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Shangyu Luo,1 Xueqin Hu,2 Yunjun Hong,1 Yunchun Gao,1 Xianglin Liu,1 Yu Peng,1 Xueqing Tong,3 Xiaobo Zhang,1 Jun Wen1 1Department of Neurology, Changde Hospital, Xiangya School of Medicine, Central South University (The First People’s Hospital of Changde City), Changde City, Hunan Province, People’s Republic of China; 2Department of Neurosurgery, Changde Hospital, Xiangya School of Medicine, Central South University (The First People’s Hospital of Changde City), Changde City, Hunan Province, People’s Republic of China; 3Department of Brain Electrophysiology, Changde Hospital, Xiangya School of Medicine, Central South University (The first People’s hospital of Changde city), Changde City, Hunan Province, People’s Republic of ChinaCorrespondence: Xiaobo Zhang; Jun Wen, Fax +86 0736 7788009 ; +86 0736 7788010, Email 285058041@qq.com; cdwenjun1973@163.comPurpose: Research on post-stroke depression (PSD) following the lifting of coronavirus disease 2019 (COVID-19) restrictions remains sparse. This study aimed to investigate the factors associated with PSD after the easing of COVID-19 restriction measures.Patients and Methods: This cross-sectional study was conducted with 947 stroke patients (cerebral hemorrhage and cerebral infarction) meeting the inclusion criteria. Participants completed a demographic questionnaire and the Patient Health Questionnaire-9 (PHQ-9). Additionally, data were collected on C-reactive protein (CRP), homocysteine (Hcy), modified Rankin Scale (mRS), stroke site, National Institutes of Health Stroke Scale (NIHSS), thyroid-stimulating hormone (TSH), and the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification. This study assessed correlations between these indices and PSD.Results: Stroke patients with a PHQ-9 score ≥ 5 were identified as having PSD, with a prevalence rate of 14.15%. No significant correlation was found between previous COVID-19 infection and PSD. However, multiple regression analysis revealed associations between PSD and the following factors: TSH (OR: 0.87, 95% CI: 0.76– 1), CRP levels (OR: 1.01, 95% CI: 1– 1.02), family history of stroke (OR: 4.25, 95% CI: 1.66– 10.88), migraine history (OR: 8.63, 95% CI: 2.49– 29.85), and shorter sleep duration (OR: 0.6, 95% CI: 0.51– 0.71) (all P

Yan Ji,1 Haorong Li,1 Jiguo Li,2 Guangqiang Yang,1 Wenli Zhang,1 Yan Shen,1 Bohui Xu,3 Jianping Liu,1 Jingyuan Wen,4 Wenting Song1 1Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China; 2Nanjing Miaobang Meiye Enterprise Management Co, LTD, Nanjing, People’s Republic of China; 3School of Pharmacy, Nantong University, Nantong, 226001, People’s Republic of China; 4School of Pharmacy, Faculty of Medical and Health Sciences, the University of Auckland, Auckland, New ZealandCorrespondence: Wenting Song, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing, 211198, People’s Republic of China, Email songwenting908@163.com Jingyuan Wen, School of Pharmacy, Faculty of Medical and Health Sciences, the University of Auckland, Auckland, New Zealand, Email j.wen@auckland.ac.nzPurpose: Acne vulgaris is a chronic inflammatory skin disorder centered on hair follicles, making hair follicle-targeted delivery of anti-acne drugs a promising option for acne treatment. However, current researches have only focused on the delivering to healthy hair follicles, which are intrinsically different from pathologically clogged hair follicles in acne vulgaris.Patients and Methods: Azelaic acid (AZA) micro/nanocrystals with different particle sizes were prepared by wet media milling or high-pressure homogenization. An experiment on AZA micro/nanocrystals delivering to healthy hair follicles was carried out, with and without the use of physical enhancement techniques. More importantly, it innovatively designed an experiment, which could reveal the ability of AZA micro/nanocrystals to penetrate the constructed clogged hair follicles. The anti-inflammatory and antibacterial effects of AZA micro/nanocrystals were evaluated in vitro using a RAW264.7 cell model stimulated by lipopolysaccharide and a Cutibacterium acnes model. Finally, both the anti-acne effects and skin safety of AZA micro/nanocrystals and commercial products were compared in vivo.Results: In comparison to commercial products, 200 nm and 500 nm AZA micro/nanocrystals exhibited an increased capacity to target hair follicles. In the combination group of AZA micro/nanocrystals and ultrasound, the ability to penetrate hair follicles was further remarkably enhanced (ER value up to 9.6). However, toward the clogged hair follicles, AZA micro/nanocrystals cannot easily penetrate into by themselves. Only with the help of 1% salicylic acid, AZA micro/nanocrystals had a great potential to penetrate clogged hair follicle. It was also shown that AZA micro/nanocrystals had anti-inflammatory and antibacterial effects by inhibiting pro-inflammatory factors and Cutibacterium acnes. Compared with commercial products, the combination of AZA micro/nanocrystals and ultrasound exhibited an obvious advantage in both skin safety and in vivo anti-acne therapeutic efficacy.Conclusion: Hair follicle-targeted delivery of AZA micro/nanocrystals provided a satisfactory alternative in promoting the treatment of acne vulgaris.Keywords: acne vulgaris, azelaic acid, hair follicle, micro/nanocrystals, targeted delivery

