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Abstract Disruption of ciliary homeostasis in vascular endothelial cells has been implicated in the development of atherosclerosis. However, the molecular basis for the regulation of endothelial cilia during atherosclerosis remains poorly understood. Herein, we provide evidence in male mice that the accumulation of lipid droplets in vascular endothelial cells induces ciliary loss and contributes to atherosclerosis. Triglyceride accumulation in vascular endothelial cells differentially affects the abundance of free fatty acid species in the cytosol, leading to stimulated lipid droplet formation and suppressed protein S-palmitoylation. Reduced S-palmitoylation of ciliary proteins, including ADP ribosylation factor like GTPase 13B, results in the loss of cilia. Restoring palmitic acid availability, either through pharmacological inhibition of stearoyl-CoA desaturase 1 or a palmitic acid-enriched diet, significantly restores endothelial cilia and mitigates the progression of atherosclerosis. These findings thus uncover a previously unrecognized role of lipid droplets in regulating ciliary homeostasis and provide a feasible intervention strategy for preventing and treating atherosclerosis.

BackgroundChidamide is subtype-selective histone deacetylase (HDAC) inhibitor that showed promising result in clinical trials to improve prognosis of angioimmunoblastic T-cell lymphoma (AITL) patients. However, in real world settings, contradictory reports existed as to whether chidamide improve overall survival (OS). Therefore, we aimed to develop an interpretable machine learning (Machine learning)–based model to predict the 2-year overall survival of AITL patients based on chidamide usage and baseline features.MethodsA total of 183 patients with AITL were randomly divided into training set and testing set. We used 5 ML algorithms to build predictive models. Recursive feature elimination (RFE) method was used to filter for the most important features. The ML models were interpreted and the relevance of the selected features was determined using the Shapley additive explanations (SHAP) method and the local interpretable model–agnostic explanationalgorithm.ResultsA total of 183 patients with newly diagnosed AITL from 2012 to 2022 from 3 centers in China were enrolled in our study. Seventy-one patients were dead within 2 years after diagnosis. Five ML algorithms were built based on chidamide usage and 16 baseline features to predict 2-year OS. Catboost model presented to be the best predictive model. After RFE screening, 12 variables demonstrated the best performance (AUC = 0.8651). Using chidamide ranked third among all the variables that correlated with 2-year OS.ConclusionThis study demonstrated that the Catboost model with 12 variables could effectively predict the 2-year OS of AITL patients. Combining chidamide in the treatment therapy was positively correlated with longer OS of AITL patients.

BackgroundNeonatal deaths often result from preventable conditions that can be addressed with appropriate interventions. This study aims to analyze the distribution of the causes of neonatal death and explore genetic variations that lead to congenital anomalies in Northwest China.MethodsThis multi-center observational study was conducted across six medical centers in Shaanxi province, Northwest China. Clinical data were retrospectively collected from neonates admitted between 2016 and 2020. Kaplan-Meier analysis was utilized to estimate survival rates, while high-throughput sequencing platforms were employed to detect mutations causing congenital anomalies.ResultsAmong 73,967 neonates requiring hospital care, 424 neonatal deaths were recorded, leading to a neonatal mortality rate of 0.57%. The primary causes of death included neonatal respiratory distress syndrome (23.8%), birth asphyxia (19.8%), neonatal septicemia (19.3%), and congenital anomalies (13.6%). The leading causes of neonatal deaths due to congenital anomalies were congenital heart defects (38.6%), bronchopulmonary dysplasia (14.0%), and inherited metabolic disorders (10.5%). Genetic analysis identified 83 pathogenic or likely pathogenic variants in 23 genes among the neonates with congenital anomalies, including four novel mutations (c.4198+1G>T, c.1075delG, c.610-1G>A, c.7769C>T) in the ABCC8, CDKL5, PLA2G6, and NIPBL genes.ConclusionCongenital anomalies represent a significant and preventable cause of neonatal deaths in Northwest China. Early detection of congenital anomalies through genetic testing and comprehensive prenatal care are crucial for reducing neonatal mortality rates and improving pregnancy outcomes.

