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Xiao-Feng Chen, Shaoxiu Ji School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of ChinaCorrespondence: Xiao-Feng Chen, School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, No. 1166, Liutai Avenue, Wenjiang District, Chengdu, People’s Republic of China, Tel +86-28-61800219, Email xiaofengchen@cdutcm.edu.cnBackground: Liver fibrosis is an independent contributor of chronic liver diseases, and regressing liver fibrosis is considered a potential therapeutic target for chronic liver diseases. We aimed to explore the effects and mechanism of sorafenib in liver fibrosis.Methods: Male Sprague Dawley (SD) rats were subjected to subcutaneous injection of carbon tetrachloride (CCl4) for 8 weeks to induce liver fibrosis and then treated with sorafenib. The degree of liver fibrosis was analyzed by hematoxylin–eosin (H&E) staining, Masson staining, and Picrosirius red (PSR) staining. Serum biochemical indexes were detected by fully automatic biochemical analyzer or enzyme-linked immunosorbent assay (ELISA). Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression of pro-fibrotic genes. Immunohistochemical staining and Western blotting were carried out to evaluate the levels of lysine crotonylation.Results: Liver index was reduced with oral sorafenib in CCl4-induced rats. Serum liver function (alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL)) and fibrosis indicators (type III procollagen (PC-III), hyaluronic acid (HA), and laminin (LN)) were attenuated with sorafenib treatment. Sorafenib improved the hepatic structure and fibrotic progression. The expression of fibrosis-related genes was remarkely reduced with sorafenib treatment. Meanwhile, sorafenib inhibited α-SMA and collagen I cumulation induced by CCl4 injection. Besides, protein lysine crotonylation especially the crotonylated H2BK12 (H2BK12cr) and crotonylated H3K18 (H3K18cr) were reversed by sorafenib, which were decreased in response to CCl4 treatment. Spearman correlation analysis shown lysine crotonylation expression was negatively correlated with serum fibrotic indicators. Conversely, crotonylation-regulated enzymes, which negatively regulate protein crotonylation, were increased in response to CCl4 treatment, while sorafenib reduced their expression.Conclusion: Sorafenib exerts significant anti-fibrotic effects through mediating crotonylation-regulated enzymes and protein crotonylation in fibrotic rats.Keywords: liver fibrosis, sorafenib, crotonylation, epigenetic regulation

Yu Cheng,1 Bi-Juan Lin,1 Jin-Hua Guo,1 Bing-Lin Huang,1 Lin-Ping Fang,1 Wan-Cai Que,1 Mao-Bai Liu,1 Xin-Feng Chen,1 Hong-Qiang Qiu1,2 1Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou 350001, People’s Republic of China; 2College of Pharmacy, Fujian Medical University, Fuzhou 350004, People’s Republic of ChinaCorrespondence: Hong-Qiang Qiu; Xin-Feng ChenDepartment of Pharmacy, Fujian Medical University Union Hospital, 29 Xin Quan Road, Gulou, Fuzhou 350001, Fujian, People’s Republic of ChinaTel +86 591 8621 8591; +86 591 8621 8371Fax +86 591 8621 8591Email hongqiangqiu@fjmu.edu.cn; fjxhcxf@163.comPurpose: The aim of this study is to assess the bioequivalence of a new generic formulation and the branded formulation of levocetirizine dihydrochloride in healthy Chinese volunteers under fasting and fed conditions, and food-intake effect on the pharmacokinetic properties is also evaluated.Patients and methods: Volunteers were randomly allocated into two groups to receive a single oral dose of generic formulation and branded formulation under fasting or fed conditions, respectively. Blood samples were collected at designated time points. Plasma concentrations of levocetirizine were determined by UFLC-MS/MS. Safety evaluations were carried out through the study. The main pharmacokinetic parameters of the two formulations of levocetirizine were calculated using non-compartmental analysis incorporated in WinNonlin® 7.0 software.Results: Forty-nine volunteers were enrolled; 46 completed the studies. Under fasting and fed conditions, the 90% confidence intervals for the geometric mean of generic/branded ratios were in the range of 94.75–107.24% and 99.98–114.69% for the maximum observed concentration, and 97.13–102.50% and 98.36–103.98% for the area under the concentration–time curve. As a result of food intake before administration, the reduced rate and extent of absorption of levocetirizine were observed. Both formulations were generally well tolerated, with no serious adverse reactions reported.Conclusion: The two formulations demonstrated essentially identical pharmacokinetic profiles and were all well within the FDA/CFDA bioequivalence standards. Meanwhile, food intake can delay the absorption rate and reduced the bioavailability of levocetirizine in healthy Chinese volunteers.Keywords: levocetirizine, pharmacokinetics, bioequivalence, food effect, healthy Chinese volunteers

