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Abstract Triglyceride-glucose (TyG) index has emerged as a novel biomarker for detecting insulin resistance (IR) and has been proven to be associated with various diseases. However, its correlation with the prognosis of severe sepsis remains unraveled. This retrospective cohort study utilized patient records from the Medical Information Mart for Intensive Care (MIMIC-IV, version 2.2) to examine the outcomes of patients with sepsis. The primary outcomes were hospital mortality and intensive care unit (ICU) mortality. The correlation between the TyG index and outcomes was evaluated through the Kaplan-Meier method, the Log-rank test, and univariate and multivariate Cox regression analyses. Additionally, restricted cubic spline (RCS) regression analysis was employed to delve into the nonlinear relationship between baseline TyG index and outcomes, with trend significance assessed through quartile levels. Subgroup analyses were conducted to evaluate the consistency of the TyG index’s prognostic value across various influencing factors. The study included 1,742 patients with sepsis requiring intensive care. The in-hospital mortality rate was 19.75% (344/1,742), and the ICU mortality rate was 14.75% (257/1,742). Cox regression analysis revealed that, in comparison to the first quartile (Q1), patients in the fourth quartile (Q4) had a 63% higher risk of in-hospital mortality (HR 1.63 [95% CI 1.22 to 2.18], P

Abstract LLC series resonant converter (LLC‐SRC) has attracted much attention due to its simple circuit structure and easy realization of soft‐switching. To get a better efficiency, rectifier stage can be realized by the active switches instead of the diodes. Meanwhile, more control variables can be selected besides the switching frequency, such as single phase shifted (SPS) angle, dual phase shifted (DPS) angle, and extended phase shifted (EPS) angle. Considering the simplicity of the implementation of the control strategy, this paper focused on the converter model with frequency and SPS control. Different from the common modelling method with the Fundamental Harmonic Approximation (FHA), the precise time‐domain mathematic model is built. By a comparison between the two modelling results, it can be proved the FHA model may be failure in some operating condition while the proposed time‐domain model can still show a good accuracy. According to the proposed model, two simple fixed‐frequency SPS control strategies are proposed. The first one can realize infinite soft‐switching margin with no restrictions on the transformer magnetizing inductance. The second one can greatly improve the efficiency of the converter. All the theoretical results are verified by a 1‐kW experiment prototype.

Abstract The aboveground biomass (AGB) of grassland, a crucial indicator of productivity, is anticipated to widespread changes in key ecosystem attributes, functions and dynamics. Variations in grassland AGB have been extensively documented across various spatial and temporal scales. However, a precise method to disentangle long-term effects from short-term effects on grassland AGB and assess the attribution of explanatory factors for AGB change remains elusive. This study aimed to quantify the impact of key climatic factors, soil properties, and grazing intensity on grassland AGB changes, utilizing data spanning the 1980s and the 2000s in Northern China. The Co-regression model was explored to separate the long-term effects and short-term effects of grassland AGB, while the Generalized Linear Model (GLM) was utilized to analyze the contributions of key variables to AGB. This approach effectively avoids issues related to regression to the mean and mathematical coupling. The results revealed that the influence of climatic variables, soil texture and grazing intensity on grassland AGB changes could be decomposed into long-term, short-term and random effects. Long-term effects explained 73.6% of AGB variation, whereas short-term effect only accounted for 5.9% of AGB change. Additionally, the short-term effect was divided into direct and indirect effects, with the direct effect explaining 1.3% of AGB variation, and the indirect effect explained 4.6% of AGB dynamics. The relative importance of key variables in grassland AGB was assessed, identifying soil parameters and precipitation as the main driving factors in the study area. This study introduces a robust methodology to enhance model performance in distinguishing long-term and short-term effects on grassland AGB, contributing to the sustainable development of grassland ecology in similar regions.

Although aboveground biodiversity has been extensively studied, the impact of nutrient enrichment on soil microbial populations remains unclear. Soil microorganisms serve as important indicators in shaping soil nutrient cycling processes and are typically sensitive to nutrient additions. For this, we employed a factorial combination design to examine the impact of nutrient additions on the composition and function of soil bacteria in a temperate steppe. Nitrogen addition promoted the growth of copiotrophic bacteria (Proteobacteria, Firmicutes, and Bacteroidota) but inhibited the growth of oligotrophic bacteria (Acidobacteria, Chloroflexi, and Verrucomicrobiota). Phosphorus addition alleviated phosphorus deficiency, resulting in a decrease in the abundance of phoD-harboring bacteria (Actinobacteria and Proteobacteria). Significant enhancement of soil bacterial alpha diversity was observed only in treatments with added phosphorus. Changes in NO3−-N, NH4+-N, available phosphorus, and dissolved organic carbon resulting from nutrient addition may have a greater impact on microbial community structure than changes in soil pH caused by nitrogen addition. Moreover, nutrient addition may indirectly impact microbial ecological function by altering nutrient availability in the soil. In conclusion, our study suggests that soil nutrient availability, particularly available phosphorus, affects soil bacterial communities and potentially regulates the biogeochemical cycles of soil ecosystems.

Miscanthus sacchariflorus is previously demonstrated to be a potential candidate for remediation of cadmium (Cd) pollution. To explore its resistance strategy to Cd, a hydroponic experiment was conducted to determine the variations of photosynthetic activity in leaves and physiological response in roots of this plant. Results showed that the root of M. sacchariflorus was the primary location for Cd accumulation. The bioconcentration factor in the roots and rhizomes was >1, and the translocation factor from underground to aboveground was

Abstract. Background:. With an increasing number of patients with hematological malignancies being treated with umbilical cord blood transplantation (UCBT), the correlation between immune reconstitution (IR) after UCBT and graft-versus-host disease (GVHD) has been reported successively, but reports on double-negative T (DNT) cell reconstitution and its association with acute GVHD (aGVHD) after UCBT are lacking. Methods:. A population-based observational study was conducted among 131 patients with hematological malignancies who underwent single-unit UCBT as their first transplant at the Department of Hematology, the First Affiliated Hospital of USTC, between August 2018 and June 2021. IR differences were compared between the patients with and without aGVHD. Results:. The absolute number of DNT cells in the healthy Chinese population was 109 (70–157)/μL, accounting for 5.82 (3.98–8.19)% of lymphocytes. DNT cells showed delayed recovery and could not reach their normal levels even one year after transplantation. Importantly, the absolute number and percentage of DNT cells were significantly higher in UCBT patients without aGVHD than in those with aGVHD within one year (F = 4.684, P = 0.039 and F = 5.583, P = 0.026, respectively). In addition, the number of DNT cells in the first month after transplantation decreased significantly with the degree of aGVHD increased, and faster DNT cell reconstitution in the first month after UCBT was an independent protective factor for aGVHD (HR = 0.46, 95% confidence interval [CI]: 0.23–0.93; P = 0.031). Conclusions:. Compared to the number of DNT cells in Chinese healthy people, the reconstitution of DNT cells in adults with hematological malignancies after UCBT was slow. In addition, the faster reconstitution of DNT cells in the early stage after transplantation was associated with a lower incidence of aGVHD.

Abstract Taking thin gauge strip as an example, the deformation process of metal strip in bending roll straightening was studied. Based on the theory of discrete, curvature integral and elastic–plastic mechanics, the strip travel trajectory of the bending roll straightening process is analyzed, and the numerical analytical calculation method of the continuous straightening process of the strip bending roll is established. The results are verified by establishing MARC finite element simulation and designing straightening experiment. The effects of yield strength, plastic rate and bending amount on residual stress after straightening were studied. In the straightening process, with the increase of the amount of bending roll, the residual strain converges to the region Γ, and with the increase of the yield strength, the region Γ decreases. With the increase of the yield strength, the amount of bending roll and the plastic rate, the wave height increases. The results of the calculation of residual stress, finite element simulation and experiment are close and the trend is consistent. The results show that the logic of the calculation method is reasonable, and the prediction error is within the scope of engineering application, which is helpful to the realization of process intelligence in the process of bending roller straightening.

