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Abstract The effect of immune‐based therapies on patients with epidermal growth factor receptor (EGFR)-positive advanced non-small cell lung cancer (NSCLC) resistant to EGFR tyrosine kinase inhibitor (TKI) therapy remains unclear. The ALTER-L038 study aimed to evaluate efficacy and safety of a chemotherapy-free combination of benmelstobart, an anti-programmed cell death ligand 1 antibody, and anlotinib, a small-molecule multi-target anti-angiogenic TKI, in EGFR-positive advanced NSCLC patients who progressed after EGFR TKI therapy. Patients were enrolled in a phase I/II study. In phase I (dose-escalation), patients received anlotinib (8, 10, 12 mg) plus benmelstobart (1200 mg). Recommended phase II dose, determined during phase I, was used in phase II dose-expansion cohort. Primary endpoints were maximum tolerable dose in phase I and progression-free survival (PFS) in phase II. At the data cutoff date (March 10, 2024), 55 patients were enrolled in phase II dose-expansion cohort. Median PFS of patients included in phase II cohort was 9.0 months, median overall survival was 28.9 months, objective response rate was 25.5%, disease control rate was 87.3%, and median duration of response was 19.8 months. Incidence of grade ≥3 treatment-related adverse events in study population was 25.5% (14/55), whereas grade ≥3 immune-related adverse events occurred in 10.9% (6/55) of patients. Benmelstobart plus anlotinib showed promising anti-tumor efficacy with tolerable safety profile, supporting the value of further development of this convenient chemotherapy-free regimen for patients with EGFR-positive advanced NSCLC who progressed after EGFR TKI therapy. Trial Registration: ChiCTR1900026273.

Abstract Asymmetric catalysis for enantioselective intramolecular hydroamination of alkenes is a critical method in the construction of enantioenriched nitrogen-containing rings, often prevalent in biologically active compounds and natural products. Herein, we demonstrate a facile enantioselective intramolecular hydroamination of alkenes for the synthesis of chiral pyrrolidine, piperidine, and indoline moieties, using a manganese (II) chiral aprotic cyclic urea catalyst. The cyclic ligand hinders the inversion of the N atom of the urea and effectively discriminate between the enantiomers of substrates. High-resolution mass spectrometry, deuterium labeling experiments, and molecular orbital energy analysis clearly reveal the intermediates and mechanism of the transformation. As a key step, oxygen coordination by chiral aprotic urea presents a robust control over the asymmetric intra-HA reaction through the involvement of a convergent assembly of two vital intermediates (Mn-N and C-Mn-Br), providing access to chiral cyclic amine systems in high yields with excellent enantioselectivity.

Abstract The scavenging process significantly affects the combustion and emission performance of marine low-speed two-stroke dual-fuel engines. Optimizing scavenging air pressure and temperature can enhance the engine's combustion efficiency and emission control performance, thereby achieving more environmentally friendly and efficient operation of dual-fuel engines. This study focuses on marine low-speed two-stroke dual-fuel engines, analyzing the effects of scavenging air pressure (3.0 bar, 3.25 bar, 3.5 bar, and 3.75 bar) and scavenging air temperature (293 K, 303 K, and 313 K) on engine performance and emission products. The results indicate that scavenging air pressure has a greater impact on engine performance than scavenging air temperature. An increase in scavenging air pressure leads to higher thermal efficiency and power. As the scavenging air pressure increases from 3 to 3.75 bar, the indicated thermal efficiency (ITE) increases from 44.02 to 53.26%, and indicated mean effective pressure (IMEP) increases by approximately 0.35 MPa. Increased scavenging air pressure improves nitrogen oxide (NOx) and hydrocarbons (HC) emissions. For every 0.25 bar increase in scavenging air pressure, NOx emissions decrease by 3.53%, HC emissions decrease by 33.35%, while carbon dioxide (CO2) emissions increase by 0.71%. An increase in scavenging air temperature leads to lower ITE and IMEP. As the air temperature changes from 293 to 313 K, the ITE decreases by approximately 1%, and IMEP decreases by about 0.04 MPa. Increased scavenging air temperature improves CO2 emissions. For every 10 K increase in the air temperature, the CO2 emissions decrease by 0.02%, while NOx emissions increase by 4.84%, HC emissions increase by 34.39%. Therefore, controlling scavenging air pressure is more important than scavenging air temperature in the operational management of marine two-stroke engines. Higher power and lower NOx and HC emissions can be achieved by increasing the scavenging air pressure.

Objective: To evaluate the therapeutic effects of Epimedium brevicornu Maxim. (EBM, Yin Yang Huo) on breast cancer using network pharmacology and in vitro validation. It also aimed to explore the novel targets and mechanisms of EBM in the treatment of breast cancer to facilitate the discovery of new drugs and their clinical application. Methods: Network pharmacology was used to identify and screen the components and targets of EBM for breast cancer treatment. Molecular docking was further screened the effective components and targets of EBM. Wound-healing assays and flow cytometry analysis were used to detect the ability of two compounds to intervene in the migration and apoptosis of MDA-MB-231 cells, and their mechanism of action was further explored using western blotting experiments. Results: EBM contained 19 active components. Among them were β-anhydroicaritin (Anhy) and isoliquiritigenin (Iso), which were selected for in vitro experiments. Treatment resulted in a dose-dependent suppression of MDA-MB-231 cell viability, with an IC50 of 23.73 μmol/L for Iso and 21.28 μmol/L for Anhy. In the wound healing assay, cells in Anhy and Iso groups exhibited considerable inhibition of migration at 48 h. In flow cytometry analysis, treatment with Iso (20 μmol/L) for 96 h resulted in significantly higher levels of both early and late apoptosis in the Iso group than that in the control group (P = .004 and P = .014, respectively). Additionally, both Iso (20 μmol/L) and Anhy (10 and 20 μmol/L) induced cell necrosis at 96 h. Western blotting revealed that Anhy and Iso increased the expression of Bax and TBK1/NAK. Conclusion: These findings suggested that Anhy and Iso, the two components of EBM, inhibit MDA-MB-231 cell proliferation and migration of and induce their apoptosis, providing substantial support for future studies on breast cancer.

Abstract Background The accumulation of visceral and ectopic fat comprise a major cause of cardiometabolic diseases. However, novel drug targets for reducing unnecessary visceral and ectopic fat are still limited. Our study aims to provide a comprehensive investigation of the causal effects of the plasma proteome on visceral and ectopic fat using Mendelian randomization (MR) approach. Methods We performed two-sample MR analyses based on five large genome-wide association study (GWAS) summary statistics of 2656 plasma proteins, to screen for causal associations of these proteins with traits of visceral and ectopic fat in over 30,000 participants of European ancestry, as well as to assess mediation effects by risk factors of outcomes. The colocalization analysis was conducted to examine whether the identified proteins and outcomes shared casual variants. Results Genetically predicted levels of 14 circulating proteins were associated with visceral and ectopic fat (P

Abstract Background Hyperlipidemia is a major risk factor for many diseases. Previous studies have shown that diet is closely associated with hyperlipidemia. However, the relationship between cooking methods and hyperlipidemia remains unclear. The objective of this study was to identify the major cooking patterns existing in the Eastern Chinese population and evaluate their association with the prevalence of hyperlipidemia. Methods We interviewed 4,710 residents in Eastern China regarding the consumption frequency of each cooking method when they prepare food at home or when eating out and regarding the prevalence of hyperlipidemia. Factor analysis, Chi-square tests, analysis of variance, and binary logistic regression analysis were used to identify the cooking patterns and analyze the characteristics of participants’ categories of cooking patterns and the relationship between different cooking patterns and prevalence of hyperlipidemia. Results Three major cooking patterns were identified: Traditional Chinese, Bland (little or no oil is used to process the food), and High-temperature cooking patterns. After controlling for potential confounders, participants in the highest quartile of the Bland cooking pattern had lower odds of hyperlipidemia than those in the lowest quartile. Nevertheless, no significant associations were observed between the Traditional Chinese and High-temperature cooking patterns and the prevalence of hyperlipidemia. Conclusions This study confirms the association between cooking patterns and the prevalence of hyperlipidemia and indicates that the Bland cooking pattern is associated with a reduced prevalence of hyperlipidemia.