Xiaofeng Chen,1,* Yu Liu,1,* Leiying Miao,1 Yangyang Wang,2 Shuangshuang Ren,1 Xuebin Yang,3 Yong Hu,4 Weibin Sun1 1Department of Periodontology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Materials Science and Engineering, College of Materials Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu, People’s Republic of China; 3Biomaterials and Tissue Engineering Group, Leeds Dental Institute, University of Leeds, Leeds, UK; 4Institute of Materials Engineering, National Laboratory of Solid State Micro Structure, College of Engineering and Applied Sciences, Nanjing University, Nanjing, Jiangsu, People’s Republic of China *These authors contributed equally to this work Abstract: Periodontitis is a major cause for tooth loss, which affects about 15% of the adult population. Cementum regeneration has been the crux of constructing the periodontal complex. Cementum protein 1 (CEMP1) is a cementum-specific protein that can induce cementogenic differentiation. In this study, poly(ethylene glycol) (PEG)-stabilized amorphous calcium phosphate (ACP) nanoparticles were prepared by wet-chemical method and then loaded with recombinant human CEMP1 (rhCEMP1) for controlled release. An electrospun multiphasic scaffold constituted of poly(ε-caprolactone) (PCL), type I collagen (COL), and rhCEMP1/ACP was fabricated. The effects of rhCEMP1/ACP/PCL/COL scaffold on the attachment proliferation, osteogenic, and cementogenic differentiations of human periodontal ligament cells, (PDLCs) were systematically investigated. A critical size defect rat model was introduced to evaluate the effect of tissue regeneration of the scaffolds in vivo. The results showed that PEG-stabilized ACP nanoparticles formed a core-shell structure with sustained release of rhCEMP1 for up to 4 weeks. rhCEMP1/ACP/PCL/COL scaffold could suppress PDLCs proliferation behavior and upregulate the expression of cementoblastic markers including CEMP1 and cementum attachment protein while downregulating osteoblastic markers including osteocalcin and osteopontin when it was cocultured with PDLCs in vitro for 7 days. Histology analysis of cementum after being implanted with the scaffold in rats for 8 weeks showed that there was cementum-like tissue formation but little bone formation. These results indicated the potential of using electrospun multiphasic scaffolds for controlled release of rhCEMP1 for promoting cementum regeneration in reconstruction of the periodontal complex. Keywords: nanofiber scaffold, rhCEMP1, controlled release, cementum regeneration, in vivo

Ji-Wei Wang,1,* Li Sun,1,2,* Ning Ding,3 Jiang Li,4 Xiao-Huan Gong,1 Xue-Fen Chen,1 Dong-Hui Yu,5 Zheng-Nian Luo,6 Zheng-Ping Yuan,7 Jin-Ming Yu1 1School of Public Health and Key Laboratory of Public Health Safety, Fudan University, Shanghai, 2Changzhou Center for Disease Control and Prevention, Changzhou, Jiangsu Province, People’s Republic of China; 3Centre for Research and Action in Public Health, The University of Canberra, Canberra, ACT, Australia; 4Jonathan and Karin Fielding School of Public Health, University of California, Los Angeles, CA, USA; 5College of Clinical Medicine, Anhui Medical University, Hefei, Anhui Province, 6Shanghai Health Education Association, 7Shanghai Cancer Rehabilitation Club, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: Cancer survivors with certain comorbidities had lower quality of life (QOL). This study was performed to investigate the prevalence of comorbidities and the association between comorbidities and the QOL among Chinese colorectal cancer survivors (CCS). Methods: A cross-sectional study was conducted among 1,398 CCS between April and July 2013 in Shanghai, People’s Republic of China. All the participants were asked to complete a simplified Chinese version of the European Organization for Research and Treatment quality of life version 3 questionnaire and questions on sociodemographic characteristics and comorbidities. In order to mitigate the bias caused by confounding factors, multiple linear regression models were employed to calculate the adjusted means of QOL scores. Results: The proportion of participants without any comorbidity was only 20.2%. The CCS with comorbidities except hypertension scored significantly lower on the European Organization for Research and Treatment quality of life version 3 questionnaire global health and functioning scales and Functional Assessment of Cancer Therapy-General scales but higher on the European Organization for Research and Treatment quality of life version 3 questionnaire symptom scores, indicating that they had poorer QOL, particularly for cardiovascular, respiratory, digestive, and musculoskeletal diseases. Conclusion: There exists a significant association between comorbidities and QOL among Chinese CCS, and participants with comorbidities generally reported lower QOL scores. These findings suggested comprehensive care for CCS. Keywords: colorectal cancer survivors, quality of life, comorbidities, cancer care