Abstract Quantitative analysis of the biologically-active metabolites of vitamin D (VitD), which are crucial in regulating various physiological and pathological processes, is important for clinical investigations. Liquid chromatography-tandem mass spectrometry (LC-MS) has been widely used for this purpose but existing LC-MS methods face challenges in achieving highly sensitive and accurate quantification of low-abundance VitD metabolites while maintaining high throughput and robustness. Here we developed a novel pipeline that combines a trapping-micro-LC-(T-µLC) with narrow-window-isolation selected-reaction monitoring MS(NWI-SRM) for ultra-sensitive, robust and high-throughput quantification of VitD metabolites in serum samples after derivatization. The selective-trapping and delivery approach efficiently removes matrix components, enabling high-capacity sample loading and enhancing sensitivity, throughput, and robustness. The NWI-SRM further improves the sensitivity by providing high selectivity. The lower limits of quantification (LOQs) achieved were markedly lower than any existing LC-MS methods: 1.0 pg/mL for 1,25(OH)2D3, 5.0 pg/mL for 24,25(OH)2D3, 30 pg/mL for both 25(OH)D2 and 25(OH)D3, all within a 9-min cycle. The method is applied to quantify VitD metabolites from 218 patients with multiple sclerosis. This study revealed negative correlations(r=− 0.44 to − 0.51) between the levels of 25(OH)D2 and all the three D3 metabolites in multiple sclerosis patients.

ABSTRACTThe presence of airborne allergenic pollen causes a variety of immune reactions and respiratory diseases, threatening human life in severe cases. Climate change is exacerbating the allergenic pollen-induced health risks and adding a significant economic burden to societies. Despite the pressing threats, vital health-related information is not available to the public to date, and the reshaping of future geographic allergenic pollen patterns remains unknown. To help establish a critical allergenic pollen forecasting capacity, a systematic review was conducted and three promising future directions were identified: (1) resolving heterogeneous urban plant species distribution and phenology using fine-resolution satellite constellations; (2) acquiring ancillary information about allergenic pollen and patient symptoms from emerging geospatial big data, such as social media; (3) deciphering the coupled effect of climate change and urbanization on future geographic patterns and phenology of allergenic species. On this basis, we recommend an optimized workflow that combines real-time pollen monitoring networks with high-resolution vegetation information and weather forecast systems, comprehensively considering the production and diffusion process of pollen to establish advanced prediction models. By focusing on critical knowledge gaps, this review provides much needed insight to propel the allergenic pollen forecasting research and eventually benefit the management of urban public health.

Background: Dalpiciclib is a novel cyclin-dependent kinase 4/6 inhibitor which showed tolerability and preliminary efficacy as monotherapy for pretreated advanced breast cancer (BC). Objectives: To further assess dalpiciclib with endocrine therapy (ET) in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative BC. Design: A multicenter, open-label, phase Ib trial. Methods: Patients with locally recurrent or metastatic BC were enrolled in five cohorts. Patients without prior treatment for advanced disease (cohorts 1–2) were given dalpiciclib (125 or 150 mg) plus letrozole/anastrozole; patients who progressed after ET (cohorts 3–5) were given dalpiciclib (125, 150, or 175 mg) plus fulvestrant. Dalpiciclib was administered orally once daily in 3-weeks-on/1-week off schedule. The primary endpoint was safety. Results: A total of 58 patients received dalpiciclib with letrozole/anastrozole and 46 received dalpiciclib with fulvestrant. No maximum tolerated dose of dalpiciclib was reached with letrozole/anastrozole or fulvestrant. Across all cohorts, 86.7%–93.8% of patients had a grade ⩾3 adverse event, with the most common being neutropenia (grade 3, 40.0% for dalpiciclib 175 mg and 61.8%–87.5% for lower doses; grade 4, 46.7% and 4.2%–20.6%, respectively) and leukopenia (grade 3, 80.0% for 175 mg and 33.3%–54.2% for lower doses; grade 4, 0% for all doses). At tested dose levels, steady-state areas under the concentration curve and peak concentration of dalpiciclib increased with dose when combined with letrozole/anastrozole and fulvestrant. Dalpiciclib at 150 mg was associated with a numerically higher objective response rate in both patients untreated for advanced disease (67.6%; 95% confidence interval (CI) 49.5–82.6) and patients progressing after ET (53.3%; 95% CI 26.6–78.7); as of July 30, 2022, the median progression-free survival with dalpiciclib 150 mg was 24.1 months (95% CI 16.9–46.0) with letrozole/anastrozole and 16.7 months (95% CI 1.9–24.1) with fulvestrant. Conclusion: Dalpiciclib plus letrozole/anastrozole or fulvestrant showed an acceptable safety profile. The recommended phase III dose of dalpiciclib was 150 mg. Trial registration: ClinicalTrials.gov identifier: NCT03481998.

BackgroundMedical security work for the 2022 Beijing Winter Olympic and Paralympics faced enormous challenges under COVID-19. This study aimed to investigate the mental status of those medical team members to provide a reference for scientifically implementing medical security services for large-scale events.MethodsIn this prospective cohort study, the Patient Health Questionnaire-9, Self-rating Anxiety Scale, General Self-Efficacy Scale, and Psychological Questionnaire for Emergent Events of Public Health (PQEEPH) were administered to 145 members of the medical team. A generalized mixed linear model was used to analyze the impact of work duration, position, on/off rotation, and gender on psychological status.ResultsWork duration significantly impacted depression, anxiety, self-efficacy, and all dimensions of PQEEPH. Women scored higher than men in the PQEEPH dimensions of depression, neurasthenia, fear, and total score. Working status affected the dimensions of depression, neurasthenia, and total score. Deterioration in emotional state became apparent in the fourth week and recovered 1 week after the task concluded, while self-efficacy decreased from beginning to end.ConclusionAll the medical team members experienced emotional deterioration and decreased self-efficacy in medical security tasks. To maintain a medical team’s psychological wellbeing during large-scale activities, rotation times should be set reasonably, and adequate mental health services should be provided.

Background and objectiveHemorrhagic stroke, characterized by acute bleeding due to cerebrovascular lesions, is associated with plasma lipids and endothelial damage. The causal relationship between genetic plasma lipid levels and hemorrhagic stroke remains unclear. This study employs a two-sample Mendelian randomization (MR) analysis to explore the causal relationship between plasma lipid profiles with different fatty acid chains and the risk of intracerebral and subarachnoid hemorrhage, the two main subtypes of hemorrhagic stroke.MethodsThe datasets for exposure and outcome summary statistics were obtained from publicly available sources such as the GWAS Catalog, IEU OpenGWAS project, and FinnGen. The two-sample MR analysis was employed to initially assess the causal relationship between 179 plasma lipid species and the risk of intracerebral and subarachnoid hemorrhage in the Finnish population, leading to the identification of candidate lipids. The same methods were applied to reanalyze data from European populations and conduct a meta-analysis of the candidate lipids. The Inverse Variance Weighting (IVW) method served as the primary analysis for causal inference, with additional methods used for complementary analyses. Sensitivity analysis was conducted to clarify causal relationships and reduce biases.ResultsTwo analyses using Mendelian randomization were performed, followed by meta-analyses of the results. A causal relationship was established between 11 specific lipid species and the occurrence of intracerebral hemorrhage within the European population. Additionally, 5 distinct lipid species were associated with subarachnoid hemorrhage. Predominantly, lipids with linoleic acid and arachidonic acid side chains were identified. Notably, lipids containing arachidonic acid chains (C20:4) such as PC 18:1;0_20:4;0 consistently showed a decreased risk of both intracerebral hemorrhage [p

IntroductionPostoperative recurrence and metastasis of gastric cancer (GC) are primary factors that contribute to poor prognosis. GC recurs at a rate of approximately 70%–80% within 2 years after local treatment and approximately 90% within 5 years. “Yang-deficient toxic node” is the core pathogenesis of GC recurrence and metastasis. The Yiqi Wenyang Jiedu prescription (YWJP), a form of complementary and alternative medicine in China, is an empirical remedy to prevent postoperative recurrence and metastasis of GC. Taking the main therapeutic principles of “nourishing Qi and warming Yang, strengthening Zhengqi, and detoxifying” can aid in preventing the recurrence and metastasis of GC in patients during the watchful waiting period after surgery and adjuvant chemotherapy. This approach aims to enhance the quality of life of patients. However, high-quality evidence to support this hypothesis is lacking. This study will aim to investigate the efficacy and safety of YWJP to prevent and treat postoperative metastasis and GC recurrence.MethodsThe study will be a multicenter, randomized, double-blind, placebo-parallel-controlled clinical trial. A total of 212 patients who completed adjuvant chemotherapy within 8 months of radical gastrectomy will be enrolled. Patients in the intervention group will receive the YWJP, whereas those in the control group will receive a placebo. The main outcome was the disease-free survival (DFS) rate 2 years after surgery. The secondary outcomes included DFS time, overall survival, annual cumulative recurrence and rate of metastasis after 1–3 years, cumulative annual survival after 1–3 years, fat distribution-related indicators, tumor markers, peripheral blood inflammatory indicators, prognostic nutritional index, symptoms and quality of life evaluation, medication compliance, and adverse reaction rate.DiscussionThere is a lack of effective therapy after the completion of adjuvant therapy during the postoperative period of watchful waiting. This study will be the first randomized clinical trial to evaluate whether complementary and alternative medical interventions can effectively prevent recurrence and metastasis during the watchful waiting period after GC surgery and to provide evidence for surveillance treatment management after GC surgery.Clinical trial registrationClinicalTrials.gov, identifier NCT05229809.