The imperative of gender diversity in corporate governance and the adoption of a human-centric governance paradigm are intensifying globally. The structure of board directors, key influencers to corporate decisions, notably shape policies, crucially in emerging markets like China where gender issues are still evolving. Therefore, employing a penal dataset comprising 8,973 firm-year observations from publicly A-share-listed Chinese firms spanning 2006 to 2021, this study empirically examines the impact of board gender diversity on the responsiveness to both employee monetary incentives and non-monetary rewards. The findings unveil a positive correlation, indicating an augmentation in per-employee compensation and an increased likelihood of implementing non-monetary programs, including stock-ownership plans, retirement benefits, and occupational safety certification, in the presence of higher board gender diversity. Notably, these positive associations are more accentuated in state-owned firms, as well as those with lower executive compensation and diminished institutional ownership. Our results remain consistent after considering robustness as well as endogeneity. This empirical evidence not only contributes robust statistical support to the ongoing global initiatives advocating for gender diversity in corporate governance but also underscores the efficacy of boards of directors in effectively managing stakeholder interests, particularly in fostering employee-friendly practices within emerging markets like China.

To evaluate the efficacy and safety of flumatinib in the later-line treatment of Chinese patients with Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia (CP-CML previously treated with tyrosine kinase inhibitors (TKIs). Patients with CML-CP were evaluated for the probabilities of responses including complete hematologic response (CHR), cytogenetic response, and molecular response (MR) and adverse events (AEs) after the later-line flumatinib therapy. Of 336 enrolled patients with median age 50 years, median duration of treatment with flumatinib was 11.04 (2-25.23) months. Patients who achieved clinical responses at baseline showed maintenance of CHR, complete cytogenetic response (CCyR)/2-log molecular response (MR2), major molecular response (MMR), and 4-log molecular response or deep molecular response (MR4/DMR) in 100%, 98.9%, 98.6%, and 92.9% patients, respectively. CHR, CCyR/MR2, MMR, and MR4/DMR responses were achieved in 86.4%, 52.7%, 49.6%, and 23.5% patients respectively, which showed the lack of respective clinical responses at baseline. The patients without response at baseline, treated with flumatinib as 2L TKI, having no resistance to prior TKI or only resistance to imatinib, with response to last TKI, and with BCR::ABL ≤10% had higher CCyR/MR2, MMR, or MR4/DMR. The AEs observed during the later-line flumatinib treatment were tolerable and consistent with those reported with the first-line therapy. Flumatinib was effective and safe in patients who are resistant or intolerant to other TKIs. In particular, 2L flumatinib treatment induced high response rates and was more beneficial to patients without previous 2G TKI resistance, thus serving as a probable treatment option for these patients.

Background: The development of tyrosine kinase inhibitor (TKI) therapy has positively impacted the survival rates of patients with chronic myeloid leukemia (CML). It is common in medical practice to adjust the dosage of TKI downward because of TKI-associated adverse events, financial burden, comorbidity, or an attempt at treatment-free remission. Objectives: This investigation sought to explore the feasibility of employing a reduced dosage of TKI for treating CML. Design: This was a retrospective study. Methods: Patients with CML in its chronic phase who had been on a reduced dose of TKI for a minimum of 3 months for various reasons in a practical clinical environment, irrespective of molecular response, were included. Regular molecular monitoring was performed, and changes in adverse events were recorded after dose reduction. Results: This research included a total of 144 participants. Upon reducing the dosage, 136 of 144 patients achieved major molecular response or deeper, and 132 of 144 achieved molecular response 4 (MR4). Following a median observation period of 16 months, the calculated 1- and 2-year survival rates free from MR4 failure were estimated to be 96.5% (95% CI: 90.8–98.7) and 90.5% (95% CI: 81.3–95.3), respectively. MR4 failure-free survival was better in patients with longer MR4 durations (⩾34 months) before dose reduction ( p = 0.02). The median interval from dose reduction to MR4 loss was 15 months. Improved TKI-associated adverse events after dose reduction were observed in 61.3% of patients. Conclusion: Lowering the TKI dose can effectively preserve a deep molecular response over time while relieving adverse events caused by TKIs.

