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Abstract This study aimed to investigate the structural properties of tobacco polysaccharide (TP) and its mechanism of modulating hyperlipidemia in high-fat diet-induced mice. The structural properties of TP were characterized by FT-IR, 1HNMR, SEM, AFM and thermogravimetric analysis. And the regulatory mechanism of TP on lipid metabolism was investigated in hyperlipidemia mice. These results showed that TP had a high composition of reducing monosaccharide and the glycosidic bond type was α-glycosidic bond. The intervention by TP resulted in a significant reduction of body weight and improvement in lipid accumulation. And the modulation mechanism by which TP ameliorated the abnormalities of lipid metabolism was associated with the expression levels of lipid metabolism-related genes and serum exosomes miRNA-128-3p, as well as the modulation of structure and abundance of the gut microbiota in mice. In addition, TP treatment significantly increased the content of short-chain fatty acids (SCFAs) in mice feces. The results of molecular docking and dual-luciferase assay exhibited a good interaction between propionic acid and PPAR-α, and it was hypothesized that the interaction might further ameliorate the hyperlipidemia. Therefore, TP can regulate the expression levels of lipid metabolism-related genes through miRNAs from serum exosomes and SCFAs from gut microbiota.

The negative impacts of greenhouse gas emissions, particularly CO2 emissions, have garnered widespread attention. Various old residential areas in China, built more than 20 years ago, have been undergoing urgent transformation to improve citizens’ quality of life, which may significantly reduce carbon emissions. This study developed a carbon emissions accounting framework for residential areas to account the emissions impact of residential transformation. The framework addressed the inventory classifications of landscape greening, residential buildings, water resources, solid waste, infrastructure and transportation. The consumption-based calculation model and bottom-up data collection methods were used. The results show that the transformation of two old residential areas achieved considerable carbon reductions of 17.16% and 33.37% in South and North China, respectively. The macro guidance of local policies, specifically those regarding local urban infrastructure construction, significantly aided the carbon emissions reductions. Based on the calculation results, a list of recommended technologies was proposed to reduce carbon emissions, and four measures (adding greening, improving the garbage recovery rate, separating rain and sewage and transforming envelope structures for energy savings in northern China) were recommended to promote low carbon development in residential areas.

In industrial detection scenarios, achieving high accuracy typically relies on extensive labeled datasets, which are costly and time-consuming. This has motivated a shift towards semi-supervised learning (SSL), which leverages labeled and unlabeled data to improve learning efficiency and reduce annotation costs. This work proposes the unsupervised spectral clustering labeling (USCL) method to optimize SSL for industrial challenges like defect variability, rarity, and complex distributions. Integral to USCL, we employ the multi-task fusion self-supervised learning (MTSL) method to extract robust feature representations through multiple self-supervised tasks. Additionally, we introduce the Enhanced Spectral Clustering (ESC) method and a dynamic selecting function (DSF). ESC effectively integrates both local and global similarity matrices, improving clustering accuracy. The DSF maximally selects the most valuable instances for labeling, significantly enhancing the representativeness and diversity of the labeled data. USCL consistently improves various SSL methods compared to traditional instance selection methods. For example, it boosts Efficient Teacher by 5%, 6.6%, and 7.8% in mean Average Precision(mAP) on the Automotive Sealing Rings Defect Dataset, the Metallic Surface Defect Dataset, and the Printed Circuit Boards (PCB) Defect Dataset with 10% labeled data. Our work sets a new benchmark for SSL in industrial settings.

Estrogen is imperative to mammalian reproductivity, metabolism, and aging. However, the hormone activating estrogen receptor (ERs) α can cause major safety concerns due to the enrichment of ERα in female tissues and certain malignancies. In contrast, ERβ is more broadly expressed in metabolic tissues and the skin. Thus, it is desirable to generate selective ERβ agonist conjugates for maximizing the therapeutic effects of ERs while minimizing the risks of ERα activation. Here, we report the design and production of small molecule conjugates containing selective non-steroid ERβ agonists Gtx878 or genistein. Treatment of aged mice with our synthesized conjugates improved aging-associated declines in insulin sensitivity, visceral adipose integrity, skeletal muscle function, and skin health, with validation in vitro. We further uncovered the benefits of ERβ conjugates in the skin using two inducible skin injury mouse models, showing increased skin basal cell proliferation, epidermal thickness, and wound healing. Therefore, our ERβ-selective agonist conjugates offer novel therapeutic potential to improve aging-associated conditions and aid in rejuvenating skin health.

Ward-acquired infections (WAIs) has become a critical concern, particularly for ships with limited resources. An assessment approach combining validated computational fluid dynamics and the novel Wells-Riley assessment method is proposed to evaluate risks in a shipboard ward. Subsequently, the effects of ventilation, bed-side curtains, and non-adiabatic boundaries on substantial aerosol dispersion are analysed, including X/Y directional walkways (activity zones). Results show that patients with severe symptoms can be prioritized for the exhaust zone rather than the supply zone, and the maximum reduction in suspended particles can differ up to 3-folds. Bed-side curtains can decrease the average risk by −26 % and −48 %/−32 %, respectively, for X/Y directional walkways. Moreover, the average risk increases by approximately +21 % and +14 %/+11 % for X/Y directional walkways under a low air change rate (ACH) of 6 h−1. Considering the non-adiabatic boundary, the average risk reduction is approximately −6.2 % for winter and −7.0 % for summer. It supports that bed-side curtains and a recommended ACH of 12 h−1 are effective in reducing risk. The heat transfer through walls has a marginal effect on risks. Overall, this study provides a framework for predicting and analysing spatial-temporal exposure risks. Better strategies can be developed for protecting medical staff from WAIs.

Abstract Background The patients with multisystem and risk organ involvement Langerhans cell histiocytosis (MS-RO + LCH) have poor prognosis. The patients with MS-LCH who failed front-line therapy have a high mortality rate and the standard salvage treatment has not been established. The combination of cytarabine (Ara-c), vincristine (VCR) and prednisone might be effective for refractory/relapse MS-RO + LCH, with low toxicity. Methods We retrospectively analyzed pediatric refractory/relapse MS-RO + LCH patients treated with the low-dose Ara-c (100mg/m2/d×5days) or high-dose Ara-c (500mg/m2/d×5days) combined with vindesine (VDS) and prednisone in a single center. The efficacy, outcomes and adverse events were analyzed. Results From January 2013 to December 2016, 13 patients receiving the low-dose Ara-c chemotherapy (LAC) and 7 patients receiving the high-dose Ara-c chemotherapy (HAC) were included in the study. 11 (84.6%) of the 13 patients treated with the LAC regimen and 6 (85.7%) of the 7 patients treated with the HAC regimen had response after four courses of the therapy. All patients in the study were alive during follow-up and the 3-year event-free survival rate (EFS) was 53.7% and 85.7% in the LAC and HAC groups. The most frequent adverse event was Grade 1/2 myelosuppression, which was observed in 38.5% (5/13) and 42.9% (3/7) of the patients receiving the LAC and HAC regimen. Conclusions A combination of Ara-c, VDS and prednisone was effective and safe for some patients with refractory/relapse MS-RO + LCH. The high-dose Ara-c regimen was associated with a numerically higher EFS rate.

