nano systems in water at a clinical dosage (2%, 0.2 mL) without excipient addition, and led to different sensory block durations and acute systemic toxicities, which were affected by the self-delivery and self-release behaviors of the salts in vivo. These differences were mainly caused by intermolecular π–π stacking under different conditions, which was proved by the unique supramolecular arrangement of gourd-shaped Janus particles. π–π stacking in lidocaine nano systems can be enhanced by carbon dioxide addition or the exchange of counter ions from Br− to Cl−. Without π–π stacking, nano systems self-assembled by lidocaine hydrobromide achieved 7.8 h sensory block by intradermal administration on rats, which is much longer than the efficacy of classical local anesthetics and more suitable for postoperative treatment. [ABSTRACT FROM AUTHOR]

Background: Anaemia is a common clinical manifestation observed in Takayasu's arteritis (TAK), but few studies have been conducted. This study investigated whether improvement of inflammatory indicators was associated with improvement of anaemia in TAK. We also investigated whether iron supplement treatment could benefit in addition to immunosuppressant therapy in the anaemia patients with TAK. Methods: This was a retrospective cohort study of 160 patients diagnosed with TAK. All patients were further assigned into anaemia group (67 cases) or non‐anaemia group (93 cases) according to their haemoglobin levels. Fifty two anaemia patients completed follow‐up (median 5.2 months). Results: There were 67 (41.88%) anaemia patients among all 160 TAK patients. Compared to TAK patients without anaemia, the average age [32 (24, 45) vs. 40 (31, 48), p = 0.002], disease duration [36 (7, 120) vs. 72 (14, 162), p = 0.017] and BMI [21.43 (18.96, 23.81) vs. 22.86 (20.09, 25.81), p = 0.008] were significantly lower in TAK patients with anaemia. The levels of ESR [23 (15, 51) vs. 11 (5.5, 22), p = 0.0001] and CRP [9.33 (1.99, 27.8) vs. 1.99 (0.45, 6.68), p = 0.0001] were significantly increased in TAK patients who complicated with anaemia. After follow‐up, decrease of ESR, CRP and disease activity score (NIH and ITAS) were significantly associated with improvement of anaemia. One unit decrease of ESR and CRP, the hazard ratio of the improvement rate of anaemia was 1.02 [95% CI (1.00, 1.03); p = 0.027] and 1.04 [95% CI (1.02, 1.07); p < 0.001] respectively. One point decrease of NIH and ITAS‐A was associated with a higher probability of anaemia improvement [HR 95% CI: 1.25 (1.02, 1.41), p = 0.022, HR 95% CI: 1.62 (1.21, 2.17), p = 0.001]. These relationships were consistent between iron supplement treatment group and without iron supplement treatment group. We found no significant difference in cumulative hazard between the two groups (p = 0.692). Conclusion: Anaemia was a common complication in TAK. Decrease of ESR, CRP and disease activity score (NIH and ITAS) were significantly associated with improvement of anaemia, even after adjusting for various covariates. Moreover, these relationships were consistent between iron supplement treatment group and without iron supplement treatment group. There was no significant difference in the improvement of anaemia in patients receiving immunosuppressant therapy with or without iron supplement treatment. [ABSTRACT FROM AUTHOR]