Objective: The aim of this study was to compare the differences in incident population, comorbidities, and glucose-lowering drug prescriptions between newly diagnosed patients with early-onset type 2 diabetes mellitus (T2DM) and those with late-onset T2DM to provide real-world evidence for clinical practice. Methods: This study was based on the Shanghai Hospital Link Database (SHLD). Anonymized electronic medical record (EHR) data from 2013 to 2021 were included in this study. Newly diagnosed patients with T2DM were defined as those without related diagnostic records or glucose-lowering medicine prescriptions in the past 3 years. Early-onset T2DM was defined as patients who were aged 18–40 years old at the first visit for T2DM to represent those who were born after the 1980s. And late-onset T2DM was defined as those aged 65–80 years old to represent those who were born in a relatively undeveloped period. Descriptive statistical analyses were performed to describe their incidence number, glucose-lowering drug prescriptions, and comorbidities at the first visit to the hospital between two T2DM groups. Results: There were a total of 35,457 newly diagnosed patients with early-onset T2DM and 149,108 newly diagnosed patients with late-onset T2DM included in this study. Patients with late-onset T2DM constituted the majority and their number increased by 2.5% on average by years, while the number of patients with early-onset T2DM remained stable each year. Compared with late-onset T2DM patients, more early-onset T2DM patients had dyslipidemia at the first visit to hospitals (9.5% vs 7.7%, P < 0.01) despite their significant age differences. Patients with early-onset T2DM were more likely to use metformin (74.8% vs 46.5, P < 0.01), dipeptidyl peptidase-4 inhibitors (DDP-4i) (16.7% vs 11.2%, P < 0.01), thiazolidinediones (TZD) (14.9% vs 8.4%, P < 0.01), sodium glucose cotransporter 2 inhibitors (SGLT2-i) (0.8% vs 0.3%, P < 0.01), and glucagon-like peptide 1 receptor agonists (GLP-1 RA) (3.7% vs 0.5%, P < 0.01) at their first visit to the hospital. Conclusions: Different characteristics were observed between patients with early-onset T2DM and those with late-onset T2DM. Compared with patients with late-onset T2DM, those with early-onset T2DM were more prone to dyslipidemia and had novel organ-protective drugs prescribed.

The reversible photo-induced conformation transition of a single molecule with a [5]helicene backbone has garnered considerable interest in recent studies. Based on such a switching process, one can build molecular photo-driven switches for potential applications of nanoelectronics. But the achievement of high-performance reversible single-molecule photoswitches is still rare. Here, we theoretically propose a 13,14-dimethylcethrene switch whose photoisomerization between the ring-closed and ring-open forms can be triggered by ultraviolet (UV) and visible light irradiation. The electronic structure transitions and charge transport characteristics, concurrent with the photo-driven electrocyclization of the molecule, are calculated by the non-equilibrium Green’s function (NEGF) in combination with density functional theory (DFT). The electrical conductivity bears great diversity between the closed and open configurations, certifying the switching behavior and leading to a maximum on–off ratio of up to 103, which is considerable in organic junctions. Further analysis confirms the evident switching behaviors affected by the molecule–electrode interfaces in molecular junctions. Our findings are helpful for the rational design of organic photoswitches at the single-molecule level based on cethrene and analogous organic molecules.

In northern China, plastic-shed vegetable production significantly contributes to nitrogen (N)-induced groundwater eutrophication due to excessive fertilization and irrigation. However, the impact of optimized farming practices on N leaching has seldom been systematically examined. We conducted a four-season field study to evaluate the impacts of optimal farming measures on tomato yield, water percolation, N concentration in leachate, and total N (TN) leaching. The treatments included conventional fertilization and flood irrigation (CON), fertilization decreased by 20% and flood irrigation (OPT1) or drip fertigation (OPT2), fertilization decreased by 30% and drip fertigation (OPT3), and no fertilization with flood irrigation (CK). Compared with the CON treatment, the optimal treatments significantly reduced annual TN leaching by 9.92–50.7% without affecting tomato yield (57.1–98.2 t ha−1 for CON and 48.1–106 t ha−1 for three optimal treatments). Drip irrigation contributed 73.8–79.0% to the mitigation of TN leaching. The N originating from soil and irrigation water exhibited a similar contribution to TN leaching (45.4–58.6%) to that of fertilizer N. The daily TN leaching at the basal fertilization stage was much greater than that at the top-dressing stage, due to over-fertilization. Optimizing fertilization, particularly basal fertilization, in combination with drip irrigation could substantially reduce N leaching in plastic-shed vegetable production. Other optimal practices, such as decision support systems (DSSs) and fertilizer amendments, could also be investigated to further mitigate the N leaching.

Abstract Searching for multiferroic materials with ferromagnetic (FM) and ferroelectric (FE) properties holds promise for ultra‐high‐density and low‐energy‐consumption memory device applications, but 2D materials with both properties are rare. Herein, a general strategy to achieve nonvolatile electric field control of magnetism in the bilayer (BL) α‐In2Se3 by hole doping is proposed. By first‐principles calculations, it is demonstrated that hole doping can induce robust ferromagnetism in the bilayer α‐In2Se3 due to its unique flat Mexican‐hat‐shape valence band structure. Such band edges cause van Hove singularities (VHS), and proper hole doping can lead to time‐reversal symmetry breaking. The bilayer α‐In2Se3 exhibits ferromagnetism and ferroelectricity within a wide range of doping concentrations, resulting in an unexpected multiferroic phase. Furthermore, when the electrical polarization of α‐In2Se3 flips from downward to upward, it becomes non‐magnetic (NM) from ferromagnetic states in the As‐substituted bilayer α‐In2Se3, which can work as a nonvolatile magnetic storage unit. Remarkably, the As‐substituted bilayer α‐In2Se3 exhibits an enhanced magnetic moment of 1.2 μB per AsSe due to substantial charge transfer across the interface. Notably, the mechanism of electrically controlled magnetism is elucidated as the coupling among the Mexican‐hat‐like dispersion, ferromagnetism, and ferroelectricity. The findings offer a promising strategy for electrical writing and the magnetic reading memory device.

Abstract The topological Hall effect (THE) presents hump signals in the Hall resistance versus magnetic field hysteresis loop, showing promise for future spintronics due to its robust chiral magnetic textures. Here, it is shown that solid‐state protonic gating can control possible topological magnetic structures in CoGd thin films. Injecting H+ leads to sizable hump signals in the film. Magneto‐optical Kerr microscopy shows that induced hump signals in transporting measurements do not scale with magnetization, supporting topological magnetism. Successive hydrogen ion extraction completely erases the effect. Thus, topological magnetism manipulations are reversible, nonvolatile, and effective. Ab inito calculations and effective chiral spin models demonstrate that hydrogen injection remarkably enhances the Dzyaloshinskii–Moriya interaction over fourfold, stabilizing chiral structures contributing to the large THE. These findings reveal the vital role of hydrogen ions in topological magnetism and suggest that amorphous ferrimagnetic CoGd thin films are outstanding platforms for realizing controllable topological spintronics at room temperature.