Berberine (BBR) is a compound derived from Chinese herbal medicine, known for its anticancer properties through multiple signaling pathways. However, whether BBR can inhibit tumor growth by participating in ferroptosis remains unconfirmed. In this study, we demonstrated that berberine synergistically inhibited NSCLC in combination with multiple ferroptosis inducers, and this combination synergistically down-regulated the mRNA and protein expression of SLC7A11, GPX4, and NRF2, resulting in ferroptosis accompanied by significant depletion of GSH, and aberrant accumulation of reactive oxygen species and malondialdehyde. In a lung cancer allograft model, the combination treatment exhibited enhanced anticancer effects compared to using either drug alone. Notably, p53 is critical in determining the ferroptosis sensitivity. We found that the combination treatment did not elicit a synergistic anticancer effect in cells with a p53 mutation or with exogenous expression of mutant p53. These findings provide insight into the mechanism by which combination induces ferroptosis and the regulatory role of p53 in this process. It may guide the development of new strategies for treating NSCLC, offering great medical potential for personal diagnosis and treatment.

Phospholipids (PLs) and long-chain polyunsaturated fatty acids (LCPUFAs) are naturally present in breast milk and play important roles in promoting the growth of the infant. Several studies have investigated the effects of the combination of PLs and LCPUFAs on neurodevelopment. However, data on the effectiveness of infant formula containing both PLs and LCPUFAs on the neurodevelopment of infants is still scarce. This randomized, double-blind, controlled clinical study was designed to evaluate the effect of an infant formula enriched with PLs and LCPUFAs on growth parameters and neurodevelopmental outcomes in term infants up to 365 days of age. Infants were enrolled within 30 days of birth who were then randomly assigned to either a control group (n = 150) or an investigational group (n = 150). Both groups consist of cow’s milk-based formula which were generally identical in terms of composition, except that the investigational formula was additionally supplemented with PLs and LCPUFAs. The infants were followed for the first year of life. Breastfed infants were the reference (n = 150). Bayley Scales of Infant Development [3rd edition (Bayley-III)], Carey Toddler Temperament Scales (TTS), MacArthur-Bates Communicative Development Inventories (CDI), Single Object Attention and Free Play Tasks were used to evaluate neurodevelopmental outcomes of infant at 365 days of age. In addition, Ages and Stages Questionnaires (ASQ) were also conducted at 120, 180, and 275 days of age. Compared to breastfeeding, both infant formulas were well-tolerated and provided adequate growth, with no adverse events being reported throughout the study. Infants of the investigational group showed higher mean scores in Bayley-III cognitive performance (104.3 vs. 99.0, p

IntroductionGrass-livestock interaction is of great value in maintaining ecological balance, regional economic development, and the sustainability of grassland husbandry, which has gained attention in recent years in both academia and practice, however, study on grass-livestock interaction possesses cognitive bias and gaps.MethodsThis study clarified the latest research progress and development trend in the grass-livestock interaction field by illuminating publication trend, cooperative network, keyword co-occurrence relationship, keyword clustering during 2000 to 2022 based on the Web of Science core database.ResultsThe results indicated that the annual number of publications in the grass-livestock interaction field showed a globally increasing with interdisciplinary and international collaboration, and the United States of America ranked firstly, followed by Brazil, England, Australia, China. Agricultural Research Service, the U.S. Department of Agricultures was the organization with the highest number of publications, and Rangeland Ecology & Management, Agriculture, Ecosystems & Environment, Grass and Forage Science were the top three journals. Furthermore, in terms of the temporal evolution, the research targeting the grass-livestock interaction mainly went through three stages: initial exploration period (2000–2011), to the period of rapid development (2012–2016) to transitional development period (2017–2022), and the notable existing keywords was Management, Livestock, Cattle, Vegetation, Growth, Soil. In terms of the structural composition, four broad divisions including mechanism of human activities, grassland resource monitoring and management, grassland livestock competition/adaptability, grassland land/soil research were identified. The results provide positive and objective insights into that grassland sustainability and grazing control through strengthening cross-disciplinary and cross-regional cooperation, and applying of standard methods based on evaluation system in the grass-livestock interaction field.DiscussionThe overall contribution of the work is provision of novel insight into the intellectual structure and temporal progression of grass-livestock interaction research at a macroscopic scale and the directions in which the field is headed currently.

Protein glutaminase (PG), originating from Chryseobacterium proteolyticum, can catalyze the deamidation of glutamine residues in plant proteins into glutamic acid, thus enhancing its functional properties. However, the low yield of PG limits its industrial production. In this study, the yield of PG in C. proteolyticum TM1040 increased by 121 %, up to 7.30 U/mL in a 15 L fermenter after medium optimization. Subsequently, purified PG was obtained by cation exchange chromatography (CEX) coupled with hydrophobic interaction chromatography (HIC). The degree of deamidation (DD) of wheat gluten after purified PG deamidation was 87.11 %, which is superior to chemical deamidation in safety and DD. The emulsifying and foaming properties of deamidated wheat gluten were 2.67 and 18.86 times higher, and the water- and oil-holding properties were 4.23 and 18.77 times higher, respectively. The deamidated wheat gluten with enhanced functional properties was used to improve the flavor and texture in baking cakes.

Abstract We conducted a systematic search across medical databases, including PubMed, Web of Science, EMBASE, and Cochrane Library, up to March 2023. A total of 1944 subjects or individuals from 17 studies were included in our final analysis. The correlation coefficient (r) between sKlotho and calcium was [0.14, (0.02, 0.26)], and a moderate heterogeneity was observed (I2 = 66%, P

BackgroundOwing to individual heterogeneity, patients with idiopathic membranous nephropathy (IMN) exhibit varying sensitivities to immunotherapy. This study aimed to establish and validate a model incorporating pathological and clinical features using deep learning training to evaluate the response of patients with IMN to immunosuppressive therapy.MethodsThe 291 patients were randomly categorized into training (n = 219) and validation (n = 72) cohorts. Patch-level convolutional neural network training in a weakly supervised manner was utilized to analyze whole-slide histopathological features. We developed a machine-learning model to assess the predictive value of pathological signatures compared to clinical factors. The performance levels of the models were evaluated using the area under the receiver operating characteristic curve (AUC) on the training and validation tests, and the prediction accuracies of the models for immunotherapy response were compared.ResultsMultivariate analysis indicated that diabetes and smoking were independent risk factors affecting the response to immunotherapy in IMN patients. The model integrating pathologic features had a favorable predictive value for determining the response to immunotherapy in IMN patients, with AUCs of 0.85 and 0.77 when employed in the training and test cohorts, respectively. However, when incorporating clinical features into the model, the predictive efficacy diminishes, as evidenced by lower AUC values of 0.75 and 0.62 on the training and testing cohorts, respectively.ConclusionsThe model incorporating pathological signatures demonstrated a superior predictive ability for determining the response to immunosuppressive therapy in IMN patients compared to the integration of clinical factors.

