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Abstract Multiple synchronous lung cancers (MSLCs) constitute a unique subtype of lung cancer. To explore the genomic and immune heterogeneity across different pathological stages of MSLCs, we analyse 16 MSLCs from 8 patients using single-cell RNA-seq, single-cell TCR sequencing, and bulk whole-exome sequencing. Our investigation indicates clonally independent tumours with convergent evolution driven by shared driver mutations. However, tumours from the same individual exhibit few shared mutations, indicating independent origins. During the transition from pre-invasive to invasive adenocarcinoma, we observe a shift in T cell phenotypes characterized by increased Treg cells and exhausted CD8+ T cells, accompanied by diminished cytotoxicity. Additionally, invasive adenocarcinomas exhibit greater neoantigen abundance and a more diverse TCR repertoire, indicating heightened heterogeneity. In summary, despite having a common genetic background and environmental exposure, our study emphasizes the individuality of MSLCs at different stages, highlighting their unique genomic and immune characteristics.

Bacteria are present in the environment around us, including in the air, water, and soil. Moreover, infection-causing bacteria are transmitted indirectly through the air, food, and water, as well as through direct contact. Upon entering the human body, they multiply and cause various discomforts or diseases. To combat such diseases, antibiotics are the current choice of the primary treatment. However, their overuse has led to a major issue referred to as bacterial resistance. Metal NPs possess great potential in microbial detection along with disease diagnosis and treatment. Zinc is an essential trace element crucial for human growth and development, and zinc oxide (ZnO) nanoparticles (NPs) are an inorganic material with broad-spectrum antibacterial activity. Therefore, in this review article, we provide a detailed overview of the antibacterial mechanisms of ZnONPs, thereby providing theoretical support for their application.

ObjectiveTo assess the clinical impact of unilateral laminotomy for bilateral decompression (ULBD) in managing patients with adjacent vertebrae following lumbar fusion.MethodsA retrospective analysis was conducted on 21 patients, with a mean age of 67.4 years, who underwent ULBD for adjacent vertebra disease at our department from January 2021 to November 2023. We reviewed demographic data, surgical techniques, imaging studies, and patient-reported outcomes. The study compared Visual Analog Scale (VAS) scores, Numeric Rating Scale (NRS) scores, Japanese Orthopaedic Association (JOA) scores, Short Form-36 (SF-36) scores, and imaging outcomes before surgery, immediately post-surgery, and at 1 month, 6 months, and 12 months post-surgery.ResultsEvaluation of 21 patients with adjacent segment disease (ASD) (13 males, 8 females; mean age 67.42 years) was performed with follow-ups at various intervals post-surgery. Postoperative VAS, NRS, JOA, and SF-36 scores showed significant improvements compared to preoperative scores. Immediately after surgery, there were significant improvements in NRS score (2.76 ± 0.70 vs. 3.71 ± 0.85, P

Previous studies have delved into slope break zones in faulted basins, yet foreland basins, with their gentle slopes toward the forebulge, underdeveloped large-scale structures, and small terrain undulations, have received limited research on slope-fault belts. During the deposition periods of the 4th and 5th members of the Late Triassic Xujiahe Formation, a foreland basin developed in the Sichuan Basin. Scholars have noted the control exerted by the gentle slope break zone on the sedimentary lithofacies in the central and western Sichuan, particularly in the west of the Luzhou-Kaijiang Paleo-uplift, but related studies remain limited. By interpreting the tectonic slope break zones in seismic reflection profiles of the Sichuan Basin and incorporating existing regional geological data, this study employed particle flow numerical simulation to clarify the types of slope break zones in the central and western Sichuan regions, as well as their relationship with gravity sliding structures. It also analyzed the characte-ristics of new types of oil and gas traps associated with gravity-sliding structures. The findings are as follows: (1) The study area developed a fault slope break zone, with each side bounded by a "front squeezing and rear extension" tectonic combinations formed by gravity sliding. The tectonic deformation is weaker than those of gravity-sliding structures at passive continental margins. (2) The edge fault of the tectonic slope break zone controls the sedimentary facies and sand body types. (3) In the gentle slope zone, the stretching area of gravity-sliding structures lead to the uplift of the footwalls of normal faults, forming syndepositional anticlines with developed sandstones. These sandstones, juxtaposed with organic-rich mudstones within the contemporaneous fault depression, form "side-generated and lateral storage" hydrocarbon reservoirs. (4) In the steep slope zone, gravity sliding forms syndepositional anticlines in the 5th member of the Xujiahe Formation, which are bounded by flank mudstones and post-sliding deposited mudstones, forming in-source sand body reservoirs. (5) Syndepositional anticline hydrocarbon reservoirs related to gravity-sliding structures represent a new type of in-source hydrocarbon accumulation. The 5th member of the Xujiahe Formation in the study area likely contains such reservoirs, distributed in a NE-trending pattern parallel to the slope break zone.

Abstract Background Multi-b-value diffusion-weighted imaging (DWI) with different postprocessing models allows for evaluating hepatocellular carcinoma (HCC) proliferation, spatial heterogeneity, and feasibility of treatment strategies. We assessed synergistic effects of bufalin+sorafenib in orthotopic HCC-LM3 xenograft nude mice by using intravoxel incoherent motion (IVIM), diffusion kurtosis imaging (DKI), a stretched exponential model (SEM), and a fractional-order calculus (FROC) model. Methods Twenty-four orthotopic HCC-LM3 xenograft mice were divided into bufalin+sorafenib, bufalin, sorafenib treatment groups, and a control group. Multi-b-value DWI was performed using a 3-T scanner after 3 weeks’ treatment to obtain true diffusion coefficient Dt, pseudo-diffusion coefficient Dp, perfusion fraction f, mean diffusivity (MD), mean kurtosis (MK), distributed diffusion coefficient (DDC), heterogeneity index α, diffusion coefficient D, fractional order parameter β, and microstructural quantity μ. Necrotic fraction (NF), standard deviation (SD) of hematoxylin-eosin staining, and microvessel density (MVD) of anti-CD31 staining were evaluated. Correlations of DWI parameters with histopathological results were analyzed, and measurements were compared among four groups. Results In the final 22 mice, f positively correlated with MVD (r = 0.679, p = 0.001). Significantly good correlations of MK (r = 0.677), α (r = -0.696), and β (r= -0.639) with SD were observed (all p < 0.010). f, MK, MVD, and SD were much lower, while MD, α, β, and NF were higher in bufalin plus sorafenib group than control group (all p < 0.050). Conclusion Evaluated by IVIM, DKI, SEM, and FROC, bufalin+sorafenib was found to inhibit tumor proliferation and angiogenesis and reduce spatial heterogeneity in HCC-LM3 models. Relevance statement Multi-b-value DWI provides potential metrics for evaluating the efficacy of treatment in HCC. Key points • Bufalin plus sorafenib combination may increase the effectiveness of HCC therapy. • Multi-b-value DWI depicted HCC proliferation, angiogenesis, and spatial heterogeneity. • Multi-b-value DWI may be a noninvasive method to assess HCC therapeutic efficacy. Graphical Abstract

PurposeThis study aimed to investigate the neural mechanism by which virtual chatbots' gender might influence users' usage intention and gender differences in human–machine communication.ApproachEvent-related potentials (ERPs) and subjective questionnaire methods were used to explore the usage intention of virtual chatbots, and statistical analysis was conducted through repeated measures ANOVA.Results/findingsThe findings of ERPs revealed that female virtual chatbots, compared to male virtual chatbots, evoked a larger amplitude of P100 and P200, implying a greater allocation of attentional resources toward female virtual chatbots. Considering participants' gender, the gender factors of virtual chatbots continued to influence N100, P100, and P200. Specifically, among female participants, female virtual chatbots induced a larger P100 and P200 amplitude than male virtual chatbots, indicating that female participants exhibited more attentional resources and positive emotions toward same-gender chatbots. Conversely, among male participants, male virtual chatbots induced a larger N100 amplitude than female virtual chatbots, indicating that male participants allocated more attentional resources toward male virtual chatbots. The results of the subjective questionnaire showed that regardless of participants' gender, users have a larger usage intention toward female virtual chatbots than male virtual chatbots.ValueOur findings could provide designers with neurophysiological insights into designing better virtual chatbots that cater to users' psychological needs.