Abstract Tobacco polysaccharides were extracted by hot water extraction, and purified and separated using DEAE-52 cellulose chromatography columns, and three purified polysaccharide fractions, YCT-1, YCT-2, and YCT-3, were finally obtained. The physicochemical properties of the three fractions were analyzed by ultraviolet spectroscopy, high-performance liquid chromatography and high-performance gel chromatography. The in vitro antioxidant activity of tobacco polysaccharides was compared among different fractions by using DPPH radical, hydroxyl radical scavenging assay and potassium ferricyanide method. The in vitro hypoglycemic activity was compared using α-amylase and α-glucosidase activity inhibition assay. And the in vitro hypolipidemic activity were investigated by using pancreatic lipase activity inhibition assay and HepG-2 intracellular lipid accumulation assay. All the results showed that the constituent monosaccharides of the three tobacco polysaccharide fractions were similar, but the molar percentages of each monosaccharide were different. The average molecular weights of the three components were 27,727 Da, 27,587 Da, and 66,517 Da, respectively, and the scavenging activities on DPPH radicals and hydroxyl radicals were at a high level with good quantitative-effect relationships. The reducing power were much lower than that of the positive control VC, and the three polysaccharide fractions had a weak inhibitory ability on α-amylase activity, but showed excellent inhibitory ability on α-glucosidase and pancreatic lipase activity. In addition, the results of cellular experiments showed that all three fractions were able to inhibit lipid over-accumulation in HepG-2 cells by increasing the mRNA expression levels of PPAR-α, CPT-1A, and CYP7A1 genes, and the tobacco polysaccharide YCT-3 showed the best effect. The mechanism by which YCT-3 ameliorated the over-accumulation of intracellular lipids in HepG-2 cells was found to be related to its influence on the expression of miR-155-3p and miR-17-3p in the exosomes of HepG-2 cells. Graphical Abstract

Abstract Background The European LeukemiaNet (ELN) risk classification system for acute myeloid leukemia (AML) patients has been used worldwide. In 2022, the ELN risk classification system modified risk genes including CEBPA mutation status, myelodysplasia‐related (MR) gene mutations and internal tandem duplications of FLT3 (FLT3‐ITD). Methods We include newly diagnosed de novo AML patients at our center from January 2017 to December 2021, regardless of the further treatment received. Clinical data and date of survival were included. Survival analysis were performed using the Kaplan–Meier method, and the log‐rank test was used to compare survival between different risk groups. Results We include 363 newly diagnosed de novo AML patients from 2017 to 2021 to assess the accuracy of the ELN risk classification system. Their survival results show that the ELN‐2022 risk classification system is not superior to the ELN‐2017 version; for patients with FLT3‐ITD mutations but without FLT3 inhibitor treatment, their survival is similar to the ELN‐2022 adverse risk group. The ELN‐2022 risk classification system cannot accurately clarify ECOG performance status (PS) 2–4 patients, especially in the ELN‐2022 favorable risk group. Conclusion The ELN‐2022 risk stratification system may not be appropriate for patients unable to receive intensive therapy or FLT3 inhibitor; more real‐world data is needed to straify patients with worse ECOG PS and inferior intensive therapy.

AbstractContext Periplaneta americana L. (Blattariae) is used as a treatment for ulcerative colitis (UC) in Chinese traditional medicine.Objective To evaluate the antioxidative activity of P. americana whole body ethanol extract (PAE) on UC mice and whether glycine and proline could be used for quality control and identification of active PAE components.Materials and methods NCM460 cells were pre-incubated in PAE, AA-L, AA-M, and AA-H (low, high and medium doses of proline and glycine), then treated with recombinant human TNF-α. The glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD) and reactive oxygen (ROS) levels were determined. UC mice were fed with water containing 2.5% dextran sulfate sodium (w/v) after pre-treatment with different doses of PAE once a day for 7 days. ELISA was used to detect the concentrations of inflammation-related factors. Colon tissues of mice were used to detect the activity of myeloperoxidase (MPO), GSH, MDA, and SOD. Histological changes were observed using H&E staining. The expression of target proteins was determined by western blotting.Results In vivo, PAE treatment reduced the DAI score more than in the model group, restoring the weight and colonic length. It also reduced the severity of colitis, and inflammatory and oxidative stress intensity. Additionally, western blotting showed that the Nrf2 pathway was activated by PAE. In vitro PAE significantly alleviated TNF-α-induced cell damage and oxidative stress, which is relevant to the activation of the Nrf2 pathway.Conclusions PAE may relieve oxidative stress through the Nrf2 signaling pathway, and proline and glycine may be used as active components of its antioxidative stress activity.

Pores are common defects generated during fabrication, which restrict the application of carbon/carbon (C/C) composites. To quantitatively understand the effects of pores on mechanical strength, this paper proposes a representative volume element model of unidirectional (UD) C/C composites based on the finite element method. The Hashin criterion and exponential degraded rule are used as the failure initiation and evolution of pyrolytic carbon matrices, respectively. Interfacial zones are characterized using the cohesive constitutive. At the same time, periodic boundary conditions are employed to study transverse tensile, compressive, and shear deformations of UD C/C composites. Predicted results are compared with the experimental results, which shows that the proposed model can effectively simulate the transverse mechanical behaviors of UD C/C composites. Based on this model, the effects of microstructural parameters including porosity, pore locations, the distance between two pores, pore clustering, and pore shapes on the mechanical strength are investigated. The results show that porosity markedly reduces the strength as porosity increases. When the porosity increases from 4.59% to 12.5%, the transverse tensile, compressive, and shear strengths decrease by 35.91%, 37.52%, and 30.76%, respectively. Pore locations, the distance between two pores, and pore clustering have little effect on the shear strength of UD C/C composites. For pore shapes, irregular pores more easily lead to stress concentration and matrix failure, which greatly depresses the bearing capacity of UD C/C composites.

Needled carbon/carbon composites contain complex microstructures such as irregular pores, anisotropic pyrolytic carbon, and interphases between fibers and pyrolytic carbon matrices. Additionally, these composites have hierarchical structures including weftless plies, short-cut fiber plies, and needled regions. To predict the effective elastic properties of needled carbon/carbon composites, this paper proposes a novel sequential multiscale method. At the microscale, representative volume element (RVE) models are established based on the microstructures of the weftless ply, short-cut fiber ply, and needled region, respectively. In the microscale RVE model, a modified Voronoi tessellation method is developed to characterize anisotropic pyrolytic carbon matrices. At the macroscale, an RVE model containing hierarchical structures is developed to predict the effective elastic properties of needled carbon/carbon composites. For the data interaction between scales, the homogenization results of microscale models are used as inputs for the macroscale model. By comparing these against the experimental results, the proposed multiscale model is validated. Furthermore, the effect of porosity on the effective elastic properties of needled carbon/carbon composites is investigated based on the multiscale model. The results show that the effective elastic properties of needled carbon/carbon composites decrease with the increase in porosity, but the extent of decrease is different in different directions.

