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Jing Yuan,1 Ze-Yin Liang,2 Yu-Jun Dong,2 Han-Yun Ren2 1Department of Hematology, The Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Hematology, Peking University First Hospital, Beijing, People’s Republic of ChinaCorrespondence: Ze-Yin Liang; Han-Yun Ren, Department of Hematology, Peking University First Hospital, Beijing, People’s Republic of China, Email woaifeiyan1513@163.com; cinderella8886@163.comObjective: To describe the incidence, possible risk factors, and treatment options of autoimmune hemolytic anemia (AIHA) occurring after cord blood transplantation (CBT).Methods: We retrospectively analyzed the patients who underwent CBT at Peking University First Hospital between January 2004 and July 2022.Results: We totally identified thirty-six patients who received CBT. Median age was 27.5 years (range, 1.6– 52). With a median 6 (range 0.6– 10.0) years survivor follow-up, six patients developed AIHA (2 Evans syndrome included) at a median of 168 (range, 122– 264) days post-CBT for 8% cumulative incidence density 3 years. Its mortality was 50% and mainly associated with concomitant infections (CMV reactivation rate nearly 100%). The possible risk factors for developing AIHA are CMV reactivation, GvHD and HLA mismatch.Conclusion: AIHA is a clinically significant common complication in recipients post-CBT. Corticosteroids combined with intravenous immunoglobulin (IvIg) is recommended for the treatment of warm antibody AIHA after CBT.Keywords: autoimmune hemolytic anemia, cord blood transplantation, combination therapy, prognosis

Zheng-Yang Song, Han-Yun Ren, Yu-Jun Dong, Yuan Li, Yue Yin, Yu-Hua Sun, Qian Wang, Wei-Lin Xu, Wei Liu, Jin-Ping Ou, Ze-Yin Liang Department of Hematology, Peking University First Hospital, Peking University, Beijing, People’s Republic of ChinaCorrespondence: Han-Yun Ren; Ze-Yin LiangDepartment of Hematology, Peking University First Hospital, No. 8 Xi Shi Ku Street, Xi Cheng District, Beijing 100034, People’s Republic of ChinaTel/Fax +86 10-83575082Email renhy0813@163.com; walzyaw@163.comPurpose: To explore the efficacy of low-dose rabbit antithymocyte globulin (rATG) in matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) for patients with acute leukemia or myelodysplastic syndrome.Patients and Methods: We performed a retrospective study of 79 patients with hematologic malignancies who received MSD-HSCT. All patients received standard graft-versus-host disease (GVHD) prophylaxis comprising cyclosporine, mycophenolate mofetil and short-term methotrexate. Among them, 38 were administered 5 mg/kg rATG as part of GVHD prophylaxis. Clinical outcomes including overall survival (OS), GVHD and relapse were analyzed.Results: No graft failure occurred in the antithymocyte globulin (ATG) or non-ATG group. The cumulative incidences of grade 2– 4 and 3– 4 acute GVHD at day +100 were 13.3% versus 19.5% (p=0.507) and 5.7% versus 15.2% (p=0.196), respectively. The 2-year cumulative incidences of chronic GVHD (cGVHD) were 35.4% and 60.4% (p=0.039), and those of extensive cGVHD were 12.9% and 40.0% (p=0.015), respectively. In a multivariate analysis, the use of low-dose rATG was an independent protective factor for extensive cGVHD (hazard ratio [HR] 0.256; 95% confidence interval [CI], 0.080 to 0.822, p=0.022). The 2-year OS was 88.1% and 68.4% (p=0.038), respectively, and the use of low-dose rATG was the only protective factor in the multivariate analysis (HR 0.216; 95% CI, 0.059 to 0.792, p=0.021). There was no significant difference between the two groups in terms of the 2-year cumulative incidence of relapse, leukemia-free survival or GVHD-free and relapse-free survival.Conclusion: Low-dose rATG used in MSD-HSCT as part of the conditioning regimen results in a reduced incidence of cGVHD and improves survival outcomes.Keywords: low-dose rATG, hematopoietic stem cell transplantation, matched sibling donor, graft-versus-host disease

Qing Ya Wang,* Yuan Li,* Ze Yin Liang, Yue Yin, Wei Liu, Qian Wang, Yu Jun Dong, Yu Hua Sun, Wei Lin Xu, Han Yun Ren Department of Hematology, Peking University First Hospital, Peking University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuan Li; Han Yun RenDepartment of Hematology, Peking University First Hospital, Peking University, No.8 Xi Shi Ku Street, Xi Cheng District, Beijing 100034, People’s Republic of ChinaTel +86 1083575746; +86 1083575680Email drliyuan75@163.com; renhy0813@163.comPurpose: To evaluate the role of Decitabine in the allo-HSCT conditioning regimen for intermediate- and high-risk patients with MDS or AML.Patients and methods: Retrospective analysis of data pertaining to 76 intermediate- and high-risk patients with MDS or AML who underwent allo-HSCT between December 2005 and June 2018 at the Peking University First Hospital. Forty patients received Decitabine-containing conditioning regimen before transplantation, while thirty-six patients received regimen without Decitabine.Results: Over a median follow-up of 40 months (range, 1 to 155), the cumulative incidence of grade II to IV acute graft versus host disease was 12.4% [95% confidence interval (CI) 4.9–30.9%] in the Decitabine group and 41.5% (95% CI 28.1–61.2%) in the non-Decitabine group (P=0.005). On multivariate analysis, Decitabine-containing conditioning regimen was found to protect against grade II to IV aGVHD (HR=0.279, 95% CI 0.102–0.765, P=0.013). Incidence of respiratory infection in the Decitabine and non-Decitabine groups was 22.5% and 52.78%, respectively (P=0.012). No significant between-group difference was observed with respect to 3-year OS, DFS, or RR (P=0.980, 0.959, and 0.573, respectively), while the median relapse time was longer in the Decitabine group [7 months (range, 2–12) versus 3 months (range, 2–4), P=0.171]. Decitabine-containing conditioning showed a tendency for lower relapse rate among higher risk patients, as assessed by IPSS R; however, the between-group difference was not statistically significant (P=0.085).Conclusion: Inclusion of Decitabine in the conditioning regimen for allo-HSCT in intermediate- and high-risk patients may lower the incidence of aGVHD and respiratory infections, and contribute to longer median relapse time.Keywords: myelodysplastic syndrome, acute myeloid leukemia, Decitabine, transplantation conditioning, graft versus host disease, allogeneic hematopoietic stem cell transplantation

Yingpeng Li,1 Xiuyan Li,2 Qingxia Guan,2 Chunjing Zhang,2 Ting Xu,2 Yujing Dong,2 Xinyu Bai,2 Weiping Zhang3 1College of Pharmacy, Tianjin University of Traditional Chinese Medicine, Tianjin, 2College of Pharmacy, Heilongjiang University of Traditional Chinese Medicine, Harbin, People’s Republic of China; 3Pope John XXIII High School, Everett, MA, USA Background: Enhancing drug delivery is an ongoing endeavor in pharmaceutics, especially when the efficacy of chemotherapy for cancer is concerned. In this study, we prepared and evaluated nanosized HKUST-1 (nanoHKUST-1), nanosized metal-organic drug delivery framework, loaded with 5-fluorouracil (5-FU) for potential use in cancer treatment.Materials and methods: NanoHKUST-1 was prepared by reacting copper (II) acetate [Cu(OAc)2] and benzene-1,3,5-tricarboxylic acid (H3BTC) with benzoic acid (C6H5COOH) at room temperature (23.7°C±2.4°C). A central composite design was used to optimize 5-FU-loaded nanoHKUST-1. Contact time, ethanol concentration, and 5-FU:material ratios were the independent variables, and the entrapment efficiency of 5-FU was the response parameter measured. Powder X-ray diffraction, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and nitrogen adsorption were used to determine the morphology of nanoHKUST-1. In addition, 5-FU release studies were conducted, and the in vitro cytotoxicity was evaluated.Results: Entrapment efficiency and drug loading were 9.96% and 40.22%, respectively, while the small-angle X-ray diffraction patterns confirmed a regular porous structure. The SEM and TEM images of the nanoHKUST-1 confirmed the presence of round particles (diameter: approximately 100 nm) and regular polygon arrays of mesoporous channels of approximately 2–5 nm. The half-maximal lethal concentration (LC50) of the 5-FU-loaded nanoHKUST-1 was approximately 10 µg/mL.Conclusion: The results indicated that nanoHKUST-1 is a potential vector worth developing as a cancer chemotherapeutic drug delivery system. Keywords: 5-fluorouracil, drug delivery, nanoparticles, nano-MOFs

