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Jian-Jun Xi,1,* Yu Cao,1,* Ruo-Yu He,1 Jian-Kang Zhang,2 Yan-Mei Zhao,1 Qiao Tong,1 Jian-Feng Bao,1 Yi-Chen Dong,3 Rang-Xiao Zhuang,1 Jin-Song Huang,1 Yongping Chen,4 Shou-Rong Liu1 1Department of Pharmacy, Hangzhou Xixi Hospital Affiliated to Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2School of Medicine, Zhejiang University City College, Hangzhou, People’s Republic of China; 3Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, People’s Republic of China; 4Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Hepatology Institute of Wenzhou Medical University, Wenzhou Key Laboratory of Hepatology, Wenzou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yongping Chen, Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou Key Laboratory of Hepatology, Hepatology Institute of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325025, People’s Republic of China, Email 13505777281@163.com Shou-Rong Liu, Department of Infectious Diseases, Hangzhou Xixi Hospital Affiliated to Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310023, People’s Republic of China, Email lsr85463990@126.comObjective: Silibinin, a natural product extracted from the seeds of the Silybum marianum, is versatile with various pharmacological effects. However, its clinical application was strongly hampered by its low bioavailability and poor water solubility. Herein, a series of glycosylated silibinin derivatives were identified as novel anti-tumor agents.Materials and Methods: The cell viability was evaluated by CCK8 assay. Furthermore, cell apoptosis and cell cycle progression were tested by flow cytometry. In addition, the pharmacokinetic assessment of compound 15 and silibinin through intravenous administration (i.v., 2 mg/kg) to ICR mice were performed.Results: The synthesized compounds showed better water solubilities than silibinin. Among them, compound 15 exhibited inhibitory activity against DU145 cells with IC50 value of 1.37 ± 0.140 μM. Moreover, it arrested cell cycle at G2/M phase and induced apoptosis in DU145 cells. Additionally, compound 15 also displayed longer half-life (T1/2 = 128.3 min) in liver microsomes than that of silibinin (T1/2 = 82.5 min) and appropriate pharmacokinetic parameters in mice.Conclusion: Overall, glycosylation of silibinin would be a valid strategy for the development of silibinin derivatives as anti-tumor agents.Graphical Abstract: Keywords: glycosylation, silibinin derivatives, solubility, anti-proliferative activity

Ya-Fei Qin,1,2 Guang-Ming Li,1,2 Grace Wang,3 De-Jun Kong,1,2 Hong-Da Wang,1,2 Yi-Ming Zhao,1,2 Jing-Peng Hao,4 Hong Qin,1,2 Da-Qing Sun,5 Hao Wang1,2 1Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 3Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; 4Department of Anorectal Surgery, The Second Hospital of Tianjin Medical University, Tianjin, People’s Republic of China; 5Department of Pediatric Surgery, Tianjin Medical University, Tianjin, People’s Republic of ChinaCorrespondence: Da-Qing Sun; Hao Wang Email sdqchris2019@tmu.edu.cn; hwangca272@hotmail.com; hwang1@tmu.edu.cnObjective: This study aimed to discover the ceRNAs network in the pathophysiological development of human colorectal cancer (CRC) and to screen biomarkers for target therapy and prognosis by using integrated bioinformatics analysis.Methods: Data on gene expressions of mRNAs, miRNAs, and circRNAs and clinical information were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases, respectively. Differentially expressed mRNAs (DEmRNAs) were identified by using the DESeq2 package of R software. Functional enrichment analysis was conducted using the ClusterProfiler package of R software. The protein–protein interaction (PPI) network was shown by the STRING website. Survival analysis of hub genes was performed using the survival package in R software. Interactions among hub genes, differentially expressed miRNAs (DEmiRNAs), and differentially expressed circRNAs (DEcircRNAs) were used to construct the ceRNAs network.Results: A total of 412 DEmRNAs including 82 upregulated and 330 downregulated genes were screened out between 473 CRC and 41 normal samples. Two hundred and sixty DEcircRNAs including 253 upregulated and 7 downregulated genes were altered between 23 CRC and 23 normal samples. One hundred and ninety DEmiRNAs including 82 upregulated and 108 downregulated genes were obtained between 450 CRC and 8 normal samples. A ceRNAs and PPI network were successfully constructed, and TIMP1 associated with prognosis was employed.Conclusion: The present study identified a novel circRNAs-miRNAs-mRNA ceRNAs network, which implied that TIMP1 and related miRNAs, circRNAs were potential biomarkers underlying the development of CRC, providing new insights for survival predictions and therapeutic targets.Keywords: circRNAs, colorectal cancer, ceRNAs, TIMP1, bioinformatic analysis

Jian Li,1 Yi-Ming Zhao2 1Department of Neurology, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 2Center for Clinical Epidemiology, Peking University Third Hospital, Beijing, 100191, People’s Republic of ChinaCorrespondence: Jian LiDepartment of Neurology, Peking University Third Hospital, No. 49 Huayuan North Road, Haidian District, Beijing, 100191, People’s Republic of ChinaTel +86 010-82265032Email jlmndr_999@163.comObjective: Magnetic resonance imaging (MRI) of brain white matter demyelination often focuses on demyelinating disease, cerebral small vascular disease diagnosis, and follow-up of cognitive dysfunction for observation. This study explored MRI findings and clinical manifestations of demyelinating degeneration of white matter in young patients.Methods: A total of ninety-four patients with white matter degeneration diagnosed with MRI were enrolled in this study from January 2014 to July 2018. These patients were divided into two groups: the demyelinating disease group (n = 43) and the non-demyelinating disease group (n = 51). The imaging findings and clinical manifestations of the two groups were analyzed.Results: Compared with the non-demyelinating group, there were more female than male patients in the demyelinating group (P < 0.05). In addition, of the 45 patients with an imaging result of “demyelinating degeneration of white matter and multiple sclerosis,” 39 patients met the diagnosis of multiple sclerosis (86.7%). In comparison, of the 49 patients with an imaging result of “demyelinating degeneration of white matter,” only four patients met the diagnosis for demyelinating disease (8.2%).Conclusion: In patients complaining of headaches, dizziness, vertigo, and other symptoms and in the case of an imaging result showing the demyelinating degeneration of white matter alone, the possibility of a clinical diagnosis of a demyelinating disease is minimal.Keywords: young patients, MRI, demyelinating degeneration of white matter, headache, dizziness