Accurate load prediction is a prerequisite for the design, operation, scheduling, and management of energy systems. In the context of the development of smart grids, the extensive integration of highly volatile distributed energy generation into the power system has brought new challenges to the accuracy, reliability, real-time performance, and intelligence of short-term load forecasting. Therefore, this article proposes a novel short-term power load composite prediction model based on AM–CNN–Bi–LSTM. First, CNN is used to extract relevant feature quantities of power load coupling characteristics. Then, AM is used to evaluate the importance of the feature data, highlighting the features that have a greater impact on the prediction results. Finally, the Bi-LSTM network captures bidirectional temporal information from multiple time steps for prediction. Taking one year of measured data as an example, the error comparison of the prediction results of the composite prediction model overlay shows that compared with other models, the composite prediction model has improved prediction accuracy, feature extraction, generalization ability, and other aspects. The research results improve the accuracy of short-term power load forecasting while providing effective model references for decision-making in power system optimization scheduling, safe operation, and reasonable pricing.

Background: Tocilizumab is a well-practiced strategy to manage cytokine release syndrome (CRS) after chimeric antigen receptor T cell (CAR-T) therapy. However, varied efficiency in CRS mitigation by tocilizumab has been reported to highlight affecting variables such as tumor types and timing of the administration. Objective: The objective of this study is to identify different curative effect between diffuse large B-cell lymphoma (DLBCL) and acute lymphoblastic leukemia (ALL) by early use of tocilizumab for prophylaxis and treatment of CRS. Methods: By retrospectively summarizing our institution's experience with a CAR-T clinical trial targeting CD19, 11 cases were analyzed: 5 DLBCL, and 6 ALL. The two groups were compared with patient characteristics, CRS information and clinical outcomes. 3 patients were pretreated with tocilizumab for prophylaxis and the rest were treated with tocilizumab at CRS diagnosis. Results: CRS occurred in 81.8% of patients (9/11), grade 3 or higher occurred in 55.6% of the CRS patients (5/9). The two group were similar in patient characteristics, CAR-T and CRS profile. However, tocilizumab produced much better efficacy against CRS in DLBCL group compared with ALL group (80% versus 16.7%, P ​= ​0.08). Conclusions: Despite the statistical was non-significant, possibly due to small case pool and bias was unavoidable, our analysis suggested that early use of tocilizumab was more effective for DLBCL than ALL in the prophylaxis and treatment of CRS. A treatment algorithm for management of CRS with regard to DLBCL and ALL is proposed, which may extend to other local or systemic malignancies and warrant further investigation.

With advantages of strong drive capability, nested-loop secondary linear machine (NLS-LM) has great potentiality in linear metro. For its secondary structure with multiple loops, it is difficult to calculate the electromagnetic thrust of NLS-LM reasonably. Hence, in this paper, one thrust calculation method is proposed considering variable loop inductance and transient loop current. Firstly, to establish the secondary winding function, the modeling domain is confined to a limited range, and the equivalent loop span is employed by analyzing the coupling relationship between primary and secondary. Then, in order to obtain the secondary flux density, the transient secondary current is solved based on the loop impedance and induced voltage. Finally, the electromagnetic thrust can be calculated reasonably by the given primary current sheet and the calculated secondary flux density. Comprehensive simulations and experiments have demonstrated the effectiveness of the proposed method.

Abstract Improving vitality has been a major bottleneck in the revitalization of traditional village heritage worldwide. The vitality of traditional village (VTV) varies greatly depending on socioeconomic factors and natural conditions. Significant spatial variation exists in VTV, even within the same urban jurisdictions in China; however, the main determinants for this have not yet been quantified owing to the difficulty of obtaining data from large rural samples, making targeted invigoration difficult. Thus, we applied point of interest data, which are easily accessible big data, to bridge the data source gap. To assess the VTV’s influencing factors and analyze the spatial variations among the factors’ impacting intensity, we used the Ordinary Least Squares and Geographically Weighted Regression models and conducted empirical studies involving 148 traditional villages in Lishui, China. Seven factors influenced the vitality of traditional villages in the study area, with the most significant being topographic relief, elevation, scenic spots and commercial industry. Moreover, the factors’ impacting intensity varied by region. Topographic relief and elevation had the greatest impact intensity in the north and south of Lishui, whereas primary education, transportation facility and agricultural bases had the greatest impact in the north, and scenic spots and commercial industry had the greatest impact in the middle of Lishui. Taken together, this method makes a large sample of VTV’s impact factor analysis feasible, has global implications, and can provide a foundation for the scientific and precise regional promotion of VTV, which is beneficial for rural heritage revitalization.

The importance of thermal acclimation for the Thermal Death Time (TDT) landscape of the common soil living springtail, Folsomia candida (Collembola, Isotomidae), was investigated. To this aim, we acclimated adult springtails at 10 °C (cold-acclimation) and 20 °C (warm-acclimation), respectively. In static thermal tolerance assays, we found the relationship between survival and exposure time at a number of stressful high and low temperatures. Using logistic modelling, we found, at each exposure temperature, the time until 50% mortality had been reached (Lt50). The exponential functions of TDT curves were found by linear regression of log10 Lt50 values against exposure temperature. Results showed that cold acclimation significantly increased cold tolerance and increased the temperature dependence of cold injury accumulation rate (increased the slope by 4 orders of magnitude) in F. candida. Hence, cold acclimation changed the status of this species from chill-susceptible to moderately chill-tolerant. The cellular injury accumulation at sub-zero temperatures was not related to freezing of body water in this study. Congruently, we found a significant negative effect of cold acclimation on heat tolerance and that cold acclimation decreased the thermal sensitivity of the heat injury accumulation rate. Different slopes of the TDT curves between acclimation groups indicated that acclimation shifted the proportional importance of cellular injury mechanisms or the nature of injury mechanisms. Finally, we compare and combine the TDT curves at extreme high and low temperatures with previously published results on longevity at benign temperatures (from 0 to 30 °C) and describe the full thermal niche of F. candida.

Aims: Excessive alcohol consumption can lead to alcoholic liver diseases (ALDs). Tetrastigma hemsleyanum Diels et Gilg is a rare Chinese medicinal herb. Tetrastigma hemsleyanum Diels et Gilg has been validated to be highly effective for treating hepatitis. Kaempferol and nicotiflorin are two highly representative flavonoids, which have exhibit therapeutic effects on liver disease. Therefore, the protective mechanism of kaempferol and nicotiflorin on alcohol-induced liver injury were investigated. Main methods: Forty mice were used in this study. After treatment of Kaempferol and nicotiflorin, serum and liver were collected and used for determination of biochemical indicators, H&E staining, and molecular detection. The interaction of miRNAs from serum extracellular vehicles (EVs) with mRNAs and 16S rRNA sequencing of gut microbiota were also investigated. Key findings: The results showed that kaempferol and nicotiflorins significantly ameliorated alcohol-induced liver damage and observably regulated gut microbiota. Specifically, the levels of malondialdehyde (MDA) and CYP2E1 in the liver significantly reduced, and the activity of superoxide dismutase (SOD) and glutathione (GSH) in the liver evidently increased. They also significantly relieved liver oxidative stress and lipid accumulation by suppressing miR-138-5p expression, inversely enhancing deacetylase silencing information regulator 2 related enzyme-1 (SIRT1) levels and then decreasing farnesoid X receptor (FXR) acetylation, which then modulated Nrf2 and SREBP-1c signaling pathways to regulate oxidative stress and lipid metabolism induced by alcohol. Significance: Kaempferol and nicotiflorin reduced alcohol-induced liver damage by enhancing alcohol metabolism and reducing oxidative stress and lipid metabolism. The intestinal microorganism disorder was also ameliorated after oral kaempferol and nicotiflorin.