The study aimed to evaluate the impact of varying modulus of elasticity (MOE) values of dental implants on the deformation and von Mises stress distribution in implant systems and peri-implant bone tissues under dynamic cyclic loading. The implant-bone interface was characterised as frictional contact, and the initial stress was induced using the interference fit method to effectively develop a finite element model for an immediately loaded implant-supported denture. Using the Ansys Workbench 2021 R2 software, an analysis was conducted to examine the deformation and von Mises stress experienced by the implant-supported dentures, peri-implant bone tissue, and implants under dynamic loading across three simulated masticatory cycles. These findings were subsequently evaluated through a comparative analysis. The suprastructures showed varying degrees of maximum deformation across zirconia (Zr), titanium (Ti), low-MOE-Ti, and polyetheretherketone (PEEK) implant systems, registering values of 103.1 μm, 125.68 μm, 169.52 μm, and 844.06 μm, respectively. The Zr implant system demonstrated the lowest values for both maximum deformation and von Mises stress (14.96 μm, 86.71 MPa) in cortical bone. As the MOE increased, the maximum deformation in cancellous bone decreased. The PEEK implant system exhibited the highest maximum von Mises stress (59.12 MPa), whereas the Ti implant system exhibited the lowest stress (22.48 MPa). Elevating the MOE resulted in reductions in both maximum deformation and maximum von Mises stress experienced by the implant. Based on this research, adjusting the MOE of the implant emerged as a viable approach to effectively modify the biomechanical characteristics of the implant system. The Zr implant system demonstrated the least maximum von Mises stress and deformation, presenting a more favourable quality for preserving the stability of the implant-bone interface under immediate loading.

Abstract Wheel polygonal wear can immensely worsen wheel/rail interactions and vibration performances of the train and track, and ultimately, lead to the shortening of service life of railway components. At present, wheel/rail medium- or high-frequency frictional interactions are perceived as an essential reason of the high-order polygonal wear of railway wheels, which are potentially resulted by the flexible deformations of the train/track system or other external excitations. In this work, the effect of wheel/rail flexibility on polygonal wear evolution of heavy-haul locomotive wheels is explored with aid of the long-term wheel polygonal wear evolution simulations, in which different flexible modeling of the heavy-haul wheel/rail coupled system is implemented. Further, the mitigation measures for the polygonal wear of heavy-haul locomotive wheels are discussed. The results point out that the evolution of polygonal wear of heavy-haul locomotive wheels can be veritably simulated with consideration of the flexible effect of both wheelset and rails. Execution of mixed-line operation of heavy-haul trains and application of multi-cut wheel re-profiling can effectively reduce the development of wheel polygonal wear. This research can provide a deep-going understanding of polygonal wear evolution mechanism of heavy-haul locomotive wheels and its mitigation measures.

Doxorubicin (DOX)-induced cardiotoxicity seriously limits its clinical applicability, and no therapeutic interventions are available. Ferroptosis, an iron-dependent regulated cell death characterised by lipid peroxidation, plays a pivotal role in DOX-induced cardiotoxicity. N6-methyladenosine (m6A) methylation is the most frequent type of RNA modification and involved in DOX-induced ferroptosis, however, its underlying mechanism remains unclear. P21 was recently found to inhibit ferroptosis by interacting with Nrf2 and is regulated in a P53-dependent or independent manner, such as through m6A modification. In the present study, we investigated the mechanism underlying m6A modification in DOX-induced ferroptosis by focusing on P21. Our results show that fat mass and obesity–associated protein (FTO) down-regulation was associated with DOX-induced cardiotoxicity. FTO over-expression significantly improved cardiac function and cell viability in DOX-treated mouse hearts and H9C2 cells. FTO over-expression significantly inhibited DOX-induced ferroptosis, and the Fer-1 inhibition of ferroptosis significantly reduced DOX-induced cardiotoxicity. P21 was significantly upregulated by FTO and activated Nrf2, playing a crucial role in the anti-ferroptotic effect. FTO upregulated P21/Nrf2 in a P53-dependent manner by mediating the demethylation of P53 or in a P53-independent manner by mediating P21/Nrf2 directly. Human antigen R (HuR) is crucial for FTO-mediated regulation of ferroptosis and P53–P21/Nrf2. Notably, we also found that P21 inhibition in turn inhibited HuR and P53 expression, while HuR inhibition further inhibited FTO expression. RNA immunoprecipitation assay showed that HuR binds to the transcripts of FTO and itself. Collectively, FTO inhibited DOX-induced ferroptosis via P21/Nrf2 activation by mediating the m6A demethylation of P53 or P21/Nrf2 in a HuR-dependent manner and constituted a positive feedback loop with HuR and P53–P21. Our findings provide novel insight into key functional mechanisms associated with DOX-induced cardiotoxicity and elucidate a possible therapeutic approach.