In order to overcome the problems of complex chiral molecular structure, high molecular weight and consumption of equivalent heavy metal salts in purely chemical S/R interconversion of amino acids, a novel method for S/R interconversion of amino acids was developed by using structurally simple 2-hydroxycamphor or 3-hydroxycamphor. The reaction conditions were optimized by assessing the base, solvent and reaction temperature. Then the S/R interconversion of racemic and enantiopure amino acids with different side chains were carried out. The result shows that the best interconversion effect is obtained at 40 ℃ with potassium tert-butoxide as the base and isopropanol as the solvent. Various amino acids with fatty and aromatic side chains are well tolerated in the reactions and the S/R interconversion of amino acids can be carried out efficiently, showing excellent stereoselectivities, and the hydroxycamphors can be reused. The mechanism study shows that the high stereoselectivity of dynamic resolution is thermodynamically controlled. This method has the advantages of using structurally simple and recyclable chiral reagents, avoiding the synthesis of specific substrates from amino acids and giving good reaction conversions and stereoselectivity, which provides a novel approach for purely chemical S/R-interconversion of amino acids.

Abstract Angiotensin converting enzyme 2 (ACE2) played a critical role in regulating renin‐angiotensin‐aldosterone system (RAAS). In this research, 68Ga‐cyc‐DX600 was synthesized as PET tracer of ACE2 imaging. ACE2 positron emission tomography/magnetic resonance (PET/MR) was preliminary administered on twelve healthy volunteers, and the images were normalized and registered to establish the standard model of ACE2 PET. In diseased conditions, 68Ga‐cyc‐DX600 PET and 18F‐FDG PET were compared for COVID‐19 (one in acute phase and three in post‐COVID), anemia (n = 1) and malignancies (n = 2) to evaluate the diagnostic efficiency. 68Ga‐cyc‐DX600 PET was of a definite ACE2 dependence. For the tracer uptake of ACE2 PET/MR of female and male, differences existed in salivary glands, upper respiratory tract and kidneys, meanwhile, age, and body mass index (BMI) were also the confounding factors. RAAS‐related tissue and organs were of the relatively higher tracer uptake, such as SUVmean of cardiac chamber (3.786 ± 1.495), liver (5.342 ± 2.267), spleen (4.465 ± 2.508), and kidney (4.906 ± 1.619 for female and 8.431 ± 5.179 for male). For COVID‐19, ACE2 PET revealed ACE2 fluctuations, particularly in the susceptible organs, including liver, spleen and testis. In the case of anemia, the activated local RAS in the bone marrow was of diffuse high tracer uptake. ACE2 PET of malignancies added supplementary information to FDG PET. 68Ga‐cyc‐DX600‐based ACE2 PET models were established for visually monitoring of whole‐body ACE2 expression. The feasibility of ACE2 PET in supervising disease was primarily proved in COVID‐19, anemia and malignancies as providing a comprehensive view on the disease process and functional recovery.

Summary: Patients with type 2 diabetes mellitus (T2DM) are at a heightened risk of living with multiple comorbidities. However, the comprehension of the multimorbidity characteristics of T2DM is still scarce. This study aims to illuminate T2DM’s prevalent comorbidities and their interrelationships using network analysis. Using electronic medical records (EMRs) from 496,408 Chinese patients with T2DM, we constructed male and female global multimorbidity networks and age- and sex-specific networks. Employing diverse network metrics, we assessed the structural properties of these networks. Furthermore, we identified hub, root, and burst diseases within these networks while scrutinizing their temporal trends. Our findings uncover interconnected T2DM comorbidities manifesting as emergence in clusters or age-specific outbreaks and core diseases in each sex that necessitate timely detection and intervention. This data-driven methodology offers a comprehensive comprehension of T2DM’s multimorbidity, providing hypotheses for clinical considerations in the prevention and therapeutic strategies.

Remote sensing images acquired by different sensors exhibit different characteristics due to their distinct imaging mechanisms. The fusion of Synthetic Aperture Radar (SAR) and optical remote sensing images is valuable for specific remote sensing image applications, as it enables the extraction of texture features from SAR images while preserving the spectral information of optical images. Several existing fusion approaches have been proposed in recent years, including the Nonsubsampled Shearlet Transform Pulse Coupled Neural Network (NSST-PCNN), which is a typical and effective fusion method. However, it suffers from the inconsistency in regional edge information. To address this issue, we propose a new method called MS-NSST-PCNN for multi-model fusion of SAR and optical remote sensing images. This method incorporates the multiScale morphological gradient (MSMG) into NSST-PCNN to detect edges and enhance the utilization of edge characteristics. The fusion results of two polarization modes, VV and VH are evaluated in combination with existing methods, using image fusion accuracy and visual interpretation criteria. The results demonstrate that for Sentinel 1 and Landsat 8 OLI image fusion the proposed MS-NSST-PCNN method achieves higher correlation coefficients and lower spectral distortion with VV polarization compared to traditional methods in two study areas. Moreover, the proposed method also exhibits better performance for GF3 and GF2 images with higher spatial resolution. In subsequent applications of land classification in urban and rural scenarios, the fusion results of the proposed method achieve higher accuracy than those of other fusion methods or source images applied directly.

Abstract Background All‐cause mortality risk prediction models for patients with type 2 diabetes mellitus (T2DM) in mainland China have not been established. This study aimed to fill this gap. Methods Based on the Shanghai Link Healthcare Database, patients diagnosed with T2DM and aged 40‐99 years were identified between January 1, 2013 and December 31, 2016 and followed until December 31, 2021. All the patients were randomly allocated into training and validation sets at a 2:1 ratio. Cox proportional hazards models were used to develop the all‐cause mortality risk prediction model. The model performance was evaluated by discrimination (Harrell C‐index) and calibration (calibration plots). Results A total of 399 784 patients with T2DM were eventually enrolled, with 68 318 deaths over a median follow‐up of 6.93 years. The final prediction model included age, sex, heart failure, cerebrovascular disease, moderate or severe kidney disease, moderate or severe liver disease, cancer, insulin use, glycosylated hemoglobin, and high‐density lipoprotein cholesterol. The model showed good discrimination and calibration in the validation sets: the mean C‐index value was 0.8113 (range 0.8110–0.8115) and the predicted risks closely matched the observed risks in the calibration plots. Conclusions This study constructed the first 5‐year all‐cause mortality risk prediction model for patients with T2DM in south China, with good predictive performance.

Designing scaled electronic devices for neuromorphic applications remains a challenge. Here, Zhang et al. develop an artificial molecular synapse based on self-assembled peptide molecule monolayer whose conductance can be dynamically modulated and used for waveform recognition.

IntroductionAlthough the subthalamic nucleus (STN) has proven to be a safe and effective target for deep brain stimulation (DBS) in the treatment of primary dystonia, the rates of individual improvement vary considerably. On the premise of selecting appropriate patients, the location of the stimulation contacts in the dorsolateral sensorimotor area of the STN may be an important factor affecting therapeutic effects, but the optimal location remains unclear. This study aimed to define an optimal location using the medial subthalamic nucleus border as an anatomical reference and to explore the influence of the location of active contacts on outcomes and programming strategies in a series of patients with primary dystonia.MethodsData from 18 patients who underwent bilateral STN-DBS were retrospectively acquired and analyzed. Patients were assessed preoperatively and postoperatively (1 month, 3 months, 6 months, 1 year, 2 years, and last follow-up after neurostimulator initiation) using the Toronto Western Spasmodic Torticollis Rating Scale (for cervical dystonia) and the Burke–Fahn–Marsden Dystonia Rating Scale (for other types). Optimal parameters and active contact locations were determined during clinical follow-up. The position of the active contacts relative to the medial STN border was determined using postoperative stereotactic MRI.ResultsThe clinical improvement showed a significant negative correlation with the y-axis position (anterior–posterior; A+, P−). The more posterior the electrode contacts were positioned in the dorsolateral sensorimotor area of the STN, the better the therapeutic effects. Cluster analysis of the improvement rates delineated optimal and sub-optimal groups. The optimal contact coordinates from the optimal group were 2.56 mm lateral, 0.15 mm anterior, and 1.34 mm superior relative to the medial STN border.ConclusionSTN-DBS was effective for primary dystonia, but outcomes were dependent on the active contact location. Bilateral stimulation contacts located behind or adjacent to Bejjani’s line were most likely to produce ideal therapeutic effects. These findings may help guide STN-DBS preoperative planning, stimulation programming, and prognosis for optimal therapeutic efficacy in primary dystonia.