Shousi Lu,1,2 Shanshan Guo,1 Pingxiang Xu,1 Xiaorong Li,1 Yuming Zhao,1 Wei Gu,3 Ming Xue1 1Department of Pharmacology, Beijing Laboratory for Biomedical Detection Technology and Instrument, School of Basic Medical Sciences, Capital Medical University, 2China Rehabilitation Research Center, 3Department of Chemistry and Biology, School of Chemical Biology and Pharmaceutical Sciences, Capital Medical University, Beijing, China Abstract: Nitrogen-doped carbon dots (N-CDs) were synthesized using a one-pot hydrothermal treatment with citric acid in the presence of polyethylenimine. Transmission electron microscopy analysis revealed that the N-CDs were monodispersed and quasi-spherical with an average size of ~2.6 nm. Under ultraviolet irradiation the N-CDs emitted a strong blue luminescence with a quantum yield as high as 51%. Moreover, the N-CDs exhibited a negligible cytotoxicity and could be applied as efficient nanoprobes for real-time imaging of live cells. In addition, the ability of the N-CDs to cross the blood–brain barrier (BBB) in a concentration-dependent manner was demonstrated using an in vitro BBB model. Therefore, these PEI-passivated N-CDs with real-time live-cell imaging and BBB-penetration capabilities hold promise for traceable drug delivery to the brain. Keywords: hydrothermal synthesis, nitrogen-doped carbon dots, bioimaging

Wen-Jin Du,1 Ji-Ping Tan,1 Fang Yi,1 Yong-Ming Zou,1 Ya Gao,1 Yi-Ming Zhao,2 Lu-Ning Wang1 1Department of Geriatric Neurology, Clinical Division of South Building, Chinese PLA General Hospital, 2Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, People’s Republic of China Background: Physical activity is generally considered to be effective in reducing the prevalence of depression and promoting remission of its symptoms. However, large-scale epidemiological research on this issue is lacking in older Chinese adults. We performed a nationwide epidemiological survey to determine the relationship between physical activity and depressive symptoms in older Chinese veterans in the community, with adjustment for potential confounders.Methods: A cross-sectional study was conducted in a representative sample of 9,676 community-dwelling older Chinese veterans. Depressive symptoms were identified using the Center for Epidemiological Studies Depression Scale. Physical activity was self-reported using a one-year physical activity questionnaire. Information about covariates was obtained by questionnaire-based interview. Relationships between study variables and symptoms of depression were estimated using unadjusted and adjusted analyses.Results: The median age was 82.29 (interquartile range 80.25–84.60) years. In total, 81.84% of the study participants engaged in physical activity that was predominantly light in intensity. In unadjusted analyses, physical activity was associated with a significantly decreased likelihood of depressive symptoms (5.43% versus 18.83%, P

YM Zou,1 JP Tan,2 N Li,3 JS Yang,4 BC Yu,5 JM Yu,6 YM Zhao,3 LN Wang2 1Department of Neurology, Huanhu Hospital, Tianjin, 2Department of Geriatric Neurology, Chinese PLA General Hospital, 3Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, 4Department of Neurology, General Hospital of Lanzhou Military Command, Lanzhou, 5Department of Gerontology, Bethune International Peace Hospital, Shijiazhuang, 6Department of Neurology, Chinese PLA 107 Hospital, Yantai, People’s Republic of China Background: The purpose of this study was to investigate risk factors for and factors protecting against Parkinson’s disease (PD) in elderly Chinese veterans.Methods: Using a database containing detailed information on the health status of the nervous system in elderly Chinese veterans, univariate and multivariate analyses of factors that may be associated with PD were performed. Univariate analysis of qualitative data was done using the Pearson Chi-square and Fisher’s exact tests, and the Mann–Whitney U nonparametric test was used for univariate analysis of quantitative data. Multivariate logistic regression analysis was used to identify independent risk factors for and factors protecting against PD in elderly Chinese veterans.Results: A total of 9,676 elderly Chinese veterans were enrolled, including 228 cases with PD and 183 cases with Parkinson’s syndrome, with 9,265 non-PD subjects serving as controls. Age (odds ratio [OR] 1.343, 95% confidence interval [CI] 1.028–1.755) and medical history of essential tremor (OR 1.228, 95% CI 1.081–1.396) were identified as independent risk factors for PD, with age being the most important risk factor. Physical exercise (OR 0.478, 95% CI 0.355–0.643) and reading (OR 0.513, 95% CI 0.357–0.735) were identified as independent factors protecting against PD, and physical exercise showed better protection against PD relative to reading. Smoking, alcohol use, anemia, cerebral trauma, education level, and electromagnetic field exposure showed no association with PD.Conclusion: Physical exercise and reading may be independent factors that protect against PD among elderly Chinese veterans, while advancing age and medical history of essential tremor may be independent risk factors for PD. This study was cross-sectional, so further research is needed to confirm its results. Keywords: Chinese veterans, Parkinson’s disease, physical exercise, reading, age, medical history, essential tremor

Hongbo Wei*, Shuyi Wu*, Zhihong Feng, Wei Zhou, Yan Dong, Guofeng Wu, Shizhu Bai, Yimin Zhao Department of Prosthodontics, School of Stomatology, Fourth Military Medical University, Xi'an, People's Republic of China *These authors contributed equally to this workAbstract: Infection and epithelial downgrowth are major problems associated with maxillofacial percutaneous implants. These complications are mainly due to the improper closure of the implant–skin interface. Therefore, designing a percutaneous implant that better promotes the formation of a stable soft tissue biologic seal around percutaneous sites is highly desirable. Additionally, the fibroblast has been proven to play an important role in the formation of biologic seals. In this study, titania nanotubes were filled with 11.2 kDa C-terminal CCN2 (connective tissue growth factor) fragment, which could exert full CCN2 activity to increase the biological functionality of fibroblasts. This drug delivery system was fabricated on a titanium implant surface. CCN2 was loaded into anodized titania nanotubes using a simplified lyophilization method and the loading efficiency was approximately 80%. Then, the release kinetics of CCN2 from these nanotubes was investigated. Furthermore, the influence of CCN2-loaded titania nanotubes on fibroblast functionality was examined. The results revealed increased fibroblast adhesion at 0.25, 0.5, 1, 2, 4, and 24 hours, increased fibroblast viability over the course of 5 days, as well as enhanced actin cytoskeleton organization on CCN2-loaded titania nanotubes surfaces compared to uncoated, unmodified counterparts. Therefore, the results from this in vitro study demonstrate that CCN2-loaded titania nanotubes have the ability to increase fibroblast functionality and should be further studied as a method of promoting the formation of a stable soft tissue biologic seal around percutaneous sites.Keywords: anodization, titania nanotubes, adhesion, connective tissue growth factor, fibroblast

The aim of this article was to demonstrate a novel approach to designing facial prostheses using the transplantation concept and computer-assisted technology for extensive, large, maxillofacial defects that cross the facial midline. [ABSTRACT FROM AUTHOR]

A diarylethene ligand-anchored two-dimensional Hofmann-type compound [Fe II (BTEPy){Pt(CN) 4 }](CH 3 OH) (BTEPy = 1,2-bis[2-methyl-5-(4-pyridyl)-3-thienyl]cyclopentene) is synthesized, which undergoes a two-step spin-state transition and dual photoinduced magnetic switching.