The effects of different concentrations of growth hormone (GH) on in vitro maturation (IVM), fertilization (IVF) and culture (IVC) of bovine oocyte/embryos in CR1aa or CR2aa media using a simple CO2 incubator were investigated. The IVM/IVF/IVC of oocytes were carried out in the presence of 0, 50, 100 and 200 ng/ml GH in the medium. The proportion of metaphase II oocytes was significantly higher (p < 0.05) in 200 ng/ml compared with 0 ng/ml GH in CR1aa medium (59 versus 85%, respectively), but this effect was not observed under CR2aa. Higher concentrations of GH yielded lower rates of unfertilized ova and thus superior cleavage rates (36.5 ± 0.2 and 63.5 ± 2.0% versus 17.5 ± 0.2 and 82.5 ± 1.5% or 40.4 ± 0.6 and 59.6 ± 1.4% versus 16.6 ± 1.2 and 83.4 ± 6.2% for 0 and 200 ng/ml GH in portable or ordinary incubator, respectively) in CR1aa. This dose-dependent effect was also observed in the percentages of transferable embryos, although not statistically different (17.2 ± 1.7 versus 27.3 ± 1.8% and 16.6 ± 3.1 versus 26.0 ± 1.4%, for 0 versus 200 ng/ml GH in portable and ordinary incubator, respectively). In contrast to the CR1aa, different concentrations of GH in CR2aa medium did not increase either fertilization or cleavage rates. In fact, higher concentrations of GH in this medium negatively affected the rate of transferable embryos. Hence, percentages of transferable embryos obtained in the portable incubator under 0 or 50 ng/ml GH were higher (p < 0.05) compared with those obtained in 100 or 200 ng/ml GH (35.4 ± 5.7 or 40.5 ± 5.4% versus 22.4 ± 2.4 or 15.5 ± 2.1%, respectively). There was however, no significant difference in the rate of transferable embryos in an ordinary incubator employing CR2aa medium, but the trend was more or less similar to that observed in the portable incubator. Despite the fact that relatively fewer oocytes were employed for the culture in the ordinary incubator, overall results observed employing the simple portable CO2 incubator were within the range of those obtained in an ordinary incubator; implying that the simple portable incubator can effectively be employed for the in vitro production of bovine embryos under field conditions. [ABSTRACT FROM AUTHOR]

DOP1 leucine zipper-like protein A (DOPEY1), a member of the DOPEY family, is mainly localized in the Golgi apparatus, endosomes, and cytoplasmic compartments within cells. The involvement of DOPEY1 in H. pylori infection-induced carcinogenesis has remained unresolved. Here, we report that DOPEY1 is upregulated in GC tissues compared to adjacent normal tissues, correlating with poor prognosis. Mechanistically, H. pylori infection increases DOPEY1 expression and promotes p53 degradation through a CagA-dependent pathway. Using the String database and liquid chromatography-mass spectrometry, we identified DOPEY1-interacting proteins, confirming through co-immunoprecipitation that DOPEY1 interacts with USP7 and TRIP12. H. pylori infection enhances the expression of DOPEY1, USP7, and TRIP12, leading to p53 degradation, which is reversed by DOPEY1 silencing. Moreover, USP7 overexpression rescues p53 degradation in DOPEY1-silenced cells. Functionally, DOPEY1 knockdown reduces GC cell proliferation and suppresses tumor growth in mouse models. Immunohistochemistry analysis further reveals a link between DOPEY1, USP7, and TRIP12 expression, H. pylori infection, and GC progression. These findings demonstrate that H. pylori-induced upregulation of DOPEY1 drives p53 degradation via the USP7/TRIP12 axis, contributing to gastric tumorigenesis, and highlight DOPEY1 as a potential therapeutic target for H. pylori-associated GC., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: This study was approved by the ethics committee of The First Affiliated Hospital of Nanchang University ((2023) CDYFYYLK (01-009)), and written informed consent was obtained from all patients. The animal study was reviewed and approved by the ethics committees of Nanchang University (NCULAE-20221228028). All methods were performed in accordance with the relevant guidelines and regulations., (© 2025. The Author(s), under exclusive licence to Springer Nature Limited.)

Cadmium (Cd) is a toxic heavy metal with a high propensity to accumulate within the body, and Cd accumulation has been shown to cause organ damage. However, it is unclear whether Cd accumulation is a cause of impaired decidualization, which induces to spontaneous abortion (SA). In this study, we found that the decidual Cd concentration was increased in patients with SA and positively correlated with the occurrence of SA. The levels of two decidualization markers (prolactin, PRL and insulin-like growth factor binding protein 1, IGFBP1) were reduced in the decidua of all-cause SA patients. Using 8-week ICR female mice, we further established a uterus-specific Cd accumulation mouse model and verified that Cd-accumulating mice had increased numbers of absorbed fetuses and defective decidualization. Finally, using in vitro-cultured human ENdometrial stromal cells (hEnSCs), we found that Cd accumulation significantly inhibited decidualization; and moreover, Cd treatment downregulated the regulatory genes upstream of PRL and IGFBP1 such as PGR, ESR1, ESR2 and FOXO1. This study suggests that Cd accumulation could produce impaired decidualization by downregulating the upstream regulators of PRL and IGFBP1, thereby increasing the risk of SA. Our study offered new possibilities for the prevention and treatment of spontaneous abortion., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Lead halide perovskites demonstrate outstanding luminescent characteristics. However, the inclusion of lead components restricts their extensive utilization. Halide perovskite materials, formulated as A 2 M(III)M(I)X 6 or A 2 M(IV)X 6 , possess the potential to serve as stable and eco-friendly substitutes for optoelectronic applications. Nevertheless, their wide bandgap (>3 eV) hinders the practical implementation across various domains. Here, the variable valence Ce-based Cs₂CeAgBr₆ perovskite nanocrystals (NCs) are first synthesized with a bandgap of 2.65 eV. Intriguingly, the coexistence of trivalent and tetravalent Ce can cause localized spin of the f-layer electrons of Ce, leading to Ce 3+/4+ (the Ce valence state ranges between III and IV) defects. By manipulating trivalent and tetravalent Ce source proportions, a dual Ce-based perovskite achieves a minimal Ce 3+/4+ defect content of 1.4%. The as-prepared Cs₂CeAgBr₆ NCs exhibit exceptional efficiency in CO 2 reduction driven by sunlight, with a CH 4 selectivity greater than 70% and a super high charge transfer rate of 802.5 µmol·g -1  h -1 , far surpassing previously reported findings. Additionally, theoretical calculations have elucidated the photocatalytic mechanism involved in CO₂ reduction. The outcomes of this investigation are expected to stimulate design and fabrication of novel lead-free perovskite nanocrystals., (© 2024 Wiley‐VCH GmbH.)

Objective: Recent studies have indicated a close relationship between intracranial arterial stenosis and white matter hyperintensities (WMHs), but few have reported on the correlation between the characteristics of intracranial arterial wall plaques and WMHs. The aim of this study was to comprehensively assess the correlation between intracranial atherosclerosis plaques and WMHs using 3.0T high-resolution magnetic resonance imaging (HR-MRI)., Patients and Methods: Ninety-two ischemic stroke patients with middle cerebral artery (MCA) stenosis <50% on cranial magnetic resonance angiography (MRA) underwent conventional MRI and HR-MRI examinations. T2-weighted fluid-attenuated inversion recovery (T2-FLAIR) images were processed using 2D VBNeT automatic segmentation technology to segment WMH volume. HR-MRI images were analyzed using ImageJ software to evaluate the luminal area, outer wall area, plaque distribution, luminal stenosis rate, remodeling patterns, and other plaque parameters at the stenosis site and reference points of the MCA M1 segment. The correlation between the presence of plaques, plaque distribution, luminal stenosis rate, T1 hyperintensity, remodeling patterns, remodeling ratio (RR), eccentric plaques, and plaque burden with the volume of cerebral WMHs was analyzed., Results: Compared with the no-plaque group, the plaque group had significantly higher age, male ratio, total WMH volume, periventricular WMH (PVWMH) volume, deep WMH (DWMH) volume, and juxtacortical WMH (JCWMH) volume (all p < 0.05). The Kruskal-Wallis H test showed that patients with plaques on the superior and dorsal sides of the MCA M1 segment had higher levels of total WMH volume, PVWMH volume, DWMH volume, and JCWMH volume than patients with plaques on the inferior and ventral sides (all p < 0.05). Age, diabetes, previous stroke events, plaque distribution, positive remodeling, eccentric plaques, and RR were positively correlated with total WMH volume, PVWMH volume, and JCWMH volume (all p < 0.05). The presence of plaques, plaque distribution, and positive remodeling were independent risk factors for total WMH volume (all p < 0.05)., Conclusion: The presence of intracranial atherosclerotic plaques, plaque distribution, and positive remodeling are closely associated with increased cerebral WMHs burden in patients with ischemic stroke, which further supports the relationship between large artery atherosclerosis and CSVD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Zhang, Bu, Meng, Li, Dong, Cao, Gao, Zhang and Ren.)