Abstract To evaluate the association of uric acid (UA) with adverse outcomes and its potential mediator in patients with left ventricular diastolic dysfunction (LVDD) and pulmonary hypertension (PH). We retrospectively analyzed 234 patients with LVDD and PH. The baseline characteristics of patients with low UA (≤ 330 µmol/L) group were compared with high UA (> 330 µmol/L) group. Adverse outcomes included all-cause mortality, cardiac death and heart failure (HF) hospitalization. Their association with UA and the mediator were evaluated using Cox regression and mediation analysis. The mediation proportion was further quantified by the R mediation package. During a mean follow-up of 50 ± 18 months, there were 27 all-cause deaths, 18 cardiovascular deaths and 41 incidents of HF hospitalization. Multivariable Cox regression analysis showed UA was an independent risk factor of adverse outcomes in LVDD and PH patients, even after adjusting for age, sex, body mass index, medical histories, systolic blood pressure, fasting blood glucose, total cholesterol, triglyceride, eGFR, BNP and medications. The hazard ratios (HRs) for UA (per 10 µmol/L increase) were as below: for all-cause mortality, HR 1.143, 95% CI 1.069–1.221, P

Abstract Lower limb augmentation exoskeletons (LLAE) have been applied in several domains to enforce human walking capability. As humans can adjust their joint moments and generate different amounts of mechanical energy while walking on different terrains, the LLAEs should provide adaptive augmented torques to the wearer in multi-terrain environments, which requires LLAEs to implement accurate terrain parameter recognition. However, the outputs of previous terrain parameter recognition algorithms are more redundant, and the algorithms have higher computational complexity and are susceptible to external interference. Therefore, to resolve the above issues, this paper proposed a neural network regression (NNR)-based algorithm for terrain slope parameter recognition. In particular, this paper defined for the first time a unified representation of terrain parameters: terrain slope (TS), a single parameter that can provide enough information for exoskeleton control. In addition, our proposed NNR model uses only basic human parameters and LLAE joint motion posture measured by an Inertial Measurement Unit (IMU) as inputs to predict the TS, which is computationally simpler and less susceptible to interference. The model was evaluated using K-fold cross-validation and the results showed that the model had an average error of only 2.09 $$^\circ $$ ∘ . To further validate the effectiveness of the proposed algorithm, it was verified on a homemade LLAE and the experimental results showed that the proposed TS parameter recognition algorithm only produces an average error of 3.73 $$^\circ $$ ∘ in multi-terrain environments. The defined terrain parameters can meet the control requirements of LLAE in urban multi-terrain environments. The proposed TS parameter recognition algorithm could facilitate the optimization of the adaptive gait control of the exoskeleton system and improve user experience, energy efficiency, and overall comfort.

Online medical service robots (OMSRs) are becoming increasingly important in the medical industry, and their design has become a highly focused issue. This study investigated the neuroeconomics underlying the formation of usage intention, specifically evaluating the impact of anthropomorphic appearance and age on users' intentions to use OMSRs. Event-related potentials were used to analyze electroencephalography signals recorded from participants. This study found that OMSRs with a low anthropomorphic appearance induced larger P200 and P300 amplitudes, resulting in increased attentional resources compared to OMSRs with a moderate or high anthropomorphic appearance. OMSRs with moderate anthropomorphic appearances captured more attention and elicited larger P200 and P300 than those with high anthropomorphic appearances. Regarding age characteristics, OMSRs with senior features attracted more attention and induced larger P200 and P300 amplitudes. In terms of usage intention, compared to the others, users demonstrate a stronger usage intention towards the low anthropomorphism of OMSRs. Additionally, compared to the senior ones, users also exhibit a stronger usage intention toward a young appearance of OMSRs. These findings provide valuable insights for robot designers and practitioners to improve the appearance of OMSRs.

Marine pollution, a major disturbance to the sustainable use of oceans, is becoming more prevalent around the world. Multidimensional and sustainable ocean governance have become increasingly focused on managing, reducing, and eliminating marine pollution. Artificial intelligence has been used more and more in recent years to monitor and control marine pollution. This systematic literature review, encompassing studies from the Web of Science and Scopus databases, delineates the extensive role of artificial intelligence in marine pollution management, revealing a significant surge in research and application. This review aims to provide information and a better understanding of the application of artificial intelligence in marine pollution. In marine pollution, 57% of AI applications are used for monitoring, 24% for management, and 19% for prediction. Three areas are emphasized: (1) detecting and responding to oil pollution, (2) monitoring water quality and its practical application, and (3) monitoring and identifying plastic pollution. Each area benefits from the unique capabilities of artificial intelligence. If the scientific community continues to explore and refine these technologies, the convergence of artificial intelligence and marine pollution may yield more sophisticated solutions for environmental conservation. Although artificial intelligence offers powerful tools for the treatment of marine pollution, it does have some limitations. Future research recommendations include (1) transferring experimental outcomes to industrial applications in a broader sense; (2) highlighting the cost-effective advantages of AI in marine pollution control; and (3) promoting the use of AI in the legislation and policy-making about controlling marine pollution.

Abstract The responses of sea cucumbers to salinity changes are reflected in the expression profiles of multiple genes and microRNAs. The miR‐2008 and Pleckstrin Homology Domain Containing A3 (PLEKHA3) were previously shown to be involved in responses to salinity changes in sea cucumbers. To better understand the relationship between miR‐2008 and PLEKHA3, the miR‐2008 and PLEKHA3 predicted interaction was investigated using luciferase reporter assays and gene knockdowns. Dual‐luciferase reporter gene analysis indicated that miR‐2008 overexpression decreased luciferase activity in the PLEKHA3‐WT group. The miR‐2008 expression in coelomocytes was increasingly downregulated in the agomir group with salinity acclimation. PLEKHA3 expression patterns in the miR‐2008 agomir group were upregulated after 6 and 48 h and downregulated after 24 h of low‐salinity stress. The miR‐2008 expression in the miR‐2008 agomir group peaked after 24 h of low‐salinity exposure in sea cucumbers. miR‐2008 overexpression and PLEKHA3 inhibition affected ion concentrations, osmotic pressure, Na+/K+‐ATPase (NKA) activity, and ROS levels. The changes in ion concentrations, osmotic pressure, and NKA activity after 6–24 h of salinity stress were observed. The results indicated that 6–24 h after the initiation of salinity stress may be critical to the salinity‐acclimation process in sea cucumbers.