Ginseng, a highly esteemed herbal medicine, has been utilized over 5000 years, predominantly in Far Eastern countries. Ginseng is categorized into garden ginseng (GG) and ginseng under forest (FG). However, in contrast to FG, excessive intake of GG may lead to potential adverse effects due to disruption of epithelial cell integrity, and the specific population groups that may be at higher risk. In this work, untargeted metabolomics were used to determine the heterogeneity between GG and FG, the data indicates that the content of Ethyl caffeate, Homoorientin, Citric acid and Quinic acid in GG were higher than in FG. Mass spectrometry imaging showed that ethyl caffeate and Homoorientin were concentrated on the brownish yellow exocarp of the primary root. Our experiments demonstrated that excessive exposure to ethyl caffeate and Homoorientin exacerbated the inflammatory response of HUVECs and reduced the expression of cell junctions. This suggest that the compounds causing adverse effects from excessive intake of GG are mainly concentrated in the yellow exocarp of the primary root of GG. These results suggest that untargeted metabolomics coupled with MALDI-MSI can visualize the spatial distribution of endogenous differential molecules of the same herb in different growth environments or developmental stages., Competing Interests: Declaration of competing interest We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Psoriasis, a persistent skin condition caused by the disorder of the immune system, impacts approximately 1.25 million individuals globally. Nevertheless, the presence of adverse effects in conventional clinical drugs necessitates further exploration of novel medications or combination therapies to mitigate these reactions and enhance their effectiveness., Methods: Hence, our intention here in this paper is to utilize the lipid nanoparticle delivery system for overcoming the volatility and hydrophobic properties of α-pinene, a naturally occurring compound renowned for its anti-inflammatory and antiviral effects, and further explore its potential pharmacological applications both in vitro and in vivo ., Results: The production of α-pinene lipid nanoparticles (APLNs) was achieved through the utilization of high pressure homogenization methods. APLNs was successfully fabricated with enhanced stability and water solubility. Meanwhile, the application of APLNs could drastically reduce the expression of lipopolysaccharide (LPS)-induced inflammation-related factors in THP-1 cells. Administration of APLNs to a mouse model of auricular swelling could effectively reduce redness and swelling in the auricles of mice as well. Furthermore, APLNs were also found to alleviate skin damage in mice with Imiquimod (IMQ)-induced psoriasis model, as well as decrease the levels of psoriasis-related protein nuclear factor kappa-B (NF-κB) and interleukin-17 (IL-17), interleukin-23 (IL-23), and other inflammation-related cytokines. More importantly, utilization of APLNs successfully mitigated the systemic inflammatory reactions in mice, resulting in the reduction of spleen-to-body ratio (wt%) and of inflammatory cytokines' expression in the serum., Discussion: Overall, our results suggest that with the help of lipid nanoparticle encapsulation, APLNs possess a better pharmacological effect in anti-inflammation and could potentially serve as an anti-psoriasis drug., 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 Li, Liang, Zhao, Chen, Zhu, Duan, Zou, Huang, Li and Zhang.)

Background: Post-transplant lymphoproliferative disorder (PTLD) is a rare but highly fatal complication occurring after allogeneic hematopoietic cell transplantation (allo-HCT) or solid organ transplantation (SOT). Unlike SOT, PTLD after allo-HCT usually originates from the donor and is rarely accompanied by a loss of donor chimerism., Case Summary: We report a case of Epstein-Barr virus positive PTLD manifesting as diffuse large B-cell lymphoma (DLBCL) with significantly decreased T-cell chimerism early after allo-HCT. A 30-year-old patient with acute myeloid leukemia underwent unrelated allo-HCT after first complete remission. Nearly 3 mo after transplantation, the patient developed cervical lymph node enlargement and gastric lesions, both of which were pathologically suggestive of DLBCL. Meanwhile, the patient experienced a significant and persistent decrease in T-cell chimerism. A partial remission was achieved after chemotherapy with single agent rituximab and subsequent R-CHOP combined chemotherapy., Conclusion: The loss of T-cell chimerism and the concomitant T-cell insufficiency may be the cause of PTLD in this patient., Competing Interests: Conflict-of-interest statement: The authors declare no competing interests for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objectives: To observe the protective effect of acupuncture on ovarian function and its impact on key molecules (Yes associated protein ［YAP］ and transcriptional coactivator with PDZ binding motif ［TAZ］) in the Hippo signaling pathway in poor ovarian response (POR) mice, in order to explore its mechanisms underlying improvement of POR by inhibiting ovarian cell apoptosis., Methods: The mice with regular motility cycle after screening were randomly divided into normal control, model and acupuncture groups, with 12 mice in each group. The POR model was established by gavage of tripterygium wilfordii polyglycoside suspension (50 mg · kg -1 ·d -1 ) for 2 weeks, and the mice of the normal control group was received an equal volume of 0.9% sodium chloride solution by gavage. The mice in the acupuncture group received manual acupuncture stimulation of bilateral "Taichong" (LR3) and "Sanyinjiao" (SP6), and "Zhongji" (CV3) and "Guanyuan" (CV4), with the filiform needles retained for 20 min, once daily for successive 10 days. The estrous cycle was determined by using vaginal exfoliated cell smear, and the body mass was detected weekly. The levels of serum anti Mullerian hormone (AMH), follicle stimulating hormone (FSH), estradiol (E2) and luteinizing hormone (LH) were measured using enzyme-linked immunosorbent assay (ELISA). Histopathological changes of the ovarian tissue were observed after H.E. staining, and the apoptosis of ovarian granulosa cells was measured using terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay. The expression levels of YAP, TAZ, B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X (Bax), cysteine aspartic acid specific protease-3 (Caspase-3) mRNAs and proteins were detected using real-time PCR and Western blot, respectively., Results: Compared with the normal control group, the model group had an increase in the rate of estrous cycle disorder, estrous cycle, serum FSH and LH content, and apoptosis of ovarian granulosa cells, and expression levels of Bax and Caspase-3 mRNAs and p-YAP, Bax and Caspase-3 proteins ( P <0.01), and a decrease in the body mass, number of retrieved oocytes, ovarian wet weight and ovarian index, serum AMH and E2 contents, and the expression levels of YAP, TAZ, Bcl-2 mRNAs and proteins ( P <0.01). After acupuncture intervention, modeling induced increase and decrease of indexes mentioned above were completely reversed ( P <0.05, P <0.01). H.E. staining showed deformed ovarian structure, reduced number of normal developing follicles and increased number of atretic follicles, disordered arrangement of the granulosa cells with fewer hierarchy in the model group, which was improved in the acupuncture group, such as increase in the number and improvement in the shape of normal ovarian follicles and reduction of the atretic follicles., Conclusions: Acupuncture intervention can inhibit the apoptosis of ovarian granulosa cells and improve the ovarian function of POR mice, which may be related to its effects in up-regulating the expressions of YAP, TAZ (key molecules of Hippo signaling pathway).