Introduction: Teclistamab, the first approved B-cell maturation antigen-directed bispecific antibody for treatment of triple-class exposed relapsed/refractory multiple myeloma, demonstrated deep, durable responses with a manageable safety profile in the pivotal MajesTEC-1 cohort (NCT03145181/NCT04557098). Efficacy, safety, and pharmacokinetics from the MajesTEC-1 China cohort are reported., Methods: Patients received teclistamab 1.5 mg/kg subcutaneously weekly after step-up dosing; patients could switch to less frequent dosing with continued response., Results: In the China cohort (N = 26; median age, 66 years; median prior lines of therapy, 5) 15-month median follow-up, overall response rates, very good partial response or better, and complete response or better (≥CR) were 76.9%, 76.9%, and 57.7%, respectively. Median time to first response and ≥CR were 1.4 and 6.3 months, respectively; among patients with ≥CR and have available MRD samples, MRD negativity was achieved in 14/15 (93.3%) patients. Median duration of response, progression-free survival, and overall survival were not reached; 12-month duration of response, progression-free survival, and overall survival rates were 78.5%, 68.0%, and 83.5%, respectively. The safety profile was consistent with the pivotal cohort. Although infections occurred in 96.2% of patients, incidence decreased over time with six patients experiencing infections for >12 to 18 months. There were no discontinuations because of adverse events and no dose reductions. Ten patients switched to less frequent dosing. Teclistamab serum concentrations were consistent with the pivotal cohort, with a slightly lower mean pharmacokinetics profile., Conclusions: Teclistamab demonstrated efficacy and safety profiles in the China cohort consistent with the pivotal cohort, supporting teclistamab as a promising treatment option for triple-class exposed relapsed/refractory multiple myeloma in China., (© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Objectives: To conduct a comprehensive review of the literature pertaining to the broader autism phenotype, the paper endeavors to delineate the key research directions and topics, document the current research trends, and furnish insightful analyses and novel perspectives to foster future advancements in the field, with the aid of CiteSpace and VOS viewer., Methods: CiteSpace and VOS viewer are two kinds of software for visualizing citations that is intended to examine academic literature and identify possible sources of knowledge. The Web of Science Core Collection database was used to retrieve articles from 1994 to 2024 that discussed the autism phenotype in general. Following data collection, analyses were conducted using CiteSpace V.6.2.R4 (64-bit) on a number of topics, such as annual publication output, highly cited journals, affiliations with countries and institutions, eminent authors, cited references, and keywords. Knowledge maps, collaborative network analysis, cluster analysis, and strongest citation burst analysis were among the tools used to visualize the data., Results: A total of 1,075 articles about the broader autism phenotype were found. Roughly speaking, the annual number of publications is rising. With 546 articles on the subject, the United States is the nation with the greatest amount of authority and influence (centrality of 0.32), with England (218 articles) and Canada (115 articles) coming in second and third, respectively. The cited journals and institutions are mainly from the United States. The research consistently emphasizes the academic achievement and engagement of broader autism phenotype when analyzing the most cited references and authors., Conclusion: This study used CiteSpace to analyze the state of the larger autism phenotype field and then identified research frontiers and hotspots. As new findings are made, global trends in more thorough studies of the autism phenotype suggest that interest in these studies will only grow., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Qiao, Li, Du, Cheng, Sun, Qiang, Dong and Wang.)

Intelligent controlled-release nanopesticides have been a crucial tactic in advanced precision agriculture during the past few years, which can improve pesticide utilization and reduce environmental pollution. Herein, a novel hydroxypropyl methylcellulose-based nanopesticide carrier (PCH) with pH-/enzyme-/near-infrared multiple responses was constructed by the initial cross-linking with dimethyl diallyl ammonium chloride and the subsequent copper ion chelation and polydopamine coating. Avermectin (Av) was further loaded to create the intelligent pesticide release system (APCH) by antisolvent precipitation. The release of APCH increases under near-infrared light (NIR) conditions, with an accumulative release that is 3.26 times higher than that without NIR. The contact angles of APCH on cabbage leaves are 33 and 29% lower than those of water and technical Av (Av-tech), respectively, verifying that APCH has a good wettability property. Simultaneously, APCH displays better insecticidal activity than Av formulations because of its outstanding ultraviolet (UV) light stability of Av. The degradation rate of Av in APCH is less than 2% in 50 h under UV light, which is considerably lower than that of Av-tech (∼60%). The biosafety assessments manifest that the PCH carrier has remarkable biological safety on the growth of nontarget organisms in a certain range. Overall, the APCH system is bio-friendly with multiple-response release behaviors, excellent UV light stability, and foliar deposition performance, which can offer a new strategy for sustainable agricultural development.

The class C orphan G-protein-coupled receptor (GPCR) GPR156, which lacks the large extracellular region, plays a pivotal role in auditory function through G i2/3 . Here, we firstly demonstrate that GPR156 with high constitutive activity is essential for maintaining auditory function, and further reveal the structural basis of the sustained role of GPR156. We present the cryo-EM structures of human apo GPR156 and the GPR156-G i3 complex, unveiling a small extracellular region formed by extracellular loop 2 (ECL2) and the N-terminus. The GPR156 dimer in both apo state and G i3 protein-coupled state adopt a transmembrane (TM)5/6-TM5/6 interface, indicating the high constitutive activity of GPR156 in the apo state. Furthermore, C-terminus in G-bound subunit of GPR156 plays a dual role in promoting G protein binding within G-bound subunit while preventing the G-free subunit from binding to additional G protein. Together, these results explain how GPR156 constitutive activity is maintained through dimerization and provide a mechanistic insight into the sustained role of GPR156 in maintaining auditory function., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic stem cell malignancy and the only curable therapy is allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, allo-HSCT is not appropriate for all CMML patients, and relapse is the leading cause of treatment failure. This project conducted a nationwide multicenter real-world study to develop a novel prediction scoring system for early relapse. A total of 238 CMML patients from twenty-seven medical centers treated with allo-HSCT, and 307 adult patients with CMML who underwent allo-HSCT in a publicly available research dataset from the Center for International Blood and Marrow Transplantation Registry (CIBMTR) database were included. Independent prognostic factors for the early relapse of CMML posttransplantation were identified according to competing risk regression methods. Four prognostic factors were identified: bone marrow blasts >10% (hazard ratio [HR], 4.262; P = 0.014), age >60 years (HR, 6.221; P = 0.007), hemoglobin level <100 g/L (HR, 3.695; P = 0.004), and non TET2 gene mutation (HR, 3.425; P = 0.017). A risk-grading scoring system was developed based on the regression coefficients and patients were stratified into low-risk (0-1 point), intermediate-risk (1.5-2 points) and high-risk ( > 2 points) groups. The validated internal c-statistic was 0.767 (95% confidence interval [CI], 0.674-0.860), and the external c-statistic was 0.769 (95% CI, 0.703-0.836). In the derivation cohort, the cumulative incidence rates of early relapse in the low-risk, intermediate-risk, and high-risk groups were 1.35% (95% CI: 1-4%), 10.40% (95% CI: 4-16%), and 29.54% (95% CI: 16-39%) (P < 0.001), respectively. This scoring system can be utilized to early identification of patients at a high risk of relapse and contributing to the implementation of urgent medical support., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Abstract: According to the diagnostic criteria for human herpesvirus 8 (HHV-8)-negative/idiopathic multicentric Castleman disease (iMCD) proposed by Castleman Disease Collaborative Network in 2017, there is a group of HHV-8-negative patients with multicentric Castleman disease (MCD) who do not have symptoms and hyperinflammatory state and do not meet the iMCD criteria. This retrospective study enrolled 114 such patients, described as asymptomatic MCD (aMCD), from 26 Chinese centers from 2000 to 2021. With a median follow-up time of 46.5 months (range, 4-279 months), 6 patients (5.3%) transformed to iMCD. The median time between a diagnosis of aMCD and iMCD in these 6 patients was 28.5 months (range, 3-60). During follow-up, 7 patients died; 3 of them died from progression of MCD. Despite that, 37.7% of patients received systemic treatment targeting MCD; this strategy was neither associated with a lower probability of iMCD transformation nor a lower death rate. The 5-year estimated survival of all patients with aMCD was 94.1% (95% confidence interval, 88.8-99.6). Transformation to iMCD was an important predictor of death (log-rank P = .01; 5-year estimated survival, 83.3%). This study suggests that patients with aMCD may represent a potential early stage of iMCD, who may not require immediate treatment but should be closely monitored., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

We investigated the effect of single seed directional sowing on the growth and development of peanut hypocotyl, plant photosynthetic performance, dry matter accumulation, senescence characteristics and yield of a peanut variety, Huayu 25. There are several treatments in the experiment, including single-seed random sowing (RS), radicle down (RD), radicle flat (RF) and radicle up (RU) treatments, with double seed sowing cleaning stem base soil (QK) as the control. The results showed that under the condition of single seed directional sowing, RD could increase the growth rate of peanut hypocotyl, shorten the emergence time, increase the emergence rate and cotyledon emergence rate, and had faster plant growth rate, higher leaf area index in the early stage of peanut growth, and an increased dry matter accumulation. The pod yield under RD was 8.1%, 14.4%, and 18.1% higher than that of RF, RS, and RU, respectively. Furthermore, RD significantly increased soluble protein content and the activities of superoxide dismutase, peroxidase and catalase, and reduced malondialdehyde (MDA) accumulation. Compared with QK, the soluble protein content, superoxide dismutase, peroxidase and catalase activities of RD in different periods were increased to varying degrees, while the MDA content was decreased, and there was no significant difference in pod yield. Our results suggested that RD could reduce the emergence time and the competition between plants, promote the growth of seedlings, accelerate the formation of seedling morphology, so as to establish a reasonable population structure, enhance the photosynthetic efficiency and dry matter production capacity of the population, effectively delay the aging process of the crop in the later stage, and finally increase pod yield.