Abstract Background Umbilical cord blood transplantation (UCBT) is a curable therapy for hematological disease; however, the impact of nutritional status on UCBT outcomes remains controversial. To evaluate the joint effect of clinical characteristics and nutritional status on the prognosis of patients who underwent UCBT, we screened various factors to establish a predictive model of overall survival (OS) after UCBT. Methods We performed an integrated clinical characteristic and nutritional risk factor analysis and established a predictive model that could be used to identify UCBT recipients with poor OS. Internal validation was performed by using the bootstrap method with 500 repetitions. Results Four factors, including disease status, conditioning regimen, calf skinfold thickness and albumin level, were identified and used to develop a risk score for OS, which showed a positive predictive value of 84.0%. A high-risk score (≥ 2.225) was associated with inferior 3-year OS post-UCBT [67.5% (95% CI 51.1–79.4%), P = 0.001]. Then, we built a nomogram based on the four factors that showed good discrimination with a C-index of 0.833 (95% CI 0.743–0.922). The optimism-corrected C-index value of the bootstrapping was 0.804. Multivariate analysis suggested that a high calf skinfold thickness (≥ 20.5 mm) and a low albumin level (

Abstract Background Idiopathic pulmonary fibrosis (IPF) is fibrotic lung disease with no effective treatment. It is characterized by destruction of alveolar structure and pulmonary interstitial fibrosis, leading to dyspnea and even asphyxia death of patients. Epithelial-mesenchymal transition (EMT) is considered to be a driving factor in the pathogenesis of IPF. Osteopontin (OPN) is a secreted protein widely present in the extracellular matrix and involved in the occurrence and development of a variety of diseases. Methods The original datasets were obtained from NCBI GEO databases analyzed with the online tool GEO2R and EasyGEO. Bleomycin induced mouse pulmonary fibrosis model and OPN/OPN-biotin treated mouse model were established to investigate the role of OPN in mouse pulmonary fibrosis and the target cells of OPN. A549 cells and HBE cells were used to explore the mechanism of OPN-induced epithelial-mesenchymal transition (EMT) in epithelial cells and mass spectrometry was used to detect OPN downstream receptors. Precision-cut lung slices and lentivirus-treated mice with pulmonary fibrosis were used to examine the therapeutic effect of OPN and its downstream pathways on pulmonary fibrosis. Results We demonstrate that the content of OPN in IPF bronchoalveolar lavage fluid (BALF) is high compared to the normal groups, and its expression level is correlated with prognosis. At the animal level, OPN was highly expressed at all stages of pulmonary fibrosis in mice, and the bronchoalveolar lavage fluid (BALF) could accurately reflect its expression in the lung. Next, we reveal that OPN was mainly expressed by macrophages and the main target cells of OPN were epithelial cells. Mice developed pulmonary fibrosis accompanied after treating the mice with OPN. Both in vitro and in vivo experiments confirmed that OPN could induce EMT of alveolar epithelial cells. Mechanistically, OPN binding triggered phosphorylation of FAK by CD44, thus activating snail1-mediated profibrotic protein synthesis. Inhibition of FAK phosphorylation and its downstream pathways can effectively alleviate pulmonary fibrosis in precision sections of lung tissue (PCLS) assay. OPN knockdown in bleomycin-induced lung fibrosis mice led to significantly less fibrosis. Conclusion Our data suggest that OPN mediates lung fibrosis through EMT, implicating its potential therapeutic target and prognostic indicator role for IPF. OPN may be a target for the diagnosis and treatment of IPF.

As urbanization accelerates worldwide, understanding the impact of urban expansion on habitat quality has become increasingly critical in environmental science research. This study examines the impact of urban expansion on habitat quality in Beijing, forecasting land cover changes and ecological effects by 2030. Using CA–Markov and FLUS models, the research analyzes habitat quality from 2000 to 2030 through the InVEST model, revealing a significant urban land increase of 1316.47 km2 and a consequent habitat quality decline. Predictions for 2030 indicate varying habitat quality outcomes across three scenarios: ecological priority (0.375), natural growth (0.373), and urban development (0.359). We observed that the natural growth scenario forecasts a further decline in habitat quality, primarily due to increased low–value habitat regions. Conversely, the ecological priority scenario projects a notable improvement in habitat quality. To mitigate habitat degradation in Beijing and enhance regional habitat quality and ecological conditions, it is recommended to control urban land cover expansion, adopt effective ecological conservation policies, and systematically carry out national spatial restructuring and ecological restoration. This research provides vital decision–making support for urban planning and ecological conservation, emphasizing the need for comprehensive land cover and ecological strategies in urban development. Additionally, our findings and methodologies are applicable to other rapidly urbanizing cities worldwide. This demonstrates the broader applicability and relevance of our research, providing a framework for sustainable urban planning in diverse global contexts.

To improve the wear resistance of the materials used for blades in engineering machinery, this study focused on the microstructural characteristics, mechanical properties, and wear behavior of HB500 grade wear-resistant steel developed using an optimized heat treatment system. To improve the temperature uniformity of the heat treatment furnace, the method of cyclic heating was used to heat the components. Carefully designing the quenching equipment, such as using a cross-shaped press, was employed to enhance the quenching effect and reduce the deformation of the steel plates. The crystal orientation analysis revealed a uniform and fine-grained microstructure, primarily characterized by plate-type tempered martensite, which indicated a good hardenability. The microstructure observations showed that the width of martensite is approximately 200 nm, with a significant presence of dislocations and carbides. Tensile tests and multi-temperature gradient impact tests indicated superior mechanical properties compared to similar grade wear-resistant steels, including a Rockwell hardness of 53, tensile strength of 1610 MPa, yield strength of 1404 MPa, and total elongation around 12.7%. The results of friction and wear experiments indicate that the wear rate decreases as the load increases from 100 N to 300 N, demonstrating an excellent wear resistance under a large load. Observations of the worn surfaces indicated that the wear mainly involved adhesive wear, fatigue wear, and oxidative wear. The properties’ improvements were attributed to microstructure refinement and precipitation strengthening. This study indicates that designing a heat treatment system to control temperature uniformity and stability is feasible.

Abstract Background Non-small cell lung cancer (NSCLC) with HER2 mutation has entered into the era of targeted therapy. However, both anti-HER2 antibody–drug conjugates (ADCs) and tyrosine kinase inhibitors (TKIs) showed moderate objective response rate (ORR) and median progression-free survival (PFS). The aim of this study was to investigate the molecular features of responders to pyrotinib in advanced NSCLC with HER2 mutation. Methods Patients from our two previous phase II trials were pooled analyzed. Their circulating tumor DNA (ctDNA) were detected by next-generation sequencing (NGS) panels, and the correlation with the efficacy of pyrotinib was investigated. Results This pooled analysis included 75 patients, and 50 of them with baseline plasma samples were finally enrolled with a median age of 57 years old. The overall ORR and median PFS were 28% and 7.0 months respectively. Biomarker analysis showed that 5 patients were ctDNA nonshedding. Patients with TP53 wild type were significantly associated with higher disease control rate (97.1%vs. 68.8%, p = 0.010), PFS (median 8.4 vs. 2.8 months, p = 0.001) and overall survival (OS, median 26.7 vs. 10.4 months, p

This study evaluated whether psychological stress increases the incidence of ovarian cancer. A literature search of the electronic databases PubMed and Web of Science from the date of inception to August 2022 was undertaken. Studies with data on psychosocial factors associated with ovarian cancer incidence were included in this study. A random-effect model meta-analysis was undertaken to estimate these data. We used subgroup analysis to adjust for heterogeneity. A total of 4 articles, 10 sets of data, 8 cohort studies, and 2 case–control studies from 682 records were included in this review. Meta-analyses of the included cohort study subgroups suggested that psychological factors increase the risk of ovarian cancer (effect size = 1.37, 95% CI: 1.20–1.53); the subgroup of case–control studies suggested that psychological factors did not increase ovarian cancer risk (effect size = 0.84, 95% CI: 0.70–0.98). These findings indicate that psychological stress is a possible new risk factor for ovarian cancer. Prospero registration number: CRD42022357983IMPACT STATEMENT What is already known on this subject? Psychological stress has been shown to increase the risk of many diseases. The relationship between psychological stress and the incidence of ovarian cancer has not been confirmed. What do the results of this study add? The effect of psychological stress on the risk of ovarian cancer was estimated using meta-analysis as an overall ratio. What are the implications of these findings for clinical practice and/or further research? Relaxing psychological stress and appropriate psychotherapy in clinical settings can help reduce the risk of ovarian cancer.