Aims. To evaluate the impact of neutrophil-to-lymphocyte ratio (NLR) on periprocedural pulmonary hypertension (PH) and 3-month all-cause mortality in patients with aortic stenosis (AS) who underwent transcatheter aortic valve replacement (TAVR) and to develop a nomogram for predicting the mortality for these patients. Methods and Results. 124 patients undergoing TAVR were categorized into three groups according to systolic pulmonary artery pressure (sPAP): Group I (no PH, n = 61) consisted of patients with no pre- and post-TAVR PH; Group II (improved PH, n = 35) consisted of patients with post-TAVR systolic pulmonary artery pressure (sPAP) decreased by more than 10 mmHg compared to pre-TAVR levels; and Group III (persistent PH, n = 28) consisted of patients with post-TAVR sPAP no decrease or less than 10 mmHg, or new-onset PH after the TAVR procedure. The risk of all-cause mortality within 3 months tended to be higher in Group II (11.4%) and Group III (14.3%) compared to Group I (3.3%) (P=0.057). The multinomial logistic regression analysis demonstrated a positive correlation between NLR and both improved PH (OR: 1.182, 95% CI: 1.036–1.350, P=0.013) and persistent PH (OR: 1.181, 95% CI: 1.032–1.352, P=0.016). Kaplan–Meier analysis revealed a significant association between higher NLR and increased 3-month all-cause mortality (16.1% vs. 3.1% in lower NLR group, P=0.021). The multivariable Cox regression analysis confirmed that NLR was an independent predictor for all-cause mortality within 3 months, even after adjusting for clinical confounders. A nomogram incorporating five factors (BNP, heart rate, serum total bilirubin, NLR, and comorbidity with coronary heart disease) was developed. ROC analysis was performed to discriminate the ability of the nomogram, and the AUC was 0.926 (95% CI: 0.850–1.000, P

Abstract Coronary artery occlusion (CAO) is a rare but life‐threatening complication of transcatheter aortic valve implantation (TAVI). The mechanism of CAO is the displacement of the native calcified valve leaflet over the coronary ostium. Here, we report on a woman who experienced sudden cardiac arrest and abrupt CAO during TAVI, which was caused by two different original obstructions, a rupture of aortic plaque or a partial tear of the aortic intima blocking the upper 2/3 of the left main trunk (LMT) ostium, and the transcatheter heart valve (THV) blocking the lower 1/3 of the LMT ostium. She was eventually successfully treated with the chimney stenting technique. Aortography other than coronary angiography was used to ascertain CAO. In patients presenting with abrupt cardiac arrest or cardiogenic shock with LMT occlusion, there must be prompt identification, and the causes of CAO may be various and rare. The identification of CAO relies not only on CAG but also on aortography, especially if the locations and origins of obstructions are special. Supportive therapy with an attempt at percutaneous revascularization is necessary. Pre‐procedural assessment is crucial prior to TAVI interventions. In cases with high risk of CAO, upfront coronary artery protection can be provided.

Abstract Nanomedicine technology is a rapidly developing field of research and application that uses nanoparticles as a platform to facilitate the diagnosis and treatment of diseases. Nanoparticles loaded with drugs and imaging contrast agents have already been used in clinically, but they are essentially passive delivery carriers. To make nanoparticles smarter, an important function is the ability to actively locate target tissues. It enables nanoparticles to accumulate in target tissues at higher concentrations, thereby improving therapeutic efficacy and reducing side effects. Among the different ligands, the CREKA peptide (Cys-Arg-Glu-Lys-Ala) is a desirable targeting ligand and has a good targeting ability for overexpressed fibrin in different models, such as cancers, myocardial ischemia-reperfusion, and atherosclerosis. In this review, the characteristic of the CREKA peptide and the latest reports regarding the application of CREKA-based nanoplatforms in different biological tissues are described. In addition, the existing problems and future application perspectives of CREKA-based nanoplatforms are also addressed.

This article proposes a new method for optimizing tooth profile modification amounts of cycloidal reducers. By optimizing transmission error and transmission ratio fluctuation, the objective optimization function is determined, and the influence of optimized modification amount on various transmission performances is studied. In addition, this article also conducted mechanical analysis on the cycloidal reducer and obtained the results of tooth contact force. The mathematical model for the mechanical analysis of the cycloidal reducer was established, and the variation law of force distribution between the internal and external gears of the cycloidal reducer was calculated. The results indicate that the needle tooth force, bearing force, transmission ratio, and transmission error obtained through the mechanical analysis model using optimized modification quantities tend to stabilize and exhibit periodic changes, which corresponds to the actual scenario.

Background: Intensive care unit (ICU) readmission and unexpected death are closely associated with increased length of hospitalization and total mortality. However, data about readmission or unexpected death after discharge from ICU in patients who have undergone emergency general surgery (EGS) is very limited. Methods: In total, 1133 patients who underwent EGS were identified in the Multiparameter Intelligent Monitoring in Intensive Care IV (MIMIC-IV) database. Of these 1133 patients, 124 underwent readmission into the ICU or death unexpectedly after their initial discharge. The clinical characteristics of the patients were investigated. A logistic regression model was implemented for the analysis of the independent risk factors associated with ICU readmission or unexpected death. A nomogram model was established to predict the risk of ICU readmission or unexpected death within 72 h after EGS. Results: Peripheral vascular disease and atrial fibrillation, vasopressor requirement, a higher respiratory rate or heart rate, a lower pulse oxygen saturation or a platelet count of

Due to climate change and human activities, seagrass is in crisis as the coverage of seagrass declines at an accelerated rate globally. In this paper, the severe challenges of seagrass ecosystem were briefly reviewed, including adverse effects of natural factors and human activities on seagrass beds. The research status of pollutants and pollution in seagrass bed ecosystem was reviewed, the future research directions in related fields were proposed as well. The eutrophication in coastal waters and discharge of pollutants such as sulfide, heavy metals, organic matter and microplastics caused by human activities are important reasons for seagrass loss. In addition, environmental stressors lead to reduced immunity and decreased resistance of seagrass to various pathogens, leading to seagrass wasting diseases. Future studies concerning the influence of novel pollutants, i.e., plastic waste on non-native algae, microorganisms and seagrasses, as well as their interrelationships, will be of vital importance. In addition, researches on seagrass wasting diseases and their pathogens should be much accounted in China, to fill in gaps in related fields and improve the response ability to emergent seagrass diseases. In conclusion, this review was proposed to arouse the concern about the seagrass bed pollution, and provide possible enlightening information for the protection and restoration of this significant ecosystem.

In this paper, the ultrasonic extraction technology of Forsythia suspensa leaves was optimized based on multi-index components. The contents of forsythioside A, forsythin and rutin were determined by high performance liquid chromatography (HPLC). The ethanol concentration, liquid-solid ratio, extraction time and extraction temperature were taken as the factors. The entropy weight method was used to obtain comprehensive score by calculating the weight coefficient of each index. Subsequently, the comprehensive score was taken as the index. Finally the Box-Behnken response surface methodology was adopted to optimize the extraction process. The optimum extraction conditions of Forsythia suspensa leaves were as follow: Ethanol concentration 50%, liquid to material ratio 28:1 mL/g, extraction temperature 51 ℃, extraction time 25 min. The results of the validation tests showed that under the optimal conditions, the extraction amount of forsythioside A, forsythin and rutin were 69.69, 22.87 and 22.46 mg/g, respectively, the RSD was less than 3% and comprehensive score was 32.18. The extraction technology was stable and feasible, and the extraction quantity of active components was high. It was suitable for the extraction of Forsythia suspensa leaves.