This study aims to reveal the effect and mechanism of Dendrobii Officinalis Caulis water extract on the rat model of hyperviscosity induced by a high-sugar, high-salt, and high-fat diet. Thirty-six male SD rats were randomized into normal, model, Compound Danshen Tablets(0.5 g·kg~(-1)), and low-, medium-, and high-dose(0.25, 0.5, and 1.0 g·kg~(-1), respectively) Dendrobii Officinalis Caulis water extract groups. Except the normal group, the remaining groups were fed with a high-salt and high-fat diet and received regular gavage of sucrose solution(20 g·kg~(-1)) for 12 consecutive weeks. The modeling was accompanied by gavage of corresponding drugs. During the experimental period, general signs(such as grip strength, automatic activity, vertigo time, and pain threshold), blood rheology, and blood flow in the tail microcirculation were measured. Flow cytometry was employed to detect the positive cells of intercellular cell adhesion molecule 1(ICAM-1/CD54) and vascular cell adhesion molecule 1(VCAM-1/CD106) in the peripheral blood and the Ca~(2+) fluorescence intensity. Enzyme-linked immunosorbent assay was employed to measure the levels of ICAM-1, VCAM-1, platelet endothelial cell adhesion molecule 1(PECAM-1/CD31), endothelin 1(ET-1), thromboxane A2(TXA2), prostaglandin I2(PGI2), nitric oxide(NO), interleukin-1β(IL-1β), C-reactive protein(CRP), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), and lipopolysaccharide(LPS). Hematoxylin-eosin, Masson, and Gomori's aldehyde-fuchsin staining were used to observe the pathological and morphological changes in rat colon and aorta. Fluorescence quantitative PCR was conducted to determine the mRNA levels of Toll-like receptor 4(TLR4), myeloid differentiation factor 88(MyD88), nuclear factor-kappaB(NF-κB), ICAM-1, and VCAM-1 in the aortic tissue. Western blot was employed to determine the protein levels of occludin and claudin-1 in the colon tissue and ICAM-1, VCAM-1, and IL-6 in the aortic tissue. Immunohistochemistry and immunofluorescence were employed to detect the expression of TLR4 and NF-κB in the aortic tissue. The results showed that Dendrobii Officinalis Caulis water extract significantly improved the general signs, reduced the whole blood viscosity, whole blood reducing viscosity, and whole blood flow resistance, increased the blood flow of tail microcirculation, reduced the rates of CD54, CD106-positive cells in peripheral blood, and attenuated the blood flow obstruction in the rat model of hyperviscosity. The water extract significantly lowered the serum levels of ICAM-1, VCAM-1, PECAM-1, and ET-1, elevated the PGI2 and NO level, and alleviated vascular endothelial injury. In addition, the water extract decreased the content of IL-1β, TNF-α, IL-6, and CRP in the serum and reduced the vascular inflammatory injury. Moreover, the Dendrobii Officinalis Caulis water extract improved the morphology of colon and aortic tissues, promoted the expression of occludin and claudin-1 in the colon, and down-regulated the mRNA levels of TLR4, MyD88, NF-κB, ICAM-1, and VCAM-1 as well as the protein levels of TLR4, NF-κB, and IL-6 in the aortic tissue. In conclusion, the results suggest that the Dendrobii Officinalis Caulis water extract may regulate the endothelial inflammatory injury via the TLR4/NF-κB/ICAM-1 pathway, thereby ameliorating hyperviscosity.

Objectives: This study aims to develop a robust predictive model for survival in AML patients undergoing allo-HSCT., Methods: It was performed a retrospective analysis of 336 AML patients who underwent allo-HSCT at Peking University First Hospital between September 2003 and March 2023. Univariable and multivariable Cox regression analyses were conducted to determine hazard ratios (HR) for overall survival. A predictive model was developed based on multivariable analysis results. Internal validation was carried out through bootstrap resampling, and the model's performance was assessed using the Concordance Index (C-index), Receiver Operating Characteristics (ROC) curve, calibration plots, and Decision Curve Analysis (DCA)., Results: Our prognostic model, which includes age, disease stage, donor/recipient gender, mononuclear cell counts, and the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI), effectively stratified patients into low-risk and high-risk groups. The two groups showed significant differences in overall survival (P<0.0001), disease-free survival (P<0.0001), non-relapse mortality (NRM) (P<0.0001), and relapse rates (P=0.08). The model achieved a C-index of 0.71. Calibration plots and DCA confirmed strong alignment between predicted and observed outcomes. Subgroup analysis revealed that overall survival was significantly lower in the high-risk group compared to the low-risk group in both measurable residual disease (MRD) negative and MRD positive subgroups (P=0.015 for both)., Conclusion: The developed prognostic model, which integrates comprehensive disease and patient characteristics, enhances risk stratification for AML patients undergoing allo-HSCT. This model effectively stratifies risk in both MRD-negative and MRD-positive subgroups and may facilitate more informed MRD-based treatment decisions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Production and hosting by Elsevier B.V.)