Yuqing Bu,1,* Junye Wen,2,* Fayan Wang,1,3 Shibo Dong,4 Liya He,1 Yang Li,1,5 Jinlong Liang,1,3 Hongzhen Zhang1,3,5 1Department of Oncology, Hebei General Hospital, Shijiazhuang, Hebei Province, 050051, People’s Republic of China; 2Department of Hepatobiliary Surgery, Hebei General Hospital, Shijiazhuang, Hebei Province, 050051, People’s Republic of China; 3Department of Medicine, Hebei North University, Zhangjiakou, Hebei Province, 075000, People’s Republic of China; 4Department of Imaging, Hebei General Hospital, Shijiazhuang, Hebei Province, 050051, People’s Republic of China; 5Department of Medicine, North China University of Science and Technology, Tangshan, Hebei Province, 063210, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongzhen Zhang, Email hongzhenzhang456@sohu.comAbstract: This study presents a case of dual primary liver cancer involving small cell neuroendocrine carcinoma and hepatocellular carcinoma. The 58-year-old Chinese male patient, who has a medical history of viral hepatitis B, presented with right upper abdominal pain persisting for one month. Imaging studies indicated the presence of multiple liver masses in segments V and VII–VIII, as well as a mass in the left lung. Subsequent hepatic biopsy performed on both segments confirmed the presence of hepatocellular carcinoma in segment V and small cell neuroendocrine carcinoma in segment VII–VIII. After undergoing one cycle of chemotherapy, the lung mass exhibited a reduction in size, while the liver masses showed an inadequate response. Subsequently, the patient underwent Transcatheter Arterial Chemoembolization (TACE) and Hepatic Artery Infusion Chemotherapy (HIAC), resulting in partial remission (PR). However, the patient was diagnosed with brain metastasis and subsequently treated with Sorafenib and Tirelizumab, a Programmed Death 1 (PD-1) immune checkpoint inhibitor. The efficacy evaluation indicated stability, and no severe adverse effects were observed at the time of writing. The patient’s survival time was 16 months.Keywords: synchronous tumor, liver tumor, primary tumor, small cell neuroendocrine carcinoma, hepatocellular carcinoma

Yanyi Wang,1,2,* Juan Wen,1– 3,* Tong Lu,1,2 Wei Han,2,4 Kai Jiao,5 Huang Li1,2 1Department of Orthodontics, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, People’s Republic of China; 2Medical School of Nanjing University, Nanjing, People’s Republic of China; 3Centre for Orofacial Regeneration, Reconstruction and Rehabilitation (COR3), School of Dentistry, The University of Queensland, Brisbane, Queensland, 4006, Australia; 4Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, People’s Republic of China; 5Department of Stomatology, Tangdu Hospital & State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, School of Stomatology, The Fourth Military Medical University, Xi’an, Shaanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Han, Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, 30 Central Road, Nanjing, 210008, People’s Republic of China, Email doctorhanwei@hotmail.com Huang Li, Department of Orthodontics, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, 30 Central Road, Nanjing, 210008, People’s Republic of China, Tel +86-25-83620173, Fax +86-25-83620200, Email lihuang76@nju.edu.cnAbstract: Extracellular vesicles (EVs) can deliver various bioactive molecules among cells, making them promising diagnostic and therapeutic alternatives in diseases. Mesenchymal stem cell-derived EVs (MSC-EVs) have shown therapeutic potential similar to MSCs but with drawbacks such as lower yield, reduced biological activities, off-target effects, and shorter half-lives. Improving strategies utilizing biotechniques to pretreat MSCs and enhance the properties of released EVs, as well as modifying MSC-EVs to enhance targeting abilities and achieve controlled release, shows potential for overcoming application limitations and enhancing therapeutic effects in treating bone-related diseases. This review focuses on recent advances in functionalizing MSC-EVs to treat bone-related diseases. Firstly, we underscore the significance of MSC-EVs in facilitating crosstalk between cells within the skeletal environment. Secondly, we highlight strategies of functional-modified EVs for treating bone-related diseases. We explore the pretreatment of stem cells using various biotechniques to enhance the properties of resulting EVs, as well as diverse approaches to modify MSC-EVs for targeted delivery and controlled release. Finally, we address the challenges and opportunities for further research on MSC-EVs in bone-related diseases.Keywords: extracellular vesicles, mesenchymal stem cells, functional modification, bone-related diseases