ObjectiveIt has long been debated whether rhythm control vs. rate control strategies have differing effects on mortality and morbidity for atrial fibrillation (AF). Recently, several randomized controlled studies (RCTs) and observational trials described that an early rhythm management method was linked to a lower likelihood of negative clinical outcomes in individuals with AF. We wanted to see if an early rhythm management method may help patients with AF.MethodsWe performed a systematic search to retrieve studies assessing the outcomes of early rhythm control vs. rate control in AF by using PubMed, Web of Science, Cochrane Library, and Embase published between 01/01/2000 and 15/04/2022.ResultsFinally, two RCTs, one retrospective analysis of RCTs, and four observational studies were identified. Compared with rate control, early rhythm control has been linked to lower all-cause mortality. [risk ratio (RR), 0.76; 95% CI 0.69–0.83; P < 0.00001; I2 = 77%]. The early rhythm control group was also associated with a lower risk of cardiovascular mortality (RR, 0.68; 95% CI 0.63–0.74; P < 0.00001; I2 = 33), stroke (RR, 0.77; 95% CI 0.67–0.87; P < 0.001; I2 = 64), and heart failure hospitalization (RR, 0.74; 95% CI 0.59–0.93; P = 0.0009; I2 = 93%). We found no significant difference in nights spent in hospital per year, acute coronary syndrome, major bleeding, and cardiac arrest/ventricular arrhythmia between the groups.ConclusionIn this meta-analysis, early rhythm therapy was linked to a lower risk of all-cause mortality, cardiovascular mortality, stroke, and heart failure hospitalization compared with the rate control group.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022333592.

We study the electron-acoustic instabilities in plasmas with two kappa-distributed electrons and stationary ions. The instabilities are driven by the relative drift between two electron components. The suprathermal effects of different species on growth rates and instability thresholds are analyzed and compared by numerical calculations. The present study reveals that the suprathermal electrons with slow most probable speed play more important roles than the suprathermal ones with fast most probable speed. The former significantly reduces the instabilities and raises the instability thresholds. The parameters used in this study are inspired from the observations in Earth’s magnetopause.

BackgroundThe results of studies evaluating the left atrial appendage (LAA) function and structure as predictors of atrial fibrillation (AF) recurrence after catheter ablation (CA) are contradictory. Therefore, we performed a meta-analysis to assess whether the LAA function and structure can predict the recurrence of AF after CA.MethodsThe PubMed, EMBASE, Web of Science, and Cochrane library databases were used to conduct a comprehensive literature search. Finally, 37 studies encompassing 11 LAA parameters were included in this meta-analysis.ResultsCompared with those in the non-recurrence group, the recurrence group had increased LAA volume (SMD 0.53, 95% CI [0.36, 0.71] p < 0.00001), LAA volume index, LAA orifice area, and LAA orifice short/long axis and decreased LAA emptying flow velocity (SMD -0.54, 95% CI [-0.68, -0.40], P < 0.00001), LAA filling flow velocity, and LAA ejection fraction, while there was no significant difference in LAA morphology or LAA depth.ConclusionLarge LAA structure of pre-ablation (LAA volume, orifice area, orifice long/short axis, and volume index) and decreased LAA function of pre-ablation (LAA emptying flow velocity, filling flow velocity, ejection fraction, and LASEC) increase the odds of AF recurrence after CA.Systematic review registration[https://www.crd.york.ac.uk/prospero/], identifier [CRD42022324533].

Glytrexate, developed by our team, as a novel multitarget folate antagonist, has inhibitory effects on a variety of cancer cell types, especially KB tumor cells (IC50 0.078 nM), and thus has antitumor drug development prospects. However, its pharmacokinetics and plasma protein binding properties remain unknown. In this study a selective and sensitive liquid chromatography-tandem mass spectrometry (LC‒MS/MS) method was developed and verified to facilitate biological analysis. The bioanalysis method was applied to evaluate the stability, plasma protein binding, and pharmacokinetics of glytrexate. Glytrexate is more stable in human plasma than in rat plasma and in human liver microsomes. The binding of glytrexate to human plasma proteins was higher than that to rat plasma proteins, both of which were less than 30%, suggesting that glytrexate may be at a higher concentration at the pharmacologic target receptor(s) in tissues. Pharmacokinetic characteristics were determined by noncompartmental analysis after administration of single oral (12.5, 25 and 50 mg/kg) and intravenous (2 mg/kg) doses in rats. According to the rat oral pharmacokinetic characteristics, glytrexate had linear dynamics in a dose range of 12.5–50 mg/kg and a poor oral bioavailability of 0.57–1.15%. The investigation revealed that the intravenous half-life, AUC, and Cmax of glytrexate were higher than those of pemetrexed. Pemetrexed is generally produced as an injection preparation. This provides ideas for the development of glytrexate formulations. Therefore, glytrexate injection has clinical application prospects compared to oral administration. This study provides a basis for further investigations into the pharmacological effects and clinical uses of glytrexate.

Cycloid drives are widely used in various mechanical systems due to their high reduction ratio, compact size, and high efficiency. Tooth surface wear is a major problem that affects the reliability and durability of cycloid drives. However, compared to the research on the wear of involute gears, the prediction of tooth surface wear in cycloid drives is relatively limited and less extensive. To fill this gap, the theoretical wear model of the tooth surface of cycloid-pin gear pairs is proposed based on the Hertz contact theory and Archard’s formula, with consideration of tooth profile modifications. Firstly, the loaded tooth contact analysis model is established to determine the relative sliding velocity and tooth contact stress. Secondly, the calculation steps of single tooth surface wear are presented within one gear mesh cycle. With this, the effects of the tooth profile modifications, the operating conditions such as output torque, input speed, and the assembly eccentricity on the wear depth within one gear mesh cycle are investigated. This study gives a deeper understanding of the tooth surface wear mechanisms of cycloid drives and could be employed to assist gear design and to improve the wear resistance.

In recent years, with the development of robot transmission technology, the market demand for high-performance actuators, which can be applied to lower limb exoskeleton assist robots, is increasing. These robots help achieve human–robot interaction through rigid and flexible coupling, and they can ensure the flexibility of the elderly or patients in daily walking and rehabilitation training. A novel actuator with a double-roller gear drive structure is proposed with high bearing capability and high transmission efficiency due to multi-tooth rolling contact with small tooth difference such that friction is greatly reduced in the transmission process compared to what occurs in involute planetary transmission. The bearing capacity of the tooth surface was analyzed by using the loaded contact analysis method. Finally, a prototype was manufactured with the 3D printer, and the maximum output torque of the developed actuator was tested with an experimental setup. The results show that this novel actuator, with its double-roller gear drive, has huge potential for use in the hip joint of an exoskeleton robot.

