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To overcome the shortcomings of activated bleaching clay in the decolorization of edible oil industry, such as high operating temperature, large residual oil ratio, and difficulty in the disposal of waste bleaching clay, this work developed the super-strong adsorbent material, graphene, as a new type of adsorbent for the decolorization of rapeseed oil. Graphene nanoplatelets (GNP) and graphene oxide (GO) were characterized by scanning electron microscope. Fourier infrared spectrometer and Raman spectrometer, etc After clarifying the structural characteristics of graphene, they were used for the decolorization of rapeseed oil, and the effects of graphene species, addition amount, pressure, temperature, and reaction time on the decolorization of rapeseed oil were investigated. The results showed that GNP was more effective in rapeseed oil decolorization compared with GO and exhibited unique adsorption properties for chlorophyll in oil at low temperature (45 ℃). The one-factor results showed that GNP could remove 80.6% of chlorophyll in oil under the optimized conditions of GNP addition of 2.0%, temperature of 45 ℃ and adsorption time of 5 min. GNP as adsorbent for oil decolorization has the advantages of low reaction temperature and short adsorption time, which could have the potential application prospects in low temperature moderate processing of oils and fats.

Thermal cooking is one of the major application scenarios of edible oils in Chinese cooking. Cooking oil fume (COF), which is generated from edible oils during thermal cooking, is a complex mixture of solid particles, liquid droplets and gaseous volatile organic compounds (VOCs), and COF imposes adverse effects on both the indoor atmosphere and human health. In the present review, we first elucidate the compositional characteristics of the two major harmful substances in COF, particulate matter (PM) and VOCs and their emission status during the thermal cooking of edible oils, and then summarize the influences of COF exposure on human respiratory diseases and other related health risks. Next, the major factors that affect the composition and emission characteristics of COF are discussed from the perspectives of thermal cooking methods, types of cooking ingredients, and the quality and basic properties of edible oils. Finally, an outlook is given on the optimization of edible oil processing technologies based on the compositional characteristics of COF and the development of new processing technologies, raw materials and pathways for future edible oils in the future in order to achieve precise and moderate processing of edible oils that is green with low energy consumption and to produce high-quality, nutritious and healthy edible oils for use in Chinese cooking. This review could provide some references for the future development of edible oil and fat processing technologies, and may be of guiding significance to improving the nutritional quality and safety of edible oils and fats and even helping to achieve the national strategic goals of “Healthy China” and “Double Carbon”.

The efficacy of ritlecitinib, an oral JAK3/TEC family kinase inhibitor, on active and stable lesions was evaluated in patients with active non-segmental vitiligo in a phase 2b trial (NCT03715829). Patients were randomized to placebo or daily ritlecitinib 50 mg (with or without 4-week 100-mg or 200-mg loading dose), 30 mg, or 10 mg for 24 weeks. Active lesions showed greater baseline expression of inflammatory/immune markers IFNG and CCL5, levels of CD103, and T-cell infiltrates than stable lesions. Patients with more active than stable vitiligo lesions showed higher baseline serum levels of CXCL9 and PD-L1, while patients with more stable than active lesions showed higher baseline serum levels of HO-1. At Week 24, ritlecitinib 50 mg significantly stabilized mean percent change from baseline in depigmentation extent in both active lesions and stable lesions vs. placebo-response, with stable lesions showing greater repigmentation. After 24 weeks of treatment, ritlecitinib 50 mg increased expression of melanocyte markers in stable lesions, while Th1/Th2-related and co-stimulatory molecules decreased significantly in both stable and active lesions. Serum from patients with more active than stable lesions showed decreased levels of ICOS and NK cell activation markers. These data, confirmed at transcription/protein levels, indicate that stable lesion repigmentation occurs early with ritlecitinib, while active lesions require stabilization of inflammation first. ClinicalTrials.gov: NCT03715829.

Dysregulated lysophosphatidic acid receptor 1 (LPAR1) signaling is implicated in fibrotic diseases, including systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF). Fipaxalparant (HZN‐825) is a small molecule acting as a negative allosteric modulator of LPAR1 and is in phase 2 clinical evaluations for treating diffuse cutaneous SSc and IPF. This open‐label, phase 1 study examined the pharmacokinetics (PKs), food effect, and safety of fipaxalparant in healthy volunteers. Dose proportionality was evaluated for fipaxalparant single doses of 150, 300, and 450 mg under fasted conditions. Food effect was tested with a 450‐mg single dose under fasted conditions or with a high‐fat meal. Multiple‐dose PKs for twice‐daily dosing of either 300 or 450 mg with low‐ or high‐fat meals was also assessed. Fipaxalparant was safe and well tolerated in healthy volunteers (n = 36) under all conditions. Fipaxalparant exposure increased in a less than dose‐proportional manner from 150 to 450 mg. At 450 mg, a high‐fat meal increased the maximum observed concentration and area under the curve by approximately 1.9‐ and 2.1‐fold, respectively. These results, combined with prior preclinical and phase 2a data, informed dose selection of fipaxalparant 300 mg once and twice daily with a meal for phase 2b studies. [ABSTRACT FROM AUTHOR]