Microplastics (MPs) pose significant concerns for marine ecological security due to their minuteness and ubiquity. However, comprehensive knowledge on their distribution and fate in seawater columns remains limited. This study investigated the abundances and characteristics of MPs across 3-6 water layers in the South Yellow Sea and East China Sea. Results indicate that high-abundance small MPs (< 100 µm) (average 6567 items/m 3 ) were hidden beneath the sea-surface, predominantly fine-grained particles (< 20 µm) and high-density polymers (> 1.03 g/cm 3 ). The total suspended MPs (5.0-834.2 µm) are estimated at 2.9-3.1 × 10 17 particles, with most of them occurring in upper layers. In profiles, their distribution varied by physical properties with depth; fragment-shaped and high-density MPs increased in proportion at greater depths, contrasting with fibrous MPs. These MPs originated primarily from the Yangtze River and their winter transport was driven by the Yangtze River Dilution Water, East China Sea Coastal Current, and Yellow Sea Warm Current, resulting in their accumulation in coastal and estuarine regions. Consequently, the Yangtze River Estuary ecosystem faces substantial risks from MP pollution throughout the water column. This work unveils the prevalence of small MPs in coastal water columns and intricate interaction between their fate and hydrodynamic conditions., 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.)

Ryanodane diterpenes are structurally complex natural products that are well-known for their high degree of oxidation and the challenges associated with synthesizing them within the terpene class. Herein, we present a two-stage synthetic strategy that draws inspiration from the broad biosynthesis of terpenes, allowing us to achieve the first chemical synthesis of garajonone, a ryanodane diterpenoid that occurs naturally at low abundance, as well as its epimer, 3-epi-garajonone. The key to this success lies in the rapid construction of the carbon framework of the target molecule by employing an early-stage palladium-catalyzed Heck/carbonylative esterification cascade annulation, followed by successive late-stage selective redox manipulation to establish the desired oxidation state of the molecule. This research not only showcases the synthesis of garajonone and its epimer but also provides a platform for the chemical synthesis of other members and analogs of this complex diterpenoid family., (© 2024 Wiley-VCH GmbH.)

This study aimed to optimize the extraction of Hericium erinaceus polysaccharides (HEP) using ultrasound-assisted enzymatic extraction combined with Plackett-Burman design (PBD) and response surface methodology (RSM). The optimal extraction conditions were identified as: 33 min extraction time, 30:1 liquid to material ratio, 38 °C extraction temperature, 9 g/kg cellulase amount, pH 4, and 20 % ethanol concentration. Under these conditions, the extraction yield of HEP was 5.87 ± 0.16 %, consistent with the predicted results. Additionally, the potential immunomodulatory activity of HEP on RAW 264.7 macrophage was evaluated. The results revealed that HEP improved the immunostimulatory activity of RAW264.7 cells, evident from increased production of IL-6 and TNF-α. These findings suggest that HEP is capable of enhancing the immune activity of RAW 264.7 macrophage., 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.)

In this study, we applied thermal dissipation probe technology to examine sap flow in various directions (east, south, west, and north) and at different depths (0-2, 2-4, 4-6 cm) within the stem of natural Picea mongolica trees in the eastern of Otindag Sandy Land to provide a scientific basis for accurately quantifying water consumption of P. mongolica forests through transpiration and to enhance the understanding of water relations. The results showed that the diurnal variation of sap flow in different directions displayed a unimodal curve, with the sap flow sequence being south>east>west>north. The sap flow at different sapwood depths exhibited an obvious unimodal curve, with a significant decrease as sapwood depth increased. Compared with that calculated from the mean sap flux density in four directions (23.57 kg·d -1 ), water consumption calculated using the mean value in south-east, east-west, south-west, north-east, north-south, and north-west was overestimated by 10.2%, 5.5%, 14.5%, and underestimated by 12.3%, 8.2%, 9.8%, respectively. The water consumption calculated using the values from the east, south, and west was overestimated by 6.1%, 14.4%, and 15.4%, respectively, and underestimated by 30.7% in the north. In addition, compared with the water consumption calculated from the mean value in three sapwood depths (48.51 kg·d -1 ), that calculated using sap flux density at sapwood depths of 0-2, 2-4, and 4-6 cm were overestimated by 18.8%, underestimated by 1.7%, and underestimated by 62.9%, respectively. These results indicated that sap flow of P. mongolica had significant azimuthal and radial variations, which considerably influence the estimation of tree water consumption. Installing probes at 0-2 cm simultaneously in both the north and east of the trunk could effectively reduce the estimation error of whole-tree water consumption by 4.2%. This approach enabled the accurate quantification of water consumption of individual P. mongolica trees in sandy areas, thereby improving the precision of transpiration water consumption estimates scaling up from individual level to stand level.

In computational molecular and materials science, determining equilibrium structures is the crucial first step for accurate subsequent property calculations. However, the recent discovery of millions of new crystals and super large twisted structures has challenged traditional computational methods, both ab initio and machine-learning-based, due to their computationally intensive iterative processes. To address these scalability issues, here we introduce DeepRelax, a deep generative model capable of performing geometric crystal structure relaxation rapidly and without iterations. DeepRelax learns the equilibrium structural distribution, enabling it to predict relaxed structures directly from their unrelaxed ones. The ability to perform structural relaxation at the millisecond level per structure, combined with the scalability of parallel processing, makes DeepRelax particularly useful for large-scale virtual screening. We demonstrate DeepRelax's reliability and robustness by applying it to five diverse databases, including oxides, Materials Project, two-dimensional materials, van der Waals crystals, and crystals with point defects. DeepRelax consistently shows high accuracy and efficiency, validated by density functional theory calculations. Finally, we enhance its trustworthiness by integrating uncertainty quantification. This work significantly accelerates computational workflows, offering a robust and trustworthy machine-learning method for material discovery and advancing the application of AI for science., (© 2024. The Author(s).)

Holometabolous insects undergo morphological remodeling from larvae to pupae and to adults with typical changes in the cuticle; however, the mechanism is unclear. Using the lepidopteran agricultural insect Helicoverpa armigera, cotton bollworm, as a model, we revealed that the transcription factor RUNT-like (encoded by Runt-like) regulates the development of the pupal cuticle via promoting a pupal cuticle protein gene (HaPcp) expression. The HaPcp was highly expressed in the epidermis and wing during metamorphosis and was found being involved in pupal cuticle development by RNA interference (RNAi) analysis in larvae. Runt-like was also strongly upregulated in the epidermis and wing during metamorphosis. Knockdown of Runt-like produced similar phenomena, a failure of abdomen yellow envelope and wing formation, to those following HaPcp knockdown. The insect molting hormone 20-hydroxyecdysonen (20E) upregulated HaPcp transcription via RUNT-like. 20E upregulated Runt-like transcription via nuclear receptor EcR and the transcription factor FOXO. Together, RUNT-like and HaPCP are involved in pupal cuticle development during metamorphosis under 20E regulation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