Objective: Mounting evidence has linked microbiome and metabolome to systemic autoimmunity and cardiovascular diseases (CVDs). Takayasu arteritis (TAK) is a rare disease that shares features of immune‐related inflammatory diseases and CVDs, about which there is relatively limited information. This study was undertaken to characterize gut microbial dysbiosis and its crosstalk with phenotypes in TAK. Methods: To address the discriminatory signatures, we performed shotgun sequencing of fecal metagenome across a discovery cohort (n = 97) and an independent validation cohort (n = 75) including TAK patients, healthy controls, and controls with Behçet's disease (BD). Interrogation of untargeted metabolomics and lipidomics profiling of plasma and fecal samples were also used to refine features mediating associations between microorganisms and TAK phenotypes. Results: A combined model of bacterial species, including unclassified Escherichia, Veillonella parvula, Streptococcus parasanguinis, Dorea formicigenerans, Bifidobacterium adolescentis, Lachnospiraceae bacterium 7 1 58FAA, Escherichia coli, Streptococcus salivarius, Klebsiella pneumoniae, Bifidobacterium longum, and Lachnospiraceae Bacterium 5 1 63FAA, distinguished TAK patients from controls with areas under the curve (AUCs) of 87.8%, 85.9%, 81.1%, and 71.1% in training, test, and validation sets including healthy or BD controls, respectively. Diagnostic species were directly or indirectly (via metabolites or lipids) correlated with TAK phenotypes of vascular involvement, inflammation, discharge medication, and prognosis. External validation against publicly metagenomic studies (n = 184) on hypertension, atrial fibrillation, and healthy controls, confirmed the diagnostic accuracy of the model for TAK. Conclusion: This study first identifies the discriminatory gut microbes in TAK. Dysbiotic microbes are also linked to TAK phenotypes directly or indirectly via metabolic and lipid modules. Further explorations of the microbiome–metagenome interface in TAK subtype prediction and pathogenesis are suggested. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to investigate whether PD-1 expressions are abnormal in patients with TAK. Methods: PD-1 expression was analyzed by flow cytometry. Serum cytokines IL-10, IL-7, IL-2, IL-15, CCL2, CCL3, and CXCL10 were detected using a cytokine cytometric bead array. Immunohistochemistry staining analysis was used to test PD-1 and programmed death-ligand 1 (PD-L1) expression in the aorta of three patients with TAK and three patients with atherosclerosis as controls. Results: The mean fluorescence intensity of PD-1 in CD4+PD-1+ cells was decreased in patients with TAK and the frequency of CD4+Foxp3-PD-1+ cells among CD4+T cells was also decreased in peripheral blood relative to healthy controls (P < .05). The percentage of CD4+CD25+Foxp3+PD-1+ cells in the CD4+CD25+T cell population was lower in patients with TAK than in healthy control and was lower in active TAK group (P < .05). Comparing PD-1 and PDL-1 expression in aorta tissue showed that patients with TAK tended to have lower levels than patients with atherosclerosis, but the difference was not significant (P > .05). Patients with TAK had higher serum levels of IL-10, IL-7, CCL2, and CCL3 (P < .05). Conclusions: Abnormal expression of PD-1 in serum and aorta tissue of patients with TAK may contribute to TAK pathogenesis. Key points: PD-1 expression in both peripheral blood and aorta tissue of TAK patients decreased relative to healthy controls, indicating that PD-1 might be involved in TAK pathogenesis. [ABSTRACT FROM AUTHOR]

The conserved Rap1 protein is part of the shelterin complex that plays critical roles in chromosome end protection and telomere length regulation. Previous studies have addressed how fission yeast Rap1 contributes to telomere length maintenance, but the mechanism by which the protein inhibits end fusions has remained elusive. Here, we use a mutagenesis screen in combination with high‐throughput sequencing to identify several amino acid positions in Rap1 that have key roles in end protection. Interestingly, mutations at these sites render cells susceptible to genome instability in a conditional manner, whereby longer telomeres are prone to undergoing end fusions, while telomeres within the normal length range are sufficiently protected. The protection of long telomeres is in part dependent on their nuclear envelope attachment mediated by the Rap1–Bqt4 interaction. Our data demonstrate that long telomeres represent a challenge for the maintenance of genome integrity, thereby providing an explanation for species‐specific upper limits on telomere length. Synopsis: Mutational analysis of the shelterin component Rap1 in fission yeast addresses its role beyond telomere length maintenance in protecting from chromosomal end fusions. Surprisingly, this reveals that long telomeres are vulnerable to undergoing end fusions, challenging the view that only critically short telomeres are at risk of being mistaken for DNA breaks. Rap1 functions in telomere length regulation and end protection.Mutagenesis screen identifies key residues for protecting telomeres against end fusions.Long telomeres are more prone to end fusions than normal length telomeres.Nuclear envelope attachment is critical for the protection of long telomeres. [ABSTRACT FROM AUTHOR]

Corruption in the host nation is a key issue influencing foreign direct investment. Most existing studies use the expert-knowledge-based corruption index as a proxy for corruption. However, the validity of these published corruption indexes is often questioned by scholars and experts. By introducing Internet data to evaluate public corruption awareness levels, this paper uses two different corruption proxy variables to investigate the relationship between host country corruption and China's OFDI. In addition, these relationships are further compared between the Belt and Road (B&R) countries and non-B&R countries. The empirical results show that there are negative correlations between host country corruption and China's OFDI flow for the whole sample, B&R countries and non-B&R countries. The empirical results of this paper serve as a reference for Chinese enterprises to make overseas investment decisions. [ABSTRACT FROM AUTHOR]