Alpine tundra, covering 3% of the Earth’s land surface, harbors approximately 4% of higher plant species. Changes in this vegetation significantly impact biodiversity and ecosystem services. Recent studies have primarily focused on large-scale and long-term vegetation changes in polar and high-latitude regions. However, the study of short-term vegetation changes and their primary drivers has received insufficient attention in alpine tundra. This study aimed to investigate vegetation changes and their dominant drivers in the alpine tundra of Changbai Mountains-located at the southern edge of the alpine tundra distribution in Eastern Eurasia-over a short period by re-surveying permanent plots in 2019 and comparing them with data from 2014. The results showed that significant changes were observed in alpine tundra vegetation during the study period. The importance values of typical alpine tundra plants such as Rhododendron chrysanthum, Vaccinium uliginosum, and Dryas octopetala decreased noticeably, while those of herbaceous species such as Deyeuxia angustifolia and Sanguisorba sitchensis increased significantly. Species richness, diversity, and evenness at different altitudinal gradients showed varying degrees of increase. A distinct expansion trend of herbaceous species was observed in the alpine tundra, contributing to a shift in plant community composition toward herbaceous dominance. This shift might result in the meadowization of the dwarf shrub tundra. Our findings further revealed that soil nutrients rather than climate factors, dominated the changes of plant communities over a short period. These findings provide scientific references for the conservation and management of biodiversity, as well as for projecting future vegetation dynamics in alpine tundra.

Woody plant encroachment (WPE), a global phenomenon documented across various biomes and continents, has the potential to significantly impact ecosystem carbon and water cycling. However, the impacts of WPE on carbon and water cycling in wetland ecosystems of middle and high latitudes are still lacking. In this study, the interannual and seasonal impacts of WPE on gross primary production (GPP) and evapotranspiration (ET), as well as their underlying mechanisms, within boreal wetland ecosystems located in middle-high latitude regions, were examined using remote sensing datasets spanning the period 2001–2016. Our results demonstrated that WPE enhanced annual GPP, ET, Normalized Difference Vegetation Index (NDVI), and solar-induced chlorophyll fluorescence (SIF) in boreal wetlands with impacts increasing over time. The multi-year average GPP and ET in fully encroached wetland ecosystems were approximately 31% and 3% higher, respectively, compared to pure wetland ecosystems. Prominent increases in wetland GPP occurred during the early growing season, while an exacerbation of ET was observed during the peak growing season. The impacts of WPE on wetland GPP and ET were predominantly attributed to increased vegetation greenness followed by secondary contributions from climate change. Climate change not only directly influenced the responses of GPP and ET to WPE but also exerted indirect effects by regulating vegetation greenness and the degree of encroachment. Our findings offer valuable insights into the understanding of the interaction between WPE and climate change, highlighting the importance of considering WPE effects and their drivers for accurate predictions of carbon and water cycles, as well as atmosphere–biosphere feedbacks in boreal wetlands.

Woody plant encroachment (WPE), a widespread ecological phenomenon globally, has significant impacts on ecosystem structure and functions. However, little is known about how WPE affects phenology in wetland ecosystems of middle and high latitudes. Here, we investigated the regional-scale effects of WPE on the start (SOS), peak (POS), end (EOS), and length (GSL) of the growing season in boreal wetland ecosystems, and their underlying mechanisms, using remote sensing dataset during 2001–2016. Our results showed that WPE advanced the annual SOS and POS, while delaying EOS and extending GSL in boreal wetlands with these impacts increasing over time. When boreal wetland ecosystems were fully encroached by woody plants, the SOS and POS were advanced by 12.17 and 5.65 days, respectively, the EOS was postponed by 2.74 days, and the GSL was extended by 15.21 days. We also found that the impacts of WPE on wetland SOS were predominantly attributed to the increased degree of WPE (α), while climatic factors played a more significant role in controlling the POS and EOS responses to WPE. Climate change not only directly influenced phenological responses of wetlands to WPE but also exerted indirect effects by regulating soil moisture and α. Winter precipitation and spring temperature primarily determined the effects of WPE on SOS, while its impacts on POS were mainly controlled by winter precipitation, summer temperature, and precipitation, and the effects on EOS were mainly determined by winter precipitation, summer temperature, and autumn temperature. Our findings offer new insights into the understanding of the interaction between WPE and wetland ecosystems, emphasizing the significance of considering WPE effects to ensure accurate assessments of phenology changes.