Xiaofen Chen,1 Weiting Chen,1 Weijie Hu,2 Kui Huang,3 Jing Huang,4 Yu Zhou5 1Hospital of Stomatology, Wenzhou Medical University, Wenzhou, 2People Hospital of Tiantai, Taizhou, 3Department of Orthodontics, Hospital of Stomatology, Wenzhou Medical University, Wenzhou, 4The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, 5Department of Orthodontics, Hospital of Stomatology, Wenzhou Medical University, Wenzhou, People’s Republic of China Background: Continuous positive airway pressure (CPAP) is widely recommended for the treatment of sleep apnea/hypopnea syndrome (SAHS), but its usage by patients is very low. The aim of this study was to assess intensive educational programs and nursing support for the improvement of CPAP use and outcomes in SAHS patients.Methods: Eighty new SAHS patients were randomized to receive nurse-led intensive interventions or usual support at hospital and home. The main outcome measure was CPAP use; changes in sleeping, symptoms, mood, and quality of life were also assessed after 12 months of treatment.Results: All outcome measures were improved after treatment in both groups. However, patients receiving intensive support with significantly higher CPAP use (higher daily CPAP usage by 2.2 hours/day) had greater improvements in SAHS symptoms and mood (P

Xiaonan Wu,1 Leiying Miao,2,# Yingfang Yao,3 Wenlei Wu,1 Yu Liu,1 Xiaofeng Chen,1 Weibin Sun1,# 1Department of Periodontology, Hospital of Stomatology, Medical School of Nanjing University, Nanjing, People’s Republic of China; 2Department of Cariology and Endodontics, Hospital of Stomatology, Medical School of Nanjing University, Nanjing, People’s Republic of China; 3Eco-materials and Renewable Energy Research Center, Department of Materials Science and Engineering, National Laboratory of Solid State Microstructures, Nanjing University, Nanjing, People’s Republic of China #These authors contributed equally to this work Abstract: Periodontal repair is a complex process in which regeneration of alveolar bone is a vital component. The aim of this study was to develop a biodegradable scaffold with good biocompatibility and osteoinductive ability. Two types of composite fibrous scaffolds were produced by electrospinning, ie, type I collagen/poly(є-caprolactone) (COL/PCL) and type I collagen/poly(є-caprolactone)/nanoscale hydroxyapatite (COL/PCL/nHA) with an average fiber diameter of about 377 nm. After a simulated body fluid (SBF) immersion test, the COL/PCL/nHA-SBF scaffold developed a rough surface because of the calcium phosphate deposited on the fibers, suggesting that the presence of nHA promoted the mineralization potential of the scaffold. Energy dispersive X-ray spectroscopy clearly showed the calcium and phosphorus content in the COL/PCL/nHA and COL/PCL/nHA-SBF scaffolds, confirming the findings of nHA and calcium phosphate precipitation on scanning electron micrographs. Water contact analysis revealed that nHA could improve the hydrophilic nature of the COL/PCL/nHA-SBF scaffold. The morphology of periodontal ligament cells cultured on COL/PCL-SBF and COL/PCL/nHA-SBF was evaluated by scanning electron microscopy. The results showed that cells adhered to either type of scaffold and were slightly spindle-shaped in the beginning, then extended gradually with stretched filopodia, indicating an ability to fill the fiber pores. A Cell Counting Kit-8 assay showed that both scaffolds supported cell proliferation. However, real-time quantitative polymerase chain reaction analysis showed that expression of the bone-related markers, alkaline phosphatase and osteocalcin, was upregulated only on the COL/PCL/nHA-SBF scaffold, indicating that this scaffold had the ability to induce osteogenic differentiation of periodontal ligament cells. In this study, COL/PCL/nHA-SBF produced by electrospinning followed by biomimetic mineralization had combined electrospun fibers with nHA in it. This scaffold has good biocompatibility and osteoinductive ability as a result of the characteristics of nHA, so could be innovatively applied to periodontal tissue engineering as a potential scaffold. Keywords: nanoscale hydroxyapatite, electrospinning, periodontal ligament cells