ABSTRACTBackground: Acute myeloid leukemia (AML) is the most common malignant hematological disease originating from hematopoietic stem cells. Endoplasmic reticulum stress (ERs) has been reported to be involved in multiple tumor-related biological processes. However, the prognostic role of ERs-related genes in AML has not been fully investigated.Methods: The TCGA-LAML RNA-seq dataset was downloaded from the UCSC Xena website as the training cohort. Univariate Cox regression analysis was used to identify 42 ER stress-related genes associated with prognosis. Then, a ERs risk score prognostic model was established through LASSO regression analysis. AML patients were divided into high- and low-risk groups according to the median risk score. The Kaplan-Meier survival curve, time ROC curve analysis and univariate and multivariate independent prognostic analyses were presented for the high- and low-risk groups. Moreover, we verified the ERs risk model in the TARGET-AML and GSE37642 datasets. Next, we performed immune cell infiltration analysis, immune checkpoint gene expression analysis and drug sensitivity analysis.Results: We found 42 ER stress-related genes with prognostic significance, and a prognostic model consisting of 13 genes was constructed and verified. The survival rate of AML patients in the low-risk group was better than that in the high-risk group. The tumor microenvironment and immune cell infiltration results showed that immune cell infiltration was correlated with the survival status of patients.Conclusion: This research identified a ERs risk model with significant prognostic value. These genes are expected to be potential prognostic biomarkers in AML, providing a new theoretical basis for disease management.

There is no uniform regimen for refractory Langerhans cell histiocytosis (LCH). We retrospectively described patients with refractory multisystem and risk organ involvement LCH treated with the low-dose (Ara-c, 100 mg/m2/d × 5day; 2-CDA, 5 mg/m2/d × 5day) chemotherapy (LDC) and the intermediate-dose (Ara-c, 500 mg/m2/d × 5day; 2-CDA, 9 mg/m2/d × 5day) chemotherapy (IDC). 26 patients and 10 patients receiving the LDC and IDC regimen from January 2013 to December 2016 were included in the study. The overall response rate exhibited no significant difference between the LDC and IDC groups after four courses (76.9% vs 90%, P = 0.375) and eight courses (80.8% vs 100%, P = 0.135) of treatment. No statistical differences in the overall survival rate were observed between the two groups, but 5-year event-free survival rate of patients in the IDC group was higher than that in the LDC group at the median follow-up of 6.16 and 5.07 years (88.9% vs 52.9%, P = 0.033). The patients in the IDC group had more severe myelosuppression than those in the LDC group (grade 3/4 myelosuppression, 80% vs 19.2%, P = 0.001). The intermediate-dose regimen of 2CDA and Ara-c had a higher event-free survival rate and a similar overall survival rate compared with the low-dose regimen.

Abstract Retinal degeneration is a kind of neurodegeneration characterized by progressive neuronal death and dysfunction of retinal pigment epithelium (RPE) cells, leading to permanent visual impairment. It still lacks effective therapeutic options and new drugs are highly warranted. In this study, we found the expression of IL-4, a critical regulator of immunity, was reduced in both patients and mouse models. Importantly, exogenous intravitreal IL-4 application could exert a novel neuroprotective effect, characterized by well-preserved RPE layer and neuroretinal structure, as well as amplified wave-amplitudes in ERG. The RNA-seq analysis revealed that IL-4 treatment suppressed the essential oxidative and pro-inflammatory pathways in the degenerative retina. Particularly, IL-4 upregulated the IL-4Rα on RPE cells and induced a reparative phenotype via the activation of Nrf2 both in vitro and in vivo. Furthermore, the Nrf2-/- mice displayed no recovery in response to IL-4 application, highlighting a significant role of Nrf2 in IL-4-mediated protection. Our data provides evidence that IL-4 protects against retinal neurodegeneration by its antioxidant and anti-inflammatory property through IL-4Rα upregulation and Nrf2 activation in RPE cells. The IL-4/IL-4Rα-Nrf2 axis maybe the potential targets for the development of novel therapies for neurodegenerative diseases.

Abstract Objective The purpose of this study was to explore the effect of cigarette smoke component (CSC) exposure on serum lipid levels in rats and the underlying molecular mechanism. Methods Male SPF-grade SD rats were randomly divided into a control group and a CSC exposure group, with the CSC group being exposed to CSC for 6 weeks. RT–PCR and Western blotting methods were used to detect lipid metabolism gene expression in rats, and 16S RNA gene sequencing was used to detect the gut microbiota in the rat cecum. Rat serum exosomes were prepared and identified, and the interaction of exosomal miR-291a-3p and miR-126a-5p with AMPK and CYP7A1 was detected by a dual luciferase reporter gene assay (DLRG). Results Serum indicators, including cholesterol levels and trimethylamine oxide (TMAO) content, were significantly affected in the CSC exposure group compared with the control group (P

In this study, we focused on electricity consumption and household characteristics with Dynamic Pricing(DP) experiment in the collective housing complex of a Japanese Smart Community, which had been divided into two groups, Treatment group (110 households) and Control group (65 households). We collected and analyzed a questionnaire survey on the family attributes of residents and all housing electrical appliances to understand the actual conditions of household characteristics. The annual energy consumption by smart meters had been aggregated and analyzed to understand the actual conditions of electricity end-use of the households. The results showed the main factors of household, which affect the electricity consumption, were floor area, family number, income of households, and the number of air conditioner. During dynamic pricing experiment in summer and winter, we found that the implementation of Dynamic Pricing would affect household users' habits of using electrical equipment and had a contribution to energy peak cut. Through the hierarchical cluster analysis, we divided both group into three types of household characteristics respectively. The result has revealed that the family structure would affect the electricity consumption during Dynamic Pricing implement.In this study, we focus on energy consumption and household characteristics with dynamic pricing experiment in the collective housing complex of a Japanese Smart Community. we collected and analyzed a questionnaire survey on the family attributes of residents and the lifestyle of all housing equipment to understand the actual conditions such as the attributes of the resident generation. The annual energy consumption by smart meters will be aggregated and analyzed to understand the actual conditions of electricity consumption of the resident generation. Based on the aggregated results, a database of lifestyle patterns and energy consumption is constructed, and the relationship between each factor and energy consumption, and each lifestyle pattern has been analyzed.

Nested-loop secondary linear doubly-fed machine (NLS-LDFM) is a novel linear machine evolved from rotary brushless doubly-fed induction machine, which has a good application prospect in linear metro. In order to analyze the performance of NLS-LDFM, the mechanism and action rules of end effects are investigated in this paper. Firstly, the mechanism of static and dynamic end effects is analyzed in aspect of direct coupling, winding asymmetry and transient secondary current. Furthermore, based on the winding theory for short primary linear machines, the machine parameters are established qualitatively considering pulsating magnetic field of NLS-LDFM. Finally, the NLS-LDFM performance analysis is supplemented by the finite element algorithm (FEA) simulation and experiments under different operating conditions.