Osteoporosis, a skeletal ailment marked by bone metabolism imbalance and disruption of bone microarchitecture, Neferine, a bisbenzylisoquinoline alkaloid with diverse pharmacological activities, has received limited attention in the context of osteoporosis treatment. We employed a bilateral ovariectomy (OVX) rat model to induce osteoporosis and subsequently administered Neferine treatment for four weeks following successful model establishment. Throughout the modeling and treatment phases, we closely monitored rat body weights. We assessed alterations in bone tissue microstructure through micro-CT, HE staining, and safranin O-fast green staining. Levels of bone formation and resorption markers in serum were evaluated using ELISA assay. Western blot analysis was employed to determine the expression levels of p38MAPK, p-p38MAPK, and bone formation-related genes in bone tissue. We isolated and cultured OVX rat BMSCs (OVX-BMSCs) and induced osteogenic differentiation while simultaneously introducing Neferine and the p38MAPK inhibitor SB203580 for intervention. Neferine treatment effectively curbed the rapid weight gain in OVX rats, ameliorated bone loss, and decreased serum levels of TRAP, CTX-I, PINP, and BALP. Most notably, Neferine promoted the expression of bone formation-related factors in bone tissue of OVX rats, while concurrently activating the p38MAPK signaling pathway. In in vitro experiments, Neferine facilitated the expression of bone formation-related factors in OVX-BMSCs, increased the osteogenic differentiation potential of OVX-BMSCs, and activated the p38MAPK signaling pathway. Nevertheless, SB203580 partially reversed Neferine's promotive effect. Neferine can boost the osteoblastic differentiation of BMSCs and alleviate OVX-induced osteoporosis in rats by activating the p38MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

Background: In past studies, non-medical factors in the social-healthcare-patient triad associated with the prevalence of COVID-19 have led to delays in the presentation of patients with acute appendicitis and an increase in complications. However, as research progresses, there is increasing evidence of a clinical association between COVID-19 and the development of acute appendicitis. Methods: The effect of COVID-19 prevalence and associated factors on acute appendicitis in the control (2016–2019) and exposed (2020−2023) groups was derived from a retrospective study of 3070 patients with acute appendicitis from 2016 to 2023. Results: After the implementation of the restrictions, the rate of acute appendicitis visits in the exposed group compared to the control group dropped sharply in the initial period (P = 0.047) and recovered gradually with the relaxation of the restrictions. Similar changes occurred in the number of acute complicated appendicitis visits. In addition, after the lifting of restrictions and the COVID-19 outbreak, the proportion of acute complicated appendicitis in the exposed group increased significantly (P

Abstract Globally, breast cancer continues to be the leading cause of cancer-related incidence and mortality among females. Research has shown that sleep patterns significantly influence tumor onset and progression. In this research, the association was examined through the application of a two-sample Mendelian randomization (MR) approach. For the analysis of seven sleep patterns, genetic tools were sourced from both the UK Biobank and 23andMe, including morning/evening person (chronotype) n = 177,604, morning person (chronotype) n = 248,094, daytime dozing/sleepiness n = 193,472, getting up in the morning n = 193,717, and sleeplessness n = 193,987; sleep duration n = 192,810; and nap during the day n = 166,853. The Breast Cancer Association Consortium (BCAC) supplied genome-wide association studies (GWAS) data, including 133,384 breast cancer cases and 113,789 controls, alongside subtype-specific data with 106,278 cases and 91,477 controls. We discovered that chronotype encompasses both morning and evening types contributes to the risk of overall breast cancer. While daytime dozing and morning person (chronotype) are linked to a lower risk of breast cancer in general, In subtype-specific analyses, morning person (chronotype) was negatively associated with luminal B, HER2-negative-like, and daytime dozing was negatively correlated with luminal A-like, luminal B-like, and HER2-enriched-like. The study corroborates that chronotype is a danger element for breast cancer, aligning with previous observational findings. The association between being a morning person (chronotype) or having daytime dozing and a decreased risk of breast cancer underscores the significance of sleep patterns in formulating strategies for cancer prevention.

Abstract The human endometrial decidualization is a transformative event in the pregnant uterus that involves the differentiation of stromal cells into decidual cells. While crucial to the establishment of a successful pregnancy, the metabolic characteristics of decidual cells in vivo remain largely unexplored. Here, we integrated the single-cell RNA sequencing (scRNA-seq) datasets on the endometrium of the menstrual cycle and the maternal-fetal interface in the first trimester to comprehensively decrypt the metabolic characteristics of stromal fibroblast cells. Our results revealed that the differentiation of stromal cells into decidual cells is accompanied by increased amino acid and sphingolipid metabolism. Furthermore, metabolic heterogeneity exists in decidual cells with differentiation maturity disparities. Decidual cells with high metabolism exhibit higher cellular activity and show a strong propensity for signaling. In addition, significant metabolic reprogramming in amino acids and lipids also occurs during the transition from non-pregnancy to pregnancy in the uteri of pigs, cattle, and mice. Our analysis provides comprehensive insights into the dynamic landscape of stromal fibroblast cell metabolism, contributing to our understanding of the metabolism at the molecular dynamics underlying the decidualization process in the human endometrium.

Abstract The Span-based model can effectively capture the complex entity structure in the text, thus becoming the mainstream model for nested named entity recognition (Nested NER) tasks. However, traditional Span-based models decode each entity span independently. They do not consider the semantic connections between spans or the entities’ positional information, which limits their performance. To address these issues, we propose a Bi-Directional Context-Aware Network (Bi-DCAN) for the Nested NER. Specifically, we first design a new span-level semantic relation model. Then, the Bi-DCAN is implemented to capture this semantic relationship. Furthermore, we incorporate Rotary Position Embedding into the bi-affine mechanism to capture the relative positional information between the head and tail tokens, enabling the model to more accurately determine the position of each entity. Experimental results show that compared to the latest model Diffusion-NER, our model reduces 20M parameters and increases the F1 scores by 0.24 and 0.09 on the ACE2005 and GENIA datasets respectively, which proves that our model has an excellent ability to recognise nested entities.