Abstract Three‐dimensional global precipitation observation is crucial for understanding climate and weather dynamics. While spaceborne precipitation radars provide precise but limited observations, passive microwave imagers are available much more frequently. In this study, we propose a deep learning approach to reconstruct active radar observations using passive microwave radiances. We introduce the Hybrid Deep Neural Network (HDNN) model, which utilizes reflectivity profiles from the Dual‐frequency Precipitation Radar (DPR) onboard the Global Precipitation Measurement (GPM) Core Observatory Satellite as the “target” and combines radiances from the GPM Microwave Imager (GMI) with supplementary reanalysis data to serve as the “features.” Results underscore the HDNN's exemplary performance, with a root mean square error below 4 dBZ across all altitude levels, and a consistent accuracy across different precipitation types. Its efficacy is further illustrated when applied to typhoon cases of Haishen and Khanun, emerging as a superior tool for capturing 3D structures of expansive precipitation systems.

Cotton aphids (Aphis gossypii Glover) pose a significant threat to cotton growth, exerting detrimental effects on both yield and quality. Conventional methods for pest and disease surveillance in agricultural settings suffer from a lack of real-time capability. The use of edge computing devices for real-time processing of cotton aphid-damaged leaves captured by field cameras holds significant practical research value for large-scale disease and pest control measures. The mainstream detection models are generally large in size, making it challenging to achieve real-time detection on edge computing devices with limited resources. In response to these challenges, we propose GVC-YOLO, a real-time detection method for cotton aphid-damaged leaves based on edge computing. Building upon YOLOv8n, lightweight GSConv and VoVGSCSP modules are employed to reconstruct the neck and backbone networks, thereby reducing model complexity while enhancing multiscale feature fusion. In the backbone network, we integrate the coordinate attention (CA) mechanism and the SimSPPF network to increase the model’s ability to extract features of cotton aphid-damaged leaves, balancing the accuracy loss of the model after becoming lightweight. The experimental results demonstrate that the size of the GVC-YOLO model is only 5.4 MB, a decrease of 14.3% compared with the baseline network, with a reduction of 16.7% in the number of parameters and 17.1% in floating-point operations (FLOPs). The mAP@0.5 and mAP@0.5:0.95 reach 97.9% and 90.3%, respectively. The GVC-YOLO model is optimized and accelerated by TensorRT and then deployed onto the embedded edge computing device Jetson Xavier NX for detecting cotton aphid damage video captured from the camera. Under FP16 quantization, the detection speed reaches 48 frames per second (FPS). In summary, the proposed GVC-YOLO model demonstrates good detection accuracy and speed, and its performance in detecting cotton aphid damage in edge computing scenarios meets practical application needs. This research provides a convenient and effective intelligent method for the large-scale detection and precise control of pests in cotton fields.

Aerosols exert a significant influence on the brightness temperature observed in the thermal infrared (IR) channels, yet the specific contributions of various aerosol types remain underexplored. This study integrated the Copernicus Atmosphere Monitoring Service (CAMS) atmospheric composition reanalysis data into the Radiative Transfer for TOVS (RTTOV) model to quantify the aerosol effects on brightness temperature (BT) simulations for the Advanced Himawari Imager (AHI) aboard the Himawari-8 geostationary satellite. Two distinct experiments were conducted: the aerosol-aware experiment (AER), which accounted for aerosol radiative effects, and the control experiment (CTL), in which aerosol radiative effects were omitted. The CTL experiment results reveal uniform negative bias (observation minus background (O-B)) across all six IR channels of the AHI, with a maximum deviation of approximately −1 K. Conversely, the AER experiment showed a pronounced reduction in innovation, which was especially notable in the 10.4 μm channel, where the bias decreased by 0.7 K. The study evaluated the radiative effects of eleven aerosol species, all of which demonstrated cooling effects in the AHI’s six IR channels, with dust aerosols contributing the most significantly (approximately 86%). In scenarios dominated by dust, incorporating the radiative effect of dust aerosols could correct the brightness temperature bias by up to 2 K, underscoring the substantial enhancement in the BT simulation for the 10.4 μm channel during dust events. Jacobians were calculated to further examine the RTTOV simulations’ sensitivity to aerosol presence. A clear temporal and spatial correlation between the dust concentration and BT simulation bias corroborated the critical role of the infrared channel data assimilation on geostationary satellites in capturing small-scale, rapidly developing pollution processes.