The proliferation of vascular smooth muscle cells (VSMCs) induced by injury to the intima of arteries is an important etiologic factor in vascular proliferative disorders such as atherosclerosis and restenosis. 2,3,4',5-Tetrahydroxystilbene-2-O-β-D-glucoside (TSG), an active component extracted from Polygonum multiflorum, has been found to have an antiatherosclerotic effect. The aim of this study was to investigate the effects of TSG on platelet derived growth factor (PDGF)-BB induced VSMCs proliferation and to explore the possible mechanisms of such effects. Pretreatment of VSMCs with TSG significantly inhibited PDGF-BB-induced cell proliferation in a concentration-dependent but not time-dependent manner. In addition, flow cytometry analysis of the DNA content revealed blocking of the PDGF-BB-inducible cell cycle progression by TSG. On the contrary, an inhibitory effect of TSG on VSMCs proliferation and expression of cell cycle regulators were markedly attenuated by addition of an nitric oxide (NO) synthase inhibitor, a soluble guanylate cyclase inhibitor and a cyclic GMP (cGMP)-dependent protein kinase (PKG) inhibitor: N(G)-nitro-L-arginine methyl ester (L-NAME), 1H-[1,2,4] oxadiazolo [4,3-α] quinoxalin-1-one (ODQ) and KT5823, respectively. It was also demonstrated that TSG enhanced NO and cGMP formation through up-regulating endothelial NO synthase expression in VSMCs. The findings indicate that TSG inhibited VSMCs proliferation induced by PDGF-BB may involve the NO/cGMP/PKG signal pathway. [ABSTRACT FROM AUTHOR]

Heavy metals, including Hg 2+ , Cr 6+ and Cd 2+ , have always been a major issue in environmental pollution, leading to abnormal changes in the levels of biologically active molecules including Cys in plants, seriously affecting all aspects of the growth and development of plants. This makes it essential to develop a simple and practical method to study the potential impact of heavy metals on plants. In this paper, our research group has developed near-infrared fluorescent probe WRM-S, which has the advantages of fast response, sensitivity to Cys, and successfully applying it to cells and zebrafish. Moreover, it combined the close relationship between heavy metal stress on plants and Cys, using Cys as the detection target, monitoring the internal environment changes of two plants under Hg 2+ , Cr 6+ , and Cd 2+ stress in the environment, and then conducting 3D imaging. The results indicated that the probe has strong penetration ability in plant tissues, and revealed abnormal changes in plant Cys levels caused by heavy metal stress-induced cellular oxidative stress or cytotoxicity. Thus, the in-situ imaging detection of this probe provides a direction for the physiological dynamics research of plant environmental stress., 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: There exist serious cardiovascular complications subsequent to SARS-Cov2 infection (COVID-19); however, the association between COVID-19 and atrial fibrillation (AF) remains to be elucidated. We aimed to assess the prevalence of AF among COVID-19 patients and its associated risk of death., Methods: The present systematic review was performed in accordance with the PRISMA guidelines. The protocol was registered with CRD42022306523. A comprehensive literature search was performed across PubMed, Embase, and Cochrane databases to identify studies reporting on the prevalence of pre-existing or new-onset fibrillation (AF), and/or the associated clinical outcomes in patients with COVID-19 from January 2020 to December 2023. The random-effect model was used to estimate the prevalence of AF and its related mortality., Results: A total of 80 studies, including 39,062,868 COVID-19 patients, were identified in the present investigation. The prevalence rates of pre-existing AF or new-onset AF were 10.5% (95% CI [9.3-11.7%]) or 10.3% (95% CI [6.2-14.5%]), respectively. Subgroup analysis revealed a two fold higher incidence of AF in older patients (≥65 years) compared to younger patients (<65 years) (14.4% vs . 6.4%). The highest rate of AF was observed in Europeans (10.7%, 95% CI [10.2-11.2%]), followed by Northern Americans (10.0%, 95% CI [8.2-11.7%]), while Asians demonstrated a lower prevalence (2.7%, 95% CI [2.2-3.3%]). Notably, severe COVID-19 patients displayed a significantly elevated prevalence of AF at 14.l% (95% CI [13.3-14.9%]), which was approximately 2.5-fold higher than that in non-severe patients (5.2%, 95% CI [4.8-5.5%]). Both pre-existing (HR: 1.83, 95% CI [1.49-2.17]) and new-onset AF (HR: 3.47, 95% CI [2.26-5.33]) were associated with an increased mortality risk among COVID-19 patients. Furthermore, the effect on mortality risk was more significant in Asians (HR: 5.33, 95% CI [1.62-9.04]), compared to Europeans (HR: 1.68, 95% CI [1.24-2.13]) and North Americans (HR: 2.01, 95% CI [1.18-2.83])., Conclusion: This study comprehensively investigated the association between AF and COVID-19 in a real-world setting. Notably, a high prevalence of AF was observed among older individuals, severe COVID-19 patients, and in Europe and Northern America. Moreover, co-existing AF was found to be associated with an increased risk for mortality. Further investigations are warranted to improve the management and outcomes of COVID-19 patients with AF., Competing Interests: The authors declare that they have no competing interests., (© 2024 Shen et al.)