Highlights Elephant trunk-inspired anisotropic wrinkling structures were formed on a sandwich-like conductive film through a controlled shrinking method. The wrinkled conductive network could withstand up to 200% tensile strain and exhibits a strain-enhanced electromagnetic interference shielding effectiveness when stretching parallel to the electric field polarization direction.

Abstract Background The treatment for bilateral synchronous multiple primary lung cancers (MPLC) remains challenging. Simultaneous bilateral video-assisted thoracic surgery (VATS) may be an optimal treatment with curative intent, but its safety and feasibility are controversial. Methods One hundred and fifty-eight patients who underwent simultaneous bilateral VATS (simultaneous group) and 79 who underwent two-staged bilateral VATS (two-staged group) were included in this study. Their medical records were retrospectively reviewed and analyzed. Results The majority of patients were female and non-smokers. The most common surgical plan was lobectomy and contralateral wedge resection in both groups. There was no significant difference in the postoperative complication rate between the simultaneous groups and two-staged group (13.3% vs. 11.4%, p = 0.73). Patients who underwent simultaneous bilateral resection had shorter hospital stays, shorter anesthesia time and less chest drainage compared with those who underwent two-staged resection. Advanced TNM stage, complicated surgical plan and aggressive lymph node resection were risk factors for postoperative complications in simultaneous bilateral VATS. Patients in two groups had similar overall survival and disease free survival (p = 0.2). Conclusions Simultaneous bilateral VATS for bilateral lung nodule resection is as safe and feasible as two-staged bilateral VATS. Patients who underwent simultaneous bilateral resection had similar or even better outcomes compared to that of the two-staged group. Simultaneous bilateral VATS is potentially an optimal treatment option for patients with erarly cTNM stage and good physical condition.

Abstract Background Culex tritaeniorhynchus is widely distributed in China, from Hainan Island in the south to Heilongjiang in the north, covering tropical, subtropical, and temperate climate zones. Culex tritaeniorhynchus carries 19 types of arboviruses. It is the main vector of the Japanese encephalitis virus (JEV), posing a serious threat to human health. Understanding the effects of environmental factors on Culex tritaeniorhynchus can provide important insights into its population structure or isolation patterns, which is currently unclear. Results In total, 138 COI haplotypes were detected in the 552 amplified sequences, and the haplotype diversity (Hd) value increased from temperate (0.534) to tropical (0.979) regions. The haplotype phylogeny analysis revealed that the haplotypes were divided into two high-support evolutionary branches. Temperate populations were predominantly distributed in evolutionary branch II, showing some genetic isolation from tropical/subtropical populations and less gene flow between groups. The neutral test results of HNQH (Qionghai) and HNHK(Haikou) populations were negative (P

Abstract Background Norepinephrine and phenylephrine are commonly used vasoactive drugs to treat hypotension during the perioperative period. The increased release of endogenous norepinephrine elicits prothrombotic changes, while parturients are generally in a hypercoagulable state. Therefore, this trial aims to investigate whether there is a disparity between equivalent doses of prophylactic norepinephrine infusion and phenylephrine infusion on prothrombotic response in patients undergoing cesarean section under spinal anesthesia. Methods Sixty-six eligible parturients will be recruited for this trial and randomly assigned to the norepinephrine or phenylephrine group. The “study drug” will be administered at a rate of 15 ml/h starting from the intrathecal injection. The primary outcome are plasma coagulation factor VIII activity (FVIII: C), fibrinogen, and D-dimer levels. The secondary outcomes include hemodynamic variables and umbilical artery blood pH value. Discussion Our study is the first trial comparing the effect of norepinephrine and phenylephrine on prothrombotic response in patients undergoing cesarean section under spinal anesthesia. Positive or negative results will all help us better understand the impact of vasoactive drugs on patients. If there are any differences, this trial will provide new evidence for maternal choice of vasoactive medications in the perioperative period. Trial registration Chinese Clinical Trial Registry ChiCTR2300077164. Registered on 1 November 2023. https://www.chictr.org.cn/ .

Cascaded H-bridge inverter (CHBI) with supercapacitors (SCs) and dc-dc stage shows significant promise for medium to high voltage energy storage applications. This paper investigates the voltage balance of capacitors within the CHBI, including both the dc-link capacitors and SCs. Balance control over the dc-link capacitor voltages is realized by the dc-dc stage in each submodule (SM), while a hybrid modulation strategy (HMS) is implemented in the H-bridge to balance the SC voltages among the SMs. Meanwhile, the dc-link voltage fluctuations are analyzed under the HMS. A virtual voltage variable is introduced to coordinate the balancing of dc-link capacitor voltages and SC voltages. Compared to the balancing method that solely considers the SC voltages, the presented method reduces the dc-link voltage fluctuations without affecting the voltage balance of SCS. Finally, both simulation and experimental results verify the effectiveness of the presented method.

Abstract Background This study aims to construct a model predicting the probability of RF in AECOPD patients upon hospital admission. Methods This study retrospectively extracted data from MIMIC-IV database, ultimately including 3776 AECOPD patients. The patients were randomly divided into a training set (n = 2643) and a validation set (n = 1133) in a 7:3 ratio. First, LASSO regression analysis was used to optimize variable selection by running a tenfold k-cyclic coordinate descent. Subsequently, a multifactorial Cox regression analysis was employed to establish a predictive model. Thirdly, the model was validated using ROC curves, Harrell’s C-index, calibration plots, DCA, and K-M curve. Result Eight predictive indicators were selected, including blood urea nitrogen, prothrombin time, white blood cell count, heart rate, the presence of comorbid interstitial lung disease, heart failure, and the use of antibiotics and bronchodilators. The model constructed with these 8 predictors demonstrated good predictive capabilities, with ROC curve areas under the curve (AUC) of 0.858 (0.836–0.881), 0.773 (0.746–0.799), 0.736 (0.701–0.771) within 3, 7, and 14 days in the training set, respectively and the C-index was 0.743 (0.723–0.763). Additionally, calibration plots indicated strong consistency between predicted and observed values. DCA analysis demonstrated favorable clinical utility. The K-M curve indicated the model’s good reliability, revealed a significantly higher RF occurrence probability in the high-risk group than that in the low-risk group (P