Primary hemophagocytic lymphohistiocytosis (pHLH) is a rare immune disorder and hematopoietic stem cell transplan- tation (HSCT) is the only potentially curative treatment. Given the high pre-HSCT mortality of pHLH patients reported in the HLH-2004 study (17%), more regimens to effectively control the disease and form a bridge with HSCT are needed. We conducted a retrospective study of pHLH children treated by ruxolitinib (RUX)-based regimen. Generally, patients received RUX until HSCT or unacceptable toxic side-effect. Methylprednisolone and etoposide were added sequentially when the disease was suboptimally controlled. The primary end point was 1-year overall survival. Twenty-one pHLH patients (12 previously treated and 9 previously untreated) were included with a median follow-up of 1.4 years. At last follow-up, 17 (81.0%) patients were alive with a 1-year overall survival of 90.5% (95% confidence interval: 84.1-96.9). Within the first 8 weeks, all patients had an objective response, of which 19 (90.5%) achieved complete response (CR) and two (9.5%) achieved partial response (PR) as a best response. Seventeen (81.0%) patients received HSCT, of which 13 (76.5%) had CR, three (17.6%) had PR and one (5.9%) had disease reactivation at the time of HSCT. Fifteen (88.2) patients were alive post- HSCT. Notably, eight (38.1%) patients received zero doses of etoposide, suggesting the potential of RUX-based regimen to reduce chemotherapy intensity. Patients tolerated RUX-based regimen well and the most frequently observed adverse events were hematologic adverse events. Overall, RUX-based regimen was effective and safe and could be used as a bridge to HSCT for pHLH children.

BackgroundPatients with early gastric cancer have increased risk of developing multiple primary malignancies (MPM) due to improved survival rates. The purpose of this study was to evaluate the clinicopathological features of MPM and to generate a useful tool for predicting the development of MPM after early gastric cancer.MethodsWe selected 1025 early gastric cancer patients with complete medical records for a retrospective analysis. The Cox proportional risk regression model was used to analyze the independent risk factors for the development of MPM in early gastric cancer. RStudio software was used to compare the OS of early gastric cancer patients with and without MPM, and a nomogram was established to predict the probability of MPM 1-, 2-, 3-year after early gastric cancer. The predictive effectiveness of the nomogram was evaluated by the C-index and calibration curve. Decision curve analysis (DCA) measured the applicability of the nomogram to clinical practice.ResultsOf the 1025 patients with early gastric cancer, 66 patients (6.4%) had 69 primary cancers other than early gastric cancer. They had a median follow-up of 41 months, and their cumulative incidence of MPM was 4.9%, 5.4% and 5.9% after 1-, 2-, and 3- year, respectively. Oesophageal cancer was the most frequently detected MPM, followed by lung and colorectal cancers. Male (p=0.038), age ≥65 years (p=0.003), smoking history (p=0.036), and lymph node metastasis (p=0.013) were independent risk factors for MPM in patients with early gastric cancer. Patients with early gastric cancer with MPM had a worse OS prognosis than patients with early gastric cancer without MPM (p

Accurately characterizing the intrinsic stellar photometric noise induced by stellar astrophysics, such as stellar activity, granulation, and oscillations, is of crucial importance for detecting transiting exoplanets. In this study, we investigate the relation between the intrinsic stellar photometric noise, quantified by the Kepler combined differential photometric precision (CDPP) metric, and the level of stellar chromospheric activity, indicated by the S -index of Ca ii H K lines derived from LAMOST spectra. Our results reveal a clear positive correlation between the S -index and robust rms values of CDPP, with the correlation becoming more significant at higher activity levels and on longer timescales. We have therefore built an empirical relation between the robust rms values of CDPP and the S -index as well as T _eff , $\mathrm{log}$ g , [Fe/H], and the apparent magnitude, with the XGBoost regression algorithm, using the LAMOST–Kepler common star sample as the training set. This method achieves a precision of ∼20 ppm for inferring the intrinsic noise from the S -index and other stellar labels on a 6 hr integration duration. We have applied this empirical relation to the full LAMOST DR7 spectra database and obtained the intrinsic noise predictions for 1,358,275 stars. The resultant catalog is publicly available and expected to be valuable for optimizing target selection for future exoplanet-hunting space missions, such as the Earth 2.0 mission.

Urban transportation, e.g., linear metro, driven by linear induction machine (LIM) has been paid more attention by both academia and industry recently for its direct thrust drive, strong climbing ability, flexible line choice, smaller cross section area, lower noise, etc. However, this system is greatly different with traditional rotary induction machine (IM) due to its cut-open primary (end effect), normal force resulted from the asymmetric structure, eddy current in the secondary, and so on. There exists great difficulty for accurate modelling and advanced control strategies for LIM influenced by nonlinear circuit, partial magnetic saturation, internal and external disturbance, etc. This paper will introduce one new reasonable equivalent circuit for LIM performance analysis, as well as some specific design and control case studies. Afterwards, advanced control strategies, like efficiency optimization control (EOC), model predictive control (MPC), will be employed to further increase the LIM drive indexes, such as average thrust, efficiency, etc.

Abstract Chimeric antigen receptor-engineered T (CAR-T) cells have shown promising efficacy in patients with relapsed/refractory B cell acute lymphoblastic leukemia (R/R B-ALL). However, challenges remain including long manufacturing processes that need to be overcome. We presented the CD19-targeting CAR-T cell product GC007F manufactured next-day (FasTCAR-T cells) and administered to patients with R/R B-ALL. A total of 21 patients over 14 years of age with CD19+ R/R B-ALL were screened, enrolled and infused with a single infusion of GC007F CAR-T at three different dose levels. The primary objective of the study was to assess safety, secondary objectives included pharmacokinetics of GC007F cells in patients with R/R B-ALL and preliminary efficacy. We were able to demonstrate in preclinical studies that GC007F cells exhibited better proliferation and tumor killing than conventional CAR-T (C-CAR-T) cells. In this investigator-initiated study all 18 efficacy-evaluable patients achieved a complete remission (CR) (18/18, 100.00%) by day 28, with 17 of the patients (94.4%) achieving CR with minimal residual disease (MRD) negative. Fifteen (83.3%) remained disease free at the 3-month assessment, 14 patients (77.8%) maintaining MRD negative at month 3. Among all 21 enrolled patients, the median peak of CAR-T cell was on day 10, with a median peak copy number of 104899.5/µg DNA and a median persistence period of 56 days (range: 7–327 days). The incidence of cytokine release syndrome (CRS) was 95.2% (n = 20), with severe CRS occurring in 52.4% (n = 11) of the patients. Six patients (28.6%) developed neurotoxicity of any grade. GC007F demonstrated superior expansion capacity and a less exhausted phenotype as compared to (C-CAR-T) cells. Moreover, this first-in-human clinical study showed that the novel, next-day manufacturing FasTCAR-T cells was feasible with a manageable toxicity profile in patients with R/R B-ALL.