Abstract Background Treatment‐free remission (TFR) has become the main target for chronic myeloid leukemia (CML). Tyrosine kinase inhibitors (TKI) dose optimization is crucial in managing adverse events, and improving adherence in clinical practice. In persons achieving a deep molecular response (DMR), some data suggest TKI dose reduction before discontinuation does not change success rate of achieving TFR, but this is controversial. However, data on quality‐of‐life (QoL) and mental health in CML patients with full‐dose TKI, low‐dose TKI, and TKI discontinuation are limited. Moreover, recent evidence indicating the feasibility of TKI dose reduction and discontinuation after dose reduction, which may change CML patients' perspectives on TKI discontinuation. Methods We conducted a cross‐sectional study using online questionnaires to explore the QoL, mental health in patients with diverse TKI dose, and perspective on TKI dose reduction as a prelude to discontinuation. Results 1450 responses were included in the analysis. 44.3% of respondents reported a moderate‐to‐severe impact of TKI treatment on their QoL. 17% of respondents had moderate‐to‐severe anxiety. 24.4% of respondents had moderate‐to‐severe depression. In 1326 patients who had not discontinued their medication, 1055 (79.6%) patients reported they would try TKI discontinuation because of concerns over side effects of long‐term medication (67.9%), financial burden (68.7%), poor QoL (77.9%), pregnancy needs (11.6%), anxiety and depression while taking TKI (20.8%), inconvenience of TKI treatment (22.2%). 613 of 817 (75.0%) patients on full‐dose TKI therapy indicated they preferred trying a dose reduction before discontinuing TKI therapy after dose reduction compared with 31 (3.8%) preferring no dose reduction before stopping. Conclusions TKI dose reduction showed a significant improvement of patients' QoL and mental health, comparable to the effect of TKI discontinuation. Most patients indicated they preferred dose reduction before stopping TKI therapy. In clinical practice, TKI dose reduction can be considered as a bridge from full‐dose treatment to discontinuation. Our results showed that tyrosine kinase inhibitors (TKI) dose reduction showed a significant improvement of patients' quality‐of‐life and mental health, comparable to the effect of TKI discontinuation. Most patients desire to discontinue TKI in the future. TKI discontinuation after dose reduction is more acceptable compared to discontinuing it directly. In clinical practice, TKI dose reduction can be considered as a bridge from full‐dose treatment to discontinuation. Please do not hesitate to contact me in case further clarification is needed with this submission.

Abstract Hematopoietic stem cell transplantation (HSCT) is an effective treatment for many malignant hematological diseases. Mesenchymal stem cells (MSCs) are nonhematopoietic stem cells with strong self-renewal ability and multidirectional differentiation potential. They have the characteristics of hematopoietic support, immune regulation, tissue repair and regeneration, and homing. Recent studies have shown that HSCT combined with MSC infusion can promote the implantation of hematopoietic stem cells and enhance the reconstruction of hematopoietic function. Researchers have also found that MSCs have good preventive and therapeutic effects on acute and chronic graft-versus-host disease (GVHD), but there is still a lack of validation in large-sample randomized controlled trials. When using MSCs clinically, it is necessary to consider their dose, source, application time, application frequency and other relevant factors, but the specific impact of the above factors on the efficacy of MSCs still needs further clinical trial research. This review introduces the clinical roles of MSCs and summarizes the most recent progress concerning the use of MSCs in the field of HSCT, providing references for the later application of the combination of MSCs and HSCT in hematological diseases.

Abstract Background Myeloid sarcoma (MS) is a rare, extramedullary tumor consisting of myeloid blasts. Little is known about the genetic background of MS and the prognostic value of genetic abnormalities in MS. In particular, the broad variety of gene fusions that occur in MS is marginally covered by traditional testing methods due to lack of fresh tumor specimens. Methods Here, we analyzed the clinical and genetic features of 61 MS cases. We performed RNA sequencing (RNA‐seq) on formalin‐fixed paraffin‐embedded (FFPE) or fresh samples to analyze fusion genes in 26 cases. In addition, we performed genetic abnormalities‐based risk stratification using fusion genes and gene mutations. Results A total of 305 fusion genes were identified in 22 cases, including the following five recurrent fusion genes: RUNX1‐RUNX1T1, CBFβ‐MYH11, ETV6‐MECOM, FUS‐ERG, and PICALM‐MLLT10. The prognosis in the adverse‐risk group was significantly worse than that in the favorable/intermediate‐risk group (median survival: 12 months vs. not reached; p = 0.0004). Conclusion These results indicated the efficacy of RNA‐seq using FFPE‐derived RNA as a clinical routine for detecting fusion genes, which can be used as markers for risk stratification in MS.