Lin Sheng,1– 4,* Yumeng Wei,1,3,* Chao Pi,1,3,* Ju Cheng,3,4 Zhilian Su,1– 4 Yuanyuan Wang,1,5 Tao Chen,1– 4 Jie Wen,1– 4 Yuxun Wei,1– 4 Jingwen Ma,1– 4 Jia Tang,1– 4 Huiyang Liu,1– 4 Zerong Liu,6,7 Hongping Shen,8 Ying Zuo,9 Wenwu Zheng,10 Ling Zhao2– 4 1Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, People’s Republic of China; 2Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 3Key Laboratory of Medical Electrophysiology, Ministry of Education, Development Planning Department of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 4Central Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 5Department of Clinical Pharmacy, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 6Central Nervous System Drug Key Laboratory of Sichuan Province, Sichuan Credit Pharmaceutical CO., Ltd. Luxian County, Luzhou City, People’s Republic of China; 7Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400030, People’s Republic of China; 8Clinical Trial Center, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 9Department of Comprehensive Medicine, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 10Department of cardiology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenwu Zheng, Department of Cardiology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China, Tel/Fax +86 830 3165311, Email zhengwenwu888@163.com Ling Zhao, Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, No. 182, Chunhui Road, Longmatan District, Luzhou, Sichuan, 646000, People’s Republic of China, Tel/Fax +86 830 3160093, Email zhaoling@swmu.edu.cnPurpose: The early stage of this study verified that a turmeric extract (TUR) including 59% curcumin (CU), 22% demethoxycurcumin (DMC), and 18% bisdemethoxycurcumin (BDMC), could enhance the stability of CU and had greater antidepressant potential in vitro. The objective of the study was to develop a nano-delivery system containing TUR (TUR-NE) to improve the pharmacokinetic behavior of TUR and enhance its antidepressant effect.Methods: The antidepressant potential of TUR was explored using ABTS, oxidative stress-induced cell injury, and a high-throughput screening model. TUR-NE was fabricated, optimized and characterized. The pharmacokinetic behaviors of TUR-NE were evaluated following oral administration to normal rats. The antidepressant effect of TUR-NE was assessed within chronic unpredictable mild stress model (CUMS) mice. The behavioral and biochemical indexes of mice were conducted.Results: The results depicted that TUR had 3.18 and 1.62 times higher antioxidant capacity than ascorbic acid and CU, respectively. The inhibition effect of TUR on ASP+ transport was significantly enhanced compared with fluoxetine and CU. TUR-NE displayed a particle size of 116.0 ± 0.31 nm, polydispersity index value of 0.121 ± 0.007, an encapsulation rate of 98.45%, and good release and stability in cold storage. The results of pharmacokinetics indicated the AUC(0-t) of TUR-NE was 8.436 and 4.495 times higher than that of CU and TUR, while the Cmax was 9.012 and 5.452 times higher than that of CU and TUR, respectively. The pharmacodynamic study confirmed that the superior antidepressant effect of TUR-NE by significantly improving the depressant-like behaviors and elevating the content of 5-hydroxytryptamine in plasma and brain in CUMS mice. TUR-NE showed good safety with repeated administration.Conclusion: TUR-NE, which had small and uniform particle size, enhanced the bioavailability and antidepressant effect of TUR. It could be a promising novel oral preparation against depression.Keywords: turmeric extract, curcuminoids, nanoemulsion, stability, antidepressant effect, 5-hydroxytryptamine

Xueyuan Zhou, Yan Li, Jun Chen, Zhou Fang, Wei Kong, Ji Wen, Qiyao Zhang Reproductive Medical Center, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250000, People’s Republic of ChinaCorrespondence: Ji Wen; Qiyao Zhang, Reproductive Medical Center, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250000, People’s Republic of China, Tel +86 531-82436297, Email 72050580@sdutcm.edu.cn; qiyaozh@163.comPurpose: Transcutaneous electrical acupoint stimulation (TEAS) can be used in patients with infertility. This study explored the impact of TEAS on brain-derived neurotrophic factor (BDNF) levels and in-vitro fertilization (IVF) outcomes in patients with infertility.Patients and Methods: This quasi-experimental study included infertile women undergoing IVF and embryo transfer (IVF-ET) at one hospital between January 2018 and December 2021. The TEAS group received TEAS before IVF, while the placebo group received mock stimulation. The primary outcomes were serum and follicular fluid (FF) BDNF expression levels. Finally, 510 and 518 participants were included in TEAS and placebo groups.Results: The serum (P< 0.001) and FF (P< 0.001) BDNF expression levels were higher in the TEAS group than in the placebo group. The TEAS group had a lower total dose of gonadotropins (P=0.007), higher fertilization rates (P=0.006), higher high-quality embryo rates (P=0.013), and higher pregnancy rates per ET (P=0.031). The subgroup analysis showed that the Val/Val genotype was associated with the differences in serum and FF BDNF between the TEAS and placebo groups (all P< 0.05).Conclusion: In conclusion, TEAS might increase serum and FF BDNF expression levels and improve IVF embryological and clinical outcomes. Patients with the Val/Val genotype might be more likely to benefit from TEAS.Keywords: transcutaneous electrical acupoint stimulation, brain-derived neurotrophic factor, infertility, in-vitro fertilization, embryo transfer, quasi-experimental study