Aim: Systemic lupus erythematosus (SLE) with severe coronary artery disease (CAD) is associated with increased mortality. This study aimed to assess the characteristics and risk factors of severe CAD in SLE. Method: This multicenter, cross‐sectional study enrolled consecutive patients with SLE included in the Chinese Rheumatism Date Center registry. Patients with severe CAD including angiography‐confirmed stenosis ≥50% in the left main, ≥70% in other major coronary arteries, or myocardial infarction were classified into the CAD group. Patients without CAD were classified into the control group. Subgroups were stratified according to age (set as above and below 45 and 50 for men and women, respectively) and gender. Binary logistic regression analysis was performed to determine independent risk factors of severe CAD in SLE. Results: Forty‐three patients had severe CAD from a total of 3744 patients with SLE, 30 of whom were female; 35 belonged to the older age group and 8 belonged to the younger age group. In older patients, independent risk factors included age, 5 major CAD risk factors, SLE Disease Activity Index 2000 (SLEDAI‐2K), hyperuricemia, and corticosteroid exposure. In younger patients, the risk factors were 5 major CAD risk factors and positive antiphospholipid antibody (APL). Male risk factors were age and 5 major CAD risk factors, whereas female risk factors were age, 5 major CAD risk factors, SLEDAI‐2K, and positive APL. Three‐vessel disease was most prevalent in patients with severe CAD. Conclusion: We recommend screening for severe CAD in patients with SLE with age‐ and gender‐stratified risk factors. [ABSTRACT FROM AUTHOR]

The slip rates of active faults in the northeastern Tibetan Plateau (NETP) require clarification to understand the lateral expansion of the Tibetan Plateau and assess the seismic hazards in this region. To obtain the continuous slip rates of active faults at the NETP, we constructed a three-dimensional (3D) numerical geomechanics model that includes a complex 3D fault system. The model also accounts for the physical rock properties, gravity fields, fault friction coefficients, initial stress, and boundary conditions. Following this, we present the long-term kinematics of NETP based on the horizontal and vertical velocities and fault slip rates acquired from the model. The fault kinematic characteristics indicate that the Laohushan, middle–southern Liupanshan, and Guguan–Baoji faults, as well as the junction area of the Maxianshan and Zhuanglanghe faults, are potential hazard areas for strong earthquakes. However, as these faults are currently in the stress accumulation stage, they are unlikely to cause a strong earthquake in the short term. In contrast, it is likely that the Jinqiangshan–Maomaoshan fault will generate a earthquake with a surface-wave magnitude (MS) of 7.1–7.3 in the coming decades. In addition, the velocity profiles across the NETP imply that the plate rotation is the primary deformation mechanism of the NETP even though the intra-block straining and faulting are non-negligible. [ABSTRACT FROM AUTHOR]

Objectives: It has been known that aorta, subclavian, and extracranial arteries are commonly involved in Takayasu arteritis (TA). However, the involvement of intracranial artery in TA has not been well explored. The purpose of this study was to describe the clinical characteristics of intracranial artery lesions in TA patients and identify associated risk factors. Methods: A total of 160 patients diagnosed with TA at Beijing Anzhen Hospital from November 2012 to November 2019 were retrospectively enrolled in this study and assigned to different groups according to the presence or absence of intracranial artery lesions. Results: Our data showed that 20% of the enrolled 160 patients developed intracranial artery lesions and the right internal carotid artery (ICA) was the most common involved artery (53%). The average age of patients with intracranial artery lesions was significantly older compared to that of patients without intracranial artery involvement (43.56 ± 11.40 vs 36.41 ± 12.22, p = 0.003). In addition, more patients in the intracranial artery group had concomitant disease histories of stroke and/or hypertension (p = 0.010, 0.033). Chest tightness, chest pain, palpitation, coronary artery lesions, and extracranial segment lesions of ICA were more commonly observed in patients with intracranial artery lesions (p < 0.001, 0.017, 0.015, < 0.001, 0.003). Furthermore, we discovered that patients with coronary artery involvement, extracranial segment lesions of ICA, and higher Vasculitis Damage Index (VDI) score had an increased risk of developing intracranial artery lesions (p = 0.013, 0.019, 0.019). Conclusion: Our study showed that the intracranial artery disease was common in TA and was associated with coronary artery lesions, extracranial segment lesions of ICA, and higher VDI score. Key Points •Intracranial artery disease in TA patients had advanced age and higher triglyceride level. •Besides coronary artery lesions, intracranial artery disease in TA patients was associated with the extracranial segment lesions of ICA and higher VDI score. [ABSTRACT FROM AUTHOR]