Purinostat Mesylate (PM) is a novel highly selective and active HDAC I/IIb inhibitor, and the injectable formulation of PM (PMF) based on the compound prescription containing cyclodextrin completely can overcome PM's poor solubility and improves its stability and pharmacokinetic properties. Here, we showed that PM effectively repressed the survival of Ph+ leukemia cells and CD34+ leukemia cells from CML patients in vitro. In vivo studies demonstrated that PMF significantly prevented BCR-ABL(T315I) induced CML progression by restraining leukemia stem cells (LSCs), which are insensitive to chemotherapy and responsible for CML relapse. Mechanism studies revealed that targeting HDAC I/IIb repressed several important factors for LSCs survival including c-Myc, β-Catenin, E2f, Ezh2, Alox5, and mTOR, as well as interrupted some critical biologic processes. Additionally, PMF increased glutamate metabolism in LSCs by increasing GLS1. The combination of PMF and glutaminase inhibitor BPTES synergistically eradicated LSCs by altering multiple key proteins and signaling pathways which are critical for LSC survival and self-renewal. Overall, our findings represent a new therapeutic strategy for eliminating LSCs by targeting HDAC I/IIb and glutaminolysis, which potentially provides a guidance for PMF clinical trials in the future for TKI resistance CML patients.

Abstract Tread wear and rolling contact fatigue (RCF) damage propagated on railway wheels are the two extremely important focal points as they can tremendously deteriorate wheel/rail interactions and hunting stability and destroy wheel surface materials, and subsequently, cut down the lifetime of the wheels. The on-board anti-slip controllers are of essence aiming to hold back the striking slipping of the powered wheelsets under low-adhesion wheel/rail conditions. This paper intends to investigate the impact of anti-slip control on wheel tread wear and fatigue damage under diverse wheel/rail friction conditions. To this end, a prediction model for wheel wear and fatigue damage evolution on account of a comprehensive vehicle-track interaction model is extended, where the wheel/rail non-Hertzian contact algorithm is used. Furthermore, the effect of frictional wear on the fatigue damage at wheel surface is considered. The simulation results indicate that the wheel/rail contact is full-slip under the low-adhesion conditions with braking effort. The wear amount under the low-adhesion conditions is observably higher than that under the dry condition. It is further suggested that the wheel tread is prone to suffering more serious wear and fatigue damage issues with a higher anti-slip control threshold compared to that with a lower one.

A planar Langmuir probe, which can be used for both ion electric propulsion beam characteristics measurement and plasma diagnosis, was developed and applied to plume measurement and diagnosis experiments of an 8 cm Kaufman ion thruster to address the growing demand for miniaturized ion thruster plume measurement and diagnosis. The experimental results show that the plume area exhibits good symmetry along the central axis, and the beam dispersion angle of the 8 cm ion thruster is approximately 22.7°. The radial distributions of the floating potential, plasma space potential and ion density are similar, showing a high distribution in the middle and a relatively low distribution at the two ends. The miniaturized ion thruster plume measurement and diagnosis system is not only easy to manipulate, but also fast and efficient for plasma plume measurement and diagnosis, which provides more complete data support for analyzing the working state of the miniaturized ion thrusters and optimizing the design of the thruster structure.

Abstract Background Central diabetes insipidus (CDI) is a rare complication of myelodysplastic syndrome (MDS). Although the cytogenetic features of patients with MDS and CDI are not clear, CDI in patients with acute myeloid leukemia (AML) is associated with chromosome 7 and/or 3 anomalies. Case presentation In this report, we describe two patients with MDS and concurrent CDI, and in one of them, CDI was the first manifestation. One patient had monosomy 7 on metaphase cytogenetics (MC). Monosomy 7 and numerous cytogenetic abnormalities were found in the other patient using single-nucleotide polymorphism array (SNP-A) karyotyping, while the MC did not uncover monosomy 7. In this manuscript we also reviewed reported cases of MDS with diabetes insipidus (DI-MDS) to summarize the relationship between DI-MDS and karyotype, and explore the best treatment strategy for DI-MDS. Conclusions DI-MDS is closely related to monosomy 7. Allogeneic hematopoietic stem cell transplantation may be the only effective treatment for DI-MDS. The SNP-A-based karyotyping is helpful to reveal subtle cytogenetic abnormalities and unveil their roles in the clinical features of MDS.