Abstract It is of great practical significance to explore the relationship between urbanization and CO2 emissions for the low-carbon development of cities. However, the multiscale assessment of spatial relationship between population, land and economic urbanization and CO2 emissions is lacked. In this study, we first adopted the spatial statistical methods to evaluate the spatial pattern of China’s CO2 emissions in 2019. Then, we spatially quantified China’s urbanization of land, population and economy based on statistical data. Finally, we used the geo-weighted regression model to explore the spatial relationship between urbanization and CO2 emissions at the national-economic zone-province scale. The results displayed that there is obvious spatial heterogeneity in the relationship between China’s urbanization and CO2 emissions. The significant positive correlation between urbanization and CO2 emissions were mainly located in the northeastern, eastern and southwestern regions, consistent with the characteristics of the Heihe–Tengchong Line. The uneven development of land, population and economic urbanization would lead to more CO2 emissions. We suggest that China should attend the balanced development of urban land, population and economy, and avoid the additional carbon emissions caused by incongruence, to further the development of low-carbon cities.

Abstract Temporal information in event streams plays a critical role in event‐based video frame interpolation as it provides temporal context cues complementary to images. Most previous event‐based methods first transform the unstructured event data to structured data formats through voxelisation, and then employ advanced CNNs to extract temporal information. However, voxelisation inevitably leads to information loss, and processing the sparse voxels introduces severe computation redundancy. To address these limitations, this study proposes a point‐image fusion network (PIFNet). In our PIFNet, rich temporal information from the events can be directly extracted at the point level. Then, a fusion module is designed to fuse complementary cues from both points and images for frame interpolation. Extensive experiments on both synthetic and real datasets demonstrate that our PIFNet achieves state‐of‐the‐art performance with high efficiency.

Abstract Bridged chiral biaryls are axially chiral compounds with a medium-sized ring connecting the two arenes. Compared with plentiful methods for the enantioselective synthesis of biaryl compounds, synthetic approaches for this subclass of bridged atropisomers are limited. Here we show an atroposelective synthesis of 1,3-diaxial bridged eight-membered terphenyl atropisomers through an Co/SPDO (spirocyclic pyrrolidine oxazoline)-catalyzed aerobic oxidative coupling/desymmetrization reaction of prochiral phenols. This catalytic desymmetric process is enabled by combination of an earth-abundant Co(OAc)2 and a unique SPDO ligand in the presence of DABCO (1,4-diaza[2.2.2]bicyclooctane). An array of diaxial bridged terphenyls embedded in an azocane can be accessed in high yields (up to 99%) with excellent enantio- (>99% ee) and diastereoselectivities (>20:1 dr).

Abstract Introduction Listeriosis is a severe food-borne disease caused by Listeria monocytogenes infection. The data of listeriosis in Xi’an population are limited. The aim of this study is to evaluate the clinical features and fatality risk factors for listeriosis in three tertiary-care hospitals in Xi’an, China Methods The characteristics of demographic data, underlying diseases, clinical manifestations, laboratory indicators, cranial imaging examination, antibiotics therapeutic schemes, and clinical outcomes were collected between 2011 and 2023. Logistic regression analysis was performed. Results Seventy-one etiologically confirmed listeriosis patients were enrolled, including 12 neonatal and 59 non-neonatal cases. The majority of neonatal listeriosis presented as preterm (50%) and fetal distress (75%). The main clinical manifestations of non-neonatal listeriosis included fever (88%), headache (32%), disorder of consciousness (25%), vomiting (17%), abdominal pain (12%), and convulsions (8%). The fatality rate in neonatal cases was higher than in non-neonatal listeriosis (42 vs. 17%). Although no deaths were reported in maternal listeriosis, only two of 23 patients had an uneventful obstetrical outcome. Five maternal listeriosis delivered culture-positive neonates, three of whom decreased within 1 week post-gestation due to severe complications. Twenty-eight cases were neurolisteriosis and 43 cases were bacteremia. Neurolisteriosis had a higher fatality rate compared with bacteremia listeriosis (36 vs. 12%). The main neuroradiological images were cerebral edema/hydrocephalus, intracranial infection, and cerebral hernia. Listeria monocytogenes showed extremely low resistance to ampicillin (two isolates) and penicillin (one isolate). The fatality risk factors were the involvement of the central nervous system, hyperbilirubinemia, and hyponatremia for all enrolled subjects. Hyperuricemia contributed to the elevation of fatality risk in non-neonatal listeriosis. Conclusions When the patients suffered with symptoms of fever and central nervous system infection, they should be alert to the possibility of listeriosis. Early administration of ampicillin- or penicillin-based therapy might be beneficial for recovery of listeriosis.

This study delved into the potential application of Platanus acerifolia leaf extract (PALE) as an environmentally benign corrosion inhibitor. Evaluation of corrosion inhibition was conducted using electrochemical methods, field emission scanning electron microscopy equipped with energy dispersive spectrometer. The results reveal that PALE offers efficient protection for Q235 steel across the temperature range of 298 K–318 K, achieving a maximum corrosion inhibition efficiency of approximately 93%. Furthermore, Density functional theory (DFT) calculations and molecular dynamics (MD) simulations were performed to elucidate the spontaneous and stable adsorption of PALE molecules onto the surface of Q235 steel. This adsorption impedes the diffusion of corrosive substances towards the steel surface, thereby endowing Q235 steel with robust corrosion resistance.