ConspectusElectrides make up a fascinating group of materials with unique physical and chemical properties. In these materials, excess electrons do not behave like normal electrons in metals or form any chemical bonds with atoms. Instead, they "float" freely in the gaps within the material's structure, acting like negatively charged particles called anions (see the graph). Recently, there has been a surge of interest in van der Waals (vdW) electrides or electrenes in two dimensions. A typical example is layered lanthanum bromide (LaBr 2 ), which can be taken as [La 3+ (Br 1- ) 2 ] + •(e - ). Each excess free electron is trapped within a hexagonal pore, forming dense dots of electron density. These anionic electrons are loosely bound, giving vdW electrides some unique properties such as ferromagnetism, superconductivity, topological features, and Dirac plasmons. The high density of the free electron makes electrides very promising for applications in thermionic emission, organic light-emitting diodes, and high-performance catalysts.In this Account, we first discuss the discovery of numerous vdW electrides through high-throughput computational screening of over 67,000 known inorganic crystals in Materials Project. A dozen of them have been newly discovered and have not been reported before. Importantly, they possess completely different structural prototypes and properties of anionic electrons compared to widely studied electrides such as Ca 2 N. Finding these new vdW electrides expands the variety of electrides that can be made in the experiment and opens up new possibilities for studying their unique properties and applications.Then, based on the screened vdW electrides, we delve into their various emerging properties. For example, we developed a new magnetic mechanism specific to atomic-orbital-free ferromagnetism in electrides. We uncover the dual localized and extended nature of the anionic electrons in such electrides and demonstrate the formation of the local moment by the localized feature and the ferromagnetic interaction by the direct overlapping of their extended states. We further show the effective tuning of the magnetic properties of vdW electrides by engineering their structural, electronic, and compositional properties. Besides, we show that the complex interaction between the multiple quantum orderings in vdW electrides leads to many interesting properties including valley polarization, charge density waves, a topological property, a superconducting property, and a thermoelectrical property.Moreover, we discuss strategies to leverage the unique intrinsic properties of vdW electrides for practical applications. We show that these properties make vdW electrides potential candidates for advanced applications such as spin-orbit torque memory devices, valleytronic devices, K-ion batteries, and thermoelectricity. Finally, we discuss the current challenges and future perspectives for research using these emerging materials.

Objective: To evaluate the efficacy of EECP in the prevention of contrast-induced nephropathy (CIN) in patients with chronic kidney disease (CKD)., Methods: A prospective trial was undertaken in the participants. A total of 280 patients with an estimated glomerular filtration rate (eGFR) of <60 ml/min/1.73 m 2 who underwent percutaneous coronary artery procedures were enrolled and divided into two groups: the control group ( n  = 100) and the EECP group ( n  = 180). All patients received extracellular fluid volume expansion therapy with 0.9% normal saline, and patients in the EECP groups were also treated with EECP. The renal function indexes of the two groups were determined 48-72 h after coronary artery procedures., Results: In the EECP group, the BUN and serum creatinine (Scr) after coronary artery procedures were significantly lower than those before coronary artery procedures (BUN: 8.4 ± 3.5 vs. 6.6 ± 2.7 mmol/L, p  < 0.001; Scr: 151.9 ± 44.7 vs. 144.5 ± 48.3 μmol/L, p  < 0.001), while the eGFR was significantly increased (43.6 ± 11.4 vs. 47.1 ± 13.9 ml/min/1.73 m 2 , p  < 0.001). The degree of Scr elevation was lower in the EECP group than in the control group (12.4 ± 15.0 vs. 20.9 ± 24.8 μmol/L, p  = 0.026). Additionally, the EECP group had a lower incidence of post-procedures Scr elevation than the control group (36.5 vs. 48.0%, p  = 0.042), a higher incidence of post-procedures eGFR elevation (62.2 vs. 48.0%, p  = 0.021), and a lower risk of CIN (1.1 vs. 6.0%, p  = 0.019)., Conclusion: EECP therapy has a protective effect on renal function and can reduce the risk of CIN in patients with CKD.

The effective method for trypsin purification should be established because trypsin has important economic value. In this work, a novel and simple strategy was proposed for fabricating micron-sized magnetic Fe 3 O 4 @agarose-benzamidine beads (MABB) with benzamidine as a ligand, which can efficiently and selectively capture trypsin. The micro-sized MABB, with clear spherical core-shell structure and average particle size of 6.6 μm, showed excellent suspension ability and magnetic responsiveness in aqueous solution. The adsorption capacity and selectivity of MABB towards target trypsin were significantly better than those of non-target lysozyme. According to the Langmuir equation, the maximum adsorption capacity of MABB for trypsin was 1946 mg g -1  at 25 °C, and the adsorption should be a physical sorption process. Furthermore, the initial adsorption rate and half equilibrium time of MABB toward trypsin were 787.4 mg g -1  min -1 and 0.71 min, respectively. To prove the practicability, MABB-based magnetic solid-phase extraction (MSPE) was proposed, and the related parameters were optimized in detail to improve the purification efficiency. With Tris-HCl buffer (50 mM, 10 mM CaCl 2 , pH 8.0) as extraction buffer, Tris-HCl buffer (50 mM, 100 mM CaCl 2 , pH 8.0) as rinsing buffer, acidic eluent (0.01 M HCl, 0.5 M NaCl, pH 2.0) as eluent buffer and alkaline buffer (1 M Tris-HCl buffer, pH 10.0) as neutralization solution, the MABB-based MSPE was successfully used for trypsin purification from the viscera of grass carp (Ctenopharyngodon idella). The molecular weight of purified trypsin was determined as approximate 23 kDa through sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The purified trypsin was highly active from 30 °C to 60 °C, with an optimum temperature of 50 °C, and was tolerant to pH variation, exhibiting 85 % of maximum enzyme activity from pH 7.0 to 10.0. The results demonstrated that the proposed MABB-based MSPE could effectively purify trypsin and ensure the biological activity of purified trypsin. Therefore, we believe that the novel MABB could be applicable for efficient purification of trypsin from complex biological systems., 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.)

Through the report of 4 cases of occupational heatstroke among sanitation workers working in high-temperature weather, this study analyzes the risk of occupational heatstroke among workers in the environmental sanitation industry working in high-temperature weather, and provides scientific suggestions for standardizing occupational health management, safeguarding the health rights and interests of workers, and preventing the occurrence of occupational heatstroke in summer. Through case analysis, we aim to raise high awareness of the occupational health of sanitation workers in the whole society, in order to provide a scientific and healthy working environment for sanitation workers and promote their physical and mental health.