Defects play a crucial role in modulating the properties of solid-state materials by inducing localized states that often benefit magnetic moments. Recently, direct experimental observations have shown the appearance of bunches of eight-atom-ring line defects in the T-phase VSe2 monolayer, a remarkable room-temperature two-dimensional magnetic metal. Using first-principles calculations, we have found that these line defects could enhance the magnetic moments, and half-metallicity (nearly 100% spin polarization) can be achieved in the structure with the densest defects. Furthermore, our analysis of the partial charge density distribution shows that a closer inter-defect distance between the d-states of vanadium atoms and p-states of selenium atoms increases the penalty of electrons occupying the spin-minority states. Moreover, we have discovered the high conductivity channel exhibits negative differential resistance characteristics within a bias range of 0.2 to 0.4 V (–0.4 to –0.2 V). Our findings broaden the scope of the applications of two-dimensional materials in spintronics and provide some theoretical guidance for the design of high-performance spintronic devices.

Abstract The 2050 carbon‐neutral vision spawns a novel energy structure revolution, and the construction of the future energy structure is based on equipment innovation. Insulating material, as the core of electrical power equipment and electrified transportation asset, faces unprecedented challenges and opportunities. The goal of carbon neutral and the urgent need for innovation in electric power equipment and electrification assets are first discussed. The engineering challenges constrained by the insulation system in future electric power equipment/devices and electrified transportation assets are investigated. Insulating materials, including intelligent insulating material, high thermal conductivity insulating material, high energy storage density insulating material, extreme environment resistant insulating material, and environmental‐friendly insulating material, are categorised with their scientific issues, opportunities and challenges under the goal of carbon neutrality being discussed. In the context of carbon neutrality, not only improves the understanding of the insulation problems from a macro level, that is, electrical power equipment and electrified transportation asset, but also offers opportunities, remaining issues and challenges from the insulating material level. It is hoped that this paper envisions the challenges regarding design and reliability of insulations in electrical equipment and electric vehicles in the context of policies towards carbon neutrality rules. The authors also hope that this paper can be helpful in future development and research of novel insulating materials, which promote the realisation of the carbon‐neutral vision.

Objective: To investigate the value of dual-energy CT left ventricular iodinogram imaging and plasma B-type natriuretic peptide level in the early diagnosis and prediction of heart failure and severity in patients with acute myocardial infarction. Methods: AMI patients admitted to our hospital from January 2018 to December 2019 were selected to complete dual-energy coronary artery CTA and plasma BNP examination, and cardiac function grading was assessed within 1 week after admission. Myocardial iodine content was measured to evaluate the myocardial perfusion on dual-energy CT. The correlation between myocardial iodine content, left ventricular ejection fraction and BNP level was analyzed, and the differences of myocardial perfusion, LVEF and BNP levels among different Killip cardiac function grading groups in HF patients were compared. Results: A total of 115 patients with AMI were enrolled, including 42 patients in HF group and 73 patients in non-HF group. There were significant differences in myocardial iodine concentration, LVEF and BNP between the two groups. Iodine concentration and LVEF were negatively correlated with BNP (r=−0.527, −0.674). The ROC curve showed that the AUC of myocardial iodine concentration combined with BNP in predicting HF after AMI was higher than that of iodine map and BNP alone. Among the 42 HF patients after AMI, with the increase of Killip grade, serum BNP level increased, LVEF and iodine content of infarct myocardial decreased, and there were statistically significant differences in BNP, LVEF and iodine content of infarct myocardial among different grade groups. Conclusion: Dual-energy CT left ventricular iodinogram combined with BNP level has predictive value on the occurrence of heart failure after acute myocardial infarction, and has a certain correlation with the clinical severity of heart failure.

IntroductionExtended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae pose a huge threat to human health, especially in the context of complicated urinary tract infections (cUTIs). Carbapenems and piperacillin–tazobactam (PTZ) are two antimicrobial agents commonly used to treat cUTIs.MethodsA monocentric retrospective cohort study focused on the treatment of cUTIs in adults was conducted from January 2019 to November 2021. Patients with a positive urine culture strain yielding ≥ 103 colony-forming units per milliliter (CFU/mL), and sensitive to PTZ and carbapenems, were included. The primary endpoint was clinical success after antibiotic therapy. The secondary endpoint included rehospitalization and 90-day recurrence of cUTIs caused by ESBL-producing Enterobacteriaceae.ResultsOf the 195 patients included in this study, 110 were treated with PTZ while 85 were administered meropenem. The rate of clinical cure was similar between the PTZ and meropenem groups (80% vs. 78.8%, p = 0.84). However, the PTZ group had a lower duration of total antibiotic use (6 vs. 9; p < 0.01), lower duration of effective antibiotic therapy (6 vs. 8; p < 0.01), and lower duration of hospitalization (16 vs. 22; p < 0.01).DiscussionIn terms of adverse events, the safety of PTZ was higher than that of meropenem in the treatment of cUTIs.

The construction of artificial synapse based on the electric field‐controlled ion migration has been developed to be a prospective approach to achieving intelligent devices with advantage of low‐energy consumption. However, it is still a very challenging task for artificial synapses to imitate the complex synapse diversity of biological system. Herein, the ionic liquid gating induced oxygen ion migration to realize the reversible phase transition between insulating SrCoO2.5 and metallic SrCoO3 with anisotropic dynamics due to the fast oxygen transport channel along [110] crystal orientation is used. The crystal orientation‐dependent oxygen ion migration and resultant metal–insulator transition offer an intriguing opportunity to build up a variety of artificial synapses with different performances, like excitatory or inhibitory characters, learning accuracy, and cooperation capability. Our findings not only give an insight into the anisotropic ion migration in oxides but also could be a fundamental step toward the development of diverse oxide‐based artificial neural networks.

Objective: The association between insulin therapy and the risk of biliary tract cancer (BTC) is uncertain. We aimed to assess this risk in type 2 diabetic patients. Methods: Using electronic medical data from the Shanghai Hospital Link database, 202,557 patients with type 2 diabetes (164,997 insulin never-users and 37,560 insulin ever-users) were identified in this study between January 1, 201 3, and December 31, 2016, with follow-up until December 31, 2019. By propensity score matching, an ever-user was matched with a never-user. Cox proportional hazards regression analysis was used to estimate risk ratios (HRs) and 95% CIs for three subtypes of BTC (intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), and gallbladder cancer (GBC)). Results: At a mean follow-up of 5.33 years, 143 cases of BTC were observed. The crude incidence rates (per 100,000 person-years) of ECC, ICC, and GBC in ever-users:never-users were 10.22:3.63, 2.04:2.04, and 8.17:6.01, respectively. Insulin therapy was associated with an increased risk of ECC (HR, 4.10; 95% CI, 1.54–10.92; P = 0.005) compared to patients who never used insulin. No statistically s ignificant results were observed for insulin and ICC/GBC. Consistent results were also found in the original cohort. Conclusions: The relationship between insulin therapy and BTC is type-speci fic. Further studies are warranted to provide evidence on the identification of ECC risk groups among type 2 diabetic patients.