Due to their advantages of compact size, high reduction ratio, large stiffness and high load capacity, RV reducers have been widely used in industrial robots. The dynamic characteristics of RV reducers in terms of vibratory response and dynamic transmission error have a significant influence on positioning accuracy and service life. However, the current dynamic studies on RV reducers are not extensive and require deeper study. To bridge this gap, a more effective and realistic lumped parameter dynamic model for RV reducers is developed, considering the tooth profile modification of cycloid gears and system errors. Firstly, for an efficient solution, the equivalent pressure angle and equivalent mesh stiffness of the cycloid–pin gear pair are introduced in the dynamic model based on the loaded tooth contact analysis. Secondly, the differential equations of the system are derived by analyzing the relative displacement relationships between each component, which are solved using the Runge–Kutta method. With this, the effects of errors such as machining errors, assembly errors and bearing clearances on the dynamic behaviors and transmission precision are investigated by comparison to quantify or qualify their influence. This research is helpful in characterizing the multi-tooth mesh and dynamic behavior, and revealing the underlying physics of the RV reducer.

Titanium alloy is a crucial structural material in the modern aerospace field due to its strong corrosion resistance and strength, low density, and reduced sensitivity to vibration load and impact load, as well as its ability to resist expansion in the case of cracks. However, during high-speed cutting of titanium alloy, it is prone to periodic saw-tooth chip formation, which can cause high-frequency fluctuations in the cutting force, aggravate the vibration of the machine tool system, and ultimately reduce the tool’s service life and the workpiece’s surface quality. In this study, we investigated the influence of the material constitutive law in modeling the Ti-6AL-4V saw-tooth chip formation and proposed a joint material constitutive law JC-TANH which was developed based on the Johnson–Cook constitutive law and the TANH constitutive law. It has two advantages of the two models (JC law and TANH law), which means that it can describe the dynamic properties accurately, the same as the JC model, not only under low strain but also under high strain. The most important thing is that it does not need to fit the JC curve at the early stage of strain changes. Additionally, we established a developed cutting model, which integrates the new material constitutive, and the improved SPH method to predict chip morphology, cutting and thrust forces which are collected by the force sensor; we also compared the data with experimental results. Experimental results show that this developed cutting model can better explain the shear localized saw-tooth chip formation and correctly estimate its morphology as well as the cutting forces.

According to the classical Windkessel model, the heart is the only power source for blood flow, while the arterial system is assumed to be an elastic chamber that acts as a channel and buffer for blood circulation. In this paper we show that in addition to the power provided by the heart for blood circulation, strain energy stored in deformed arterial vessels in vivo can be transformed into mechanical work to propel blood flow. A quantitative relationship between the strain energy increment and functional (systolic, diastolic, mean and pulse blood pressure) and structural (stiffness, diameter and wall thickness) parameters of the aorta is described. In addition, details of blood flow across the aorta remain unclear due to changes in functional and other physiological parameters. Based on the arterial strain energy and fluid-structure interaction theory, the relationship between physiological parameters and blood supply to organs was studied, and a corresponding mathematical model was developed. The findings provided a new understanding about blood-flow circulation, that is, cardiac output allows blood to enter the aorta at an initial rate, and then strain energy stored in the elastic arteries pushes blood toward distal organs and tissues. Organ blood supply is a key factor in cardio-cerebrovascular diseases (CCVD), which are caused by changes in blood supply in combination with multiple physiological parameters. Also, some physiological parameters are affected by changes in blood supply, and vice versa. The model can explain the pathophysiological mechanisms of chronic diseases such as CCVD and hypertension among others, and the results are in good agreement with epidemiological studies of CCVD.

ObjectiveThere is evidence that metabolic disorder, dysfunction and abnormal apoptosis of immune cells are closely related to immunosuppression in sepsis. Single monitoring of exhaustion receptors does not reflect well the immune status of septic patients; therefore, we monitored immune status in relation to metabolism, function and apoptosis of immune cells to find good prognostic indicators for sepsis.DesignA single-center prospective observational study.SettingTeaching hospital including an academic tertiary care center.Patients81 patients with sepsis and 22 without sepsis admitted to the ICU.InterventionsPatients were divided according to Sequential Organ Failure Assessment (SOFA) score: mild sepsis 2–5 points and severe sepsis ≥6 points. SOFA score was recalculated daily. If it changed by ≥2 points within 2 days, T-cell metabolism, function and apoptotic makers [mammalian target of rapamycin (mTOR), T-bet, interferon (IFN)-γ, granzyme B, and programmed cell death (PD)-1] were continuously monitored on days 1, 3 and 5 after admission.Measurements and Main ResultsThe overall status of immune cells was compared among patients with different severity of sepsis. Patients with severe sepsis, compared with mild and no sepsis, had lower lymphocyte counts, higher expression of receptors associated with cell metabolism, activation and apoptosis, and lower expression of functional receptors. Multivariate regression analysis revealed that frequency of CD4+ T cells expressing mTOR, IFN-γ and PD-1 at admission was an independent predictor of 28-day mortality. Receiver operating characteristic curve analysis indicated that frequency of CD4+ T cells expressing mTOR, IFN-γ and PD-1 predicted 28-day mortality, with cutoffs of 30.57%, 12.81% and 22.46%, respectively. The expression of related receptors on CD8+ T cells showed similar trend to that on CD4+ T cells, but no significant difference was found.ConclusionsAbnormally increased expression of metabolic and apoptotic receptors on CD4+ T cells and decreased expression of functional factors are associated with poor prognosis in ICU patients with sepsis. Poor prognosis can be identified by early detection of expression of mammalian target of rapamycin (mTOR), IFN-γ and PD-1 on CD4+ T cells.

As the resolution of airborne hyperspectral imagers (AHIs) continues to improve, the demand for accurate boresight calibration also increases. However, the high cost of ground control points (GCPs) and the low horizontal resolution of open digital elevation model (DEM) datasets limit the accuracy of AHI’s boresight calibration. We propose a method to enhance the accuracy of DEM-based boresight calibration using coplanarity constraints to address this issue. Our approach utilizes the relative accuracy of DEM in low-resolution DEM datasets. To make better use of the DEM, we apply coplanarity constraints to identify image features that display similar displacement in overlapping areas, and extract their corresponding elevation values from the DEM. These features and their relative heights are then incorporated into an optimization problem for boresight calibration. In the case of low-resolution DEM datasets, our method fully utilizes the relative accuracy of the DEM to improve the boresight correction precision. We have proven that the relative accuracy of elevation is more reliable than absolute accuracy in this situation. Our approach has been tested on the dataset from AHI, and the results have shown that the proposed method has better accuracy on low-resolution DEM datasets. In summary, our method provides a novel approach to improving the accuracy of DEM-based boresight calibration for AHIs, which can benefit applications, such as remote sensing and environmental monitoring. This research highlights the importance of utilizing the relative accuracy of low-resolution DEM datasets for improving the accuracy of boresight calibration.