Responsive spin-crossover (SCO) metal-organic cages (MOCs) are emerging dynamic platforms with potential for advanced applications in magnetic sensing and molecular switching. Among these, Fe III -based MOCs are particularly noteworthy for their air stability, yet they remain largely unexplored. Herein, we report the synthesis of two novel Fe III MOCs using a bis-bidentate ligand approach, which exhibit SCO activity above room temperature. These represent the first SCO-active Fe III cages and feature an atypical {FeN 6 }-type coordination sphere, uncommon for Fe III SCO compounds. Our study reveals that these MOCs are sensitive to acid/base variations, enabling reversible magnetic switching in solution. The presence of multiple active proton sites within these SCO-MOCs facilitates multisite, multilevel proton-induced spin-state modulation. This behavior is observed at room temperature through 1 H NMR spectroscopy, capturing the subtle proton-induced spin-state transitions triggered by pH changes. Further insights from extended X-ray absorption fine structure (EXAFS) and theoretical analyses indicate that these magnetic alterations primarily result from the protonation and deprotonation processes at the NH active sites on the ligands. These processes induce changes in the secondary coordination sphere, thereby modulating the magnetic properties of the cages. The capability of these Fe III MOCs to integrate magnetic responses with environmental stimuli underscores their potential as finely tunable magnetic sensors and highlights their versatility as molecular switches. This work paves the way for the development of SCO-active materials with tailored properties for applications in sensing and molecular switching.

Rationale and Objectives: To investigate the predictive value of coronary CT angiography (CCTA)-based radiomics for vessel-specific ischemia by stress dynamic CT myocardial perfusion imaging (MPI)., Materials and Methods: Patients with typical angina/atypical angina/non-angina chest pain who underwent both stress dynamic CT MPI and CCTA scans were retrospectively enrolled. The following models were constructed for ischemic prediction using logistic regression and CCTA-derived quantitative and radiomic features: plaque quantitative model, lumen quantitative model, CT-fractional flow reserve (CT-FFR) model, integrative quantitative model, plaque radiomic model, peri-coronary adipose tissue (pCAT) radiomic model, integrative radiomic model, and quantitative and radiomic fusion model. A relative myocardial blood flow ≤ 0.75 on stress dynamic CT MPI was considered ischemic. The models' performances were quantified by the area under the receiver-operating characteristic curve (AUC)., Results: 386 coronary vessels (stenosis grade: 25%∼75%; training set: 200 [ischemia/non-ischemia=96/104]; test set:186 [ischemia/non-ischemia=79/107]) from 326 patients were included. The plaque radiomic model (training/test set: AUC=0.81/0.80) outperformed (p < .05) both the plaque quantitative (training/test set: AUC=0.71/0.68) model and the lumen quantitative (training/test set: AUC=0.69/0.65) model in identifying ischemia. The integrative radiomic model (training/test set: AUC=0.83/0.82) outperformed (p < .05) the CT-FFR model (training/test set: AUC=0.74/0.73) for ischemic prediction. The quantitative and radiomic fusion model (training/test set: AUC=0.86/0.84) outperformed (p < .05) the integrative quantitative model (training/test set: AUC=0.79/0.77) for ischemic detection., Conclusion: The plaque and pCAT radiomic features were superior to the plaque and pCAT quantitative features in predicting ischemia and the addition of the radiomic features to the quantitative features for ischemic identification yielded incremental discriminatory value., 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 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

In this study, a targeted nanocarrier was developed by functionalizing graphene oxide with polyethyleneimine and folic acid, intended for loading oridonin. The nanocarrier was successfully synthesized and characterized using an ultraviolet spectrum, Fourier transform infrared spectroscopy and scanning electron microscopy. The nanocarrier demonstrated a remarkable oridonin loading capacity, reaching 424.8 μg/mg, as determined by ultra-high performance liquid chromatography. In vitro drug release experiments exhibited a pH-dependent release profile, with a higher cumulative release in an acidic environment. The release mechanism followed the Ritger-Peppas equation model. Cytotoxicity assays indicated minimal toxicity of the nanocarrier. Enhanced cellular uptake by MCF7 cells was observed for carriers functionalized with folate and polyethyleneimine. These findings highlight the potential of functionalized graphene oxide as a promising carrier for oridonin delivery in biomedical applications., (© 2024 John Wiley & Sons Ltd.)

Fine tuning of the metal site coordination environment of a single-atom catalyst (SAC) to boost its catalytic activity for oxygen reduction reaction (ORR) is of significance but challenging. Herein, we report a new SAC bearing Fe-N 3 C-N sites with asymmetric in-plane coordinated Fe-N 3 C and axial coordinated N atom for ORR, which was obtained by pyrolysis of an iron isoporphyrin on polyvinylimidazole (PVI) coated carbon black. The C@PVI-(NCTPP)Fe-800 catalyst exhibited significantly improved ORR activity ( E 1/2 = 0.89 V vs RHE) than the counterpart SAC with Fe-N 4 -N sites in 0.1 M KOH. Significantly, the Zn-air batteries equipped with the C@PVI-(NCTPP)Fe-800 catalyst demonstrated an open-circuit voltage (OCV) of 1.45 V and a peak power density ( P max ) of 130 mW/cm 2 , outperforming the commercial Pt/C catalyst (OCV = 1.42 V; P max = 119 mW/cm 2 ). The density functional theory (DFT) calculations revealed that the d-band center of the asymmetric Fe-N 3 C-N structure shifted upward, which enhances its electron-donating ability, favors O 2 adsorption, and supports O-O bond activation, thus leading to significantly promoted catalytic activity. This research presents an intriguing strategy for the designing of the active site architecture in metal SACs with a structure-function controlled approach, significantly enhancing their catalytic efficiency for the ORR and offering promising prospects in energy-conversion technologies.

This study reports on three patients with Shwachman-Diamond syndrome (SDS) who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the First Affiliated Hospital of Zhejiang University School of Medicine. Based on relevant literature, the clinical manifestations and genetic mutation characteristics of SDS were summarized, and the efficacy and timing of allo HSCT for such patients were explored. Three SDS patients were all male, with transplant ages of 32, 33, and 32 years old, respectively. All three patients were diagnosed in childhood. Case 1 presented with anemia as the initial clinical manifestation, which gradually progressed to a decrease in whole blood cells; Case 2 and 3 both present with a decrease in whole blood cells as the initial clinical manifestation. Case 1 and 3 have intellectual disabilities, while case 3 presents with pancreatic steatosis and chronic pancreatitis. All three patients have short stature. Three patients all detected heterozygous mutations in the SBDS: c.258+2T>C splice site. The family members of the three patients have no clinical manifestations of SDS. All three patients were treated with a reduced dose pre-treatment regimen (Fludarabine+Busulfan+Me-CCNU+Rabbit Anti-human Thymocyte Globulin). Case 1 and case 2 underwent haploid hematopoietic stem cell transplantation, while case 3 underwent unrelated donor hematopoietic stem cell transplantation. Case 1 was diagnosed with myelodysplastic syndrome transforming into acute myeloid leukemia before transplantation, but experienced early recurrence and death after transplantation; Case 2 is secondary implantation failure, dependent on platelet transfusion; Case 3 was removed from medication maintenance treatment after transplantation, and blood routine monitoring was normal.