Ethnopharmacological Relevance: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with reproductive dysfunction and metabolic abnormalities, particularly characterized by insulin resistance and chronic low-grade inflammation. Multiple clinical studies have clearly demonstrated the significant efficacy and safety of the combination of Bailing capsules (BL) in the treatment of PCOS, but its pharmacological effects and mechanisms still require further study., Aim of the Study: To evaluate the effect of BL on improving PCOS in mice and explore the mechanism., Methods: In this study, Dehydroepiandrosterone (DHEA) injection was administered alone and in combination with a high-fat and high-sugar diet to induce PCOS-like mouse. They were randomly divided into five groups: normal group (N), PCOS group (P), Bailing capsule low-dose group (BL-L), Bailing capsule high-dose group (BL-H) and Metformin + Daine-35 group (M + D). Firstly, the effects of BL on ovarian lesions, serum hormone levels, HOMA-IR, intestinal barrier function, inflammation levels, along with the expression of IRS1, PI3K, AKT, TLR4, Myd88, NF-κB p65, TNF-α, IL-6, and Occludin of the ovary, liver and colon were investigated. Finally, the composition of the gut microbiome of fecal was tested., Results: The administration of BL significantly reduced body weight, improved hormone levels, improved IR, and attenuated pathological damage to ovarian tissues, up-regulated the expression of IRS1, PI3K, and AKT in liver. It also decreased serum LPS, TNF-α, and IL-6 levels, while downregulating the expression of Myd88, TLR4, and NF-κB p65. Additionally, BL improved intestinal barrier damage and upregulated the expression of Occludin. Interestingly, the abundance of norank&#95;f&#95;&#95;Muribaculacea and Lactobacillus was down-regulated, while the abundance of Akkermansia was significantly up-regulated., Conclusion: The results of the study showed that BL exerts a treatment PCOS effect, which may be related to the modulation of the gut microbiota, the improvement of insulin resistance and the intestinal-derived LPS-TLR4 inflammatory pathway. Our research will provide a theoretical basis for the clinical treatment of PCOS., Competing Interests: Declaration of competing interest The authors declare that none of the work reported in this study could have been influenced by any known competing financial interests or personal relationships., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The development of gut-liver axis metabolic immune crosstalk is intimately associated with intestinal barrier disorder, intestinal SCFAs-Th17/Treg immunological imbalance, and disorders of the gut microbiota. Prior research has discovered that Dendrobium officinale National Herbal Drink (NHD), a traditional Chinese medicine drink with enhanced immunity, may enhance the immunological response in animals with impaired immune systems brought on by cyclophosphamide by repairing intestinal barrier function and controlling turbulence in the gut microbiota. However, whether NHD can further improve the gut-liver axis metabolic immune crosstalk and its related mechanisms need to be systematically studied., Objectives: The purpose of this study is to clarify the function and mechanism of NHD in enhancing the gut-liver axis metabolic immunological crosstalk brought on by excessive alcohol intake., Methods: In this work, we set up a mouse model to analyze the metabolic and immunological crosstalk involving the gut-liver axis across 7 weeks of continuous, excessive drinking. At the same time, high and low doses (20,10 ml/kg) of NHD were given by gavage. The effect of NHD on improving the metabolism of gut-liver axis was evaluated by blood lipid, liver lipid deposition, liver function and intestinal pathophysiology. By measuring serum immunological indices, intestinal barrier, and intestinal immune barrier, the impact of NHD on enhancing immune and intestinal barrier function was assessed. Furthermore, immunohistochemistry, immunofluorescence, 16S rRNA, Western blot, q-PCR and other methods were used to detect gut microbiota, SCFAs-GPR41/43 pathway, intestinal Th17/Treg immune cells and PPAR-α-NPC1L1/SREBP1 pathway to elucidate the mechanism by which NHD enhances the gut-liver axis' metabolic immune crosstalk., Results: Our study demonstrated that NHD has the potential to improve the pathophysiological damage caused by gut-liver axis in model mice. NHD also ameliorated the disorder of lipid metabolism. In addition, it regulated the levels of peripheral blood T cell immunity and serum immune factors. And NHD can restore intestinal mechanical and immune barrier damage. NHD has a favorable impact on the quantity of beneficial bacteria, including uncultured&#95;bacterium&#95;g&#95;&#95;norank&#95;f&#95;&#95;muribaculacea and uncultured&#95;bacterium&#95;g&#95;&#95;Turicibacter. Additionally, it raised the model mice's levels of SCFAs (n-butyric acid, isovaleric acid, etc.). This resulted in the promotion of intestinal GPR41/43-ERK1/2 expression and the reshaping of intestinal CD4 + T cell Th17/Treg homeostasis. As a consequence, colon IL-22 and IL-10 levels increased, while colon IL-17A levels decreased. Lastly, NHD raised the amount of intestinal IAP/LPS, regulated the development of PPAR-α-NPC1L1/SREBP1 pathway in gut-liver axis, and improve lipid metabolism disorder., Conclusions: Our study found that NHD can improve the gut-liver axis metabolic immune crosstalk in model mice caused by excessive drinking. The mechanism might be connected to how NHD controls gut microbiota disorders in model mice, the activation of intestinal SCFAs-GPR41/43 pathway, the remodeling of Th17/Treg immune homeostasis of intestinal CD4 + T cells, the improvement of IAP/LPS abnormality, and further mediating the PPAR-α-NPC1L1/SREBP1 pathway of lipid metabolism in gut-liver axis., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: Galectins (GALs) are a family of mammalian sugar-binding proteins specific for β-galactosides. Our previous studies have shown that the larval development of the diamondback moth (Plutella xylostella) is significantly disturbed when fed with recombinant mammalian galectin 1 (GAL1) derived from Escherichia coli. To further explore its applicability, two GAL1-overexpressed Arabidopsis [GAL1-Arabidopsis (whole plant) and GAL1-Arabidopsis-vas (vascular bundle-specific)] lines were established for insecticidal activity and mechanism studies., Results: The expression level of GAL1 in transgenic Arabidopsis is 1-0.5% (GAL1-Arabidopsis) and 0.08-0.01% (GAL1-Arabidopsis-vas) of total leaf soluble protein. Survival, body weight, and food consumption significantly decreased in a time-dependent manner in P. xylostella larvae (with chewing mouthparts) fed on GAL1-Arabidopsis. The mortality of Kolla paulula (with piercing-sucking mouthparts and xylem feeder) fed on GAL1-Arabidopsis-vas was also significantly higher than that fed on wild-type Arabidopsis (WT-Arabidopsis), but was lower than that fed on GAL1-Arabidopsis. The histochemical structure and results of immunostaining suggested that the binding of GAL1 to the midgut epithelium of P. xylostella fed on GAL1-Arabidopsis was dose- and time-dependent. Ultrastructural studies further showed the disruption of microvilli, abnormalities in epithelial cells, and fragments of the peritrophic membrane (PM) in P. xylostella larvae fed on GAL1-Arabidopsis., Conclusion: The insecticidal mechanism of GAL1 involves interference with PM integrity and suggests that GAL1 is a potential candidate for bioinsecticide development. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

The discovery of novel antitumor agents derived from natural plants is a principal objective of anticancer drug research. Frankincense, a widely recognized natural antitumor medicine, has undergone a systematic review encompassing its species, chemical constituents, and diverse pharmacological activities and mechanisms. The different species of frankincense include Boswellia serrata, Somali frankincense, Boswellia frereana, and Boswellia arabica. Various frankincense extracts and compounds exhibit antitumor, anti-inflammatory, and hepatoprotective properties and antioxidation, memory enhancement, and immunological regulation capabilities. They also have comprehensive effects on regulating flora. Frankincense and its principal chemical constituents have demonstrated promising chemoprophylactic and therapeutic abilities against tumors. This review provides a systematic summary of the mechanism of action underlying the antitumor effects of frankincense and its major constituents, thus laying the foundations for developing effective tumor-combating targets., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

This study aimed to investigate the effects and potential mechanism of Polygonati Rhizoma aqueous extract on chronic obstructive pulmonary disease(COPD) in rats. Forty-eight Sprague-Dawley rats were randomly assigned to the normal, model,Yupingfeng Granules(1. 5 g·kg~(-1)), and low-, medium-, and high-dose(0. 25, 0. 5, and 1 g·kg~(-1), respectively) Polygonati Rhizoma aqueous extract groups. The rat model of COPD was established by cigarette smoke inhalation for 8 weeks, and then the modeled rats received corresponding treatment for 4 weeks. The grip strength and fecal moisture content were measured, and the lung index was calculated. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the levels of interleukin(IL)-6 and tumor necrosis factor(TNF)-α in the lung tissue. Hematoxylin-eosin(HE) staining and Masson staining were performed to assess the pathological changes in the lung tissue. Flow cytometry was used to analyze T lymphocytes and their subpopulations in the peripheral blood, and the immunofluorescence assay and Western blot were employed to measure the protein levels of Toll-like receptor 4(TLR4), phosphorylated nuclear factor-kappaB(p-NF-κB), NF-κB, phosphorylated inhibitory kappa B-α(p-IκBα), IκBα, IL-6,and TNF-α in the lung tissue. The results indicated that the treatment with Polygonati Rhizoma aqueous extract significantly reduced the fecal moisture content, enhanced the grip strength, and inhibited inflammatory infiltration and fibrosis in the lung tissue. The treatment increased the Th/Tc ratio and Th cell proportion and decreased the Tc cell proportion in the peripheral blood. Furthermore,the treatment down-regulated the expression levels of TLR4, IL-6, and TNF-α and the p-NF-κB/NF-κB and p-IκBα/IκBα ratios in the lung tissue. In conclusion, Polygonati Rhizoma aqueous extract can ameliorate lung tissue damage in the rat model of COPD by inhibiting the TLR4/NF-κB signaling pathway and the production of inflammatory mediators.