Abstract The algorithm for cord blood (CB) unit selection is still somewhat ambiguous. We retrospectively analyzed 620 cases of acute leukemia between 2015 and 2020, who were treated with myeloablative single‐unit umbilical CB transplantation (UCBT). We found that, when human leukocyte antigen (HLA) mismatch was ≤3/10, CD34+ cell dosage

Abstract Aim Pyrotinib (an irreversible pan‐ErbB small‐molecular tyrosine kinase inhibitor) was approved in human epidermal growth factor receptor 2 (HER2)‐positive breast cancer and showed great antitumor activity in preclinical studies of gastric cancer (GC). This study was first designed to prospectively assess pyrotinib in pretreated HER2‐positive GC. Methods This multicenter, phase I study followed a standard “3 + 3” design and included two parts. In the pyrotinib part, pyrotinib was administered orally, once per day at dose levels of 240, 320, 400, and 480 mg. In the pyrotinib plus docetaxel part, patients received pyrotinib (qd, d1‐21, q3W) combined with docetaxel (60 mg/m2, d1, q3W) at dose levels of 240, 320, and 400 mg. Primary endpoints were to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of pyrotinib as monotherapy or coadministered with docetaxel. Results A total of 25 patients were enrolled and received pyrotinib (n = 15) or pyrotinib plus docetaxel (n = 10). One DLT was observed in pyrotinib monotherapy part (Grade 3 uncontrolled diarrhea after supportive care) and pyrotinib plus docetaxel part (Grade 4 neutropenia and leukopenia). In the pyrotinib monotherapy part, MTD was not reached. Diarrhea, anemia, neutropenia, and leukopenia were the most common treatment‐related adverse events (TRAEs). The RP2D for pyrotinib monotherapy was recommended as 400 mg. After combining with docetaxel, the risk of leukopenia and neutropenia was increased. Grade ≥3 TRAEs were reported for four patients in the monotherapy part and for eight patients in the combination part. Mean t1/2 was approximately 20 h. Pyrotinib exposure was dose‐dependent with a nonlinear relationship versus dose. There were five patients who had confirmed partial response (monotherapy: one each at 240, 400, and 480 mg dose cohort; combination therapy: two at 240 mg dose cohort), resulting in an objective response rate of 21% and 20%, respectively. Conclusions Pyrotinib alone and combined with docetaxel showed acceptable toxicities in patients with pretreated HER2‐positive GC. Trial Registration This study was registered with ClinicalTrials.gov, NCT02378389.

Hematopoietic syndrome of acute radiation syndrome (h-ARS) is an acute illness resulted from the damage of bone marrow (BM) microenvironment after exposure to radiation. Currently, the clinical management of h-ARS is limited to medication-assisted treatment, while there is still no specific therapy for the hematopoietic injury from high-dose radiation exposure. Our study aimed to assemble biomimetic three-dimensional (3D) BM microniches by co-culture of hematopoietic stem and progenitor cells (HSPCs) and mesenchymal stem cells (MSCs) in porous, injectable and viscoelastic microscaffolds in vitro. The biodegradable BM microniches were then transplanted in vivo into the BM cavity for the treatment of h-ARS. We demonstrated that the maintenance of HSPCs was prolonged by co-culture with MSCs in the porous 3D microscaffolds with 84 μm in pore diameter and 11.2 kPa in Young's modulus compared with 2D co-culture system. Besides, the minimal effective dose and therapeutic effects of the BM microniches were investigated on a murine model of h-ARS, which showed that the intramedullary cavity-injected BM microniches could adequately promote hematopoietic reconstitution and mitigate death from acute lethal radiation with a dose as low as 1000 HSPCs. Furthermore, the mRNA expression of Notch1 and its downstream target gene Hes1 of HSPCs were increased when co-cultured with MSCs, while the Jagged1 expression of the co-cultured MSCs was upregulated, indicating the significance of Notch signaling pathway in maintenance of HSPCs. Collectively, our findings provide evidence that biomimetic and injectable 3D BM microniches could maintain HSPCs, promote hematopoiesis regeneration and alleviate post-radiation injury, which provides a promising approach to renovate conventional HSPCs transplantation for clinical treatment of blood and immune disorders.

Abstract Although radiation therapy (RT) improves locoregional recurrence and overall survival in breast cancer (BC), it is not yet clear whether RT affects the risk of patients with BC developing second esophageal cancer (SEC). We enrolled patients with BC as their first primary cancer from nine registries in the Surveillance, Epidemiology, and End Results (SEER) database between 1975 and 2018. Fine–Gray competing risk regressions were assessed to determine the cumulative incidence of SECs. The standardized incidence ratio (SIR) was used to compare the prevalence of SECs among BC survivors to that in the general population of the US. Kaplan–Meier survival analysis was applied to calculate the 10-year overall survival (OS) and cancer-specific survival (CSS) rates for SEC patients. Among the 523,502 BC patients considered herein, 255,135 were treated with surgery and RT, while 268,367 had surgery without radiotherapy. In a competing risk regression analysis, receiving RT was associated with a higher risk of developing an SEC in BC patients than that in the patients not receiving RT (P = .003). Compared to the general population of the US, the BC patients receiving RT showed a greater incidence of SEC (SIR, 1.52; 95% confidence interval [CI], 1.34–1.71, P

The multi-frequency noisy vibration of an autonomous underwater vehicle (AUV) is a significant factor affecting the performance of shear probes mounted on the head of AUVs. Many efforts have been made to suppress mechanical radiation noise; however, conventional noise reduction methods have their limitations, such as mode mixing. In order to extract thorough information from the aliasing modes and achieve multi-frequency mode targeted correction, a multi-frequency noise reduction method is proposed, based on secondary decomposition and the multi-mode coherence correction algorithm. Weak impulses in aliasing shear mode are enhanced, and mixing frequencies are isolated for thorough decomposition. Noisy mechanical vibrations in the shear modes are eliminated with the use of the acceleration modes along the identical central frequency series. The denoised modes are used to reconstruct the cleaned shear signal, and the updated spectra are aligned with the standard Nasmyth spectrum. Compared with the raw profiles, the variation in the dissipation rate estimated from the corrected shear is reduced by more than an order of magnitude.

The biaxially-oriented PA56/512 has excellent mechanical strength, extensibility and water–oxygen barrier properties and has broad application prospects in green packaging, lithium battery diaphragm and medical equipment materials. The correlation between the aggregation structure evolution and macroscopic comprehensive properties of copolymer PA56/512 under biaxial stretching has been demonstrated in this work. The structure of the random copolymerization sequence was characterized by 13C Nuclear magnetic resonance (NMR). The typical isodimorphism behavior of the co-crystallization system of PA56/512 and its BOPA-56/512 films was revealed by differential scanning calorimetry (DSC) and X-ray diffraction (XRD) tests. And the aggregation structure, including the hydrogen bond arrangement, crystal structure and crystal morphology of PA56/512 before and after biaxial stretching, was investigated by XRD, Fourier-transform infrared spectroscopy (FTIR) and polarized optical microscopy (POM) tests. Furthermore, the effect of the biaxially-oriented stretching process on the mechanical properties of PA56/512 has been demonstrated. In addition, a deep insight into the influence of the structure on the crystallization process and physical–mechanical performance has been presented. The lowest melting point at a 512 content of 60 mol% is regarded as a “eutectic” point of the isodimorphism system. Due to the high disorder of the structural units in the polymer chain, the transition degree of the folded chain (gauche conformation) is relatively lowest when it is straightened to form an extended chain (trans conformation) during biaxially-oriented stretching, and part of the folded chain can be retained. This explains why biaxially stretched PA56/512 has high strength, outstanding toughness and excellent barrier properties at the pseudo-eutectic point. In this study, using the unique multi-scale aggregation structure characteristics of a heterohomodymite polyamide at the pseudo-eutectic point, combined with the new material design scheme and the idea of biaxial-stretching processing, a new idea for customized design of high-performance multifunctional polyamide synthetic materials is provided.