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) dysregulates antiviral signaling, immune response, and cell metabolism in human body. Viral genome and proteins hijack host metabolic network to support viral biogenesis and propagation. However, the regulatory mechanism of SARS‐CoV‐2‐induced metabolic dysfunction has not been elucidated until recently. Multiomic studies of coronavirus disease 2019 (COVID‐19) revealed an intensive interaction between host metabolic regulators and viral proteins. SARS‐CoV‐2 deregulated cellular metabolism in blood, intestine, liver, pancreas, fat, and immune cells. Host metabolism supported almost every stage of viral lifecycle. Strikingly, viral proteins were found to interact with metabolic enzymes in different cellular compartments. Biochemical and genetic assays also identified key regulatory nodes and metabolic dependencies of viral replication. Of note, cholesterol metabolism, lipid metabolism, and glucose metabolism are broadly involved in viral lifecycle. Here, we summarized the current understanding of the hallmarks of COVID‐19 metabolism. SARS‐CoV‐2 infection remodels host cell metabolism, which in turn modulates viral biogenesis and replication. Remodeling of host metabolism creates metabolic vulnerability of SARS‐CoV‐2 replication, which could be explored to uncover new therapeutic targets. The efficacy of metabolic inhibitors against COVID‐19 is under investigation in several clinical trials. Ultimately, the knowledge of SARS‐CoV‐2‐induced metabolic reprogramming would accelerate drug repurposing or screening to combat the COVID‐19 pandemic.

PurposeTo investigate clinical characteristics, management, and prognosis of Epstein-Barr virus (EBV)-positive lymphoma-associated hemophagocytic syndrome (LAHS) patients in real-world practice.MethodsThis was a retrospective, single-center cohort study. EBV-positive LAHS patients diagnosed from January 2010 to December 2021 in our center were enrolled. Clinical characteristics, treatment, overall response rate (ORR), and overall survival (OS) were investigated. Univariate and multivariate analysis of potential factors were conducted.ResultsOf the 51 patients, 44 were T/NK cell lymphoma; five were B cell lymphoma; two were Hodgkin lymphoma. EBV-positive T/NK cell LAHS patients were significantly younger and showed lower fibrinogen levels and C-reactive protein levels than EBV-positive B cell LAHS patients (P=0.033, P=0.000, and P=0.004, respectively). Combined treatment of anti-hemophagocytic lymphohistiocytosis (HLH) and anti-lymphoma treatment was conducted in 24 patients; anti-HLH treatment was conducted in 18 patients; anti-lymphoma treatment was conducted in three patients; glucocorticoid treatment was conducted in one patient. ORR was 47.8%, and the median OS was 61 (95% confidence interval 47.9-74.1) days for overall patients. Patients who received anti-HLH treatment and turned to anti-lymphoma treatment early displayed higher ORR and OS than those of anti-HLH patients (P=0.103, and P=0.003, respectively). Elevated alanine aminotransferase level was the independent risk factor of EBV-positive LAHS prognosis.ConclusionsPrognosis of EBV-positive LAHS patients was poor. Anti-lymphoma treatment should be initiated as soon as HLH was rapidly controlled.

Post-translational O-linked β-N acetylglucosamine (O-GlcNAc) modification acts as a nutrient-sensing mechanism. Here the authors report that O-GlcNAc transferase inhibits adipose tissue lipolysis via O-GlcNAcylation of the lipid droplet protein perilipin 1 and thus promotes diet-induced obesity.

Scientific measurement of the appreciation effect of house prices after the installation of elevators in old residential areas would help build a reasonable urban renewal investment mechanism. Based on the transaction data of second-hand houses in old residential areas with elevators installed in Beijing from 2016 to 2021, a multiperiod DID model is constructed to measure the appreciation effect, dynamic effect, and heterogeneity effect brought by the installation of elevators and to explore the mechanism of the appreciation effect. The research results show that, overall, the installation of elevators boosts the house prices of the entire community, and the appreciation effect appears in advance due to good market expectations. However, the effect of house prices varies by floor. The higher the floor, the greater the appreciation of house prices, while low-rise residential buildings are depreciated by the installation of elevators. Mechanistic research shows that the appreciation of house prices on high floors is mainly due to the improvement in the living environment, and factors such as noise and poor lighting lead to depreciation on lower floors. The results of quantile regression analysis show that the appreciation effect brought by the installation of elevators increases with the increase in the residential value.