Abstract The objective of this study was to predict the preoperative pathological grading and survival period of Pseudomyxoma peritonei (PMP) by establishing models, including a radiomics model with greater omental caking as the imaging observation index, a clinical model including clinical indexes, and a combined model of these two. A total of 88 PMP patients were selected. Clinical data of patients, including age, sex, preoperative serum tumor markers [CEA, CA125, and CA199], survival time, and preoperative computed tomography (CT) images were analyzed. Three models (clinical model, radiomics model and combined model) were used to predict PMP pathological grading. The models’ diagnostic efficiency was compared and analyzed by building the receiver operating characteristic (ROC) curve. Simultaneously, the impact of PMP’s different pathological grades was evaluated. The results showed that the radiomics model based on the CT’s greater omental caking, an area under the ROC curve ([AUC] = 0.878), and the combined model (AUC = 0.899) had diagnostic power for determining PMP pathological grading. The imaging radiomics model based on CT greater omental caking can be used to predict PMP pathological grading, which is important in the treatment selection method and prognosis assessment.

With the increasingly maturing technology of unmanned surface vehicles (USVs), their applications are becoming more and more widespread. In order to meet operational requirements in complex scenarios, the real-time interaction and linkage of a large amount of information is required between USVs, between USVs and mother ships, and between USVs and shore-based monitoring systems. Visual images are the main perceptual information gathered from USVs, and their efficient transmission and recognition directly affect the real-time performance of information exchange. However, poor maritime communication signals, strong channel interference, and low bandwidth pose great challenges to efficient image transmission. Traditional image transmission methods have difficulty meeting the real-time and image quality requirements of visual image transmissions from USVs. Therefore, this paper proposes an efficient method for visual image transmission from USVs based on semantic communication. A self-encoder network for semantic encoding which compresses the image into low-dimensional latent semantics through the encoding end, thereby preserving semantic information while greatly reducing the amount of data transmitted, is designed. On the other hand, a generative adversarial network is designed for semantic decoding. The decoding end decodes and reconstructs high-quality images from the semantic information transmitted through the channel, thereby improving the efficiency of image transmission. The experimental results show that the performance of the algorithm is significantly superior to traditional image transmission methods, achieving the best image quality while transmitting the minimum amount of data. Compared with the typical BPG algorithm, when the compression ratio of the proposed algorithm is 51.6% of that of the BPG algorithm, the PSNR and SSIM values are 7.6% and 5.7% higher than the BPG algorithm, respectively. And the average total time of the proposed algorithm is only 59.4% of that of the BPG algorithm.

Change detection based on multi-temporal synthetic aperture radar (SAR) images plays a significant role in environmental and earth observations. With the advancement in deep neural networks, existing work in the literature mainly concentrates on developing self-supervised methods to generate pseudo-labeled samples to guide the subsequent deep learning based detection. However, this way of selecting sample inevitably introduces erroneous labels and imbalance between unchanged and changed classes, thus causing deterioration in change detection performance. To mitigate these issues, we have proposed a SAR change detection network based on visual saliency and multi-hierarchical fuzzy clustering. Specifically, with multi-dimensional difference feature representations, a visual saliency based difference map is constructed for accurate difference feature extraction. By integrating neighborhood information and hierarchical clustering, the multi-hierarchical fuzzy local information C-means clustering algorithm has been developed to identify potential changed regions for sample selection. A class-balanced adaptive focal loss has further been incorporated into the network training to obtain accurate predictions. Extensive experiments and comparisons on five datasets have been performed. The proposed method has achieved averaged accuracy of 99.07% and Kappa coefficient of 79.87%, outperforming other state-of-the-art algorithms both visually and quantitatively.

Cooking methods can change the composition of foods and have important effects on human health. The Chinese people have developed many distinct and unique cooking methods. However, the daily cooking patterns of Chinese people and the characteristics and evolution of trends in cooking patterns commonly used by Chinese consumers remain unclear. The objective of this study was to identify the major cooking patterns and discuss their effects on human health, as well as to identify the cooking pattern consumer clusters and the evolution of trends in Chinese consumer cooking patterns. From March to June 2021, this study interviewed 4,710 residents in Eastern China regarding the consumption frequency of each cooking method when food is prepared at home or when eating out. Exploratory factor analysis, K-Means cluster analysis, Chi-square test, pairwise comparisons of multiple sample rates, and multivariate linear regression were used to identify the cooking patterns and cooking pattern consumer clusters, to assess differences in consumption preferences between consumer clusters, and to examine the relationship between demographic characteristic variables and different cooking patterns. Results revealed three major cooking patterns, namely traditional Chinese (cooking methods with native Chinese characteristics), bland, and high-temperature cooking patterns, as well as seven cooking pattern consumer clusters and their demographic characteristics in the Eastern Chinese population. With increases in age, education level, and income, consumers tended to choose the healthy "Bland" cooking pattern. Further, there was a higher proportion of people aged 36-65 years in the C3 cluster, which is characterized by the "Bland" cooking pattern. However, participants who were male and younger made fewer healthy choices in their cooking patterns. Specifically, a higher proportion of participants aged 21-35 years were found in the C5 cluster, which is characterized by the unhealthy "High-temperature" cooking pattern. Therefore, culinary health education should focus on individuals who are male and young. Specifically, the shift in cooking patterns among people aged 21-35 years should receive special attention.

Background: Various therapeutic strategies are available for the first-line treatment of patients with advanced hepatocellular carcinoma (aHCC). But which approach is the most cost-effective remains uncertain. Objectives: This study aims to evaluate the cost-effectiveness of first-line strategies in aHCC patients from the perspective of Chinese and US payers. Design: A network meta-analysis (NMA) and cost-effectiveness study. Data sources and methods: A NMA was conducted to collect all first-line strategies with aHCC from 1 October 1 2018 until 1 January 2022. The relevant randomized controlled trial literature in PubMed, Embase, and Cochrane Library for the last 3 years were searched. The abstracts of meetings of the American Society of Clinical Oncology, European Society of Medical Oncology, and American Association for Cancer Research were also reviewed. A Markov model that included three states was developed. One-way sensitivity and probabilistic sensitivity analysis were performed to investigate the uncertainty of the economic evaluation. Scenario analysis was conducted to explore the economic benefits of treatment strategies in low-income populations. Results: Base-case analysis in China included 1712 patients showed that atezolizumab combined with bevacizumab, sintilimab combined with bevacizumab, lenvatinib (LEVA), and sorafenib (SORA) added 0.46, 1.25, 0.77, and −1.08 quality-adjusted life-years (QALYs), respectively, compared with donafenib, resulting in an incremental cost-effective ratio of $85607.88, $12109.27, and $1651.47 per QALY at a willingness-to-pay (WTP) of $11101.70/QALY. In the United States, only the incremental cost-effectiveness ratios (ICERs) of SORA was higher that were lower than the WTP threshold ($69375/QALY), and LEVA was the most cost-effective strategy with the ICERs were 25022.13/QALY. Conclusion: The NMA and cost-effectiveness analysis revealed that LEVA is the favorite choice in the first-line treatment of Chinese aHCC patients and US payers’ perspective when the WTP was $11101.70/QALY in China and $69375.0/QALY in the United States. Registration: This study has been registered on the PROSPERO database with the registration number CRD42021286575.

Knowledge of adequate diets can improve an individual's health status. Although previous studies have identified the main resources from which Chinese people acquire dietary knowledge, it is still unclear whether information sources regarding diets (ISRDs) can increase individuals' knowledge of adequate diets (KAD) and which ISRDs are most effective in conveying KAD to the Chinese population. In this study, we interviewed 4,710 residents in Eastern China regarding their ISRDs and KAD. Descriptive statistics, ANOVA, and multivariate linear regression were used to analyze the effectiveness of different ISRDs in transmitting KAD to Chinese individuals and to determine the relationship between ISRDs and KAD. Results showed that the KAD scores of the respondents were low overall in Eastern China. Providing dietary information through expert lectures, books, newspapers, magazines, and social media could significantly improve the average KAD score of Chinese individuals. Respondents with a greater number of ISRDs were more likely to have higher KAD scores. These findings suggest that the number of ISRDs should be increased. In particular, emphasis should be placed on the role of expert lectures, books, newspapers, magazines, and social media.