T-cell acute lymphoblastic leukemia (T-ALL) has a poor prognosis as a result of severe immunosuppression and rapid tumor progression with resistance to conventional chemotherapy. Excessive IgD may play a role in T cell activation via IgD Fc receptor (FcδR). Here we aimed to investigate the effects of IgD in T-ALL and demonstrated the potential benefit by targeting IgD/FcδR in T-ALL patients with IgD-Fc-Ig fusion protein. In T-ALL patients’ blood samples and cell lines, the level of IgD, the percentage of FcδR expressing cells and the binding affinity were determined by flow cytometry. T cell viability, proliferation and apoptosis were analyzed. A mouse xenograft model was used to evaluate the in vivo effect of IgD-Fc-Ig, an IgD-FcδR blocker. The levels of serum IgD and FcδR were abnormally increased in part of T-ALL patients and IgD could induce over-proliferation and inhibit apoptosis of T-ALL cells in vitro. FcδR was constitutively expressed on T-ALL cells. IgD-Fc-Ig showed similar binding affinity to FcδR and selectively blocked the stimulation effect of IgD on T-ALL cells in vitro. In vivo study exhibited that IgD-Fc-Ig may also have therapeutic benefit. IgD-Fc-Ig administration inhibited human T-ALL growth and extended survival in xenograft T-ALL mice. In conclusion, this work supports the idea of targeting IgD/FcδR in T-ALL patients with excessive IgD. IgD-Fc-Ig fusion protein might be a potential biological drug with high selectivity for T-ALL treatment.

This study aims to enhance the stability and bioavailability of nuciferine (NF) and epigallocatechin-3-gallate (EGCG) by loading NF into liposomes and then incorporating the liposomes and EGCG into porous microgels (NFEG-microgel) prepared with chitosan and proanthocyanidin. Analysis of particle size (0.5–3.0 μm), electron microscopy, rheology, stability, and simulated gastrointestinal release confirmed that the prepared microgels had high encapsulation rate and good stability and release characteristics. Intervention experiments were performed by orally administering NFEG-microgel to high-fat diet rats to evaluate its efficacy and regulatory mechanism for blood lipid metabolism. NFEG-microgel intervention significantly reduced the body weight and serum lipid level, and the mechanism was related to the expression regulation of key genes involved in lipid metabolism and miRNAs (miR-126a-5p and miR-30b-5p) in serum extracellular vesicles. In addition, NFEG-microgel improved the diversity of gut microbiota by enriching short-chain fatty acids (SCFA)-producing bacteria and reducing harmful bacteria, suggesting that it can ameliorate lipid metabolism by regulating the intestinal flora community in rats.

Donor cell-derived leukemia (DCL) is a special type of relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients with DCL generally have a poor prognosis due to resistance to conventional chemotherapy. Here, we report a case of donor cell-derived acute lymphoblastic leukemia after umbilical cord blood transplantation. The patient didn’t respond to induction chemotherapy. She then received anti-CD19 CAR-T cell therapy and achieved MRD-negative complete remission (CR). However, MRD levels rose from negative to 0.05% at 5 months after CAR-T cell therapy. Higher MRD levels were significantly associated with an increased risk of leukemia recurrence. Afterward, preemptive interferon-α treatment was administrated to prevent disease recurrence. To date, the patient has maintained MRD-negative CR for 41 months. Our results suggested that anti-CD19 CAR-T cells followed by interferon-α therapy are effective in treating donor cell-derived acute lymphoblastic leukemia. This report provides a novel strategy for the treatment of DCL.

Basal cells are multipotent stem cells of a variety of organs, including the respiratory tract, where they are major components of the airway epithelium. However, it remains unclear how diverse basal cells are and how distinct subpopulations respond to airway challenges. Using single cell RNA-sequencing and functional approaches, we report a significant and previously underappreciated degree of heterogeneity in the basal cell pool, leading to identification of six subpopulations in the adult murine trachea. Among these, we found two major subpopulations, collectively comprising the most uncommitted of all the pools, but with distinct gene expression signatures. Notably, these occupy distinct ventral and dorsal tracheal niches and differ in their ability to self-renew and initiate a program of differentiation in response to environmental perturbations in primary cultures and in mouse injury models in vivo. We found that such heterogeneity is acquired prenatally, when the basal cell pool and local niches are still being established, and depends on the integrity of these niches, as supported by the altered basal cell phenotype of tracheal cartilage-deficient mouse mutants. Finally, we show that features that distinguish these progenitor subpopulations in murine airways are conserved in humans. Together, the data provide novel insights into the origin and impact of basal cell heterogeneity on the establishment of regionally distinct responses of the airway epithelium during injury-repair and in disease conditions.

Abstract Background Rainbow trout is an economically important fish in aquaculture and is a model species in environmental physiology. Despite earlier research on the seawater adaptability of rainbow trout at different temperature regimes, the influence on the liver and intestine in this species is still unknown. Two trials were conducted to investigate the effects of constant and diel cyclic temperatures on phospholipid fatty acid (PLFA) composition in the liver and intestine of rainbow trout during seawater acclimation. Results At the end of growth trial 1, fish at 9 and 12.5 °C showed significantly higher ratios of unsaturated to saturated (U/S) and unsaturation index (UI) than those at 16 °C in liver and intestine phospholipids. After day 1 of seawater acclimation, the U/S, UI, and average chain length (ACL) of liver and intestinal phospholipids in fish at 16 °C significantly increased. Two weeks after seawater acclimation, the liver and intestinal PLFA composition adapted to salinity changes. In trial 2, significantly higher U/S, UI, and ACL were found in intestinal phospholipids at 13 ± 2 °C. On the first day after seawater acclimation, UI and ACL in liver phospholipids significantly increased at 13 °C, while fish at 13 ± 2 °C showed significantly decreased U/S, UI, and ACL in the intestine. At the end of growth trial 2, liver PLFA compositions were stable, whereas intestinal PLFA at 13 and 13 ± 1 °C showed significantly decreased U/S, UI, and ACL. A two-way analysis of variance and principal component analysis revealed significant effects of different constant temperatures, seawater acclimation, and their interaction on the liver and intestinal phospholipids, a significant effect of diel cyclic temperature on intestinal phospholipids, and the effects of seawater acclimation and its interaction with diel cyclic temperature on liver phospholipids. Conclusion Temperatures of 9 and 12.5 °C could elevate membrane fluidity and thickness in the liver and intestine of rainbow trout in freshwater, whereas no significant effects were found with diel temperature variations. After seawater acclimation, constant and diel cyclic temperatures significantly influenced the membrane fluidity and thickness of the liver and intestine. Compared with constant temperature, diel temperature variation (13 ± 2 °C) can enhance the adaptability of rainbow trout during seawater acclimation.

We investigated the effects of nuciferine rich in Lotus leaf on the amelioration of hepatic steatosis and dyslipidemia of hyperlipidemic rats, and explored the underlying mechanism on miRNAs and genes expression. Serum extracellular vesicles (EVs) from rats were prepared and characterized, and interactions between miRNAs and target mRNAs were validated in 293T cell line with the double luciferase reporter gene assay. Results showed that nuciferine significantly induced the expression of PPARα, ABCA1, CYP7A1, LXRα in liver and ABCG5 in intestine, while NPC1L1 expression was markedly reduced. In vitro, double luciferase reporter assays showed that miRNA-764-5p, miRNA-758-3p, and miRNA-126-5p interacted with the target mRNAs of PPARα, ABCA1, and CYP7A1, respectively. And the effect of nuciferine on lipid metabolism in rats was related to regulate intestinal absorption and serum EVs miRNAs. These miRNAs were able to reduce lipid levels by targeting lipid metabolism genes and up-regulating PPARα-LXRα-ABCA1 pathway and CYP7A1 expression.