Abstract A direct strategy to achieve specific treatments and reduce side effects is through cell type‐specific drug delivery. Exosomes (Exos) can be modified with folic acid (FA) to prepare drug delivery systems targeting tumor cells that highly express FA receptors. This study aimed to produce an exo drug delivery system with FA decoration and temozolomide (TMZ) loading to improve the sustained TMZ release and targeting. We used DSPE‐PEG2000‐FA to modify exos derived from astrocyte U‐87 to prepare FA‐modified exos (Astro‐exo‐FA). TMZ was encapsulated into Astro‐exo‐FA or Astro‐exo through electroporation to produce TMZ@Astro‐exo and TMZ@Astro‐exo‐FA. In vitro drug release was examined using the dialysis bag method. Through cell experiments in vitro and mouse glioma models in vivo, the effect of TMZ@Astro‐exo‐FA on U‐87 cells was determined. Exo properties were not affected by FA modification and TMZ loading. The drug release rate of TMZ@Astro‐exo‐FA was slower. TMZ@Astro‐exo‐FA uptake by U‐87 cells was higher compared to TMZ@Astro‐exo, indicating that TMZ@Astro‐exo‐FA has a stronger targeting toward U‐87 cells. TMZ@Astro‐exo‐FA remarkably reduced U‐87 cell proliferation, migration, and invasion compared with TMZ@Astro‐exo and free TMZ. Treatment with TMZ@Astro‐exo‐FA reduced the side effects of TMZ (minimal change in body weight), prolonged survival, and inhibited tumor growth in mouse glioma models, and its efficacy was stronger than that of TMZ@Astro‐exo and free TMZ. TMZ@Astro‐exo‐FA could enhance the effect of TMZ against glioma, providing novel ideas for drug targeting delivery and exploring exos as drug carriers against glioma.

Abstract Capsaicin derivatives with thiourea structure (CDTS) is highly noteworthy owing to its higher analgesic potency in rodent models and higher agonism in vitro. However, the direct synthesis of CDTS remains t one or more shortcomings. In this study, we present reported a green, facile, and practical synthetic method of capsaicin derivatives with thiourea structure is developed by using an automated synthetic system, leading to a series of capsaicin derivatives with various electronic properties and functionalities in good to excellent yields.

Anthocyanins play crucial roles in pollen protection and pollinator attraction in flowering plants. However, the mechanisms underlying flower color determination and whether floral anthocyanin regulators participate in other processes remain largely unresolved in soybeans (Glycine max). In this study, we investigated the genetic components and mechanisms governing anthocyanin biosynthesis in soybean flowers. Molecular and genetic studies have characterized two antagonistic regulators, the positive activator GmMYBA3 and the negative repressor GmMYBR1, that modulate the gene expression of anthocyanin biosynthesis in soybean flowers. Further findings revealed a regulatory interplay between GmMYBA3 and GmMYBR1 bridged by GmTT8a, highlighting the complexity of anthocyanin regulation in different soybean organs. Exploration of additional soybean cultivars demonstrated the universality of GmMYBA3 and GmMYBR1 in regulating floral anthocyanin biosynthesis- related genes, with GmF3′5′H identified as a crucial determinant of white flower color. This study provides a molecular mechanism underlying soybean flower color determination, paving the way for the molecular modification of soybean flowers to probably enhance their resistance to abiotic stresses and attractiveness to pollinators.

Abstract Leukemias and their bone marrow microenvironments undergo dynamic changes over the course of disease. However, little is known about the circulation kinetics of leukemia cells, nor the impact of specific factors on the clearance of circulating leukemia cells (CLCs) from the blood. To gain a basic understanding of CLC dynamics over the course of disease progression and therapeutic response, we apply a blood exchange method to mouse models of acute leukemia. We find that CLCs circulate in the blood for 1–2 orders of magnitude longer than solid tumor circulating tumor cells. We further observe that: (i) leukemia presence in the marrow can limit the clearance of CLCs in a model of acute lymphocytic leukemia (ALL), and (ii) CLCs in a model of relapsed acute myeloid leukemia (AML) can clear faster than their untreated counterparts. Our approach can also directly quantify the impact of microenvironmental factors on CLC clearance properties. For example, data from two leukemia models suggest that E-selectin, a vascular adhesion molecule, alters CLC clearance. Our research highlights that clearance rates of CLCs can vary in response to tumor and treatment status and provides a strategy for identifying basic processes and factors that govern the kinetics of circulating cells.