Next-generation sequencing (NGS) is of great benefit to clinical practice in terms of identifying genetic alterations. This study aims to clarify the gene background and its influence on thyroid tumors in the Chinese population. NGS data and corresponding clinicopathological features (sex, age, tumor size, extrathyroidal invasion, metastasis, multifocality, and TNM stage) were collected and analyzed retrospectively from 2844 individual thyroid tumor samples from July 2021 to August 2022. Among the cohort, 2337 (82%) cases possess genetic alterations, including BRAF (71%), RAS (4%), RET/PTC (4%), TERT (3%), RET (2.2%), and TP53 (1.4%). Diagnostic sensitivity before surgery can be significantly increased from 0.76 to 0.91 when cytology is supplemented by NGS. Our results show that BRAF-positive papillary thyroid cancer (PTC) patients tend to have older age, smaller tumor size, less vascular invasion, more frequent tumor multifocality, and a significantly higher cervical lymph node metastatic rate. Mutation at RET gene codons 918 and 634 is strongly correlated with medullary thyroid cancer. However, it did not display more invasive clinical characteristics. TERT-positive patients are more likely to have older age, and have larger tumor size, more tumor invasiveness, and more advanced TNM stage, indicating a poor prognosis. Patients with TERT, RET/PTC1, and CHEK2 mutations are more susceptible to lateral lymph node metastasis. In conclusion, NGS can be a useful tool that provides practical gene evidence in the process of diagnosis and treatment in thyroid tumors.

Ethnopharmacological Relevance: Chuanminshen violaceum M. L. Sheh & R. H. Shan (CV) is used as a medicine with roots, which have the effects of benefiting the lungs, harmonizing the stomach, resolving phlegm and detoxifying. Polysaccharide is one of its main active components and has various pharmacological activities, but the structural characterization and pharmacological activities of polysaccharide from the stems and leaves parts of CV are still unclear., Aim of the Study: The aim of this study was to investigate the optimal extraction conditions for ultrasound-assisted extraction of polysaccharide from CV stems and leaves, and to carry out preliminary structural analyses, anti-inflammatory and antioxidant effects of the obtained polysaccharide and to elucidate the underlying mechanisms., Materials and Methods: The ultrasonic-assisted extraction of CV stems and leaves polysaccharides was carried out, and the response surface methodology (RSM) was used to optimize the extraction process to obtain CV polysaccharides (CVP) under the optimal conditions. Subsequently, we isolated and purified CVP to obtain the homogeneous polysaccharide CVP-AP-I, and evaluated the composition, molecular weight, and structural features of CVP-AP-I using a variety of technical methods. Finally, we tested the pharmacological activity of CVP-AP-Ⅰ in an LPS-induced model of oxidative stress and inflammation in intestinal porcine epithelial cells (IPEC-J2) and explored its possible mechanism of action., Results: The crude polysaccharide was obtained under optimal extraction conditions and subsequently isolated and purified to obtain CVP-AP-Ⅰ (35.34 kDa), and the structural characterization indicated that CVP-AP-Ⅰ was mainly composed of galactose, galactose, rhamnose and glucose, which was a typical pectic polysaccharide. In addition, CVP-AP-Ⅰ attenuates LPS-induced inflammation and oxidative stress by inhibiting the expression of pro-inflammatory factor genes and proteins and up-regulating the expression of antioxidant enzyme-related genes and proteins in IPEC-J2, by a mechanism related to the activation of the Nrf2/Keap1 signaling pathway., Conclusion: The results of this study suggest that the polysaccharide isolated from CV stems and leaves was a pectic polysaccharide with similar pharmacological activities as CV roots, exhibiting strong anti-inflammatory and antioxidant activities, suggesting that CV stems and leaves could possess the same traditional efficacy as CV roots, which is expected to be used in the treatment of intestinal diseases., Competing Interests: Declaration of competing interest 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 Elsevier B.V. All rights reserved.)