Ethnopharmacological Relevance: Pitongshu (PTS) is a clinically effective empirical formula for the treatment of FD. The efficacy and safety of PTS have been demonstrated in randomized, controlled, double-blind trials, but there is a lack of understanding of the systematic evaluation of the efficacy of PTS and its material basis., Objective: To investigate the efficacy of PTS in Functional dyspepsia (FD) mice and possible Q-markers., Method: In this study, we used "irregular feeding + chronic unpredictable chronic stimulation" to establish a mice model of FD with hepatogastric disharmony. The efficacy of PTS was assessed from hair condition, behavioral, pain, gastrointestinal function, and serum 5-HT, GAS, MTL levels in mice by instillation of different doses of PTS. In addition, the composition of drugs in blood was analyzed by LC-QTOF-MS and potential Q-markers were selected by combining network pharmacology, molecular docking and actual content., Result: Our study showed that different doses of PTS increased pain threshold and writhing latency, decreased the number of writhings, increased gastric emptying rate and small intestinal propulsion rate, decreased total acidity of gastric contents and gastric acid secretion, and increased serum levels of 5-HT, GAS, and MTL in mice to different degrees. Enrichment analysis showed that PTS may be anti-FD through multiple pathways such as Serotonergic synapse, thyroid hormone signaling pathway, cholinergic synapse, and dopaminergic synapse. In addition, potential active ingredient substances were explored by LC-QTOF-MS combined with bioinformatics. Combined with the actual contentselected six constituents, hesperidin, neohesperidin, naringin, paeoniflorin, magnolol and honokiol, possible as Q-markers., Conclusion: PTS may exert its anti-FD effects through multi-component, multi-target and multi-pathway". Constituents, hesperidin, neohesperidin, naringin, paeoniflorin, magnolol and honokiol may be the Q-markers of its anti-FD effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Low immunity and sleep disorders are prevalent suboptimal health conditions in contemporary populations, which render them susceptible to the infiltration of pathogenic factors. LJC, which has a long history in traditional Chinese medicine for nourishing the Yin and blood and calming the mind, is obtained by modifying Qiyuan paste. Dendrobium officinale Kimura et Migo has been shown to improve the immune function in sleep-deprived mice. In this study, based on the traditional Chinese medicine theory, LJC was prepared by adding D. officinale Kimura et Migo to Qiyuan paste decoction., Methods: Indicators of Yin deficiency syndrome, such as back temperature and grip strength, were measured in each group of mice; furthermore, behavioral tests and pentobarbital sodium-induced sleep tests were performed. An automatic biochemical analyzer, enzyme-linked immunosorbent assay kit, and other methods were used to determine routine blood parameters, serum immunoglobulin (IgG, IgA, and IgM), cont (C3, C4), acid phosphatase (ACP) and lactate dehydrogenase (LDH) levels in the spleen, serum hemolysin, and delayed-type hypersensitivity (DTH) levels. In addition, serum levels of γ-aminobutyric acid (GABA) and glutamate (Glu) were detected using high-performance liquid chromatography (HPLC). Hematoxylin-eosin staining and Nissl staining were used to assess the histological alterations in the hypothalamus tissue. Western blot and immunohistochemistry were used to detect the expressions of the GABA pathway proteins GABRA1, GAD, GAT1, and GABAT1 and those of CD 4+ and CD 8+ proteins in the thymus and spleen tissues., Results: The findings indicated that LJC prolonged the sleep duration, improved the pathological changes in the hippocampus, effectively upregulated the GABA content in the serum of mice, downregulated the Glu content and Glu/GABA ratio, enhanced the expressions of GABRA1, GAT1, and GAD, and decreased the expression of GABAT1 to assuage sleep disorders. Importantly, LJC alleviated the damage to the thymus and spleen tissues in the model mice and enhanced the activities of ACP and LDH in the spleen of the immunocompromised mice. Moreover, serum hemolysin levels and serum IgG, IgA, and IgM levels increased after LJC administration, which manifested as increased CD 4+ content, decreased CD 8+ content, and enhanced DTH response. In addition, LJC significantly increased the levels of complement C3 and C4, increased the number of white blood cells and lymphocytes, and decreased the percentage of neutrophils in the blood., Conclusions: LJC can lead to improvements in immunocompromised mice models with insufficient sleep. The underlying mechanism may involve regulation of the GABA/Glu content and the expression levels of GABA metabolism pathway-related proteins in the brain of mice, enhancing their specific and nonspecific immune functions., (© 2024. The Author(s).)

Objectives: To elucidate the therapeutic effects and mechanisms of Atractylodes macrocephala extract crystallize (BZEP) and BZEP self-microemulsion (BZEPWR) on metabolic dysfunction-associated fatty liver disease (MAFLD) induced by "high sugar, high fat, and excessive alcohol consumption" based on the gut-liver axis HDL/LPS signaling pathway., Methods: In this study, BZEP and BZEPWR were obtained via isolation, purification, and microemulsification. Furthermore, an anthropomorphic MAFLD rat model of "high sugar, high fat, and excessive alcohol consumption" was established. The therapeutic effects of BZEPWR and BZEP on the model rats were evaluated in terms of liver function, lipid metabolism (especially HDL-C), serum antioxidant indexes, and liver and intestinal pathophysiology. To determine the lipoproteins in the serum sample, the amplitudes of a plurality of NMR spectra were derived via deconvolution of the composite methyl signal envelope to yield HDL-C subclass concentrations. The changes in intestinal flora were detected via 16 S rRNA gene sequencing. In addition, the gut-liver axis HDL/LPS signaling pathway was validated using immunohistochemistry, immunofluorescence, and western blot., Results: The findings established that BZEPWR and BZEP improved animal signs, serum levels of liver enzymes (ALT and AST), lipid metabolism (TC, TG, HDL-C, and LDL-C), and antioxidant indexes (GSH, SOD, and ROS). In addition, pathological damage to the liver, colon, and ileum was ameliorated, and the intestinal barrier function of the model rats was restored. At the genus level, BZEPWR and BZEP exerted positive effects on beneficial bacteria, such as Lactobacillus and norank&#95;f&#95;&#95;Muribaculaceae, and inhibitory effects on harmful bacteria, such as unclassified&#95;f&#95;&#95;Lachnospiraceae and Blautia. Twenty HDL-C subspecies were detected, and their levels were differentially increased in both BZEPWR and BZEP groups, with BZEPWR exhibiting a stronger elevating effect on specific HDL-C subspecies. Also, the gut-liver axis HDL/LPS signaling pathway was studied, which indicated that BZEPWR and BZEP significantly increased the expressions of ABCA1, LXR, occludin, and claudin-1 proteins in the gut and serum levels of HDL-C. Concomitantly, the levels of LPS in the serum and TLR4, Myd88, and NF-κB proteins in the liver were decreased., Conclusion: BZEPWR and BZEP exert restorative and reversal effects on the pathophysiological damage to the gut-liver axis in MAFLD rats, and the therapeutic mechanism may be related to the regulation of the intestinal flora and the HDL/LPS signaling pathway., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

This study aimed to evaluate the effectiveness of the endometrial receptivity array (ERA), endometrial immune profiling, and a combination of both in improving the pregnancy outcomes for multiple implantation failure patients. According to patients' willingness, 1429 women who incurred at least two or more consecutive implantation failures in IVF/ICSI treatment opted for frozen embryo transfer and were divided into four groups: 'No test', 'Immune Profiling', 'ERA' and 'ERA+ Immune Profiling'. Women in three test groups underwent timed endometrial biopsy for ERA, immune profiling, a combination of both. We observed the overall incidence rates of the displaced window of implantation (WOI) and endometrial immune dysregulation were 75.14% and 79.29%, respectively. After 1:1 propensity score matching (PSM), our data revealed that the 'ERA' and 'ERA + Immune Profiling' groups demonstrated significantly higher rates of biochemical, clinical, ongoing pregnancy, and implantation compared to the 'No test' group (p < 0.01). The 'Immune Profiling' group showed a higher implantation rate compared to 'No test' group (p < 0.05). Furthermore, when comparing three test groups, the 'ERA + Immune Profiling' group exhibited notably higher rates of clinical and ongoing pregnancy compared to the 'Immune Profiling' group (p < 0.017). However, there was no association between endometrial immune profiling and ERA phases, and their results did not differ between embryo implantation and non-implantation in these patients. Our findings underline the increased implantation rates by use of ERA and endometrial immune profiling in patients with multiple implantation failure, either individually or corporately. Moreover, a combination of both could improve their pregnancy outcomes significantly., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Laryngeal paraganglioma (LP) is an exceptionally rare neuroendocrine tumor, underscoring importance of accurate identification to preclude misdiagnoses. In this review, we presented two typical misdiagnosed LPs, and offered reviews of LP cases reported over the preceding decade and all documented misdiagnosed LP cases. Furthermore, we systematically investigated the underlying causes of misdiagnosis and elucidated key points for effective differentiation. A retrospective analysis of 28 LP cases revealed a predominant occurrence in middle-aged women, with an average history of 25.1 months. Through an analysis of all misdiagnosed cases (n = 37), supraglottic LPs were frequently misidentified as laryngeal carcinomas and vascular tumors, while subglottic LPs were often misdiagnosed as thyroid cancers. And the occurrence of misdiagnosis resulted in delayed and inappropriate treatments, contributing to the deterioration of LP patients (14 cases, 37.8%). In conclusion, this review endeavored to heighten awareness of LPs, with the ultimate goal of advancing diagnostic precision and enhancing patient outcomes., (© 2024 Wiley Periodicals LLC.)