Jiajia Wen,1 Wamei Zhou,2 Yin Lin3 1Department of Psychiatry III, Hainan an Ning Hospital, Haikou, People’s Republic of China; 2Department of Neurology, Hainan an Ning Hospital, Haikou, People’s Republic of China; 3Department of Psychiatry, Hainan an Ning Hospital, Haikou, People’s Republic of ChinaCorrespondence: Yin Lin, Department of Psychiatry, Hainan an Ning Hospital, No. 10, Nanhai Avenue East, Haikou, Hainan, 570100, People’s Republic of China, Tel +8613876245292, Email 18782849833@163.comObjective: Explore the causal relationship between the ovarian cyst and depression using a two-sample Mendelian randomization approach (MR).Methods: Based on data pooled from genome-wide association studies, genetic variants of the ovarian cyst and depression were selected as instrumental variables, as well as the Mendelian randomization analysis was conducted using inverse variance weighted (IVW) as the main analysis method and MR-Egger regression analysis, MR-PRESSO and other sensitivity analysis methods as supplements.Results: The IVW analysis showed a direct causal association between ovarian cysts and depression (OR=1.040; 95% CI: 1.003, 1.078; p=0.031). Meantime, there was a causal effect of genetically predicted depression on ovarian cysts (OR=1.327.; 95% CI: 1.197, 1.470; p< 0.001). Sensitivity analyses such as MR-Egger regression analysis and MR-PRESSO indicated that the IVW results were robust and reliable.Conclusion: This study suggested since ovarian cysts and female depression are mutually causal, the comorbidity of ovarian cysts and depression in women should be actively attended to and given appropriate prevention and treatment besides the diagnosis and treatment of depression or ovarian cysts.Keywords: Mendelian randomization, depression, ovarian cyst, genetic variation

Jianjun Zhong,1,2,&ast; Juan Wen,1,3,&ast; Kuan Li4 1Key Research Institute of Humanities and Social Sciences at Tianjin Universities-Center of Vocational Education Development Research, Tianjin University of Technology and Education, Tianjin, 300222, People’s Republic of China; 2School of Vocational Education, Tianjin University of Technology and Education, Tianjin, 300222, People’s Republic of China; 3School of Psychology, Inner Mongolia Normal University, Hellinger, 011517, People’s Republic of China; 4School of Humanities, Inner Mongolia University of Technology, Hohhot, 010080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianjun Zhong, Email zhongjj709@tute.edu.cnBackground: Previous cross-sectional studies were on the basis of three categories of achievement goal orientation; therefore, it is not yet possible to fully examine whether achievement goal orientation affects academic engagement through learning strategies and self-efficacy and whether those effects vary by grade. Then, it is necessary to further explore whether different achievement goal orientations affect academic engagement through the mediation of learning strategies and academic self-efficacy from the perspective of integration of achievement goal orientation theory and social cognitive theory under the premise of four classifications of achievement goal orientation, if so, whether there is consistent-path structure between grades.Methods: Participants were 1429 high school students (647 male,782 female) were token as subjects through cluster sampling. The Achievement Goal Orientation Scale, Learning Strategies Scale, Academic self-efficacy Scale,and Academic Engagement Scale were used to measure achievement goal orientations, learning strategies, academic self-efficacy and academic engagement.Results: The mastery approach, performance approach, and performance avoidance indirectly predicted academic engagement through the chained mediated effects of learning strategies and academic self-efficacy, respectively. There were no direct or indirect predictive effects of mastery avoidance on students’ academic engagement. The path structure constructs were consistent across grades, except for grade differences in the predictive relationships between mastery approach on learning strategies and mastery avoidance on learning strategies.Conclusion: As external achievement goals originate from others, regardless of valence approach or avoidance, performance goals indirectly orient academic engagement through chain multiple mediators of learning strategies and academic self-efficacy. As internal achievement goal originates from the individual itself, the mastery approach not only directly but also indirectly orients academic engagement through chain multiple mediators of learning strategies and academic self-efficacy. The path structure remains consistent but local relations vary across school years in China. Finally, the possible psychological mechanisms of goal orientations are discussed.Keywords: academic self-efficacy, academic engagement, achievement goal orientation, learning strategies

Mingtang Zeng,1 Yao Wang,1 Maozhu Liu,1 Yuxun Wei,2 Jie Wen,3 Yuchen Zhang,1 Tao Chen,4 Nianyu He,1 Ping Fan,1 Xinhua Dai5 1Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Pharmacy, Zhongjiang County People’s Hospital, Deyang, 618000, People’s Republic of China; 3Department of Pharmacy, Shehong Municipal Hospital of Traditional Chinese Medicine, Shehong, 629600, People’s Republic of China; 4Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 5Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Xinhua Dai, Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China, Email dxh9123@163.com Ping Fan, Department of Pharmacy, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China, Email m13980602288@163.comAbstract: Carbon dots (CDs), a crucial component of nanomaterials, are zero-dimensional nanomaterials with carbon as the backbone structure and smaller than 10 nm. Due to their beneficial characteristics, they are widely used in biomedical fields such as biosensors, drug delivery, bio-imaging, and interactions with DNA. Interestingly, a novel type of carbon dot, generated by using herbal medicines as synthetic raw materials, has emerged as the most recent incomer in the family of CDs with the extensive growth in the number of materials selected for carbon dots synthesis. Herbal medicine-derived carbon dots (HM-CDs) have been employed in the biomedical industry, and are rapidly emerging as “modern nanomaterials” due to their unique structures and exceptional capabilities. Emerging trends suggest that their specific properties can be used in bleeding disorders, gastrointestinal disorders, inflammation-related diseases, and other common intractable diseases including cancer, menopausal syndrome, central nervous system disorders, and pain of various forms and causes. In addition, HM-CDs have been found to have organ-protective and antioxidant properties, as evidenced by extensive studies. This research provides a more comprehensive understanding of the biomedical applications of HM-CDs for the aforementioned disorders and investigates the intrinsic pharmacological activities and mechanisms of these HM-CDs to further advance their clinical applications. Keywords: herbal medicine, carbon dots, disease treatment, nanomaterials, potential mechanism