Background: Colorectal cancer (CRC) is a significant disease worldwide, with high mortality rates. Conventional treatment methods often lead to metastasis and drug resistance, highlighting the need to explore new drugs and their potential molecular mechanisms. In this study, we investigated the effects of arctigenin on CRC cell proliferation, migration, invasion, apoptosis, and related protein expression, as well as its potential molecular mechanisms., Methods: The CCK-8 assay, transwell migration and invasion assays, flow cytometry, immunoblotting and immunofluorescence staining, western blot and an allograft tumor transplantation model was used., Results: Our study revealed that arctigenin effectively inhibited CRC cell proliferation, migration, and invasion in a dose-dependent manner, while also inducing apoptosis. At the molecular level, arctigenin significantly downregulated the expressions of PCNA, Bcl2, MMP-2, and MMP-9 and upregulated the expressions of Bax and cleaved caspase-3. Additionally, arctigenin demonstrated the ability to inhibit the epithelial-mesenchymal transition (EMT) process by upregulating E-cadherin and downregulating mesenchymal markers, such as N-cadherin, Vimentin, Snail, and Slug. Furthermore, arctigenin could inhibit the activation of the PI3K-AKT-mTOR signaling pathway, which has been implicated in cancer progression. In vivo experiments also showed that arctigenin significantly reduced tumor volume and size compared to the control group, with no significant adverse effects on the liver., Conclusions: This is the first study to elucidate the mechanism by which arctigenin inhibits colorectal cancer metastasis through the PI3K-AKT-mTOR signaling pathway by suppressing the EMT process at the molecular level., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chen 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.)

Our objective is to evaluate radiation dose and image quality in pediatric paranasal sinus computed tomography (CT) with automatic tube current modulation (ATCM) and sinogram-affirmed iterative reconstruction algorithm (SAFIRE). CT scans from 80 patients were divided into two groups: Group A [80 kVp, pitch 1.5, 40 mAs, the filtered back projection (FBP) algorithm] and Group B (70 kVp, pitch 3, ATCM with reference at 40 mAs, SAFIRE strengths 1-5). We have evaluated image quality and radiation dose. Group B demonstrated significantly lower volume computed tomography dose index, dose-length product, and effective dose than Group A (0.13 ± 0.03 vs. 1.57 ± 0.01 mGy, 2.27 ± 0.82 vs. 19.88 ± 2.01 mGy·cm, and 0.0081 ± 0.0017 vs. 0.079 ± 0.013 mSv, respectively; P < .001). Increasing SAFIRE strengths correlated with noise reduction and SNR enhancement. Group B's noise and SNRsoft at SAFIRE strength 5 were comparable with Group A. Images reconstructed with SAFIRE strength 5 in Group B exhibit comparable image quality with FBP in Group A., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The contribution of plant hormones and energy-rich compounds and their metabolites (ECMs) in alleviating aluminum (Al) toxicity by elevated pH remains to be clarified. For the first time, a targeted metabolome was applied to identify Al-pH-interaction-responsive hormones and ECMs in Citrus sinensis leaves. More Al-toxicity-responsive hormones and ECMs were identified at pH 4.0 [4 (10) upregulated and 7 (17) downregulated hormones (ECMs)] than those at pH 3.0 [1 (9) upregulated and 4 (14) downregulated hormones (ECMs)], suggesting that the elevated pH improved the adaptation of hormones and ECMs to Al toxicity in leaves. The roles of hormones and ECMs in reducing leaf Al toxicity mediated by elevated pH might include the following aspects: (a) improved leaf growth by upregulating the levels of jasmonoyl-L-isoleucine (JA-ILE), 6-benzyladenosine (BAPR), N6-isopentenyladenosine (IPR), cis-zeatin-O-glucoside riboside (cZROG), and auxins (AUXs), preventing Al toxicity-induced reduction of gibberellin (GA) biosynthesis, and avoiding jasmonic acid (JA)-mediated defense; (b) enhanced biosynthesis and accumulation of tryptophan (TRP), as well as the resulting increase in biosynthesis of auxin, melatonin and secondary metabolites (SMs); (c) improved ability to maintain the homeostasis of ATP and other phosphorus (P)-containing ECMs; and (d) enhanced internal detoxification of Al due to increased organic acid (OA) and SM accumulation and elevated ability to detoxify reactive oxygen species (ROS) due to enhanced SM accumulation. To conclude, the current results corroborate the hypotheses that elevated pH reduces Al toxicity by upregulating the ability to maintain the homeostasis of ATP and other P-containing ECMs in leaves under Al toxicity and (b) hormones participate in the elevated pH-mediated alleviation of Al toxicity by positively regulating growth, the ability to detoxify ROS, and the internal detoxification of Al in leaves under Al toxicity. Our findings provide novel insights into the roles of hormones and ECMs in mitigating Al toxicity mediated by the elevated pH., 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 Authors. Published by Elsevier Inc. All rights reserved.)