Biofilm-associated Candida albicans infections, the leading cause of invasive candidiasis, can cause high mortality rates in immunocompromised patients. Photodynamic antimicrobial chemotherapy (PACT) is a promising approach for controlling infections caused by biofilm-associated C. albicans. This study shows the effect of Elsinochrome A (EA) against different stages of C. albicans biofilms in vitro by XTT reduction assay and crystal violet staining. The mechanism of action of EA on C. albicans biofilm was analyzed with flow cytometry, confocal laser microscopy, and the Real-Time Quantitative Reverse Transcription PCR (qRT-PCR). EA-mediated PACT significantly reduced the viability of C. albicans, with an inhibition rate on biofilm of 89.38% under a concentration of 32 μg/mL EA. We found that EA could not only inhibit the adhesion of C. albicans in the early stage of biofilm formation, but that it also had good effects on pre-formed mature biofilms with a clearance rate of 35.16%. It was observed that EA-mediated PACT promotes the production of a large amount of reactive oxygen species (ROS) in C. albicans and down-regulates the intracellular expression of oxidative-stress-related genes, which further disrupted the permeability of cell membranes, leading to mitochondrial and nuclear damage. These results indicate that EA has good photodynamic antagonizing activity against the C. albicans biofilm, and potential clinical value. [ABSTRACT FROM AUTHOR]

Aiming to identify the intellectual structure of risk management in foreign direct investment and its evolving trends, this paper introduces bibliometric analysis to systematically review the 1231 articles published between 1995 and 2022. Through the analysis of publication trends, influential indicators, cooperative networks, and citations, we draw the following important conclusions. From 1995 to 2021, the average annual growth rate of scientific production in the field reached 21.4%, with scholars from the United States and China contributing the most. Regarding the cooperation network, its structure is relatively dispersed, and the deep cooperation among a wide range of researchers has not yet been formed. As for research topics, the popularity of interest in environmental protection, carbon dioxide emissions, energy consumption, and climate change has increased significantly in recent years. Moreover, this paper points out that future research directions include new risks and challenges posed by the COVID-19 pandemic and the effects of climate risks on foreign direct investment. These results are helpful for scholars to systematically understand the current research status, research frontiers, and future trends of risk management in foreign direct investment. [ABSTRACT FROM AUTHOR]

F-box protein 5 (FBXO5), an essential subunit of the ubiquitin protein ligase complex, is increasingly recognized to exhibit important biological effects in regulating tumor occurrence and progression. The present research was intended to systematically investigate the latent roles of FBXO5 in prognosis and immunological function across cancers. Pan-cancer analyses of FBXO5 were performed based upon publicly available online databases, mainly including the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), UCSC Xena, cBioPortal, and ImmuCellAI, revealing the possible relationships between FBXO5 and prognosis, DNA methylation, tumor microenvironment (TME), infiltration of immune cells, immune-related genes, immune checkpoints, tumor mutation burden (TMB), and microsatellite instability (MSI). The results suggested that FBXO5 was expressed at a high level in numerous tumor cell lines with significant upregulation in most cancers as opposed to normal tissues. Of note, elevated expression of FBXO5 was significantly related to an unfavorable prognosis in many cancer types. Furthermore, DNA methylation and TME were confirmed to display evident correlation with the expression of FBXO5 in several malignancies. Moreover, FBXO5 expression was remarkably positively correlated with the levels of infiltrating Treg cells and Tcm cells in most tumors, but negatively correlated with tumor-infiltrating CD8+ T cells, NK/NKT cells, and Th2 cells. Meanwhile, FBXO5 was demonstrated to be co-expressed with the genes encoding immune activating and suppressive factors, chemokines, chemokine receptors, and major histocompatibility complex (MHC). Immune checkpoints, TMB, and MSI were also overtly associated with FBXO5 dysregulation among diverse kinds of cancers. Additionally, the enrichment analyses showed close relationships between FBXO5 expression and the processes related to cell cycle and immune inflammatory response. These findings provided a detailed comprehension of the oncogenic function of FBXO5. Because of its crucial roles in cancer immunity and tumorigenesis, FBXO5 may serve as a novel prognostic indicator and immunotherapeutic target for various malignancies. [ABSTRACT FROM AUTHOR]