IntroductionThe hematological manifestations of corona virus disease 2019 (COVID-19) can confound the diagnosis and therapy of other diseases. In this paper, we firstly reported a case of chronic myeloid leukemia (CML) of delayed diagnosis and intolerance to tyrosine kinase inhibitors (TKIs) concurrent with COVID-19.Case PresentationA 56-year-old female was diagnosed as COVID-19 with no obvious leukocytosis [white blood cell (WBC), ≤17 × 109/L] or splenomegaly until ablation of the virus. Bone marrow aspiration was conducted to establish the diagnosis of CML. She accepted an adjusted dosage of imatinib initially and had to suspend it after myelosuppression (day 41). After hematopoietic therapy, imatinib was given again (day 62), but she was still non-tolerant, and nilotinib at 150 mg twice a day was prescribed from day 214. At just about 4 weeks later, nilotinib was discontinued due to myelosuppression. Then, it was reduced to 150 mg per day and was re-initiated (day 349), but she was still non-tolerant to it. Similarly, from day 398, flumatinib at 200 mg per day was tried, but she was non-tolerant. Her white blood cell or platelet count fluctuated markedly with poor therapeutic response. Considering that she was relatively tolerant and responsive to imatinib, the medication was re-initiated at 200 mg and reduced to 100 mg per day. Her follow-up revealed stable WBC and PLT counts. The latest BCR-ABL-210/ABL was decreased to 0.68% at about 6 months after imatinib was re-initiated, which means an improved response.ConclusionThe offset effect between CML and SARS-CoV-2 infection was supposed to be the underlying mechanism for the absence of leukocytosis or splenomegaly. The impact of immune network by SARS-CoV-2 preserved and disrupted the patient’s response to TKIs despite the virus’ ablation. We suggest that a continued elevation of basophils may be a useful indicator for CML concurrent with COVID-19, and individualized treatment with adjusted dosage and suitable type of TKIs should be considered to improve the patient’s health outcome.

Green and energy-saving reforms, which use protection as a precondition, can, not only reduce a building’s energy use but also improve its level of comfort. Such reforms can also adapt to the new demands of modern society while extending the life of traditional architecture. Therefore, this research chose a classical, traditional house in Hangzhou Zhejiang, China, as a transformation object – attempting to implement low-cost, energy-saving technology. The building’s energy consumption and level of comfort before and after the transformation have been simulated and measured to compare the effects of the transformation. The authors hope this research will provide insights into green and energy-saving reform technology and aid the sustainable development of traditional houses.

The measurement while drilling (MWD) system in underground coal mine currently uses wire for signal transmission. However, it has shortcomings such as strict technical requirements for cable drill pipe processing and high cost of use. Electromagnetic measurement while drilling (EM-MWD) is a new technology has a high rate of information transmission with fast measurement speed and low cost and is not affected by the drilling media. Hence, it is necessary to investigate a reliable electromagnetic transmission channel which is suitable for underground coal mine. This study selects the excitation method through comparison and conducts theoretical research on this basis. Based on the classical electromagnetic theory, the equivalent transmission line method is adopted to calculate and analyze the channel characteristics, while the electrical properties of the coal seam and the surrounding rock are considered. The results demonstrate that the formation resistivity, drill pipe resistivity, and the emission frequency are the main factors affecting signal transmission. On the basis of the uniform equivalent transmission line model, the theoretical model is established by combining the segmented uniform transmission line theory. The layered equivalent transmission line model can be better used to evaluate the regional applicability of the EM-MWD system.

Müller glial cells (MGCs) play important roles in human retina during physiological and pathological conditions. However, the development process of human MGCs in vivo remains unclear, and how to obtain large numbers of human MGCs with high quality faces technical challenges, which hinder the further study and application of MGCs. Human induced pluripotent stem cell (hiPSC)-derived retinal organoids (ROs) with all retinal cell subtypes provide an unlimited cell resource and a platform for the studies of retinal development and disorders. This study explored the development of human MGCs in hiPSC-derived ROs and developed an approach to select and expand the induced MGCs (iMGCs). In ROs, retinal progenitor cells progressively differentiated into SOX9+ Ki67– MGC precursors during differentiation day (D) 60 to D90, while mature MGCs expressing markers CRALBP and GS gradually appeared since D120, which spanned the entire thickness of the neural retina layer. Cells isolated from ROs aged older than 120 days was an optimal source for the enrichment of iMGCs with high purity and expansion ability. They had typical features of human MGCs in morphological, structural, molecular and functional aspects, and could be passaged serially at least 10 times, yielding large numbers of cells in a short period. The transcriptome pattern of the expanded iMGCs was also revealed. This study firstly clarified the timecourse of human MGC development in the RO model, where the iMGCs could be enriched and expanded, paving the way for downstream investigation and application in MGC-related retinal disorders.

BackgroundT-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) expresses on leukemic stem and progenitor populations of non-M3 acute myeloid leukemia (AML) as well as T lymphocytes. TIM-3 is thought to be involved in the self-renewal of leukemic stem cells and the immune escape of AML cells, however its correlation with AML prognosis is still controversial and worthy of further investigation.Methodswe simultaneously assessed TIM-3 expression levels of leukemic blasts and T lymphocytes in the bone marrow of de novo AML patients using flow cytometry. The correlations of TIM-3 expression between leukemic blasts and T lymphocytes and the correlations of TIM-3 expression with various patient parameters were analyzed. In addition, the Cancer Genome Atlas (TCGA) data of AML patients were acquired and analyzed to verify the results.ResultsTIM-3 expression of CD34+ leukemic blasts (R2 = 0.95, p

ObjectiveTo establish the association between serial levels of inflammatory cytokines in cord blood and perinatal characteristics and bronchopulmonary dysplasia (BPD) in preterm infants.Methods147 premature infants with gestational age ≤32 weeks who were born and hospitalized in the First Affiliated Hospital of Zhengzhou University between July 2019 and August 2021 were enrolled in this retrospective case–control study. Multiple microsphere flow immunofluorescence was used to detect seven cytokines in cord blood collected within 24 h of birth. Demographics, delivery characteristics, maternal factors, neonatal characteristics, and clinical outcomes were collected for the two groups. An unconditional logistic regression model was used in this study to assess the clinical variables.ResultsIL-6 cord blood levels at birth were significantly higher in the BPD group than in the non-BPD group, but the odds ratio (OR) was very small (OR = 1). No differences in other cytokine concentrations were observed between the two groups. Multivariable logistic regression analysis demonstrated that increased maternal white blood cell (WBC) count on admission and lower birth weight increased the risk of BPD progression.ConclusionsIncreased IL-6 cord blood levels at birth in preterm infants may have trivial significance for predicting BPD. Furthermore, higher maternal WBC count on admission and lower birth weight increased the risk of BPD.

Aiming to overcome the problem of the frequency error between the reference signal and the measured signal in an analog lock-in amplifier, this paper presented a digital lock-in amplifier (DLIA) with accurate frequency automatic tracking to improve its performance. In this paper, a modular design approach based on DSP Builder was employed to develop a quadrature vector type lock-in amplifier with automatic frequency tracking. A reference signal generator with high-frequency resolution and a digital filter with good performance were implemented. The performance of the design was tested by determining the linearity, the Q value, and the noise immunity of the DLIA. The experimental results showed that the proposed DLIA has good linearity and the Q value can reach up to 82. The relative errors of the signals with amplitudes greater than 10 mV were less than 1% when the equivalent input was a sine wave signal with a frequency of 1 kHz and an amplitude of 500 mV. When the superimposed noise was less than or equal to 400 mV, the relative error was less than 2% in the same condition. The proposed DLIA has higher precision and efficient noise immunity.