For patients exhibiting a suboptimal response to the first chimeric antigen receptor (CAR) T-cell therapy (CART1) or relapse after remission, secondary CAR T-cell therapy (CART2) for the same target may be an option. We retrospectively analyzed patients with acute B-cell lymphoblastic leukemia (B-ALL) receiving CD19 CART1 at our center (n = 84) to report the clinical outcomes of CART2 and to identify the factors that may influence the outcomes. Twenty-six patients received CART2 for suboptimal response or relapse post-CART1. The incidence of cytokine release syndrome (CRS) after CART2 was 65.4% (17/26), with 11 cases classified as grade 1 (42.3%), four cases as grade 2 (15.4%), and two cases as grade 3 (7.7%). Neurotoxicity was observed in one patient (3.8%) after CART2 infusion. Fourteen patients (53.8%) achieved complete remission (CR) after CART2. CART2 exhibited an inferior response rate (CART2: 53.8%, 14/26; CART1: 81.0%, 64/79; P = 0.006) and a lower incidence of severe CRS (CART2: 7.7%, 2/26; CART1: 30.4%, 24/79; P = 0.020) compared with CART1, with a median progression-free survival (PFS) and a median overall survival (OS) of 6.2 months and 11.2 months, respectively. In particular, patients who progressed after consolidative allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CART1 and then received CART2 demonstrated promising outcomes with a response rate of 80.0% (8/10), a median PFS of 7.9 months, and a median OS of 25.1 months. After adjusting for the confounding factors, the response rate (85.7%, 6/7) of CART2 administered to this cohort was better than those who did not bridge to allo-HSCT receiving CART2 (28.6%, 2/7) or non-CART2 treatments (13.3%, 2/15). The median OS after CART2, which was not reached, was significantly better than the median OS after CART2 (3.9 months, P = 0.014) and non-CART2 treatments (6.0 months, P = 0.012) administered in patients who did not undergo consolidative allo-HSCT post-CART1. Our results indicated that, although less effective than CART1, a subset of patients can still benefit from CART2 with mild adverse effects. For patients who relapsed after consolidative allo-HSCT post-CART1, treatment with CART2 is a viable option.

Seed banks are crucial regenerative resources for aboveground vegetation. The pattern of their changes holds immense significance in understanding alterations in the belowground seed bank. This understanding is pivotal for uncovering both short-term and long-term shifts in plant communities. Additionally, it contributes to the restoration of grassland ecosystems. To better protect grassland biodiversity and provide a theoretical basis for the restoration of degraded grasslands, in this study, the germination characteristics of soil seed banks in free-grazed, enclosed and mown areas were compared, and the results were combined with those of previous studies for a comprehensive analysis. The density of soil seed bank and perennial forage soil seed bank were significantly affected by different grassland utilization and soil depths. Grazing and enclosure grassland utilization methods increased the content of the soil seed bank, and mowing reduced the content of the seed bank. The soil seed bank density of perennial grasses accounted for the highest proportion under grazing, followed by mowing, and its lowest proportion was observed in the enclosures. Grazing not only facilitated the germination of the perennial grass seed bank but also substantially augmented its content. Mowing inhibited the germination of the upper growth grasses seed bank, which was particularly significant in the 0-2 cm soil layer under grazing. The content of the upper growth grasses seed bank affected the total seed bank to a certain extent, mainly in the 5-10 cm layer. The general correlations among the perennial grasses, upper growth grasses and soil germination seed bank resulted in 84.58% information extraction, and this information has practical significance for grassland ecological restoration.

For a long time, food spoilage posed a severe impairment on food safety and public health. Although chemical preservatives are commonly used to inhibit spoilage/ pathogenic microbial growth, the disadvantages of a single target, potential toxicity and high dose of use limit the better use of preservatives. In this research, the combination of natural preservatives: Natamycin (Nat), ε-polylysine (ε-PL), and Chitosan (CS) could achieve an excellent antimicrobial effect including bacteria and fungi, and reduce the usage of a single preservative. Compound preservatives could destroy microbial morphology and damage the integrity of the cell wall/membrane by leakage of protein and alkaline phosphatase (AKP). Besides, high-throughput sequencing revealed that compound preservatives could decrease microbial diversity and richness, especially, Pseudomonas, Acinetobacter, Fusarium, and Aspergillus. Therefore, the combination of 1/8 × MIC CS, 1/4 × MIC ε-PL, and 1/2 × MIC Nat can achieve an excellent antibacterial effect, providing new ideas for food preservation.

Accurate detection of target location and type is crucial for treating ocular trauma caused by foreign bodies intrusion. However, the traditional method of manually marking CT image targets has slow recognition speed and poor detection accuracy, which cannot meet the real-time and accuracy requirements for detecting foreign bodies in clinical diagnosis. To address this issue, we propose a lightweight detection and recognition model based on feature extraction and fusion. Firstly, the normalization-based attention module and the sigmoid linear unit activation function are introduced into the inverted residual block of the backbone network to enhance the model’s attention to salient features and improve the detection accuracy. Then, the path aggregation feature pyramid network is utilized to fuse multiscale features, enabling the information interaction between different levels of the network and enhancing the accuracy foreign bodies classification. In particular, the incorporation of the space-to-depth convolution and convolutional mixing modules into the feature pyramid network significantly reduce the computational overhead while effectively capturing the key semantic features in both space and channel directions, thereby improving the lightweight level of the model. Finally, the location and type information of the foreign intraocular bodies are obtained by this model. The experimental results demonstrate the superior performance of the proposed model in terms of mAP@0.5, accuracy, sensitivity and specificity, achieving 97.2, 93.5, 98.0 and 88.0, respectively. Furthermore, the smaller number of parameters and faster detection time allow the proposed model run in real-time on poorly configured hardware, making it more suitable for clinical applications.

Abstract Background Pyrotinib (an irreversible pan-ErbB inhibitor) plus capecitabine has survival benefits and acceptable tolerability in patients with HER2-positive metastatic breast cancer. We further assessed addition of pyrotinib to trastuzumab and docetaxel in the neoadjuvant setting. Methods In this multicenter, double-blind, phase 3 study (PHEDRA), treatment-naive women with HER2-positive early or locally advanced breast cancer were randomly assigned (1:1) to receive four neoadjuvant cycles of oral pyrotinib or placebo (400 mg) once daily, plus intravenous trastuzumab (8 mg/kg loading dose, followed by 6 mg/kg) and docetaxel (100 mg/m2) every 3 weeks. The primary endpoint was the total pathological complete response (tpCR; ypT0/is and ypN0) rate per independent central review. Results Between Jul 23, 2018, and Jan 8, 2021, 355 patients were randomly assigned, 178 to the pyrotinib group and 177 to the placebo group. The majority of patients completed four cycles of neoadjuvant treatment as planned (92.7% and 97.7% in the pyrotinib and placebo groups, respectively). The tpCR rate was 41.0% (95% CI 34.0 to 48.4) in the pyrotinib group compared with 22.0% (95% CI 16.6 to 28.7) in the placebo group (difference, 19.0% [95% CI 9.5 to 28.4]; one-sided P < 0.0001). The objective response rate per investigator was 91.6% (95% CI 86.6 to 94.8) in the pyrotinib group and 81.9% (95% CI 75.6 to 86.9) in the placebo group after the neoadjuvant treatment, resulting in an increase of 9.7% (95% CI 2.7 to 16.6). The most common grade 3 or worse adverse events were diarrhea (79 [44.4%] in the pyrotinib group and nine [5.1%] in the placebo group), neutropenia (33 [18.5%] and 36 [20.3%]), and decreased white blood cell count (29 [16.3%] and 24 [13.6%]). No deaths were reported during neoadjuvant treatment. Conclusions The primary endpoint of the study was met. Neoadjuvant pyrotinib, trastuzumab, and docetaxel significantly improved the tpCR rate compared with placebo, trastuzumab, and docetaxel, with manageable toxicity, providing a new option for HER2-positive early or locally advanced breast cancer. Trial registration ClinicalTrials.gov, NCT03588091

Accurate protein mapping on whole-tissue levels provides critical insights into diseases/therapies. Here, the authors described a novel spatial proteomics method, based on tissue compartmentalization using a 3D-printed micro-scaffold, generated thousands of protein maps across a whole-tissue slice.