Abstract Background Laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) with thyroid cartilage invasion are considered T4 and need total laryngectomy. However, the accuracy of preoperative diagnosis of thyroid cartilage invasion remains lower. Therefore, the purpose of this study was to assess the potential of computed tomography (CT)-based radiomics features in the prediction of thyroid cartilage invasion from LHSCC. Methods A total of 265 patients with pathologically proven LHSCC were enrolled in this retrospective study (86 with thyroid cartilage invasion and 179 without invasion). Two head and neck radiologists evaluated the thyroid cartilage invasion on CT images. Radiomics features were extracted from venous phase contrast-enhanced CT images. The least absolute shrinkage and selection operator (LASSO) and logistic regression (LR) method were used for dimension reduction and model construction. In addition, the support vector machine-based synthetic minority oversampling (SVMSMOTE) algorithm was adopted to balance the dataset and a new LR-SVMSMOTE model was constructed. The performance of the radiologist and the two models were evaluated with receiver operating characteristic (ROC) curves and compared using the DeLong test. Results The areas under the ROC curves (AUCs) in the prediction of thyroid cartilage invasion from LHSCC for the LR-SVMSMOTE model, LR model, and radiologist were 0.905 [95% confidence interval (CI): 0.863 to 0.937)], 0.876 (95%CI: 0.830 to 0.913), and 0.721 (95%CI: 0.663–0.774), respectively. The AUCs of both models were higher than that of the radiologist assessment (all P

Introduction. When sepsis attacks the body, the excessive reactive oxygen species (ROS) production can result to endoplasmic reticulum stress (ERS) and eventually cause lymphocyte apoptosis. The mammalian target of rapamycin (mTOR) is essential for regulating lymphocyte apoptosis; we hypothesized that it mediates CD4+ T cell apoptosis during ROS-related ERS. Method. We, respectively, used ROS and ERS blockers to intervene septic mice and then detected ERS protein expression levels to verify the relationship between them. Additionally, we constructed T cell-specific mTOR and TSC1 gene knockout mice to determine the role of mTOR in ROS-mediated, ERS-induced CD4+ T cell apoptosis. Results. Blocking ROS significantly suppressed the CD4+ T cell apoptosis associated with the reduction in ERS, as revealed by lower levels of GRP78 and CHOP. ERS rapidly induced mTOR activation, leading to the induction of CD4+ T cell apoptosis. However, mTOR knockout mice displayed reduced expression of apoptotic proteins and less ER vesiculation and expansion than what was observed in the wild-type sepsis controls. Conclusion. By working to alleviate ROS-mediated, ERS-induced CD4+ T cell apoptosis, the mTOR pathway is vital for CD4+ T cell survival in sepsis mouse model.

As a systematic, preventive, and structural adjustment method of improving building energy conservation and carbon emission reduction, urban planning has received extensive attention. However, due to the insufficient interface between energy-saving technology and urban planning systems, urban planning has not properly played a role in building energy conservation. Scientific and innovative technical methods are urgently needed to explore the role of coordinating multiple effective planning elements in overall building energy conservation through urban planning means. Due to climate conditions, there is high demand for conserving building energy in severe cold regions, but research into this has not been thoroughly carried out. Harbin, located in the northeast of China, belongs to the Dwa zone of the Köppen–Geiger Climate Classification, and is also a typical city of severe cold regions where the daily average temperature is lower than 5 °C for more than 145 days in a year. This study takes Harbin as an example and uses agent-based modeling to establish an urban-scale building energy consumption simulation model. The model contains four types of agents (a global agent, building agent, residential agent, and household equipment agent) and two types of influence factor modules (an urban form module and a climate module). Three simulation scenarios were designed, including a baseline scenario, an urban form scenario, and a climate scenario. The baseline scenario provided an overview of the urban-scale building energy consumption distribution characteristics of Harbin and served as a reference group for the simulation results of other scenarios. The urban form scenario results show that when the elements with a highly significant impact change by 1 unit, the retail building block has the most obvious change in energy consumption, up to 44.7 × 106 kWh/105 m2/year, while the office building block has the lowest change, with 34.5 × 103 kWh/105 m2/year. The fluctuation of electricity is the most obvious, but the total change is lower than the heating energy consumption. The climate scenario shows that the energy consumption of residential land in urban centers will consistently rise in the next 50 years, up to 5.3 × 105 kWh/105 m2/year. Based on these results, this study puts forward future building energy conservation planning strategies for Harbin, focusing on three aspects: the planning and control of urban form, the optimization and adjustment of the climate, and the building energy conservation planning system. These research results are expected to provide scientific support for transforming Harbin into a low-carbon city.

Blockchain technology is currently evolving rapidly, and smart contracts are the hallmark of the second generation of blockchains. Currently, smart contracts are gradually being used in power system networks to build a decentralized energy system. Security is very important to power systems and attacks launched against smart contract vulnerabilities occur frequently, seriously affecting the development of the smart contract ecosystem. Current smart contract vulnerability detection tools suffer from low correct rates and high false positive rates, which cannot meet current needs. Therefore, we propose a smart contract vulnerability detection system based on the Siamese network in this paper. We improved the original Siamese network model to perform smart contract vulnerability detection by comparing the similarity of two sub networks with the same structure and shared parameters. We also demonstrate, through extensive experiments, that the model has better vulnerability detection performance and lower false alarm rate compared with previous research results.

Because steel plates of 150~300 mm cannot reach the ideal cooling rate under the industrial cooling condition, the development of a super thick plate for the seat ring and guide vane of hydropower stations cannot be successful. In this paper, the influence of the original microstructure and the quenching temperature on the austenite grain size and the analysis of the quenching temperature on the austenite transformation amount were carried out through experiments. The effect of quenching temperature on the content of austenite carbon was calculated by a phase diagram, and then the effect of quenching temperature on the cooling characteristics of the steel was simulated by JMatPro, and the microstructure changes and performance advantages of the QLT heat treatment process were studied and analyzed. Finally, the QLT heat treatment process of SXQ500/550DZ35 steel for the seat ring and guide blade of hydropower stations was researched and formulated (925 °C + 830 °C + 640 °C), and the heat treatment process optimization of a thick steel plate under insufficient cooling conditions during industrial production was solved.

The experimental temperature is 613.15~763.15 K, and the strain rate is 0.01~10 s−1. The hot compression creep test of the 6082-T6 aluminum alloy sample is carried out by Gleeble-3500 hot compression simulation compressor, and its creep behavior is studied by scanning electron microscope. The results show that the DRX crystal has an irregular shape and that content of the Mg phase, Si phase, and Mn phase in the crystal are the main factors to change the color of DRX crystal. Temperature and strain rate are important factors affecting dynamic recrystallization. Reducing temperature and increasing strain rate will weaken dynamic recrystallization, and DRX critical condition and peak stress (strain) will increase. The constitutive equation of hot creep of 6082 aluminum alloy was established by introducing the work hardening rate-rheological stress curve, and the relationship between DRX critical condition, peak stress (strain) and parameter Z during creep was explored. Based on the Av rami equation, the prediction equation of the DRX volume fraction is established. With the increase of strain, DRX volume fraction is characterized by slow increase, then rapid increase and then slowly increase. In the hot -forming extrusion process of 6082 aluminum alloy, according to the volume fraction prediction equation, the DRX can be reduced, and the internal structure of the material can be optimized by changing the extrusion conditions and particle size.

Urban researchers pay more and more attention to building energy consumption from different perspectives to obtain the results of urban overall energy conservation. The research at the micro level has yielded abundant accomplishments, but the macro-level research that can support urban planning decision making is still in the exploration stage. In this study, a multi-agent-based model, including the main panel, building agent, resident agent, and household appliance agent, is established by using Anylogic software. The model integrates Harbin urban macro-level impact factors of building energy consumption by designing and linking three sub-models: an urban morphology sub-model, climate sub-model, and energy use behavior sub-model. In the end, this study explored the building energy-saving potential of different types of land under the impact of variable factors through urban morphology and climate simulation scenarios and discussed the related energy-saving strategies. Findings and suggestions include: (1) The impact of urban morphology on overall urban building energy consumption is mainly reflected in residential and commercial land. The land development intensity (building density, floor area ratio, and building height) control and the coordination of land type layout and configuration can help to reduce the building energy consumption. (2) The energy-saving potential of residential land is more evident under climate impact, and ecological means should be used to adjust the climate to reduce the building energy consumption on different lands. (3) From the methodology perspective, this model can well realize the integration of multiple impact factors at the macro-level of the city and the dynamic simulation of energy consumption. The research results are expected to provide quantitative support for creating a sustainable built environment for the city.