ObjectiveIn the early life of preterm infants, the relationship between heart function and length of hospitalization is unclear. This study aims to examine the association between serum NT-proBNP level on the 7th day (NT-proBNP7) after birth and length of hospitalization among preterm infants.MethodsA retrospective cohort study was conducted. Patients included 709 preterm infants born at 28–31 weeks' gestational age (GA) admitted to the NICU of the First Affiliated Hospital of Zhengzhou University between December 20, 2016, to April 31, 2021. Main outcome: Late discharge (postmenstrual age at discharge was in the fourth quartile (highest) among infants born at the same GA). Exposure factor: NT-proBNP7.ResultsWe observed increased prevalence ratios for late discharge among the tertile of logarithm of NT-proBNP7 level (LnNT-proBNP7) which was positive. Compared with the lowest tertile, infants in the highest tertile of LnNT-proBNP7 had an 8.4-fold increased probability of late discharge, and the results were consistent for the subgroups. Next, a non-linear (S-shaped) relationship between LnNT-proBNP7 and late discharge was observed, whose turning points were 7.5 and 9. The effect sizes and the confidence intervals on the left of the first turning point, between two turning points and on the right of the second turning point, were 0.6 (95% CI, 0.2–1.6), 5.0 (95% CI, 2.4–10.6), and 1.1 (95% CI, 0.2–6.1), respectively. In addition, the prevalence of BPD, NEC, nosocomial infection, or any of them was highest in the group of LnNT-proBNP7 ≥ 9, lowest in the group of LnNT-proBNP7 < 7.5.ConclusionHigher NT-proBNP7 levels were associated with longer hospitalization. The relationship between LnNT-proBNP7 and late discharge was S-shaped. LnNT-proBNP7 was positively related with late discharge when LnNT-proBNP7 was between 7.5 and 9.

With the increase in mining depth, potential water inrush in the limestone-fractured aquifers of Taiyuan formation and Ordovician formation becomes seriously threatened to the mining process. Grouting reinforcement, as a common prevention method, has been widely used in mine water inrush prevention. In this paper, a model of “seepage resistance” is proposed for the slurry diffusion in a single fracture and the theoretical expression on the seepage resistance corresponding to slurry with different flow patterns is conducted. The total seepage resistance model of water-displacing diffusion by slurry in series and parallel fractures is established. With the Lagrange interfacial tracing method, the control equations of water-displacing diffusion by slurry in fracture networks are derived, which get mutually validated with the theoretical results.

Objectives: This study aimed to explore the clinical value of N-terminal pro-brain natriuretic peptide (NT-proBNP) in predicting moderate-to-severe bronchopulmonary dysplasia (BPD)/death, and to establish an effective clinical predictive nomogram.Methods: We retrospectively analyzed very low birth weight infants (VLBWs) with gestational age ≤ 32 weeks. The NT-proBNP values were determined on the 1st, 3rd, 7th, 14th, 21st, and 28th days after birth. The correlation between NT-proBNP level and moderate-to-severe BPD/death was evaluated. Receiver operating characteristic (ROC) curve analysis was used to evaluate the prediction ability. Then, we used multivariable logistic regression to build the prediction model and nomogram, and calibration of the model was assessed by calibration curve.Results: In total, 556 VLBWs were involved, among whom 229 developed BPD (mild: n = 109; moderate: n = 68; severe: n = 52) and 18 died. The NT-proBNP level in the moderate-to-severe BPD/death group was significantly higher than that in the no-to-mild BPD group from the 3rd to 28th day (P < 0.001). When the natural logarithm of the serum NT-ProBNP level increased by 1 unit at day 7 (±2 days) of life, the risk of moderate and severe BPD/death was the highest (OR = 3.753; 95% CI: 2.984~4.720), and ROC analysis identified an optimal cutoff point of 3360 ng/L (sensitivity: 80.0%; specificity: 86.2%; AUC: 0.861). After adjusting for confounding factors, the level of NT-proBNP at day 7 (±2 days) of life still had important predictive value for the development of moderate-to-severe BPD/death, significantly improving the predictive ability of the model.Conclusion: The level of NT-proBNP at day 7 (±2 days) of life can be used as an early promising biomarker for VLBWs to develop moderate-to-severe BPD/death. We constructed an early predictive nomogram to help clinicians identify high-risk populations.

Chimeric antigen receptor T (CAR-T) cell therapy has achieved remarkable clinical efficacy in treatment of many malignancies especially for B-cell hematologic malignancies. However, the application of CAR-T cells is hampered by potentially adverse events, of which cytokine release syndrome (CRS) is one of the severest and the most studied. Local cytokine-release syndrome (L-CRS) at particular parts of the body has been reported once in a while in B-cell lymphoma or other compartmental tumors. The underlying mechanism of L-CRS is not well understood and the existing reports attempting to illustrate it only involve compartmental tumors, some of which even indicated L-CRS only happens in compartmental tumors. Acute lymphoblastic leukemia (ALL) is systemic and our center treated a B-cell ALL patient who exhibited life threatening dyspnea, L-CRS was under suspicion and the patient was successfully rescued with treatment algorithm of CRS. The case is the firstly reported L-CRS related to systemic malignancies and we tentatively propose a model to illustrate the occurrence and development of L-CRS of systemic malignancies inspired by the case and literature, with emphasis on the new recognition of L-CRS.

Importance: Retinopathy of prematurity (ROP) is a preventable cause of blindness in children. Without treatment, more than 45% of eyes may suffer permanent vision loss. Current ROP screening guidelines, which include a range of birth weights (BWs) and gestational ages (GAs), may require screening many low-risk preemies who might develop severe ROP.Method: All high-risk infants in the neonatal intensive care unit (NICU) of the First Affiliated Hospital of Zhengzhou University from 2017 to 2021 were included in this retrospective cohort study. Each of the 27 candidate risk factors was evaluated in univariate analysis and adjusted for known risk factors (i.e., GA and BW). The significant results were analyzed in a backward selection multivariate logistic regression model. Receiver operating characteristic (ROC) curves and a nomogram were drawn.Results: The study included 2,040 infants who underwent ROP screening. The weight gain rate [OR, 2.65; 95% confidence interval (CI), 1.49–1.21 ≤ 12 g/d vs. > 18 g/d; P = 0.001], blood transfusion (OR, 2.03; 95% CI, 1.14–3.64; P = 0.017), invasive mechanical ventilation (OR, 1.74; 95% CI, 1.15–2.66; P = 0.009) and N-terminal segment of pro-B-type natriuretic peptide (NT-proBNP) ≥ 25,000 ng/L (OR, 1.51; 95% CI, 1.00–2.28; P = 0.048) were four new statistically independent risk factors in addition to GA and BW. The area under the curve (AUC) of the final multivariate model was 0.90 (95% CI, 0.88–0.92; P < 0.001).Conclusions and Relevance: These findings add to our understanding of ROP screening because they include all eligible infants rather than only high-risk infants, as in previous studies. Under the control of BW and GA, low weight gain rate, increased number of blood transfusion, invasive mechanical ventilation and NT-proBNP ≥ 25,000 ng/L were “new” statistically independent risk factors for ROP. The ROP risk can be calculated manually or represented by a nomogram for clinical use.