Purpose: Few studies have focused on the risk factors leading to postoperative blood transfusion after open reduction and internal fixation (ORIF) of proximal humeral fractures (PHFs) in the elderly. Therefore, we designed this study to explore potential risk factors of blood transfusion after ORIF for PHFs. We have also established a nomogram model to integrate and quantify our research results and give feedback., Methods: In this study, we retrospectively analyzed the clinical data of elderly PHF patients undergoing ORIF from January 2020 to December 2021. We have established a multivariate regression model and nomograph. The prediction performance and consistency of the model were evaluated by the consistency coefficient and calibration curve, respectively., Results: 162 patients met our inclusion criteria and were included in the final study. The following factors are related to the increased risk of transfusion after ORIF: time to surgery, fibrinogen levels, intraoperative blood loss, and surgical duration., Conclusions: Our patient-specific transfusion risk calculator uses a robust multivariable model to predict transfusion risk.The resulting nomogram can be used as a screening tool to identify patients with high transfusion risk and provide necessary interventions for these patients (such as preoperative red blood cell mobilization, intraoperative autologous blood transfusion, etc.)., (© 2024. The Author(s).)

The establishment of clinical research resource platforms, including research databases and bio-sample library, is an important development in the field of clinical research. The international academic community proposes broad informed consent to regulate the ethical management of the issue. However, the broad informed consent fails to capture the main features of incomplete informed consent and authorization, misleads researchers and managers and leads to miss ethical management for clinical research projects. Therefore, the author proposes a named partial informed consent to improve ethical management for clinical research projects. Partial informed consent separates ethical management for establishing clinical research resource platforms and clinical research projects. After reviewing the legal and ethical foundation of clinical research ethics management, the author discussed the similarities and differences between project management and task management in the two informed consent solutions, the basis for approval of exempted informed consent signatures by the ethics committee, issues to be noted in the ethics management of multi-center research at the task level, and explained the substantive differences between broad informed consent and partial informed consent.

Background: The purpose of this study was to evaluate the effectiveness and efficiency of implementing a data-driven blended online-offline (DDBOO) teaching approach in the medicinal chemistry course., Methods: A total of 118 third-year students majoring in pharmacy were enrolled from September 2021 to January 2022. The participants were randomly assigned to either the DDBOO teaching group or the traditional lecture-based learning (LBL) group for medicinal chemistry. Pre- and post-class quizzes were administered, along with an anonymous questionnaire distributed to both groups to assess students' perceptions and experiences., Results: There was no significant difference in the pre-class quiz scores between the DDBOO and LBL groups (T=-0.637, P = 0.822). However, after class, the mean quiz score of the DDBOO group was significantly higher than that of the LBL group (T = 3.742, P < 0.001). Furthermore, the scores for learning interest, learning motivation, self-learning skill, mastery of basic knowledge, teamwork skills, problem-solving ability, innovation ability, and satisfaction, as measured by the questionnaire, were significantly higher in the DDBOO group than in the traditional group (all P < 0.05)., Conclusion: The DDBOO teaching method effectively enhances students' academic performance and satisfaction. Further research and promotion of this approach are warranted., (© 2024. The Author(s).)

Cardiac fibrosis is a pathological scarring process that impairs cardiac function. N-acetyltransferase 10 (Nat10) is recently identified as the key enzyme for the N4-acetylcytidine (ac4C) modification of mRNAs. In this study, we investigated the role of Nat10 in cardiac fibrosis following myocardial infarction (MI) and the related mechanisms. MI was induced in mice by ligation of the left anterior descending coronary artery; cardiac function was assessed with echocardiography. We showed that both the mRNA and protein expression levels of Nat10 were significantly increased in the infarct zone and border zone 4 weeks post-MI, and the expression of Nat10 in cardiac fibroblasts was significantly higher compared with that in cardiomyocytes after MI. Fibroblast-specific overexpression of Nat10 promoted collagen deposition and induced cardiac systolic dysfunction post-MI in mice. Conversely, fibroblast-specific knockout of Nat10 markedly relieved cardiac function impairment and extracellular matrix remodeling following MI. We then conducted ac4C-RNA binding protein immunoprecipitation-sequencing (RIP-seq) in cardiac fibroblasts transfected with Nat10 siRNA, and revealed that angiomotin-like 1 (Amotl1), an upstream regulator of the Hippo signaling pathway, was the target gene of Nat10. We demonstrated that Nat10-mediated ac4C modification of Amotl1 increased its mRNA stability and translation in neonatal cardiac fibroblasts, thereby increasing the interaction of Amotl1 with yes-associated protein 1 (Yap) and facilitating Yap translocation into the nucleus. Intriguingly, silencing of Amotl1 or Yap, as well as treatment with verteporfin, a selective and potent Yap inhibitor, attenuated the Nat10 overexpression-induced proliferation of cardiac fibroblasts and prevented their differentiation into myofibroblasts in vitro. In conclusion, this study highlights Nat10 as a crucial regulator of myocardial fibrosis following MI injury through ac4C modification of upstream activators within the Hippo/Yap signaling pathway., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Efficient separation of deoxyribonucleic acid (DNA) through magnetic nanoparticles (MN) is a widely used biotechnology. Hedgehog-inspired MNs (HMN) possess a high-surface-area due to the distinct burr-like structure of hedgehog, but there is no report about the usage of HMN for DNA extraction. Herein, to improve the selection of MN and illustrate the performance of HMN for DNA separation, HMN and silica-coated Fe 3 O 4 nanoparticles (Fe 3 O 4 @SiO 2 ) were fabricated and compared for the high-efficient separation of pathogenic bacteria of DNA. Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) are typical Gram-negative and Gram-positive bacteria and are selected as model pathogenic bacteria. To enhance the extraction efficiency of two kinds of MNs, various parameters, including pretreatment, lysis, binding and elution conditions, have been optimized in detail. In most separation experiments, the DNA yield of HMN was higher than that of Fe 3 O 4 @SiO 2 . Therefore, a HMN-based magnetic solid-phase microextraction (MSPE) and quantitative real-time PCR (qPCR) were integrated and used to detect pathogenic bacteria in real samples. Interestingly, the HMN-based MSPE combined qPCR strategy exhibited high sensitivity with a limit of detection of 2.0 × 10 1 CFU mL -1 for E. coli and 4.0 × 10 1 CFU mL -1 for S. aureus in orange juice, and 2.8 × 10 2 CFU mL -1 for E. coli and 1.1 × 10 2 CFU mL -1 for S. aureus in milk, respectively. The performance of the proposed strategy was significantly better than that of commercial kit. This work could prove that the novel HMN could be applicable for the efficient separation of DNA from complex biological samples., 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.)