Al-Mg-Si series aluminum alloy is a heat-treatment-strengthened alloy. Research on the impact resistance of Al-Mg-Si series aluminum alloy is of great significance to expand its application in engineering. Taking 6082-T6 aluminum alloy as the concrete research object, using the split Hopkinson pressure bar (SHPB) device, the dynamic mechanical response of the material under different temperatures and average strain rates was studied, and the service performance of the material under extreme conditions was determined. The absolute temperature rise was introduced to optimize the existing constitutive model. The results show that when the environment temperature is 298.15~473.15 K under high-speed impact, the internal thermal softening effect of the material is dominant in the competition with the work hardening, resulting in a decrease in the flow stress of the material. Through the analysis of the real stress–strain curve, it was found that the elastic modulus of the material was negatively correlated with the strain rate, negatively correlated with the temperature, and showed an obvious temperature-softening effect. Yield strength was negatively correlated with temperature and positively correlated with strain rate, which showed an obvious strain rate hardening effect. Based on SEM microscopic analysis, it was found that under given conditions, adiabatic shear bands appeared in some samples, and their internal structures demonstrated obvious change. It was judged that when high-speed impact occurs, cracks are induced at the shear bands, and the cracks will continue to develop along the adiabatic shear bands, resulting in many oblique cracks which will gradually become larger and eventually lead to material failure. Finally, based on the model, the strain rate and temperature softening terms were improved, and a rise in adiabatic temperature rise was introduced. The improved model can better describe the strain rate effect of the material and accurately describe its flow stress. It provides a theoretical basis for the engineering application of materials.

Abstract Background Willows are widely distributed in the northern hemisphere and have good adaptability to different living environment. The increasing of genome and transcriptome data provides a chance for comparative analysis to study the evolution patterns with the different origin and geographical distributions in the Salix phylogeny. Results Transcript sequences of 10 Salicaceae species were downloaded from public databases. All pairwise of orthologues were identified by comparative analysis in these species, from which we constructed a phylogenetic tree and estimated the rate of diverse. Divergence times were estimated in the 10 Salicaceae using comparative transcriptomic analysis. All of the fast-evolving positive selection sequences were identified, and some cold-, drought-, light-, universal-, and heat- resistance genes were discovered. Conclusions The divergence time of subgenus Vetrix and Salix was about 17.6–16.0 Mya during the period of Middle Miocene Climate Transition (21–14 Mya). Subgenus Vetrix diverged to migratory and resident groups when the climate changed to the cool and dry trend by 14 Mya. Cold- and light- stress genes were involved in positive selection among the resident Vetrix, and which would help them to adapt the cooling stage. Universal- stress genes exhibited positive selection among the migratory group and subgenus Salix. These data are useful for comprehending the adaptive evolution and speciation in the Salix lineage.

Abstract Background To evaluate the effects of anterior capsular opening size on deviation from predicted refraction and the effective position of the intraocular lens (ELP) in cataract surgery. Methods Nonrandomized clinical trial. Eighty patients (80 eyes) with simple age-related cataracts were treated from May 2018 to September 2018 at the Fourth Affiliated Hospital of China Medical University. All patients undergoing phacoemulsification received intraocular lens based on the voluntary principle. Forty eyes were implanted with the C-loop haptic intraocular lens (AMO Tecnis ZCB00) while the other 40 eyes were implanted with the plate haptic intraocular lens (CT ASPHINA 509 M). Follow-up visits were conducted postoperatively at 1 week, 1 month, and 3 months during which patients underwent refraction and data collection after pupil dilation, which included anterior segment photography and Scheimpflug imaging by Pentacam. The area, horizontal and vertical diameter of the capsulorrhexis, circularity, decentration, and package were analysed using the image analysis software Image-Pro-Plus 6.0,then evaluated the relationship between the different shapes of capsulorrhexis with deviation from predicted refraction and ELP in cataract surgery. Results Deviation from predicted refraction and all of the parameters of capsulorrhexis were not correlative in the 509 M IOL group, however, in the Tecnis IOL group, while the deviation from predicted refraction and all of the capsulorrhexis parameters were not correlative at 1 week, the deviation from predicted refraction did correlate with capsulorrhexis area, horizontal diameter at 1 month (P = 0.029, P = 0.048), and with capsulorrhexis area, vertical diameter at 3 months (P = 0.03, P = 0.017). The ELP correlated with package in both groups postoperatively (r > 0, P 0.05). For the Tecnis IOL group, the ELP and capsulorrhexis area were correlated at 1 week and 1 month, while the ELP and horizontal diameter, the ELP and vertical diameter were correlated at 1 week, but did not correlate with the other capsulorrhexis parameters in the Tecnis IOL group (all P > 0.05). Conclusions The shape of the capsulorrhexis has an effect on postoperative refractive outcomes and the effective position of the intraocular lens in cataract surgery, and plate haptic intraocular lenses have better refractive stability than C-loop haptic intraocular lenses. Trial registration ChiCTR1800015638,2018-04-12.

Reactive oxygen species (ROS) act as a signaling intermediate to promote cellular adaptation to maintain homeostasis by regulating autophagy during pathophysiological stress. However, the mechanism by which ROS promotes autophagy is still largely unknown. Here, we show that the ATM/CHK2/ULK1 axis initiates autophagy to maintain cellular homeostasis by sensing ROS signaling under metabolic stress. We report that ULK1 is a physiological substrate of CHK2, and that the binding of CHK2 to ULK1 depends on the ROS signal and the phosphorylation of threonine 68 of CHK2 under metabolic stress. Further, CHK2 phosphorylates ULK1 on serine 556, and this phosphorylation is dependent on the ATM/CHK2 signaling pathway. CHK2-mediated phosphorylation of ULK1 promotes autophagic flux and inhibits apoptosis induced by metabolic stress. Taken together, these results demonstrate that the ATM/CHK2/ULK1 axis initiates an autophagic adaptive response by sensing ROS, and it protects cells from metabolic stress-induced cellular damage.

Polyphenols have long been used as functional compounds and are beneficial for host immunity and gut health. This three-phased study investigated the function of Ouli fermented juice (OF) in improving the immunity of cyclophosphamide (CTX)-immunosuppressed mice and regulating their intestinal microbiota and mucosal barrier. Lactobacillus plantarum fermentation increased the phenolic content in the OF. OF effectively improved host immunity and the intestinal mucosal barrier, including increasing serum immunoglobulin (Ig)A, IgG, and IgM levels and secreted IgA (sIgA) levels in the colon, and reduced CTX-induced pathological damage to the spleen and jejunum. Importantly, OF effectively increased the abundance of Lachnospiracea, Roseburia, Akkermansia, and butyric acid-producing microbes, subsequently increasing the levels of short chain fatty acids in the colon. OF with polyphenols exhibited better efficacy at altering the intestinal flora, which might affect the host immunity by changing the host-mucosal barrier-microbiota interaction.