Background: Dendrobium officinale flowers (DOF) have the effects of antiaging and nourishing yin, but it lacks pharmacological research on skin aging., Objective: Confirming the role of DOF in delaying skin aging based on the "in vitro animal-human" model., Methods: In this experiment, three kinds of free radical scavenging experiments in vitro, D-galactose-induced aging mouse model, and human antiaging efficacy test were used to test whether DOF can improve skin aging through anti-oxidation., Results: In vitro experiment shows that DOF has certain scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical, hydroxyl free radical, and superoxide free radical, and its IC 50 is 0.2090 μg/mL, 15.020, and 1.217 mg/mL respectively. DOF can enhance the activities of T-AOC, SOD, CAT, and GSH Px in the serum of aging mice, increase the content of GSH, and reduce the content of MDA when administered with DOF of 1.0, 2.0, and 4.0 g/kg for 6 weeks. In addition, it can enhance the activity of SOD in the skin of aging mice, increase the content of Hyp, and decrease the content of MDA, activated Keap1/Nrf2 pathway in the skin of aging mice. Applying DOF with a concentration of 0.2 g/mL on the face for 8 weeks can significantly improve the skin water score and elasticity value, reduce facial wrinkles, pores, acne, and UV spots, and improve the facial brown spots and roughness., Conclusion: DOF can significantly improve skin aging caused by oxidative stress, and its mechanism may be related to scavenging free radicals in the body and improving skin quality., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Platinum (Pt)-based alloys have received considerable attention due to their compositional variability and unique electrochemical properties. However, homogeneous element distribution at the nanoscale, which is beneficial to various electrocatalytic reactions, is still a great challenge. Herein, a universal approach is proposed to synthesize homogeneously alloyed and size-tunable Pt-based nanoflowers utilizing high gravity technology. Owing to the significant intensification of micro-mixing and mass transfer in unique high gravity shearing surroundings, five typical binary/ternary Pt-based nanoflowers are instantaneously achieved at room temperature. As a proof-of-concept, as-synthesized Platinum-Silver nanoflowers (PtAg NFs) demonstrate excellent catalytic performance and anti-CO poisoning ability for anodic methanol oxidation reaction with high mass activity of 1830 mA mg Pt -1 , 3.5 and 3.2 times higher than those of conventional beaker products and commercial Pt/C, respectively. The experiment in combination with theory calculations suggest that the enhanced performance is due to additional electronic transmission and optimized d-band center of Pt caused by high alloying degree., (© 2023 Wiley‐VCH GmbH.)

The potential of urine-derived stem cells (USCs) for tissue engineering and regenerative medicine has attracted much attention during the last few decades. However, it has been suggested that the effects of the USCs may be endowed by their paracrine extracellular vesicles (EVs) rather than their differentiation. Compared with the USCs, the USC-EVs can cross the barriers more easily and safely, and their inclusions may mediate intercellular communication and promote the tissue repair. This article has summarized the current knowledge and applications about the USC-EVs in tissue engineering and regenerative medicine, and discussed the prospects and challenges for using them as an alternative to cell therapy. Impact statement Urine-derived stem cells (USCs) represent a newly discovered type of stem cells, and studies have proved that the beneficial effects of the USCs may be manifested through their paracrine extracellular vesicles (EVs) rather than through their own differentiation, which opens up new avenues for tissue engineering and regenerative medicine strategies. Therefore, this review aims to summarize the latest research progress and potential clinical applications of the USC-EVs, highlighting the promising potential of the USC-EVs as a therapeutic option in kidney regeneration, genital regeneration, nerve regeneration, bone and cartilage regeneration, and wound healing.

Objective: To investigate the depersonalization status and to analyze the effect of workplace incivility perception, intrusive rumination and fear of negative evaluation on depersonalization in clinical nurses. Methods: In May 2019, 10 cities were selected as sampling cities by the method of grabbing random ball in Henan Province and Fujian Province. Using the stratified sampling, clinical nurses were selected as the research objects for a questionnaire survey in 22 tertiary hospitals and 23 secondary hospitals, included 1200 nurses. A total of 1200 questionnaires were issued and collected, and 1159 valid questionnaires were collected with effective recovery of 96.6%. Clinical nurses were investigated by Workplace Incivility Scale, Event Related Rumination Inventory, Fear of Negative Evaluation Scale, Maslach Burnout Inventory-General Survey. The demographic characteristics of nurses' depersonalization were compared and analyzed with t test and single factor analysis of variance. The influence mechanism of workplace incivility perception, intrusive rumination and fear of negative evaluation on depersonalization was analyzed with Bootstrap. Results: Depersonalization scores were (9.3±2.6) points, 467 of those had depersonalization symptoms in clinical nurses (40.3%). The scores of depersonalization of those with <3 years of service [ (10.5±2.9) points] was higher than those with 3-10 years [ (9.1±2.8) points] and 11-31 years [ (9.0±2.9) points]. The scores of depersonalization of those with monthly earning of <3000 yuan [ (10.1±2.8) points] was higher than those with 3000-7999 yuan [ (8.4±2.7) points] and 8000-12000 yuan [ (8.0±2.9) points]. The scores of depersonalization of clinical nurses in surgical departments [ (10.0±2.9) points] was higher than those in non-surgical departments [ (8.7±2.6) points]. The scores of depersonalization of clinical nurses in tertiary hospitals [ (10.0±2.7) points] was higher than those in secondary hospitals [ (8.6±2.8) points]. The differences were statistically significant ( P <0.05). Workplace incivility perception affected depersonalization through the single mediating role of intrusive rumination, fear of negative evaluation and the chain mediating role of intrusive rumination and fear of negative evaluation ( β =0.16, 0.17, 0.07, 95% CI : 0.15-0.20, 0.15-0.21, 0.03-0.09, P <0.05) . Conclusion: Workplace incivility perception directly or through the independent mediating effects of intrusive rumination or fear of negative evaluation, and the chain mediating effects of intrusive rumination and fear of negative evaluation influences the depersonalization of clinical nurses.

Aim: Atractylodes macrocephala Rhizome (AM) has been used to treat hyperlipidemia for centuries, but its functional components and mechanisms are not clear. This research aimed to investigate the active components in AM and the mechanisms that underlie its anti-hyperlipidemia effect., Methods: SD rats were fed a high-sucrose high-fat diet in conjunction with alcohol (HSHFDAC) along with different AM extracts (AMW, AMO, AME, and AMP) for 4 weeks. AM's active components were analyzed using multiple databases, and their mechanisms were explored through network pharmacology. The relationship between AM's effect of enhancing serum HDL-c and regulating the expression of reverse cholesterol transport (RCT)-related proteins (Apo-A1, LCAT, and SR-BI) was further validated in the HSHFDAC-induced hyperlipidemic rats. The kidney and liver functions of the rats were measured to evaluate the safety of AM., Results: AMO, mainly comprised of volatile and liposoluble components, contributed the most significant anti-hyperlipidemia effect among the four extracts obtained from AM, significantly improving the blood lipid profile. Network pharmacology analysis also suggested that volatile and liposoluble components, comprise AM's main active components and they might act on signaling pathways associated with elevated HDL-c. Validation experiments found that AMO substantially and dose-dependently increased HDL-c levels, upregulated the expression of Apo-A1, SR-BI, and LCAT, improved the pathological changes in the kidney and liver, and significantly reduced the serum creatinine levels in rats with hyperlipidemia., Conclusion: The main anti-hyperlipidemia active components of AM are its volatile and liposoluble components, which may enhance serum HDL-c by increasing the expression of the RCT-related proteins Apo-A1, LCAT, and SR-BI., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objective: To understand the association between vitamin D level and grip strength in people aged ≥50 years in Shanghai. Methods: Data were obtained from the WHO's Study on Global Ageing and Adult Health in Shanghai during 2018-2019. Logistic regression model was used to analyze the association between vitamin D level and grip strength, and a stratified analysis was conducted for different gender, age and dairy product intake groups. Restricted cubic spline was used to evaluate the dose-response association between vitamin D level and low grip strength. Results: A total of 4 391 participants were included in the study, including 2 054 men (46.8%), with an average age of (67.02±8.81) years. And 1 421 individuals (32.4%) had low grip strength; 1 533 individuals (34.9%) had vitamin D deficiency, and 401 individuals (9.1%) had vitamin D deficiency. After adjusted for confounding factors, the logistic regression results analysis showed that individuals with vitamin D deficiency had a higher risk for low grip strength ( OR =1.41, 95% CI : 1.09-1.83). In men, after adjusting for confounding factors, vitamin D deficiency was positively associated with the risk for low grip strength ( OR =1.67, 95% CI : 1.12-2.50), but there was no significant association between vitamin D level and grip strength in women ( OR =1.30, 95% CI : 0.97-1.74). In age group 60-69 years and ≥80 years, there was significant association between vitamin D deficiency and low grip strength after adjusting for confounding factors ( OR =1.57, 95% CI : 1.05-2.35; OR =2.40, 95% CI : 1.08-5.31). In people who had daily intake of dairy product <250 ml, there was positive association between vitamin D deficiency and low grip strength, but there was no significant association in people who had daily dairy product ≥250 ml after adjusting for confounding factors. The restrictive cubic spline demonstrated that risk of low grip strength might decreased with the increase of vitamin D levels, however, the difference was not significant ( P >0.05). Conclusions: This study demonstrated that there is association between vitamin D level and grip strength. People with vitamin D deficiency have higher risk for low grip strength.