This study aims to investigate the effect and mechanism of the EtO Ac extract of Draconis Sanguis(DSE) on improving athero sclerosis in ApoE gene knockout(ApoE~(-/-)) mice. The ApoE~(-/-) mice were randomly divided into five groups: control group, mo delgroup, positive group treated with ezetimibe of 5 mg·kg~(-1)(EG), and low(100 mg·kg~(-1)) and high dose(200 mg·kg~(-1)) groups ofDSE. xcept for the control group, all other groups were fed a high-fat diet and administered drugs for 16 successive weeks. After 16 weeks of Eadministration, the body weight, liver, and epididymal fat mass of the mice were measured; the level of blood lipid and the plaquearea of the aortic outflow tract were detected to evaluate the efficacy of DSE in vivo. In addition, in vitro cultures of human umbilical v ein endothelial cell(HUVEC) were conducted. Oxidative stress of endothelial cells was induced by oxidized low-density lipoprot ein(ox-LDL), and the effects of DSE on oxidative stress-related proteins in endothelial cells were examined. The results sho wedthat both doses of DSE significantly improved the epididymal fat mass and index of ApoE~(-/-) mice with atherosclerosis, lowered thelevels of plasma cholesterol, triglyceride, and non-high density lipoprotein cholesterol, and reduced the plaque area of the aortic ou tflow tract. totIn alvitro experiments confirmed that ox-LDL significantly increased the level of lipid peroxidation marker 4-HNE in HUVECcells, confirming that DSE improved the degree of atherosclerotic lesions in ApoE~(-/-) mice by inhibiting ox-LDL-induced oxidative stress in vascular endothelial cells.

Given the insidious and high-fatality nature of cardiovascular diseases (CVDs), the emergence of fluoride as a newly identified risk factor demands serious consideration alongside traditional risk factors. While vascular smooth muscle cells (VSMCs) play a pivotal role in the progression of CVDs, the toxicological impact of fluoride on VSMCs remains largely uncharted. In this study, we constructed fluorosis model in SD rats and A7R5 aortic smooth muscle cell lines to confirm fluoride impaired VSMCs. Fluoride aggravated the pathological damage of rat aorta in vivo. Then A7R5 were exposed to fluoride with concentration ranging from 0 to 1200 μmol/L over a 24-h period, revealing a dose-dependent inhibition of cell proliferation and migration. The further metabolomic analysis showed alterations in metabolite profiles induced by fluoride exposure, notably decreasing organic acids and lipid molecules level. Additionally, gene network analysis underscored the frequency of fluoride's interference with amino acids metabolism, potentially impacting the tricarboxylic acid (TCA) cycle. Our results also highlighted the ATP-binding cassette (ABC) transporters pathway as a central element in VSMC impairment. Moreover, we observed a dose-dependent increase in osteopontin (OPN) and α-smooth muscle actin (α-SMA) mRNA level and a dose-dependent decrease in ABC subfamily C member 1 (ABCC1) and bestrophin 1 (BEST1) mRNA level. These findings advance our understanding of fluoride as a CVD risk factor and its influence on VSMCs and metabolic pathways, warranting further investigation into this emerging risk factor., (© 2024. The Author(s).)

Herein, we present a unified chemical synthesis of three subgroups of cephalotaxus diterpenoids. Key to the success lies in adopting a synthetic strategy that is inspired by biosynthesis but is opposite in nature. By employing selective one-carbon introduction and ring expansion operations, we have successfully converted cephalotane-type C 18 dinorditerpenoids (using cephanolide B as a starting material) into troponoid-type C 19 norditerpenoids and intact cephalotane-type C 20 diterpenoids. This synthetic approach has enabled us to synthesize cephinoid H, 13-oxo-cephinoid H, 7-oxo-cephinoid H, fortalpinoid C, 7-epi-fortalpinoid C, cephanolide E, and 13-epi-cephanolide E. Furthermore, through the development of an intermolecular asymmetric Michael reaction between β-oxo esters and β-substituted enones, we have achieved the enantioselective synthesis of advanced intermediates within our synthetic sequence, thus formally realizing the asymmetric total synthesis of the cephalotaxus diterpenoids family., (© 2024 Wiley-VCH GmbH.)

The inherently huge volume expansion during Li uptake has hindered the use of Si-based anodes in high-energy lithium-ion batteries. While some pore-forming and nano-architecting strategies show promises to effectively buffer the volume change, other parameters essential for practical electrode fabrication, such as compaction density, are often compromised. Here we propose a new in situ Mg doping strategy to form closed-nanopore structure into a micron-sized SiO x particle at a high bulk density. The doped Mg atoms promote the segregation of O, so that high-density magnesium silicates form to generate closed nanopores. By altering the mass content of Mg dopant, the average radii (ranged from 5.4 to 9.7 nm) and porosities (ranged from 1.4 % to 15.9 %) of the closed pores are precisely adjustable, which accounts for volume expansion of SiO x from 77.8 % to 22.2 % at the minimum. Benefited from the small volume variation, the Mg-doped micron-SiO x anode demonstrates improved Li storage performance towards realization of a 700-(dis)charge-cycle, 11-Ah-pouch-type cell at a capacity retention of >80 %. This work offers insights into reasonable design of the internal structure of micron-sized SiO x and other materials that undergo conversion or alloying reactions with drastic volume change, to enable high-energy batteries with stable electrochemistry., (© 2024 Wiley-VCH GmbH.)

Objective: To analyze the change in human resources within China's Centers for Disease Control and Prevention (CDC) from 2010 to 2020. Methods: The self-reported information from provincial, prefectural (city), and county (district) levels of China's CDC, covering employee counts, staff composition, professional qualifications, educational backgrounds, technical titles, and tenure, were extracted from the China Disease Prevention and Control Information System. The demographic context was provided by the annual population figures from the China Statistical Yearbook (2010-2020). The profile of CDC personnel was described, and the average annual percentage rate change (AAPC), average annual percentage rate change (APC), human resource agglomeration degree (HRAD) and the difference between HRAD and population agglomeration degree (PAD) were calculated. The Joinpoint regression model was used to analyze the time trend. Results: The decade under review witnessed a net increase of 17 300 active and 18 300 enrolled personnel in the CDC, surpassing the national population growth rate with AAPCs of 0.93% and 1.03%, respectively. This upward trajectory was statistically significant ( P <0.05). The ratio of disease control personnel per 10 000 population escalated from 1.14 to 1.21. An initial decline in active CDC workforce density (from 1.31 to 1.27 per 10 000 population between 2010 and 2017) was followed by an increase (from 1.28 to 1.37 between 2018 and 2020), with APCs of -0.40% and 3.73%, respectively. The proportion of professional and technical staff in 2019 was highest in the eastern region (86.01%), followed by the western (83.75%) and central regions (79.54%). The period also saw an enhancement in the average academic degree (from 1.91 to 2.43 points) and professional title scores (from 1.39 to 1.53 points) of CDC personnel. While the average tenure in the eastern and western regions showed a slight decline, the central region experienced an increase, with HRAD values indicating a higher concentration in the eastern and central regions compared to the western region. The HRAD-PAD discrepancy revealed a negative value in the eastern region, nearing zero in the central and western regions. Conclusion: Between 2010 and 2020, China's CDC experienced notable growth in human resources and underwent structural optimization, albeit with significant regional disparities in concentration.