Renal fibrosis is the inevitable common end-point of all progressive chronic kidney diseases. The underlying mechanisms of renal fibrosis are complex, and currently there is no effective therapy against renal fibrosis. Renal microvascular rarefaction contributes to the progression of renal fibrosis; however, an imbalance between proangiogenic and antiangiogenic factors leads to the loss of renal microvasculature. Vascular endothelial growth factor (VEGF) is the most important pro-angiogenic factor. Recent studies have unraveled the involvement of VEGF in the regulation of renal microvascular rarefaction and fibrosis via various mechanisms; however, it is not clear whether it has anti-fibrotic or pro-fibrotic effect. This paper reviews the available evidence pertaining to the function of VEGF in the fibrotic process and explores the associated underlying mechanisms. Our synthesis will help identify the future research priorities for developing specialized treatments for alleviating or preventing renal fibrosis. Abbreviation: VEGF: vascular endothelial growth factor; CKD: chronic kidney disease; ESKD: end-stage kidney disease; ER: endoplasmic reticulum; VEGFR: vascular endothelial growth factor receptor; AKI: acute kidney injury; EMT: epithelial-to-mesenchymal transition; HIF: hypoxia-inducible factor; α-SMA: α smooth muscle actin; UUO: unilateral ureteral obstruction; TGF-β: transforming growth factor-β; PMT: pericyte-myofibroblast transition; NO: nitric oxide; NOS: nitric oxide synthase; nNOS: neuronal nitric oxide synthase; iNOS: inducible nitric oxide synthase; eNOS: endothelial nitric oxide synthase; sGC: soluble guanylate cyclase; PKG: soluble guanylate cyclase dependent protein kinases; UP R: unfolded protein response

Abstract Accumulating evidence suggests that hypothalamic-pituitary-adrenal axis dysfunction might play an important role in the pathophysiology of schizophrenia. The aim of this study was to explore the cortisol response to psychological stress in patients with schizophrenia. In this study, patients with schizophrenia (n = 104) and healthy volunteers (n = 59) were asked to complete psychological stress challenge tasks, which included the Paced Auditory Serial Addition Task and Mirror-Tracing Persistence Task, and pre- and post-task saliva samples were collected to measure cortisol levels. Emotions and psychopathology were assessed by the Positive and Negative Affect Schedule and Positive and Negative Syndrome Scale. The results showed (1) that the cortisol response and negative emotions in patients with schizophrenia differed significantly from those in healthy volunteers, (2) there were significant interactions between the sampling time and diagnosis for saliva cortisol levels, (3) there were significant interactions between the scoring time and diagnosis for the negative affect score of the PANAS, and (4) the changes in salivary cortisol levels and negative affect scores before and after the psychological stress challenge tasks were not correlated with clinical symptoms in patients with schizophrenia. These findings indicated an abnormal cortisol profile in patients with schizophrenia, which might be a biological characteristic of the disease.

Abstract Background TIMM8A is a protein-coding gene located on the X chromosome. There is evidence that TIMM8A plays an important role in mitochondrial morphology and fission. Studies have shown that mitophagy and fission could affect the function of immune cells. However, there is currently no research on this gene’s role in cancer occurrence and progression. Methods TIMM8A expression was analyzed via the Tumor Immune Estimation Resource (TIMER) site and UALCAN database. We evaluated the influence of TIMM8A on clinical prognosis using Kaplan-Meier plotter, the PrognoScan database, and Human Protein Atlas (HPA). The correlations between TIMM8A and cancer immune infiltrates were investigated via TIMER. Tumor Immune Dysfunction and Exclusion (TIDE) was used to evaluate the potential of tumor immune evasion. Functions of TIMM8A mutations and 50 genes significantly associated with TIMM8A mutations in breast cancer (BRCA) and uterine corpus endometrial cancer (UCEC) were analyzed by GO and KEGG in LinkedOmics database. Results We investigated the role of TIMM8A in multiple cancers and found that it was significantly associated with poor prognosis in BRCA and UCEC. After analyzing the effect of TIMM8A on immune infiltration, we found Th2 CD4+ T cells might be a common pathway by which TIMM8A contributed to poor prognosis in BRCA and UCEC. Our results suggested that myeloid-derived suppressor cells (MDSC) and tumor-associated M2 macrophages (TAM M2) might be important factors in immune evasion through T cell rejection in both cancers, and considered TIMM8A as a biomarker to predict the efficacy of this therapy in BRCA and UCEC. The results of TIMM8A enrichment analysis showed us that abnormally expressed TIMM8A might affect the mitochondrial protein in BRCA and UCEC. Conclusions Contributed to illustrating the value of TIMM8A as a prognostic biomarker, our findings suggested that TIMM8A was correlated with prognosis and immune infiltration, including CD8+ T cells, Th2 CD4+ T cells, and macrophages in BRCA and UCEC. In addition, TIMM8A might affect immune infiltration and prognosis in BRCA and UCEC by affecting mitophagy. We believed it could also be a biomarker to predict the efficacy of anti-PD-L1 therapy and proposed to improve the efficacy by eliminating MDSC and TAM M2.

Abstract Background Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important curative therapy for adult acute lymphoblastic leukemia (ALL). For patients who lack a human leukocyte antigen (HLA)-matched sibling donor, unrelated cord blood (UCB) is an alternative graft option. Previous studies have focused mainly on all T- and B-cell ALL (B-ALL) patients, while data related specifically to adult B-ALL patients after UCB transplantation (UCBT) are scarce. Methods We retrospectively compared the outcomes of UCBT and HLA-matched sibling transplantation (MST) in the treatment of adult B-ALL patients in complete remission (CR) at our center. From June 2006 to December 2020, 156 adult B-ALL patients who achieved CR before transplantation were enrolled. The main clinical outcomes of UCBT and MST were analyzed. Results Hematopoietic recovery was significantly faster in MST recipients than in UCBT recipients. Higher incidences of grades II-IV and III-IV acute graft-versus host disease (aGVHD) were found in UCBT recipients (P

The biomechanical changes following meniscal tears and surgery could lead to or accelerate the occurrence of osteoarthritis. The aim of this study was to investigate the biomechanical effects of horizontal meniscal tears and different resection strategies on a rabbit knee joint by finite element analysis and to provide reference for animal experiments and clinical research. Magnetic resonance images of a male rabbit knee joint were used to establish a finite element model with intact menisci under resting state. A medial meniscal horizontal tear was set involving 2/3 width of a meniscus. Seven models were finally established, including intact medial meniscus (IMM), horizontal tear of the medial meniscus (HTMM), superior leaf partial meniscectomy (SLPM), inferior leaf partial meniscectomy (ILPM), double-leaf partial meniscectomy (DLPM), subtotal meniscectomy (STM), and total meniscectomy (TTM). The axial load transmitted from femoral cartilage to menisci and tibial cartilage, the maximum von Mises stress and the maximum contact pressure on the menisci and cartilages, the contact area between cartilage to menisci and cartilage to cartilage, and absolute value of the meniscal displacement were analyzed and evaluated. The results showed that the HTMM had little effect on the medial tibial cartilage. After the HTMM, the axial load, maximum von Mises stress and maximum contact pressure on the medial tibial cartilage increased 1.6%, 1.2%, and 1.4%, compared with the IMM. Among different meniscectomy strategies, the axial load and the maximum von Mises stress on the medial menisci varied greatly. After the HTMM, SLPM, ILPM, DLPM, and STM, the axial load on medial menisci decreased 11.4%, 42.2%, 35.4% 48.7%, and 97.0%, respectively; the maximum von Mises stress on medial menisci increased 53.9%, 62.6%, 156.5%, and 65.5%, respectively, and the STM decreased 57.8%, compared to IMM. The radial displacement of the middle body of the medial meniscal was larger than any other part in all the models. The HTMM led to few biomechanical changes in the rabbit knee joint. The SLPM showed minimal effect on joint stress among all resection strategies. It is recommended to preserve the posterior root and the remaining peripheral edge of the meniscus during surgery for an HTMM.

Objectives: This study aims to examine the relationship between dietary inflammatory index (DII) and bone mineral density (BMD) changes among Chinese pregnant women, offering valuable insights for dietary guidance during pregnancy. Methods: 289 pregnant women were enrolled in this cohort. Serum inflammatory factors and ultrasonic BMD were measured at the first, second, and the third trimesters. DII scores were calculated based on a semi-quantitative food frequency questionnaire (FFQ) and divided into tertiles. We compared the differences in inflammatory factors in serum across the tertiles of DII and changes in BMD at the second and third trimesters across the tertiles. Results: The participants with higher DII scores had higher total energy intakes than those with lower DII scores. The serum level of interleukin-6 (IL-6) was significantly different across the tertiles of the DII. Women who had lower DII scores had higher T-scores and Z-scores in the BMD assessment. In the test of trends, after adjusting potential covariates, including educational level, physical activity, body mass index, and calcium, vitamin D, or multivitamin supplements, DII values were determined to be positively related to the maternal BMD lost. Conclusions: DII was positively associated with serum IL-6. Meanwhile, higher DII scores were associated with more bone mass loss in pregnant women. We recommend adhering to a lower-DII diet to preserve BMD during pregnancy.