Abstract FKBP4 belongs to the family of immunophilins, which serve as a regulator for steroid receptor activity. Thus, FKBP4 has been recognized to play a critical role in several hormone-dependent cancers, including breast and prostate cancer. However, there is still no research to address the role of FKBP4 on lung adenocarcinoma (LUAD) progression. We found that FKBP4 expression was elevated in LUAD samples and predicted significantly shorter overall survival based on TCGA and our cohort of LUAD patients. Furthermore, FKBP4 robustly increased the proliferation, metastasis, and invasion of LUAD in vitro and vivo. Mechanistic studies revealed the interaction between FKBP4 and IKK kinase complex. We found that FKBP4 potentiated IKK kinase activity by interacting with Hsp90 and IKK subunits and promoting Hsp90/IKK association. Also, FKBP4 promotes the binding of IKKγ to IKKβ, which supported the facilitation role in IKK complex assembly. We further identified that FKBP4 TPR domains are essential for FKBP4/IKK interaction since its association with Hsp90 is required. In addition, FKBP4 PPIase domains are involved in FKBP4/IKKγ interaction. Interestingly, the association between FKBP4 and Hsp70/RelA favors the transport of RelA toward the nucleus. Collectively, FKBP4 integrates FKBP4/Hsp90/IKK with FKBP4/Hsp70/RelA complex to potentiate the transcriptional activity and nuclear translocation of NF-κB, thereby promoting LUAD progression. Our findings suggest that FKBP4 may function as a prognostic biomarker of LUAD and provide a newly mechanistic insight into modulating IKK/NF-κB signaling.

Abstract Background Cerebral venous thrombosis (CVT) occurs rarely in the general population and is frequently associated with confused clinical findings and delayed diagnosis. Isolated cerebellar cortical vein thrombosis is a very rare phenomenon. Case presentation This report describes a case with CVT, which is manifested as space-occupying lesions of the cerebellar hemisphere and mimics a cerebellar tumor at the beginning. The diagnosis of CVT was finalized given the laboratory and brain biopsy findings. The etiology may be related to polycythemia vera with Janus Kinase 2 V617F mutation. Conclusion Isolated cerebellar vein thrombosis should be considered when swelling and enhancing cerebellar lesions are detected. Polycythemia vera, especially with a positive JAK2 V617F mutation, may be a rare risk factor for CVT.

BackgroundDepression detection has recently received attention in the field of natural language processing. The task aims to detect users with depression based on their historical posts on social media. However, existing studies in this area use the entire historical posts of the users and select depression indicator posts. Moreover, these methods fail to effectively extract deep emotional semantic features or simply concatenate emotional representation. To solve this problem, we propose a model to extract deep emotional semantic features and select depression indicator posts based on the emotional states. ObjectiveThis study aims to develop an emotion-based reinforcement attention network for depression detection of users on social media. MethodsThe proposed model is composed of 2 components: the emotion extraction network, which is used to capture deep emotional semantic information, and the reinforcement learning (RL) attention network, which is used to select depression indicator posts based on the emotional states. Finally, we concatenated the output of these 2 parts and send them to the classification layer for depression detection. ResultsExperimental results of our model on the multimodal depression data set outperform the state-of-the-art baselines. Specifically, the proposed model achieved accuracy, precision, recall, and F1-score of 90.6%, 91.2%, 89.7%, and 90.4%, respectively. ConclusionsThe proposed model utilizes historical posts of users to effectively identify users’ depression tendencies. The experimental results show that the emotion extraction network and the RL selection layer based on emotional states can effectively improve the accuracy of detection. In addition, sentence-level attention layer can capture core posts.

In this study, we demonstrated that the expression of FK506 binding protein 51 (FKBP51) is upregulated in acute monocytic leukemia (AML-M5) cells by dexamethasone and aimed to investigate the possible effects of FKBP51 on the growth and cytarabine sensitivity of AML-M5 cells. THP-1 and U937cells were used to establish AML-M5 cell models with FKBP51 overexpression and knockdown, respectively. Cell proliferation, apoptosis and response to cytarabine were investigated by cell cycle, CCK-8 and Flow cytometry analyses. The mice experiment was conducted to detect the role of FKBP51 on AML-M5 cells proliferation and antileukemia effect of Ara-C/Dexamethasone co-therapy in vivo. Western blots were employed to determine protein expression levels. FKBP51 upregulation significantly attenuated THP-1 cell proliferation and sensitized the cells to cytarabine treatment which was further enhanced by dexamethasone. These effects were indicated by decreases in cell viability, S-G2/M phase cell cycle distribution, cytarabine 50% inhibitory concentration (IC50) values and increases in apoptosis and were supported by decreased phosphorylation levels of AKT, GSK3β and FOXO1A and decreased levels of BCL-2 and increased levels of P21 and P27. In contrast, FKBP51 knockdown led to excessive U937 cell proliferation and cytarabine resistance, as indicated by increased cell viability and S-G2/M phase cell cycle distribution, decreased apoptosis, increased phosphorylation levels of AKT, GSK3β and FOXO1A, and increased BCL-2 and decreased P21 and P27 expression. In addition, an AKT inhibitor blocked cell cycle progression and reduced cell viability in all groups of cells. Furthermore, SAFit2, a specific FKBP51 inhibitor, increased U937 cell viability and cytarabine resistance as well as AKT phosphorylation. In conclusion, FKBP51 decelerates proliferation and improves the cytarabine sensitivity of AML-M5 cells by inhibiting AKT pathways, and dexamethasone in combination with Ara-C improves the chemosensitivity of AML-M5.

Accumulating evidence indicates the critical roles of group 2 innate lymphoid cells (ILC2s) in immunoregulation. However, the role of ILC2s in acute rejection after liver transplantation (LT) remains elusive. In this study, we analyzed the frequency, counts, and signature cytokines of ILC2s in liver transplant recipients by flow cytometric analysis and multiplex immunofluorescence assay. We also assessed the spatial distribution and correlation between hepatic ILC2s and Treg cells. The changes of ILC2s were dynamically monitored in the mouse LT model. We found that the frequencies of circulating ILC2s were comparable in liver transplant recipients with either rejection or non-rejection compared with the control group. The hepatic ILC2s counts were significantly increased in the rejection group than in the non-rejection and control groups, and a similar trend was observed for Treg cells. In the mouse LT model, allograft infiltrating ILC2s dramatically increased within 14 days post-transplant. The frequency of ILC2s in bone marrow significantly increased at 7 days post-transplant and rapidly decreased at 14 days after LT. Similarly, there was a significant increase in the frequency of splenic ILC2s within two weeks post-transplant. Multiplex immunofluorescence assay showed a close correlation between hepatic ILC2s and Treg cells by analyzing their spatial distribution and distance. In conclusion, the number of allograft infiltrating ILC2s was closely related to rejection after LT. Allograft infiltrating ILC2s may play inhibitory roles in posttransplant immune homeostasis, favoring resolution of liver allograft rejection by interacting with Treg cells or promoting the migration of Tregs cells into the liver allograft.