Yandan Zhou,1 Zhili Feng,2,3 Jie Wen,2,3 Chi Yang,2,3 Qiancheng Jing2,3 1Changsha Aier Eye Hospital, Aier Eye Hospital Group, Changsha, Hunan, People’s Republic of China; 2Department of Otolaryngology Head and Neck Surgery, the Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, People’s Republic of China; 3Institute of Otolaryngology Head and Neck Surgery, Hengyang Medical School, University of South China, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Qiancheng Jing, Department of Otolaryngology-Head and Neck Surgery, the Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, People’s Republic of China, Email 2022050001@usc.edu.cnBackground: Allergic rhinitis (AR) is a common allergic disease, and SLIT has shown effectiveness as a treatment method. This study focuses on the evaluation of serum TAM receptor tyrosine kinases (TYRO3, AXL, and MER) levels as potential indicators of disease severity and predictive markers for sublingual immunotherapy (SLIT) responsiveness in AR patients.Methods: A total of 160 AR subjects, including 40 mild AR (MAR) and 120 moderate-severe AR (MSAR) patients, and 40 healthy controls (HC) were recruited. Serum concentrations of TYRO3, AXL, and MER were measured and their relationships with disease severity were examined. In the MSAR group, 102 patients underwent SLIT, and the early efficacy was evaluated. The correlations between the baseline serum concentrations of TYRO3, AXL, and MER and the early responsiveness of SLIT were analyzed.Results: Serum concentrations of TYRO3, AXL, and MER were significantly reduced in AR patients, particularly in those MSAR subjects. Correlation analysis results indicated that serum TYRO3 and MER levels were negatively correlated with the visual analog scale (VAS) and the total nasal symptom score (TNSS). After one year of follow-up, 80 AR patients completed the treatment and were divided into effective and ineffective groups. Serum baseline levels of TYRO3 and MER were found to be lower in the effective group compared to the ineffective group. Additionally, there was a significant increase in serum TYRO3 and MER levels compared to baseline levels. Receiver operating characteristic (ROC) analysis revealed that circulating TYRO3 and MER had potential values for reflecting AR severity and predicting early SLIT responsiveness.Conclusion: Serum TYRO3 and MER concentrations were decreased in AR patients and negatively associated with disease severity. Circulating TYRO3 and MER seem to be promising indicators for monitoring the efficacy of SLIT in AR patients.Keywords: allergic rhinitis, sublingual immunotherapy, TAM receptor tyrosine kinases, TYRO3, AXL, MER

Zhenni Zhao,1 Jiawei Li,2 Jiamin Wen,2 Yanyan He,2 Zhiling Sun2 1Nursing Department, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Zhejiang, People’s Republic of China; 2School of Nursing, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of ChinaCorrespondence: Zhiling Sun, School of Nursing, Nanjing University of Chinese Medicine, 138 Xian Lin Road, Nanjing, People’s Republic of China, Tel +86 13813892093, Email szl@njucm.edu.cnBackground and Objective: Moxibustion is effective for low back pain (LBP), and inflammatory cytokines may play an important role in the mechanism of moxibustion treatment. The purpose of this meta-analysis was to explore the mechanism of moxibustion in LBP in terms of inflammatory cytokines.Methods: We searched China National Knowledge Infrastructure, Wanfang database, Cochrane Central Register of Controlled Trials, Ovid MEDLINE, Embase, PubMed, and Web of Science to identify eligible randomized controlled trials (RCTs). There was no restriction on the publication date.Results: Thirty RCTs measuring interleukin (IL-) 1, IL-1β, IL-6, IL-12, IL-17, IL-23, and tumor necrosis factor (TNF-) α were included in this meta-analysis. Compared to controls: single moxibustion could effectively decrease levels IL-6 and IL-23 (SMD, − 0.71, 95% CI: − 1.25 to − 0.17, p = 0.01; SMD, − 1.61, 95% CI: − 2.20 to − 1.03, p < 0.01, respectively); combined moxibustion had significant effects on IL-1, IL-1β, IL-6, IL-12, IL-17, and TNF-α (p < 0.05). Overall, for LBP, single or combined moxibustion could effectively down-regulate levels of pro-inflammatory cytokines (p = 0.007 and p < 0.00001, respectively). For safety of moxibustion, the incidence rate of side effects was similar to that of controls (RD, − 0.01, 95% CI: − 0.02 to 0.01, p = 0.59). Sensitivity analysis showed that the pooled estimates were robust, and publication bias analysis showed there was a significant small study effect (Egger’s test p = 0.0000). High statistical heterogeneity existed between included RCTs, meta-regression showed there was no potential factor explaining the source of heterogeneity.Conclusion: For LBP, moxibustion can effectively decrease levels of IL-1, IL-1β, IL-6, IL-12, IL-17, IL-23, and TNF-α to achieve analgesia. Because the side effects of moxibustion are transient, it is relatively safe for clinical use. However, based on high heterogeneity in this meta-analysis, rigorously designed RCTs are required to further confirm the results in this review.Keywords: low back pain, moxibustion, cytokines, tumor necrosis factors, interleukins