In order to compare magnetic resonance imaging (MRI) findings of patients with large vestibular aqueduct syndrome (LVAS) in the stable hearing loss (HL) group and the fluctuating HL group, this paper provides reference for clinicians' early intervention. From January 2001 to January 2016, patients with hearing impairment diagnosed as LVAS in infancy in the Department of Otorhinolaryngology, Head and Neck Surgery, Children's Hospital of Fudan University were collected and divided into the stable HL group (n = 29) and the fluctuating HL group (n = 30). MRI images at initial diagnosis were collected, and various deep learning neural network training models were established based on PyTorch to classify and predict the two series. Vgg16_bn, vgg19_bn, and ResNet18, convolutional neural networks (CNNs) with fewer layers, had favorable effects for model building, with accs of 0.9, 0.8, and 0.85, respectively. ResNet50, a CNN with multiple layers and an acc of 0.54, had relatively poor effects. The GoogLeNet-trained model performed best, with an acc of 0.98. We conclude that deep learning-based radiomics can assist doctors in accurately predicting LVAS patients to classify them into either fluctuating or stable HL types and adopt differentiated treatment methods. [ABSTRACT FROM AUTHOR]

Telomerase reverse transcriptase (TERT) and the noncoding telomerase RNA (TR) subunit constitute the core of telomerase. Additional subunits are required for ribonucleoprotein complex assembly and in some cases remain stably associated with the active holoenzyme. Pof8, a member of the LARP7 protein family is such a constitutive component of telomerase in fission yeast. Using affinity purification of Pof8, we have identified two previously uncharacterized proteins that form a complex with Pof8 and participate in telomerase biogenesis. Both proteins participate in ribonucleoprotein complex assembly and are required for wildtype telomerase activity and telomere length maintenance. One factor we named Thc1 (Telomerase Holoenzyme Component 1) shares structural similarity with the nuclear cap binding complex and the poly-adenosine ribonuclease (PARN), the other is the ortholog of the methyl phosphate capping enzyme (Bin3/MePCE) in metazoans and was named Bmc1 (Bin3/MePCE 1) to reflect its evolutionary roots. Thc1 and Bmc1 function together with Pof8 in recognizing correctly folded telomerase RNA and promoting the recruitment of the Lsm2-8 complex and the catalytic subunit to assemble functional telomerase. Most eukaryotes maintain telomeres using a specialized reverse transcriptase. Here the authors report that Thc1 (Telomerase Holoenzyme Component 1) and Bmc1 (Bin3/MePCE 1) form a complex with Pof8, a constitutive member of telomerase in fission yeast. [ABSTRACT FROM AUTHOR]

Background: DHX15 is one of the RNA helicase family members involving in several biological processes. Studies have reported that overexpression of DHX15 is related to cancer progression. However, the role of DHX15 in Burkitt lymphoma (BL) and latent Epstein-Barr virus (EBV) infection remains to be elucidated. Methods: Expression of DHX15 was measured in BL patient by immunohistochemical staining. In vitro study, a CCK-8 assay was used to analyze cell proliferation and flow cytometry was performed to assess cell cycle, apoptosis and mitochondria membrane potential. Members of NF-κB signaling pathway and apoptotic-related proteins expression were measured by western-blot. EBV latent infection products and RNA polymerase III transcripts expression were determined by quantitative real-time PCR and western-blot. In vivo study, HE, IHC, TUNEL and ISH assays were used to analyze the effect of DHX15 on subcutaneous tumor nodes formation. Results: DHX15 was overexpressed in Burkitt lymphoma patients and tends to be associated with poor progression-free survival and poor overall survival. Knockdown of DHX15 significantly inhibited BL tumor growth, reduced cell proliferation, induced cell cycle arrest and increased cell apoptosis. Further analysis showed that canonical NF-κB signaling and its downstream targets, mitochondria and Caspase were involved in the increased cell apoptosis after DHX15 gene knockdown. Furthermore, knockdown of DHX15 reduced EBV latent infection products expression and inhibited RNA polymerase III activity. Conclusion: DHX15 may be an oncogene in the development of BL and a potential therapeutic target for the treatment of BL and latent EBV infection. [ABSTRACT FROM AUTHOR]