Hepatic ischemia-reperfusion injury (IRI) is an adverse consequence of hepatectomy or liver transplantation. Recently, immune mechanisms involved in hepatic IRI have attracted increased attention of investigators working in this area. In specific, group 2 innate lymphoid cells (ILC2s), have been strongly implicated in mediating type 2 inflammation. However, their immune mechanisms as involved with hepatic IRI remain unclear. Here, we reported that the population of ILC2s is increased with the development of hepatic IRI as shown in a mouse model in initial stage. Moreover, M2 type CD45+CD11b+F4/80high macrophages increased and reached maximal levels at 24 h followed by a significant elevation in IL-4 levels. We injected exogenous IL-33 into the tail vein of mice as a mean to stimulate ILC2s production. This stimulation of ILC2s resulted in a protective effect upon hepatic IRI along with an increase in M2 type CD45+CD11b+F4/80high macrophages. In contrast, depletion of ILC2s as achieved with use of an anti-CD90.2 antibody substantially abolished this protective effect of exogenous IL-33 and M2 type CD45+CD11b+F4/80high macrophage polarization in hepatic IRI. Therefore, this exogenous IL-33 induced potentiation of ILC2s appears to regulate the polarization of CD45+CD11b+F4/80high macrophages to alleviate IRI. Such findings provide the foundation for the development of new targets and strategies in the treatment of hepatic IRI.

The South Yanchuan block is the deepest developed high-rank coalbed methane (CBM) field in China, the geological conditions in this block are complex and the main controlling factors of CBM content are various. Thus, a decision-making model of the potential of deep high-rank coalbed methane resource based on geographical information system (GIS) and weighted linear combination (WLC) is established, the influence of geological conditions on CBM content is analyzed, the favorable areas of CBM potential are divided. Results show that the buried depth, coal rank and hydrodynamic condition in the coal seam are dominant factors that control the gas content on a block scale, while the gas content has a weak correlation with maceral composition, coal thickness and the effective thickness of the overlying strata. The study area is divided into five units according to the natural breaks method, i.e., the extramely favourable area, the favourable area, the relatively favourable area, the normally favourable area and the unfavourable area, which account for 14.23%, 22.23%, 24.77%, 25.08% and 13.70% in area, respectively. The extramely favourable area is located in the northwestern of the South Yanchuan block, which is considered to be the key exploration and development area. The study will deepen the understanding of the control of CBM potential in south Yanchuan Block, and is of practical significance for CBM recovery in this area.

Although the variation in chromatin architecture during adaptive immune responses has been thoroughly investigated, the 3D landscape of innate immunity is still unknown. Herein, chromatin regulation and heterogeneity among human primary monocytes were investigated. Peripheral blood was collected from two healthy persons and two patients with systemic lupus erythematosus (SLE), and CD14+ monocytes were selected to perform Hi-C, RNA-seq, ATAC-seq and ChIP-seq analyses. Raw data from the THP1 cell line Hi-C library were used for comparison. For each sample, we constructed three Hi-C libraries and obtained approximately 3 billion paired-end reads in total. Resolution analysis showed that more than 80% of bins presented depths greater than 1000 at a 5 kb resolution. The constructed high-resolution chromatin interaction maps presented similar landscapes in the four individuals, which showed significant divergence from the THP1 cell line chromatin structure. The variability in chromatin interactions around HLA-D genes in the HLA complex region was notable within individuals. We further found that the CD16-encoding gene (FCGR3A) is located at a variable topologically associating domain (TAD) boundary and that chromatin loop dynamics might modulate CD16 expression. Our results indicate both the stability and variability of high-resolution chromatin interaction maps among human primary monocytes. This work sheds light on the potential mechanisms by which the complex interplay of epigenetics and spatial 3D architecture regulates chromatin in innate immunity.

Aberrant methylation is a hallmark of hepatocellular carcinoma and plays an important role in tumor initiation and progression. However, the epigenome-wide methylation patterns of portal vein tumor thrombosis (PVTTs) have not been fully explored. Here, we performed epigenome-wide DNA methylation of adjacent normal tissues (ANTs), paired tumor tissues and paired PVTTs using an Infinium HumanMethylation450 array (n = 11) and conducted the Sequenom EpiTYPER assays to confirm the aberrantly methylated genes. MTS and apoptosis assay were used to assess the synergistic effect of two drugs on the HCC cell lines. We found the mean global methylation levels of HCC tissues and PVTTs were significantly lower than ANTs (P 10%, P

Abstract Objectives We aimed to examine how gray matter volume (GMV), regional blood flow (rCBF), and resting‐state functional connectivity (FC) of the basal nucleus of Meynert (BNM) are altered in 40 patients with AD, relative to 30 healthy controls (HCs). Methods We defined the BNM on the basis of a mask histochemically reconstructed from postmortem human brains. We examined GMV with voxel‐based morphometry of high‐resolution structural images, rCBF with arterial spin labeling imaging, and whole‐brain FC with published routines. We performed partial correlations to explore how the imaging metrics related to cognitive and living status in patients with AD. Further, we employed receiver operating characteristic analysis to compute the “diagnostic” accuracy of these imaging markers. Results AD relative to HC showed lower GMV and higher rCBF of the BNM as well as lower BNM connectivity with the right insula and cerebellum. In addition, the GMVs of BNM were correlated with cognitive and daily living status in AD. Finally, these imaging markers predicted AD (vs. HC) with an accuracy (area under the curve) of 0.70 to 0.86. Combination of BNM metrics provided the best prediction accuracy. Conclusions By combining multimode MR imaging, we demonstrated volumetric atrophy, hyperperfusion, and disconnection of the BNM in AD. These findings support cholinergic dysfunction as an etiological marker of AD and related dementia.

Abstract The advances of mobile equipment and localization techniques put forward the accuracy of the location-based service (LBS) in mobile networks. One core issue for the industry to exploit the economic interest of the LBSs is to make appropriate point-of-interest (POI) recommendation based on users’ interests. Today, the LBS applications expect the recommender systems to recommend the accurate next POI in an anonymous manner, without inquiring users’ attributes or knowing the detailed features of the vast number of POIs. To cope with the challenge, we propose a novel attentive model to recommend appropriate new POIs for users, namely Geographical Attentive Recommendation via Graph (GARG), which takes full advantage of the collaborative, sequential and content-aware information. Unlike previous strategies that equally treat POIs in the sequence or manually define the relationships between POIs, GARG adaptively differentiates the relevance of POIs in the sequence to the prediction, and automatically identifies the POI-wise correlation. Extensive experiments on three real-world datasets demonstrate the effectiveness of GARG and reveal a significant improvement by GARG on the precision, recall and mAP metrics, compared to several state-of-the-art baseline methods.

Large SAR images usually contain a variety of land-cover types and accordingly complicated change types, which cause great difficulty for accurate change detection. The U-Net is a special fully convolutional neural network that not only can capture multiple features in the image context but also enables precise pixel-by-pixel image classification. Therefore, we explore the U-Net to describe accurately the differences between bi-temporal SAR images for high-precision change detection. However, large scene SAR images often have significantly different statistical distributions for various change types, which prevents the U-Net from working properly. We modified the U-Net by introducing the batch normalization (BN) operation at the input of every neuron to regularize the statistical distributions of its input data for avoiding the risk of gradient disappearance or dispersion during the network training. In addition, the ELU (Exponential Linear Unit) activation function replaces the ReLU (Rectified Linear Unit) function to improve further the gradients backpropagation. Then we selected bi-temporal Sentinel-1SAR data covering Jiangsu Province, China, to discuss quantitatively and qualitatively the detection performance and model complexity of the modified network with different numbers of convolutional kernels.

Objectives The aim of this study was to determine the lag between exposure to air pollutants and changes in human eosinophil counts. Material and Methods This was a retrospective study employing 246 425 physical examination records dated December 2013 – December 2016 from Chengdu, China. The authors determined the prevalence of individuals with eosinophil counts above the normal reference range each day. A distributed lag non-linear model was used to evaluate the lagged effect of each air pollutant on eosinophil counts. The lagged effects of each air pollutant were counted and presented with smoothing splines. Results The effects of air pollutants such as particulate matter (PM 2.5 , aerodynamic diameters

Although artificial Lieb lattices have been recently synthesized, the realization of a Lieb lattice in a real material is still challenging. Here the authors use tight-binding and first principle calculations to predict tunable topology and magnetism in recently discovered two-dimensional covalent-organic frameworks.