Underground coal mining will inevitably cause serious ground deformation, and therefore, preventive mining-induced deformation analysis (MIDA) is of great importance in assisting mining planning and decision-making. Current web-based Geographic Information System (webGIS)-based applications usually use 2D GIS data and lack a holistic framework. This study presents a multi-scalar oblique photogrammetry-supported unified 3D webGIS framework for MIDA applications to fill this gap. The developed web platform uses multiple open-source JavaScript libraries, and the prototype system provides user-friendly interfaces for GIS data collecting and corresponding database establishment, geo-visualization and query, dynamic prediction, and spatial overlapping analysis within the same framework. The proposed framework was tested and evaluated in the Qianyingzi mining area in eastern China. The results demonstrated that multi-scalar oblique photogrammetry balances data quality and acquisition efficiency and provides a good source of GIS datasets, and the web-based platform has a good absolute and relative spatial accuracy verified by two types of validation data. Practical application results proved the feasibility and reliability of the system. The developed web-based MIDA prototype system attains an appealing performance and can be easily extended to similar geoscience applications.

Abstract Haematologic malignancies account for a large proportion of cancers worldwide. The high occurrence and mortality of haematologic malignancies create a heavy social burden. Allogeneic haematopoietic stem cell transplantation is widely used in the treatment of haematologic malignancies. However, graft-versus-host disease and relapse after allogeneic haematopoietic stem cell transplantation are inevitable. An emerging treatment method, adoptive cellular therapy, has been effectively used in the treatment of haematologic malignancies. T cells, natural killer (NK) cells and tumour-infiltrating lymphocytes (TILs) all have great potential in therapeutic applications, and chimeric antigen receptor T (CAR-T) cell therapy especially has potential, but cytokine release syndrome and off-target effects are common. Efficient anticancer measures are urgently needed. In recent years, double-negative T cells (CD3+CD4−CD8−) have been found to have great potential in preventing allograft/xenograft rejection and inhibiting graft-versus-host disease. They also have substantial ability to kill various cell lines derived from haematologic malignancies in an MHC-unrestricted manner. In addition, healthy donor expanded double-negative T cells retain their antitumour abilities and ability to inhibit graft-versus-host disease after cryopreservation under good manufacturing practice (GMP) conditions, indicating that double-negative T cells may be able to be used as an off-the-shelf product. In this review, we shed light on the potential therapeutic ability of double-negative T cells in treating haematologic malignancies. We hope to exploit these cells as a novel therapy for haematologic malignancies.

In this study, we successfully synthesized a novel triacid monomer by means of the thermal cyclization reaction. Subsequently, a series of nitrogen-rich (A3+B2)-type fluorinated hyperbranched poly(amide-imide)s (denoted as PAI-1 and -2, respectively) were prepared by means of a one-pot method using this triacid monomer and a diamine monomer with a triphenylamine-carbazole unit as precursors. The degree of support of the prepared hyperbranched PAIs was found to be about 60% via 1H NMR calculations. Through X-ray photoelectron spectroscopy (XPS), it was found that the binding energies of C-N (398.4 eV) and -NH (399.7 eV) became lower under a current, while the binding energy peak of N+ appeared at 402.9 eV. In addition, the PAIs have good solubility and thermal stability (Tgs: 256–261 °C, T10%: 564–608 °C). Cyclic voltammetry (CV) analysis shows that the hyperbranched PAI films have good redox properties, and a range of values for the HOMO (4.83 to 4.85 eV) versus LUMO (1.85 to 1.97 eV) energy levels are calculated. The PAI films have excellent electrochromic properties: PAI-1 on coloration efficiency (CE) and transmittance change (ΔT, 852 nm) are 257 cm2/C and 62%, respectively, and have long-lasting redox properties (100 cycles). In addition, we conduct iodine adsorption tests using the structural features of PAIs with electron-drawing units, and the results show that PAI-1 had a high adsorption capacity for iodine (633 mg/g).

This investigation examined how the Bacillus vallismortis laccase (rBVL-MRL522) influenced the physicochemical characteristics, structural attributes, and functional capabilities of both dough and noodles. Incorporating rBVL-MRL522 (1 U/g) did not lead to a substantial change in the water absorption of wheat flour. However, the introduction of rBVL-MRL522 caused a significant elongation in the formation time of wheat flour dough, extending it by 88.9%, and also resulted in a 50% increase in the stabilization duration of wheat flour dough. Furthermore, adding rBVL-MRL522 led to a proportional rise in both the elastic and viscous moduli (G’’ of the dough, signifying that r-BVL (rBVL-MRL522) has a beneficial effect on the gluten strength of the dough. Integrating rBVL-MRL522 promoted the consolidation of the gluten-based cross-linked structure within the dough, decreasing the size of starch particles and, more evenly, the dispersion of these starch particles. In the noodle processing, adding rBVL-MRL522 at a rate of 1 U/g raised the L* value of the noodles by 2.34 units compared to the noodles prepared without the inclusion of rBVL-MRL522. Using a greater amount of rBVL-MRL522 (2 U/g) substantially increased the hardness of the noodles by 51.31%. Additionally, rBVL-MRL522 showed a noteworthy enhancement in the elasticity, cohesiveness, and chewiness of the noodles. In conclusion, rBVL-MRL522 promoted the cross-linking gluten, leading to a more extensive and condensed three-dimensional network structure in raw and cooked noodles. As a result, this study offers valuable insights into the environmentally friendly processing of dough and associated products.

Abstract Objective To retrospectively analyze the short and long-term efficacies of O-arm-navigated percutaneous short segment pedicle screw fixation, with or without screwing of the fractured vertebra. Methods A total of 42 patients who underwent O-arm-navigated percutaneous short segment pedicle screw fixation for the treatment of thoracolumbar fractures from February 2015 to December 2018 were selected for analysis. The patients were divided into two groups according to the surgical intervention they received: Group A received percutaneous short segment pedicle screw fixation with screwing of the fractured vertebra and Group B received percutaneous short segment pedicle screw fixation without screwing of the fractured vertebra. Radiographic analysis included Cobb angles and percentage of anterior vertebral height (AVH%). Clinical functional outcomes were assessed using the visual analog scale (VAS) for back pain and the oswestry disability index (ODI) scores. Results No significant differences were observed in the operation time and intraoperative blood loss between the two groups (P > 0.05). The length of incision was statistically significantly different between the two groups (P 0.05). However, the Cobb angle and AVH% were both significantly larger in Group A than Group B at the final follow-up (P 0.05). Conclusion In the short term, both minimally invasive treatments were safe and effective in treating thoracolumbar fracture. Although there was significant difference between the two groups in Cobb angle and vertebral body height at the last follow-up, the difference was small. Therefore, these specific parameters will be an important outcome measure in further investigations.

The strip casting technique was first used in this work to prepare the Sm2Fe17 parent alloys. Next, the Sm2Fe17N3 powders were synthesized using a gas–solid reaction of Sm2Fe17 powders with N2. Then, the anisotropic Sm2Fe17N3 powders with high performance were prepared by a surfactant-assisted grinding method in gasoline solvent. It was found that the coercivity (iHc) of ground powders increases with decreasing the average particle size (Dm), while the saturation magnetization (Ms) decreases. The maximum value of iHc of 17.5 kOe was obtained at the Dm = 1.3 µm. The ground powders with Dm of 3.1 µm show a remanence ratio (Mr/Ms) over 95% and a maximum energy product [(BH)max] of 35 MGOe. The Sm2Fe17N3 powder exhibited a very high iHc of 36.1 kOe at 10 K. Above 300 K, Sm2Fe17N3 powders mixed with epoxy resin showed a low remanence temperature coefficient of α(RT-100°C) = −0.077% °C−1.