WormBase (www.wormbase.org) is the central repository for the genetics and genomics of the nematode Caenorhabditis elegans. We provide the research community with data and tools to facilitate the use of C. elegans and related nematodes as model organisms for studying human health, development, and many aspects of fundamental biology. Throughout our 22-year history, we have continued to evolve to reflect progress and innovation in the science and technologies involved in the study of C. elegans. We strive to incorporate new data types and richer data sets, and to provide integrated displays and services that avail the knowledge generated by the published nematode genetics literature. Here, we provide a broad overview of the current state of WormBase in terms of data type, curation workflows, analysis, and tools, including exciting new advances for analysis of single-cell data, text mining and visualization, and the new community collaboration forum. Concurrently, we continue the integration and harmonization of infrastructure, processes, and tools with the Alliance of Genome Resources, of which WormBase is a founding member.

The Alliance of Genome Resources (the Alliance) is a combined effort of 7 knowledgebase projects: Saccharomyces Genome Database, WormBase, FlyBase, Mouse Genome Database, the Zebrafish Information Network, Rat Genome Database, and the Gene Ontology Resource. The Alliance seeks to provide several benefits: better service to the various communities served by these projects; a harmonized view of data for all biomedical researchers, bioinformaticians, clinicians, and students; and a more sustainable infrastructure. The Alliance has harmonized cross-organism data to provide useful comparative views of gene function, gene expression, and human disease relevance. The basis of the comparative views is shared calls of orthology relationships and the use of common ontologies. The key types of data are alleles and variants, gene function based on gene ontology annotations, phenotypes, association to human disease, gene expression, protein-protein and genetic interactions, and participation in pathways. The information is presented on uniform gene pages that allow facile summarization of information about each gene in each of the 7 organisms covered (budding yeast, roundworm Caenorhabditis elegans, fruit fly, house mouse, zebrafish, brown rat, and human). The harmonized knowledge is freely available on the alliancegenome.org portal, as downloadable files, and by APIs. We expect other existing and emerging knowledge bases to join in the effort to provide the union of useful data and features that each knowledge base currently provides.

Zeng M, Wang Y, Liu M, et al. Int J Nanomedicine. 2023;18:6503–6525. The authors have advised that Figure 2 on page 6510 was published in error. The correct Figure 2 is as follows. Figure 2 HM-CDs significantly improved blood-brain barrier (BBB) permeability. HM-CD-1 has an ultra-tiny size and abundance surface functional groups. The covalent binding of HM-CD-2 to the drug facilitates passive transport of the drug. HM-CD-3 has a strong affinity for the BBB endothelial cell membrane. The authors apologize for this error.

Forest cover change directly affects the surface energy balance by altering the radiative and non-radiative properties of the surface. These competing processes may yield considerable biophysical impacts on local and regional climate that depend on background climate and specific forest type. Here we compared the differences in land surface temperature (LST) between temperate forests and adjacent croplands/grasslands to quantify the potential biophysical effects of transitions from croplands/grasslands to forests in Northeast China, based on multiple satellite observation products from 2001 to 2016. Forests were found to show a slight lower daytime LST and strong higher nighttime LST than adjacent croplands or grasslands. As a result, the daily LST of forests was 0.15 ± 0.06 ℃ and 0.32 ± 0.04 ℃ higher than that of croplands and grasslands, respectively. On the seasonal scale, the warming effect of cropland/grassland-to-forest transition during non-growing season outweighed the cooling effect during growing season, and dominated the annual positive LST response. Moreover, the cooling effect of cropland-to-forest transition during growing season was stronger in the early growth stage than late growth stage (−1.65 ± 0.9 ℃ in May to June, −0.39 ± 0.5 ℃ in July to September). The net cooling effect of warm temperate broadleaved forests was found to shift toward net warming effect of cold temperate coniferous forests with increasing latitude. The daytime cooling effect of forests was mainly driven by increased non-radiative evapotranspiration. Overall, the radiative process related to the solar energy dominated the net warming effect of forest transitions over Northeast China. Estimating the climate feedback potential of forests could be useful to provide theoretical references for the adaptation and mitigation strategies for climate change.