Abstract Background Human adipose stromal cells-derived extracellular vesicles (haMSC-EVs) have been shown to alleviate inflammation in acute lung injury (ALI) animal models. However, there are few systemic studies on clinical-grade haMSC-EVs. Our study aimed to investigate the manufacturing, quality control (QC) and preclinical safety of clinical-grade haMSC-EVs. Methods haMSC-EVs were isolated from the conditioned medium of human adipose MSCs incubated in 2D containers. Purification was performed by PEG precipitation and differential centrifugation. Characterizations were conducted by nanoparticle tracking analysis, transmission electron microscopy (TEM), Western blotting, nanoflow cytometry analysis, and the TNF-α inhibition ratio of macrophage [after stimulated by lipopolysaccharide (LPS)]. RNA-seq and proteomic analysis with liquid chromatography tandem mass spectrometry (LC–MS/MS) were used to inspect the lot-to-lot consistency of the EV products. Repeated toxicity was evaluated in rats after administration using trace liquid endotracheal nebulizers for 28 days, and respiratory toxicity was evaluated 24 h after the first administration. In vivo therapeutic effects were assessed in an LPS-induced ALI/ acute respiratory distress syndrome (ARDS) rat model. Results The quality criteria have been standardized. In a stability study, haMSC-EVs were found to remain stable after 6 months of storage at − 80°C, 3 months at − 20 °C, and 6 h at room temperature. The microRNA profile and proteome of haMSC-EVs demonstrated suitable lot-to-lot consistency, further suggesting the stability of the production processes. Intratracheally administered 1.5 × 108 particles/rat/day for four weeks elicited no significant toxicity in rats. In LPS-induced ALI/ARDS model rats, intratracheally administered haMSC-EVs alleviated lung injury, possibly by reducing the serum level of inflammatory factors. Conclusion haMSC-EVs, as an off-shelf drug, have suitable stability and lot-to-lot consistency. Intratracheally administered haMSC-EVs demonstrated excellent safety at the tested dosages in systematic preclinical toxicity studies. Intratracheally administered haMSC-EVs improved the lung function and exerted anti-inflammatory effects on LPS-induced ALI/ARDS model rats.

Objectives Osteoporotic vertebral fractures (OVFs) are a critical public health concern requiring urgent attention, and severe OVFs impose substantial health and economic burdens on patients and society. Analysis of the risk factors for severe OVF is imperative to actively prevent the occurrence of this degenerative disorder. This study aimed to investigate the risk factors associated with the severity of OVF, with a specific focus on changes in the paraspinal muscles. Methods A total of 281 patients with a first‐time single‐level acute OVF between January 2016 and January 2023 were enrolled in the study. Clinical and radiological data were collected and analyzed. The cross‐sectional area (CSA) and degree of fatty infiltration (FI) of the paraspinal muscles, including the multifidus muscles (MFMs), erector spinae muscles (ESMs), and psoas major muscles (PSMs), were measured by magnetic resonance imaging (MRI) of the L4/5 intervertebral discs. According to the classification system of osteoporotic fractures (OF classification) and recommended treatment plan, OVFs were divided into a low‐grade OF group and a high‐grade OF group. Univariate and multivariate logistic regression analyse s were performed to identify risk factors associated with the severity of OVF. Results Ninety‐eight patients were included in the low‐grade OF group, and 183 patients were included in the high‐grade OF group. Univariate analysis revealed a significantly higher incidence of a high degree of FI of MFMs (OR = 1.71, p = 0.002) and ESMs (OR = 1.56, p = 0.021) in the high‐grade OF group. Further multivariate logistic regression analysis demonstrated that a high degree of FI of the MFMs (OR = 1.71, p = 0.002) is an independent risk factor for the severity of OVF. Conclusion A high degree of FI of the MFMs was identified as an independent risk factor for the severity of OVF. Decreasing the degree of FI in the MFMs might lower the incidence of the severity of OVF, potentially reducing the necessity for surgical intervention in OVF patients.

Crucian carp (Carassius auratus gibelio), an extensively cultivated freshwater fish, was one of the model species for the study of fish immunology. Polyclonal antibodies were advantageous molecular tools for studying teleost immune system. Specifically, polyclonal antibodies reacting with immunoglobulins (Ig) were used successfully in studies of the teleost fishes. In the present study, we produced polyclonal antibody against CH2 domains of crucian carp IgM, and measured the in vivo dynamics of IgM mRNA caused by CyHV-2 infection. The recombinant protein IgM with relative molecular weight about 53 KD was correctly expressed in prokaryotic cells. The specificity of the polyclonal antibody was evaluated by Western blotting and results revealed that the antibody not only specifically recognized crucian carp serum but also cross-reacted with grass carp serum. Quantitative RT-PCR analysis demonstrated the expression of IgM mRNA changed significantly after CyHV-2 infection. The expression of IgM in the kidney increased and reached a maximum at 6 h post-infection (hpi), while dropped to a low level at 5 days post-infection (dpi). In conclusion, the expression of IgM was significantly upregulated in the kidney of crucian carp infected with CyHV-2, indicating that IgM played a potential role in systemic immunity against viral infection. Polyclonal antibody against crucian carp IgM had certain clinical relevance, which might provide insight into the early stage of virus infection and prevention of the disease.

Objective To investigate the correlations between choroidal parameters and primary angle-closure suspect (PACS) in different age subgroups.Methods and analysis Participants aged 50 years or older in a rural area of Daxing District, Beijing, were recruited. Swept-source optical coherence tomography was used to measure the choroidal parameters. Demographic, ocular biometry parameters and choroidal parameters were compared between the PACS and non-PACS (NPACS) eyes. Logistic analysis was performed to explore the association between the choroidal parameters and PACS.Results 192 (26.89%) subjects with PACS and 509 (71.29%) with PACS were analysed. Subjects were divided into two groups: group 1 (50–60 years, n=286) and group 2 (>60 years, n=415). In group 1, the mean subfoveal choroidal thickness of PACS eyes was 341.82±88.23 µm and thicker than NPACS eyes (315.07±83.53 µm, p=0.035). The choroidal volume was greater in PACS eyes (10.61±2.78 mm3) compared with NPACS eyes (9.66±2.49 mm3, p=0.013). In group 2, no significant difference in any choroidal parameters between PACS and NPACS was found. Multivariate regression demonstrated that increased choroidal volume was associated with PACS (OR 1.298, 95% CI 1.117 to 1.510, p

Abstract Exfoliation of 2D non‐Van der Waals (non‐vdW) semiconductor nanoplates (NPs) from inorganic analogs presents many challenges ahead for further exploring of their advanced applications on account of the strong bonding energies. In this study, the exfoliation of ultrathin 2D non‐vdW chromium sulfide (2D Cr2S3) by means of a combined facile liquid‐phase exfoliation (LPE) method is successfully demonstrated. The morphology and structure of the 2D Cr2S3 material are systematically examined. Magnetic studies show an obvious temperature‐dependent uncompensated antiferromagnetic behavior of 2D Cr2S3. The material is further loaded on TiO2 nanorod arrays to form an S‐scheme heterojunction. Experimental measurements and density functional theory (DFT) calculations confirm that the formed TiO2@Cr2S3 S‐scheme heterojunction facilitates the separation and transmission of photo‐induced electron/hole pairs, resulting in a significantly enhanced photocatalytic activity in the visible region.