Diabetic nephropathy (DN) is a devastating complication associated with diabetes mellitus, and it is the leading cause of end-stage renal diseases (ESRD). Over the last few decades, numerous studies have reported the beneficial effects of stem cell administration, specifically mesenchymal stem or stromal cells (MSCs), on tissue repair and regeneration. MSC therapy has been considered a promising strategy for ameliorating the progression of DN largely based on results obtained from several preclinical studies and recent Phase I/II clinical trials. This paper will review the recent literature on MSC treatment in DN. In addition, the roles and potential mechanisms involved in MSC treatment of DN will be summarized, which may present much needed new drug targets for this disease. Moreover, the potential benefits and related risks associated with the therapeutic action of MSCs are elucidated and may help in achieving a better understanding of MSCs.

Sepsis is defined as a life-threatening disease involving multiple organ dysfunction caused by dysregulated host responses to infection. To date, sepsis remains a dominant cause of death among critically ill patients. Pyroptosis is a unique form of programmed cell death mediated by the gasdermin family of proteins and causes lytic cell death and release of proinflammatory cytokines. Although there might be some positive aspects to pyroptosis, it is regarded as harmful during sepsis and needs to be restricted. Autophagy was originally characterized as a homeostasis-maintaining mechanism in living cells. In the past decade, its function in negatively modulating pyroptosis and inflammation during sepsis has attracted increased attention. Here, we present a comprehensive review of the regulatory effect of autophagy on pyroptosis during sepsis, including the latest advances in our understanding of the mechanism and signaling pathways involved, as well as the potential therapeutic application in sepsis.

The accurate estimation of the impact of urban form on CO2 emissions is essential for the proposal of effective low-carbon spatial planning strategies. However, few studies have focused on the relationship between urban form and CO2 emissions in small and medium-sized cities, and it is especially unclear whether the relationship varies across cities with different socioeconomic characteristics. This study took 132 small and medium-sized cities in the Yangtze River Delta in China to explore how urban form affects CO2 emissions, considering the socioeconomic factors of industrial structure, population density, and economic development level. First, nighttime light data (DMSP-OLS and NPP-VIIRS) and provincial energy data were used to calculate CO2 emissions. Second, four landscape metrics were used to quantify the compactness and complexity of the urban form based on Chinese urban land-use data. Finally, panel data models were established to analyze whether and how different socioeconomic factors impacted the relationship between urban form and CO2 emissions. The results showed that the three socioeconomic factors mentioned above all had obvious influences on the relationship between urban form and per capita CO2 emissions in small and medium-sized cities. The effect of compactness on per-capita CO2 emissions increased with a rise in the proportion of the tertiary industry, population density, and per-capita GDP. However, compactness shows no effects on per-capita CO2 emissions in industrial cities and low-development-level cities. The effect of complexity on per-capita CO2 emissions only increased with the rise in population density. The results may support decision-makers in small and medium-sized cities to propose accurate, comprehensive, and differentiated plans for CO2 emission control and reduction.

Background: The high price is a critical barrier of access to new direct-anting-antiviral (DAA) therapies for hepatitis C for both the patients and the society. Many countries continue to face the challenge of financing such expensive medicines. Such examples include both high-income and middle-income countries. Existing evidence about the efforts of China to address this challenge is limited. To our knowledge, this is the first detailed description of a novel financing model and comprehensive analysis of its impact on patient financial burden of hepatitis C treatment in China. Objective: To examine the evolution of approaches to navigating patients’ barriers of access to DAA-based treatment of hepatitis C in Tianjin City, China. Methods: Review of publicly available literature, including published and grey literature. Conduct on-site data extraction and key informant interview. The patient financial burden of hepatitis C treatment was analyzed. The financial burden of hepatitis C patients with different treatment models and health insurance financing models was measured by calculating the number of annual income to cover patient out-of-pocket (OOP) expenditure for the standard treatment course accordingly. Findings: Tianjin is the first area to pilot a capitated provider payment program for the treatment of hepatitis C. Through which, the retirees and employees spend 0.7 and 1.0 months of their salary, and residents spend 5.6-6.8 months of their salary for the treatment, the financial burden of patients were much relieved. By the end of March 2019, the first-year pilot program had 876 hepatitis C patients registered the new insurance coverage and treated in Tianjin. Conclusions: The study showed that the financial barriers of access to new hepatitis C treatment for patients could be unblocked with government commitment and novel financing models. International experiences demonstrated that centralized bulk procurement is a good leverage for price negotiation, primarily when using innovative payment approaches. To replicate the initial success of Tianjin, continued efforts are needed for stronger strategic price negotiation, preferably at central level. The case of Tianjin brings implications to the other areas of China and even other developing countries that government commitment, novel financing model and pooled procurement are critical elements of stronger purchasing power and a better secure of treatment.

The lithography contact/proximity printing technique is widely used in the fabrication of microelectronic components, optical devices, and micro-fluidic chips. However, the fabrication of nano-sized structures requires high-cost equipment. This paper proposes a low-cost method to manufacture nanostructures by ultraviolet proximity exposing lithography through a microphotomask on a conventional lithographic aligner. The influence of exposure distance on photoresist pattern size is studied, and the standing wave effect on the photoresist layer is reduced by post-baking. This cost effective method can be widely applied to fabricate patterns with a nanofeature size.

The existence of pores is a very common feature of nature and of human life, but the existence of pores will alter the mechanical properties of the material. Therefore, it is very important to study the impact of different influencing factors on the mechanical properties of porous materials and to use the law of change in mechanical properties of porous materials for our daily lives. The SBFEM (scaled boundary finite element method) method is used in this paper to calculate a large number of random models of porous materials derived from Matlab code. Multiple influencing factors can be present in these random models. Based on the Monte Carlo simulation, after a large number of model calculations were carried out, the results of the calculations were analyzed statistically in order to determine the variation law of the mechanical properties of porous materials. Moreover, this paper gives fitting formulas for the mechanical properties of different materials. This is very useful for researchers estimating the mechanical properties of porous materials in advance.

The expansion curves of the continuous cooling transformation of undercooled austenite of SXQ500/550DZ35 hydropower steel at different heating temperatures and cooling rates were measured by use of a DIL805A dilatometer. Combined with metallography and Vickers hardness measurement, the continuous cooling transformation diagrams (CCT) of the studied steel under two different states were determined. The results show that in the first group of tests, after the hot-rolled specimens were austenitized at 920 °C, when the cooling rate was below 1 °C·s−1, the microstructure was composed of ferrite (F), pearlite (P) and bainite (B). With the cooling rates between 1 °C·s−1 and 5 °C·s−1, the microstructure was mainly bainite, and martensite (M) formed as the cooling rate reached 5 °C·s−1. When the cooling rate was up to 10 °C·s−1, the microstructure was completely martensite and the hardness value increased significantly. In the second group of tests, after the hot-rolled specimens were quenched at 920 °C and then heated at an intercritical temperature of 830 °C, in comparison with the first group of tests, and except for additional undissolved ferrites in each cooling rate range, the other microstructure types were basically the same. Due to the existence of undissolved ferrite, the microstructures of the specimens heated at intercritical temperatures were much finer, and the toughness values at low temperatures were better.