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.)

In the last decade, chirality-induced spin selectivity (CISS) has undergone intensive study. However, there remain several critical issues, such as the microscopic mechanism of CISS, especially transverse CISS where electrons are injected perpendicular to the helix axis of chiral molecules, quantitative agreement between experiments and theory, and at which level the molecular handedness is key to the CISS. Here, we address these issues by performing a combined experimental and theoretical study on conducting polyaniline helical nanofibers which are synthesized in the absence of any chiral species. Large spin polarization is measured in both left- and right-handed nanofibers for electrons injected perpendicular to their helix axis, and it will be reversed by switching the nanofiber handedness. We first develop a theoretical model to study this transverse CISS and quantitatively explain the experiment. Our results reveal that our theory provides a unifying scheme to interpret a number of CISS experiments, quantitative agreement between experiments and numerical calculations can be achieved by weak spin-orbit coupling, and the supramolecular handedness is sufficient for spin selectivity without any chiral species.

Both copper (Cu) excess and boron (B) deficiency are often observed in some citrus orchard soils. The molecular mechanisms by which B alleviates excessive Cu in citrus are poorly understood. Seedlings of sweet orange (Citrus sinensis (L.) Osbeck cv. Xuegan) were treated with 0.5 (Cu0.5) or 350 (Cu350 or Cu excess) μM CuCl2 and 2.5 (B2.5) or 25 (B25) μM HBO3 for 24 wk. Thereafter, this study examined the effects of Cu and B treatments on gene expression levels revealed by RNA-Seq, metabolite profiles revealed by a widely targeted metabolome, and related physiological parameters in leaves. Cu350 upregulated 564 genes and 170 metabolites, and downregulated 598 genes and 58 metabolites in leaves of 2.5 μM B-treated seedlings (LB2.5), but it only upregulated 281 genes and 100 metabolites, and downregulated 136 genes and 40 metabolites in leaves of 25 μM B-treated seedlings (LB25). Cu350 decreased the concentrations of sucrose and total soluble sugars and increased the concentrations of starch, glucose, fructose and total nonstructural carbohydrates in LB2.5, but it only increased the glucose concentration in LB25. Further analysis demonstrated that B addition reduced the oxidative damage and alterations in primary and secondary metabolisms caused by Cu350, and alleviated the impairment of Cu350 to photosynthesis and cell wall metabolism, thus improving leaf growth. LB2.5 exhibited some adaptive responses to Cu350 to meet the increasing need for the dissipation of excessive excitation energy (EEE) and the detoxification of reactive oxygen species (reactive aldehydes) and Cu. Cu350 increased photorespiration, xanthophyll cycle-dependent thermal dissipation, nonstructural carbohydrate accumulation, and secondary metabolite biosynthesis and abundances; and upregulated tryptophan metabolism and related metabolite abundances, some antioxidant-related gene expression, and some antioxidant abundances. Additionally, this study identified some metabolic pathways, metabolites and genes that might lead to Cu tolerance in leaves., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

We describe for the first time, a high-quality genome for a rare human yeast pathogen Candida mucifera, from a patient with chronic suppurative otitis media. This pathogen exhibited reduced azole susceptibility, similar to its close relatives within the Trichomonascus ciferrii species complex., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The National Nutrition Plan(2017-2030) and the Healthy China Action Plan(2019-2030) propose to vigorously develop traditional dietary care services, fully leverage the role of traditional dietary care in modern nutrition, and guide citizens to develop dietary habits that are in line with the dietary characteristics of different regions in China. Traditional dietary care has a long history in China and is one of the brilliant treasures of Chinese cuisine and traditional Chinese medicine(TCM) culture. It has played an important role in disease prevention, treatment, and health preservation and longevity. To promote the traditional culture of TCM, and guide and standardize the application and promotion of dietary care, it is necessary to develop a dietary care guideline with TCM characteristics. Based on the theories and practices of TCM, the China Academy of Chinese Medical Sciences(CACMS) has developed this guideline, which is tailored to local conditions and combined with modern nutrition, and targets people with different physical constitutions. According to the principles of dialectical diet, tailored to people, times, and local conditions, reinforcing healthy qi, correction, the combination of meat and vegetables, and the combination of four qi and five flavors, suitable ingredients are recommended(including TCM materials that are both food and medicinal materials). By promoting the popularization and development of traditional dietary care, this guideline contributes to integrating the strength of TCM into a unique nutritional and health model with Chinese characteristics.