This paper describes the current literature on the molecular pathophysiology of interleukin-6 (IL-6) in the genesis of macular edema and on the outcomes with IL-6 inhibitors in the treatment of non-infectious macular edema. The role of IL-6 in the development of macular edema has been well elucidated. IL-6 is produced by multiple cells of the innate immune system and leads to a higher likelihood of developing autoimmune inflammatory diseases, such as non-infectious uveitis, through a variety of mechanisms. These include increasing the helper T-cell population over the regulatory T-cell population and leading to the increased expression of inflammatory cytokines, such as tumor necrosis factor-alpha. In addition to being key in the generation of uveitis and subsequent macular edema through these inflammatory pathways, IL-6 also can lead to the development of macular edema through other pathways. IL-6 induces the production of vascular endothelial growth factor (VEGF) and facilitates vascular leakage by downregulating tight junction proteins in retinal endothelial cells. Clinically, the use of IL-6 inhibitors has been found to be efficacious primarily in the context of treatment-resistant non-infectious uveitis and secondary macular edema. IL-6 is a key cytokine in retinal inflammation and macular edema. It is thus not surprising that the use of IL-6 inhibitors in treatment-resistant macular edema in the setting of non-infectious uveitis has been well documented as an effective treatment option. The use of IL-6 inhibitors in macular edema secondary to non-uveitic processes has only begun to be explored.

Endocannabinoid signaling regulates food intake and is a potential therapeutic target for obesity. Here the authors show that adipocyte O-GlcNAc transferase (OGT) is required for high fat diet-induced hyperphagia via transcriptional activation of de novo lipid desaturation and accumulation of an endogenous appetite-inducing cannabinoid.

The carbon emission trading system (CETS) is a milestone policy in the history of China’s emission trading system, which is of great significance to China’s realization of “carbon peak and carbon neutralization”. As an important component of sustainable development, LUT should be related to the CETS. However, in the literature on the CETS, little material deals with its impact on land use transition (LUT). This paper will enrich this literature. Based on 30 provincial regions in China from 2011 to 2017, using the DID and entropy methods, this study investigated the impact of CETS on the trend of LUT from three perspectives: economic effects, environmental effects and Porter effects. The conclusions are that (1) the implementation of the CETS hindered economic development, but optimized energy-use efficiency; (2) the implementation of the CETS reduced the emissions of CO2 and SO2; (3) the implementation of the CETS did not produce a Porter effect; and (4) the influence of the CETS had the characteristics of a spatial cluster. These findings offer some guidance for improving CETS policies and formulating similar environmental regulation policies.

Polyacrylate emulsions were prepared by Pickering emulsion polymerization with multi-modified hectorite as a modifier. The proper wettability of modified hectorite and the stability of O/W emulsions prove that modified hectorite has good emulsification properties. The stability of polyacrylate latexes and the morphology of polymer latex particles were then investigated to explain the role of multi-modified hectorite in stabilizing polyacrylate latex. In addition, the improved mechanical properties and water resistance of the latex make it a potentially excellent coating. Multi-modified hectorite as an alternative modifier to conventional surfactants offers a potential application of nanosolid particles that meet the partial wetting conditions for water and oil as stabilizers for the production of latexes for coatings.

Abstract The new competitive mechanism of intermolecular and intramolecular hydrogen bond can be proposed with an improved mixed model. Upon the photoinduced process, the twisting intramolecular charge transfer (TICT) structure of the hydroxyphenyl imidazo [1, 2-a] pyridine (HPIP) can be obtained. TICT character prompts the fluorescent inactivation via non-radiative decay process. For exploring the photochemical and photophysical properties, the electronic spectra and the infrared (IR) vibrational spectra of titled compounds have been detailedly investigated. In addition, the frontier molecular orbitals (MOs) analysis visually reveals that the unbalanced electron population can give rise to the torsion of molecular structure. To further give an attractive insight into the non-radiative decay process, the potential energy curves have been depicted on the ground state (S0), the first excited state (S1) and the triple excited state (T1). Minimum energy crossing point (MECP) has been found in the S1 and T1 state. On the MECP, the intersystem crossing (ISC) might be dominant channel. The density functional theory (DFT) and the time-dependent density functional theory (TDDFT) methods have been throughout employed in the S0 state, T1 state and S1 state, respectively. The theoretical results are consistent with experiment in mixed and PCM model.