The effect of solution treatment and intermediate heat treatment on the microstructure and properties of a new cast nickel-based high-Cr superalloy was investigated in this paper. The results indicate that the tensile strength and elongation at 900 °C increase when the solution temperature increases from 1160 °C to 1180 °C and then decrease when the solution temperature changes from 1180 °C to 1200 °C and 1220 °C. The stress rupture test results of the high-Cr superalloy under conditions of 900 °C/275 MPa shows that the rupture time, elongation, and reduction of area initially increased and then decreased with the increase in solution treatment temperatures. The results of stress rupture tests for the alloy after intermediate heat treatment followed by furnace-cooling, air-cooling, and water-cooling show that the morphology and distribution of γ’ phase have a great influence on the tensile test results at 900 °C of the alloy but no obvious influence on the test at 900 °C/275 MPa. The microstructure analysis of the superalloy after heat treatment shows that: when the solution treatment temperatures are at 1200 °C and 1220 °C, the incipient melting appears in the interdendritic region, which can severely deteriorate mechanical properties; the morphology of γ′ phase changes gradually from cube to spherical; and a large number of fine γ’ phase precipitates in the γ channel are found with increasing cooling rate after intermediate heat treatment.

The fluorination strategy is one of the most efficient and popular molecular modification methods to develop new materials for organic photovoltaic (OPV) cells. For OPV materials, it is a broad agreement that fluorination can reduce the energy level and change the morphology of active layers. To explore the effect of fluorination on small molecule acceptors, we selected two non-fullerene acceptors (NFA) based bulk heterojunction (BHJ) films, involving PM6:Y6 and PM6:Y5 as model systems. The electron mobilities of the PM6:Y5 and PM6:Y6 BHJ films are 5.76 × 10−7 cm2V−1s−1 and 5.02 × 10−5 cm2V−1s−1 from the space-charge-limited current (SCLC) measurements. Through molecular dynamics (MD) simulation, it is observed that halogen bonds can be formed between Y6 dimers, which can provide external channels for electron carrier transfer. Meanwhile, the “A-to-A” type J-aggregates are more likely to be generated between Y6 molecules, and the π–π stacking can be also enhanced, thus increasing the charge transfer rate and electron mobility between Y6 molecules.

Background: The drug therapy of venous thromboembolism (VTE) presents a significant economic burden to the health-care system in low- and middle-income countries. To understand which anticoagulation therapy is most cost-effective for clinical decision-making , the cost-effectiveness of apixaban (API) versus rivaroxaban (RIV), dabigatran (DAB), and low molecular weight heparin (LMWH), followed by vitamin K antagonist (VKA), in the treatment of VTE in China was assessed.Methods: To access the quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs), a long-term cost-effectiveness analysis was constructed using a Markov model with 5 health states. The Markov model was developed using patient data collected from the Xijing Hospital from January 1, 2016 to January 1, 2021. The time horizon was set at 30 years, and a 6-month cycle length was used in the model. Costs and ICERs were reported in 2020 U.S. dollars. One-way sensitivity analysis and probabilistic sensitivity analysis (PSA) were used to test the uncertainties. A Chinese health-care system perspective was used.Results: In the base case, the data of 231 VTE patients were calculated in the base case analysis retrospectively. The RIV group resulted in a mean VTE attributable to 95% effective treatment. API, DAB, and VKA have a negative ICER (−187017.543, −284,674.922, and −9,283.339, respectively) and were absolutely dominated. The Markov model results confirmed this observation. The ICER of the API and RIV was negative (−216176.977), which belongs to the absolute inferiority scheme, and the ICER value of the DAB and VKA versus RIV was positive (110,577.872 and 836,846.343). Since the ICER of DAB and VKA exceeds the threshold, RIV therapy was likely to be the best choice for the treatment of VTE within the acceptable threshold range. The results of the sensitivity analysis revealed that the model output varied mostly with the cost in the DAB on-treatment therapy. In a probabilistic sensitivity analysis of 1,000 patients for 30 years, RIV has 100% probability of being cost-effective compared with other regimens when the WTP is $10973 per QALY. When WTP exceeded $148,000, DAB was more cost-effective than RIV.Conclusions: Compared with LMWH + VKA and API, the results proved that RIV may be the most cost-effective treatment for VTE patients in China. Our findings could be helpful for physicians in clinical decision-making to select the appropriate treatment option for VTE.

Recent studies have demonstrated the structural and functional changes in patients with multiple system atrophy (MSA). However, little is known about the different parameter changes of the most vulnerable regions in different types of MSA. In this study, we collected resting-state structure, perfusion, and patients with functional magnetic resonance imaging (fMRI) data of cerebellum-type of MSA (MSA-c) and Parkinson-type of MSA (MSA-p). First, by simultaneously using voxel-based morphology (VBM), arterial spin labeling (ASL), and amplitude of low-frequency fluctuation (ALFF), we analyzed the whole brain differences of structure, perfusion, and functional activation between patients with MSA-c and MSA-p. Second, we explored the relationships among structure, perfusion, function, and the clinical variables in patients with MSA. Finally, we extracted the MRI parameters of a specific region to separate the two groups and search for a sensitive imaging biomarker. As a result, compared with patients with MSA-p type, patients with MSA-c type showed decreased structure atrophy in several cerebella and vermis subregions, reduced perfusion in bilateral cerebellum_4_5 and vermis_4_5, and an decreased ALFF values in the right lingual gyrus (LG) and fusiform (FFG). Subsequent analyses revealed the close correlations among structure, perfusion, function, and clinical variables in both MSA-c and MSA-p. Finally, the receiver operating characteristic (ROC) analysis showed that the regional cerebral blood flow (rCBF) of bilateral cerebellum_4_5/vermis_4_5 could differentiate the two groups at a relatively high accuracy, yielding the sensitivity of 100%, specificity of 79.2%, and the area under the curve (AUC) value of 0.936. These findings have important implications for understanding the underlying neurobiology of different types of MSA and added the new evidence for the disrupted rCBF, structure, and function of MSA, which may provide the potential biomarker for accurately detecting different types of patients with MSA and new ideas for the treatment of different types of MSA in the future.

Background: Metabolic syndrome (MetS) is highly related to the excessive accumulation of visceral adipose tissue (VAT). Quantitative measurements of VAT are commonly applied in clinical practice for measurement of metabolic risks; however, it remains largely unknown whether the texture of VAT can evaluate visceral adiposity, stratify MetS and predict surgery-induced weight loss effects. Methods: 675 Chinese adult volunteers and 63 obese patients (with bariatric surgery) were enrolled. Texture features were extracted from VATs of the computed tomography (CT) scans and machine learning was applied to identify significant imaging biomarkers associated with metabolic-related traits. Findings: Combined with sex, ten VAT texture features achieved areas under the curve (AUCs) of 0.872, 0.888, 0.961, and 0.947 for predicting the prevalence of insulin resistance, MetS, central obesity, and visceral obesity, respectively. A novel imaging biomarker, RunEntropy, was identified to be significantly associated with major metabolic outcomes and a 3.5-year follow-up in 338 volunteers demonstrated its long-term effectiveness. More importantly, the preoperative imaging biomarkers yielded high AUCs and accuracies for estimation of surgery responses, including the percentage of excess weight loss (%EWL) (0.867 and 74.6%), postoperative BMI group (0.930 and 76.1%), postoperative insulin resistance (0.947 and 88.9%), and excess visceral fat loss (the proportion of visceral fat reduced over 50%; 0.928 and 84.1%). Interpretation: This study shows that the texture features of VAT have significant clinical implications in evaluating metabolic disorders and predicting surgery-induced weight loss effects. Funding: The complete list of funders can be found in the Acknowledgement section.