Abstract To ensure compositional consistency while mitigating potential immunogenicity for stem cell therapy, synthetic scaffolds have emerged as compelling alternatives to native extracellular matrix (ECM). Substantial progress has been made in emulating specific natural traits featuring consistent chemical compositions and physical structures. However, recapitulating the dynamic responsiveness of the native ECM involving chemical transitions and physical remodeling during differentiation, remains a challenging endeavor. Here, the creation of adaptive scaffolds is demonstrated through sequential protein‐instructed molecular assembly, utilizing stage‐specific proteins, and incorporating in situ assembly technique. The procedure is commenced by introducing a dual‐targeting peptide at the onset of stem cell differentiation. In response to highly expressed integrins and heparan sulfate proteoglycans (HSPGs) on human mesenchymal stem cell (hMSC), the peptides assembled in situ, creating customized extracellular scaffolds that adhered to hMSCs promoting osteoblast differentiation. As the expression of alkaline phosphatase (ALP) and collagen (COL‐1) increased in osteoblasts, an additional peptide is introduced that interacts with ALP, initiating peptide assembly and facilitating calcium phosphate (CaP) deposition. The growth and entanglement of peptide assemblies with collagen fibers efficiently incorporated CaP into the network resulting in an adaptive biphasic scaffold that enhanced healing of bone injuries.

Purpose: To develop and validate deep learning algorithms that can identify and classify angle-closure (AC) mechanisms using anterior segment optical coherence tomography (AS-OCT) images. Methods: This cross-sectional study included participants of the Handan Eye Study aged ≥35 years with AC detected via gonioscopy or on the AS-OCT images. These images were classified by human experts into the following to indicate the predominant AC mechanism (ground truth): pupillary block, plateau iris configuration, or thick peripheral iris roll. A deep learning architecture, known as comprehensive mechanism decision net (CMD-Net), was developed to simulate the identification of image-level AC mechanisms by human experts. Cross-validation was performed to optimize and evaluate the model. Human-machine comparisons were conducted using a held-out and separate test sets to establish generalizability. Results: In total, 11,035 AS-OCT images of 1455 participants (2833 eyes) were included. Among these, 8828 and 2.207 images were included in the cross-validation and held-out test sets, respectively. A separate test was formed comprising 228 images of 35 consecutive patients with AC detected via gonioscopy at our eye center. In the classification of AC mechanisms, CMD-Net achieved a mean area under the receiver operating characteristic curve (AUC) of 0.980, 0.977, and 0.988 in the cross-validation, held-out, and separate test sets, respectively. The best-performing ophthalmologist achieved an AUC of 0.903 and 0.891 in the held-out and separate test sets, respectively. And CMD-Net outperformed glaucoma specialists, achieving an accuracy of 89.9 % and 93.0 % compared to 87.0 % and 86.8 % for the best-performing ophthalmologist in the held-out and separate test sets, respectively. Conclusions: Our study suggests that CMD-Net has the potential to classify AC mechanisms using AS-OCT images, though further validation is needed.

Selenium (Se), a component of selenoproteins and selenocompounds in the human body, is crucial for the development of male reproductive organs, DNA synthesis, thyroid hormone, metabolism, and defence against infections and oxidative damage. In the testis, it must exceed a desirable level since either a shortage or an overabundance causes aberrant growth. The antioxidant properties of selenium are essential for preserving human reproductive health. Selenoproteins, which have important structural and enzymatic properties, control the biological activities of Se primarily. These proteins specifically have a role in metabolism and a variety of cellular processes, such as the control of selenium transport, thyroid hormone metabolism, immunity, and redox balance. Selenium nanoparticles (SeNPs) are less hazardous than selenium-based inorganic and organic materials. Upon being functionalized with active targeting ligands, they are both biocompatible and capable of efficiently delivering combinations of payloads to particular cells. In this review, we discuss briefly the chemistry, structure and functions of selenium and milestones of selenium and selenoproteins. Next we discuss the various factors influences male infertility, biological functions of selenium and selenoproteins, and role of selenium and selenoproteins in spermatogenesis and male fertility. Furthermore, we discuss the molecular mechanism of selenium transport and protective effects of selenium on oxidative stress, apoptosis and inflammation. We also highlight critical contribution of selenium nanoparticles on male fertility and spermatogenesis. Finally ends with conclusion and future perspectives.