Rosacea is a chronic inflammatory skin disease, which is prone to flares and requires continuous management and treatment. However, long-term use of drugs can lead to additional adverse drug reactions. Based on the comorbid relationship between rosacea and Parkinson's disease, bioinformatics and network pharmacology analysis were used to identify a safer drug for rosacea. It has been demonstrated that ISA has an ameliorative impact on the symptoms of Parkinson's disease. The results demonstrated that ISA exhibited anti-inflammatory properties, including reducing erythema areas and inflammatory cell infiltration in rosacea-like mice models, and inhibiting the expression of inflammatory factors in cellular inflammation models. Furthermore, the anti-inflammatory effect of ISA was associated with inhibition of the Erk, p38 and NF-κB signaling pathways and inhibition of macrophage polarization to M1 type. In addition, molecular docking and drug affinity responsive target stability experiment results indicated that VEGFA and RELA were the direct targets of ISA in the treatment for rosacea. In conclusion, these results suggested that ISA may be a potential therapeutic agent for rosacea., 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: The systemic inflammatory response index (SIRI), served as a novel inflammatory biomarker, is the synthesis of neutrophils, monocytes and lymphocytes., Aims: We hypothesized that SIRI has predictive value for contrast-associated acute kidney injury (CA-AKI) and long-term mortality in patients undergoing elective percutaneous coronary intervention (PCI)., Methods: We retrospectively observed 5685 patients undergoing elective PCI from January 2012 to December 2018. Venous blood samples were collected to obtain the experimental data on the day of admission or the morning of the next day. SIRI = neutrophil count × monocyte count/lymphocyte count. CA-AKI was defined as an increase of 50% or 0.3 mg/dl in SCr from baseline within 48 h after contrast exposure., Results: The incidence of CA-AKI was 6.1% ( n  = 352). The best cutoff value of SIRI for predicting CA-AKI was 1.39, with a sensitivity of 52.3% and a specificity of 67.3%. [AUC: 0.620, 95% confidence interval (CI): 0.590-0.651, p  < 0.001]. After adjusting for potential confounders, multivariate analysis showed that the high SIRI group (SIRI > 1.39) was a strong independent predictor of CA-AKI in patients undergoing elective PCI compared with the low SIRI group (SIRI ≤ 1.39) (odds ratio = 1.642, 95% CI: 1.274-2.116, p <  0.001). Additionally, COX regression analysis showed that SIRI > 1.39 was significantly associated with long-term mortality at a median follow-up of 2.8 years. [Hazard ratio (HR)=1.448, 95%CI: 1.188-1.765; p  < 0.001]. Besides, Kaplan-Meier survival curve also indicated that the cumulative rate of mortality was considerably higher in the high SIRI group., Conclusions: High levels of SIRI are independent predictors of CA-AKI and long-term mortality in patients undergoing elective PCI.

Background: Cancer-associated fibroblasts (CAFs) are the prominent cell type in the tumor microenvironment (TME), and CAF subsets have been identified in various tumors. However, how CAFs spatially coordinate other cell populations within the liver TME to promote cancer progression remains unclear., Methods: We combined multi-region proteomics (6 patients, 24 samples), 10X Genomics Visium spatial transcriptomics (11 patients, 25 samples), and multiplexed imaging (92 patients, 264 samples) technologies to decipher the expression heterogeneity, functional diversity, spatial distribution, colocalization, and interaction of fibroblasts. The newly identified CAF subpopulation was validated by cells isolated from 5 liver cancer patients and in vitro functional assays., Results: We identified a liver CAF subpopulation, marked by the expression of COL1A2, COL4A1, COL4A2, CTGF, and FSTL1, and named F5-CAF. F5-CAF is preferentially located within and around tumor nests and colocalizes with cancer cells with higher stemness in hepatocellular carcinoma (HCC). Multiplexed staining of 92 patients and the bulk transcriptome of 371 patients demonstrated that the abundance of F5-CAFs in HCC was associated with a worse prognosis. Further in vitro experiments showed that F5-CAFs isolated from liver cancer patients can promote the proliferation and stemness of HCC cells., Conclusions: We identified a CAF subpopulation F5-CAF in liver cancer, which is associated with cancer stemness and unfavorable prognosis. Our results provide potential mechanisms by which the CAF subset in the TME promotes the development of liver cancer by supporting the survival of cancer stem cells., (© 2024. The Author(s).)