Endothelial dysfunction is a common complication of diabetes mellitus (DM) and contributes to the high incidence and mortality of cardiovascular and cerebrovascular diseases. Aberrant epigenetic regulation under diabetic conditions, including histone modifications, DNA methylation, and non-coding RNAs (ncRNAs) play key roles in the initiation and progression of diabetic vascular complications. ASH2L, a H3K4me3 regulator, triggers genetic transcription, which is critical for physiological and pathogenic processes. In this study we investigated the role of ASH2L in mediating diabetic endothelial dysfunction. We showed that ASH2L expression was significantly elevated in vascular tissues from diabetic db/db mice and in rat aortic endothelial cells (RAECs) treated with high glucose medium (11 and 22 mM). Knockdown of ASH2L in RAECs markedly inhibited the deteriorating effects of high glucose, characterized by reduced oxidative stress and inflammatory responses. Deletion of endothelial ASH2L in db/db mice by injection of an adeno-associated virus (AAV)-endothelial specific system carrying shRNA against Ash2l (AAV-shAsh2l) restored the impaired endothelium-dependent relaxations, and ameliorated DM-induced vascular dysfunction. We revealed that ASH2L expression activated reductase STEAP4 transcription in vitro and in vivo, which consequently elevated Cu(I) transportation into ECs by the copper transporter CTR1. Excess copper produced by STEAP4-mediated copper uptake triggered oxidative stress and inflammatory responses, resulting in endothelial dysfunction. Our results demonstrate that hyperglycemia triggered ASH2L-STEAP4 axis contributes to diabetic endothelial dysfunction by modulating copper uptake into ECs and highlight the therapeutic potential of blocking the endothelial ASH2L in the pathogenesis of diabetic vascular complications., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Objective: To investigate dietary patterns of individuals aged ≥50 in Shanghai and analyze their association with frailty. Methods: Using data from the third wave of the Study on Global Ageing and Adult Health in Shanghai conducted between 2018 and 2019. We collected the frequency and average intake of food by the food frequency questionnaire. Factor analysis was used to extract dietary patterns, and a frailty index was constructed using the ratio of the cumulative total score of health deficits to 35 health-related variables considered. We used an ordinal multinomial logistic regression model to analyze the association between dietary patterns and frailty. Results: A total of 3 274 participants aged (67.9±9.2) years were included in the study, including 1 971 (60.2%) men and 1 303 (39.8%) women. We extracted four dietary patterns: high-protein-nuts pattern, potato-bean-vegetable-fruit pattern, poultry-meat pattern, and high-oil-salt pattern. After adjusting for confounding factors, the logistic regression analysis showed that compared with the high-oil-salt pattern, the high-protein-nuts pattern was negatively associated with the risk of higher frailty ( OR =0.743, 95% CI : 0.580-0.951). We did not find an association between dietary patterns and frailty between the different gender groups. In the age group 50-64, the high-protein-nuts and potato-bean-vegetable-fruit patterns were negatively correlated with a higher degree of frailty than the high-oil-salt pattern. In the low-level physical activity group, the high-protein-nuts pattern was negatively correlated with a higher degree of frailty than the high-oil-salt pattern ( OR =0.509, 95% CI : 0.361-0.720). However, we found no significant effect of the high-protein nuts pattern, potato-bean-vegetable-fruit pattern, and poultry-meat pattern on the risk of higher frailty compared to the high-oil-salt pattern in the moderate to high level of physical activity group. Conclusions: Compared to the high-oil-salt pattern, dietary patterns with a higher intake of high-protein nuts, potatoes, legumes, and fruits and vegetables might be associated with a lower risk of higher frailty in residents aged 50-64 years of age than with a high oil and salt pattern. At the same time, it may have a more significant protective effect in people with lower physical activity levels. It is suggested that a diet rich in high-protein foods, nuts, potatoes, beans, vegetables, and fruits may help reduce and delay the risk of frailty.

Adhesion G protein-coupled receptors (aGPCRs) are evolutionarily ancient receptors involved in a variety of physiological and pathophysiological processes. Modulators of aGPCR, particularly antagonists, hold therapeutic promise for diseases like cancer and immune and neurological disorders. Hindered by the inactive state structural information, our understanding of antagonist development and aGPCR activation faces challenges. Here, we report the cryo-electron microscopy structures of human CD97, a prototypical aGPCR that plays crucial roles in immune system, in its inactive apo and G13-bound fully active states. Compared with other family GPCRs, CD97 adopts a compact inactive conformation with a constrained ligand pocket. Activation induces significant conformational changes for both extracellular and intracellular sides, creating larger cavities for Stachel sequence binding and G13 engagement. Integrated with functional and metadynamics analyses, our study provides significant mechanistic insights into the activation and signaling of aGPCRs, paving the way for future drug discovery efforts., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Two-dimensional (2D) MOFs exhibit unique periodicity in surface structures and thus have attracted much interest in the fields of catalysis, energy, and sensors. However, the expanded production scale of 2D MOFs had remained a great challenge in most previous studies. Herein, a controllable and efficient crystallization method for synthesizing 2D MOF nanosheets using high-gravity reactive precipitation is proposed, significantly improving heterogeneous catalysis efficiency. The two-dimensional ZIF-L nanosheets prepared in a rotating packed bed (RPB) reactor show a smaller lateral and lamellar thickness and a higher BET surface area compared to ZIF-L nanosheets prepared in a conventional stirred tank reactor (STR), with a greatly shortened reaction time. Applying the ZIF-L-RPB nanosheets as a catalyst, the catalytic Knoevenagel condensation as a probe reaction displays a high conversion rate of benzaldehyde (99.3%) within 2 h at room temperature, greatly exceeding that displayed by ZIF-L-STR and other reported catalysts. Furthermore, ZIL-L-RPB nanosheets of only 0.2 wt% enhanced the catalytic activity for the glycolysis of poly(ethylene terephthalate) (PET) with a PET conversion and a monomer yield of 90% in a short period of 15 min at 195 °C and almost completely depolymerized PET with a monomer yield of 94% in 30 min, which was far above that achieved by ZIL-L-STR. These results indicate the promising prospects of a high-gravity reactive precipitation strategy with precise size control in an economical way to prepare high-activity 2D MOF nanosheets for a wide range of heterogeneous catalysis.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, and the development of novel therapeutic strategies for HNSCC requires a profound understanding of tumor cells and the tumor microenvironment (TME). Additionally, HNSCC has a poor prognosis, necessitating the use of genetic markers for predicting clinical outcomes in HNSCC. In this study, we performed single-cell sequencing analysis on tumor tissues from seven HNSCC patients, along with one adjacent normal tissue. Firstly, the analysis of epithelial cell clusters revealed two clusters of malignant epithelial cells, characterized by unique gene expression patterns and dysregulated signaling pathways compared to normal epithelial cells. Secondly, the examination of the TME unveiled extensive crosstalk between fibroblasts and malignant epithelial cells, potentially mediated through ligand-receptor interactions such as COL1A1-SDC1, COL1A1-CD44, and COL1A2-SDC1. Furthermore, transcriptional heterogeneity was observed in immune cells present in the TME, including macrophages and dendritic cells. Finally, leveraging the gene expression profiles of malignant epithelial cells, we developed a prognostic model comprising six genes, which we validated using two independent datasets. These findings shed light on the heterogeneity within HNSCC tumors and the intricate interplay between malignant cells and the TME. Importantly, the developed prognostic model demonstrates high efficacy in predicting the survival outcomes of HNSCC patients., (© 2023 Federation of American Societies for Experimental Biology.)

Aim: This study investigated the molecular action mechanism of a compound herb, also known as the Dendrobium officinale throat-clearing formula (QYF), by using network pharmacology and animal experimental validation methods to treat chronic pharyngitis (CP)., Methods: The active ingredients and disease targets of QYF were determined by searching the Batman-TCM and GeneCards databases. Subsequently, the drug-active ingredient-target and protein-protein interaction networks were constructed, and the core targets were obtained through network topology. The Metascape database was screened, and the core targets were enriched with Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes., Results: In total, 1403 and 241 potential targets for drugs and diseases, respectively, and 81 intersecting targets were yielded. The core targets included TNF, IL-6, and IL-1β, and the core pathways included PI3K-Akt. The QYF treatment group exhibited effectively improved general signs, enhanced anti-inflammatory ability in vitro , reduced serum and tissue expressions of TNF- α, IL-6, and IL-1β inflammatory factors, and decreased blood LPS levels and Myd88, TLR4, PI3K, Akt, and NF-κB p65 protein expression in the tissues., Conclusion: QYF could inhibit LPS production, which regulated the expression of the TLR4/PI3K/Akt/NF-κB signaling pathway to suppress the expression of the related inflammatory factors (i.e., TNF-α, IL-6, and IL-1β), thereby alleviating the CP process., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)