Summary: Background: The survival rates of patients with nasopharyngeal carcinoma (NPC) have improved significantly, but there is no consensus on whether they can be considered cured. We aimed to determine whether a statistical cure could be achieved for patients with NPC in the contemporary therapeutic landscape. Methods: This retrospective multicenter study enrolled 6315 patients with nonmetastatic NPC from nonendemic and endemic regions of China from 2007 to 2020. We applied mixture and nonmixture cure models to estimate the cure probabilities and cure times by incorporating background mortality for the general population, matching by gender, age, and diagnosed year. Findings: With death as the uncured event, the probability of patients with NPC achieving a life expectancy at par with the general population was 78.1%. Considering progression as the uncured event, the likelihood of patients attaining a life expectancy without progression equivalent to that of the general population was 72.4%. For individuals, the probabilities of achieving cure were conditional and time-dependent, requiring approximately 7.1 and 4.7 years with 95% certainty, respectively. The corresponding cure times for uncured patients were 8.9 and 6.8 years, respectively. The cure probability was correlated with age, Eastern Cooperative Oncology Group score, TNM staging, Epstein–Barr virus DNA copies, and lactate dehydrogenase. The correlation was excellent between 5-year overall survival/progression-free survival and cure fractions. Interpretation: Statistical cure is potentially achievable among patients with NPC undergoing contemporary treatment modalities. The results hold significant potential implications for both clinical practice and patient perspectives. Funding: National High Level Hospital Clinical Research Funding; Beijing Xisike Clinical Oncology Research Foundation; Beijing hope run fund.

Abstract Pain, a comorbidity of anxiety disorders, causes substantial clinical, social, and economic burdens. Emerging evidence suggests that propofol, the most commonly used general anesthetic, may regulate psychological disorders; however, its role in pain‐associated anxiety is not yet described. This study investigates the therapeutic potential of a single dose of propofol (100 mg kg−1) in alleviating pain‐associated anxiety and examines the underlying neural mechanisms. In acute and chronic pain models, propofol decreased anxiety‐like behaviors in the elevated plus maze (EPM) and open field (OF) tests. Propofol also reduced the serum levels of stress‐related hormones including corticosterone, corticotropin‐releasing hormone (CRH), and norepinephrine. Fiber photometry recordings indicated that the calcium signaling activity of CRH neurons in the paraventricular nucleus (PVNCRH) is reduced after propofol treatment. Interestingly, artificially activating PVNCRH neurons through chemogenetics interfered with the anxiety‐reducing effects of propofol. Electrophysiological recordings indicated that propofol decreases the activity of PVNCRH neurons by increasing spontaneous inhibitory postsynaptic currents (sIPSCs). Further, reducing the levels of γ‐aminobutyric acid type A receptor β3 (GABAAβ3) subunits in PVNCRH neurons diminished the anxiety‐relieving effects of propofol. In conclusion, this study provides a mechanistic and preclinical rationale to treat pain‐associated anxiety‐like behaviors using a single dose of propofol.

IntroductionHemorrhagic transformation (HT) is a serious complication that can occur spontaneously after an acute ischemic stroke (AIS) or after a thrombolytic/mechanical thrombectomy. Our study aims to explore the potential correlations between fibrinogen levels and the occurrence of spontaneous HT (sHT) and HT after mechanical thrombectomy (tHT).MethodsA total of 423 consecutive AIS patients diagnosed HT who did not undergone thrombolysis and 423 age- and sex-matched patients without HT (non-HT) were enrolled. Fibrinogen levels were measured within 24 h of admission after stroke. The cohorts were trisected according to fibrinogen levels. The HT were further categorized into hemorrhagic infarction (HI) or parenchymal hematoma (PH) based on their imaging characteristics.ResultsIn sHT cohort, fibrinogen levels were higher in HT patients than non-HT patients (p

Abstract Patients with locally advanced head and neck squamous cell carcinoma (LA‐HNSCC) have poor survival outcomes. The real‐world efficacy of nimotuzumab plus intensity modulated radiotherapy (IMRT)‐based chemoradiotherapy in patients with LA‐HNSCC remains unclear. A total of 25,442 HNSCC patients were screened, and 612 patients were matched by propensity score matching (PSM) (1:1). PSM was utilized to balance known confounding factors. Patients who completed at least five doses of nimotuzumab were identified as study group. The primary end point was 3‐year overall survival (OS) rate. Log‐rank test examined the difference between two survival curves and Cloglog transformation test was performed to compare survival at a fixed time point. The median follow‐up time was 54.2 (95% confidence interval [CI]: 52.7–55.9) months. The study group was associated with improved OS (hazard ratio [HR] = 0.75, 95% CI: 0.57–0.99, p = 0.038) and progression‐free survival (PFS) (HR = 0.74, 95% CI: 0.58–0.96, p = 0.021). Subgroup analysis revealed that aged 50–60 year, IV, N2, radiotherapy dose ≥ 60 Gy, without previous surgery, and neoadjuvant therapy have a trend of survival benefit with nimotuzumab. Nimotuzumab showed favorable safety, only 0.2% had nimotuzumab‐related severe adverse events. Our study indicated the nimotuzumab plus chemoradiotherapy provides survival benefits and safety for LA‐HNSCC patients in an IMRT era.

Introduction Peripheral vasodilation causes a redistribution of body temperature from the core to the periphery, resulting in shivering and hypothermia. These are normal pathological and physiological processes during spinal anaesthesia. Two drugs, norepinephrine and phenylephrine, have peripheral vasoconstrictive effects. It is unclear the effects of norepinephrine and phenylephrine on shivering and hypothermia in patients undergoing caesarean section under spinal anaesthesia.Methods analysis 240 eligible parturients will be recruited for this randomised, double-blind, controlled trial and randomly assigned to either the norepinephrine or phenylephrine groups. The primary outcome will be the incidence of shivering while secondary outcomes will include the severity of shivering, rectal temperature, incidence of hypothermia and umbilical artery blood pH value.Ethics and dissemination The Institutional Ethics Committee of The Second People’s Hospital of Hefei approved the trial protocol (ID: 2023-093). The results will be published in a compliant journal. The original data will be released in December 2029 on the ResMan original data-sharing platform of the China Clinical Trial Registry (http://www.medresman.org.cn).Trial registration number ChiCTR2300077164.