Alpine treeline ecotones are highly sensitive to climate warming. The low temperature-determined alpine treeline is expected to shift upwards in response to global warming. However, little is known about how temperature interacts with other important factors to influence the distribution range of tree species within and beyond the alpine treeline ecotone. Hence, we used a GF-2 satellite image, along with bioclimatic and topographic variables, to develop an ensemble suitable habitat model based on the species distribution modeling algorithms in Biomod2. We investigated the distribution of suitable habitats for B. ermanii under three climate change scenarios (i.e., low (SSP126), moderate (SSP370) and extreme (SSP585) future emission trajectories) between two consecutive time periods (i.e., current–2055, and 2055–2085). By 2055, the potential distribution range of B. ermanii will expand under all three climate scenarios. The medium and high suitable areas will decline under SSP370 and SSP585 scenarios from 2055 to 2085. Moreover, under the three climate scenarios, the uppermost altitudes of low suitable habitat will rise to 2,329 ​m a.s.l., while the altitudes of medium and high suitable habitats will fall to 2,201 and 2,051 ​m a.s.l. by 2085, respectively. Warming promotes the expansion of B. ermanii distribution range in Changbai Mountain, and this expansion will be modified by precipitation as climate warming continues. This interaction between temperature and precipitation plays a significant role in shaping the potential distribution range of B. ermanii in the alpine treeline ecotone. This study reveals the link between environmental factors, habitat distribution, and species distribution in the alpine treeline ecotone, providing valuable insights into the impacts of climate change on high-elevation vegetation, and contributing to mountain biodiversity conservation and sustainable development.

Yuqin Feng,1,2 Si Qin,3 Huarun Li,3 Yemei Yang,1 Yushi Zheng,1 Hongsheng Liu,4 Wei Yin Yap,1,5 Xianyi Zhou,1 Ju Wen2,3 1Department of Dermatology, the Third Affiliated Hospital of Southern Medical University, Guangzhou, 510630, People’s Republic of China; 2The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510280, People’s Republic of China; 3Department of Dermatology, Guangdong Second Provincial General Hospital, Guangzhou, 510317, People’s Republic of China; 4Guangdong Huace Life Medicine Research Center, Guangzhou, 511450, People’s Republic of China; 5School of International Education of Southern Medical University, Guangzhou, 510515, People’s Republic of ChinaCorrespondence: Xianyi Zhou; Ju Wen, Email zxy1962@163.com; wenju3139@163.comBackground: Hydrogel dressings have been used as a crucial method to keep the wound wet and hasten the healing process. Due to safety concerns regarding the gel components, low mechanical adhesiveness, and unsatisfactory anti-inflammatory capacity qualities for practical uses in vivo, leading to the clinical translation of wound dressings is still difficult.Methods: A type of composite hydrogel (acrylamide/polyethylene glycol diacrylate/tannic acid, ie, AM/PEGDA/TA) by double bond crosslinking, Schiff base, and hydrogen bond interaction is proposed. The mechanical characteristics, adhesiveness, and biocompatibility of the hydrogel system were all thoroughly examined. Additionally, a full-thickness cutaneous wound model was employed to assess the in vivo wound healing capacity of resulting hydrogel dressings.Results: Benefiting the mechanism of multiple crosslinking, the designed composite hydrogels showed significant mechanical strength, outstanding adhesive capability, and good cytocompatibility. Moreover, the hydrogel system also had excellent shape adaptability, and they can be perfectly integrated into the irregularly shaped wounds through a fast in situ forming approach. Additional in vivo tests supported the findings that the full-thickness wound treated with the composite hydrogels showed quicker epithelial tissue regeneration, fewer inflammatory cells, more collagen deposition, and greater levels of platelet endothelial cell adhesion molecule (CD31) expression.Conclusion: These above results might offer a practical and affordable product or method of skin wound therapy in a medical context.Keywords: hydrogel dressing, tannins, multiple-crosslinking, anti-inflammatory, full-thickness wound healing

Ying Wu,1 Jing Wen,1 Xiaohui Wang,1 Qingyao Wang,1 Wen Wang,2 Xiangjia Wang,1 Jiang Xie,1 Li Cong1 1School of Medicine, Hunan Normal University, Changsha, 410013, People’s Republic of China; 2Teaching and Research Section of Clinical Nursing, Xiangya Hospital of Central South University, Changsha, 41008, People’s Republic of ChinaCorrespondence: Li Cong, School of Medicine, Hunan Normal University, Changsha, People’s Republic of China, Tel +86-0731-88912446, Fax +86-0731-88912478, Email congli@hunnu.edu.cnBackground: The Chinese population is aging, and chronic non-communicable diseases (NCDs) prevalence is correspondingly increasing, along with associated disability and healthcare costs. Although self-management has been associated with social support and is a recognized priority, its mediating variables have not been studied in detail, particularly among old people with chronic diseases.Purpose: To examine the mediating role of e-health literacy and general self-efficacy in the relationship between social support and self-management of chronic NCDs in Chinese community home-based aging institution residents.Patients and Methods: A random sample of 289 community home-based aging institution elders (≥ 60 years) with chronic NCDs in China was recruited. Questionnaire data were recorded on self-reported socio-demographics, self-management, social support, e-health literacy, and general self-efficacy. Pearson’s correlation analysis identified the relationship between these factors and self-management. Serial multiple mediation model was used to test the hypothesized relationships.Results: The self-management mean (±SD) score was 29.39 ± 9.60, and the level of self-management was medium. Social support (r = 0.283; P

Jiamin Wen,1 Jitian Weng,2 Wei Lu,3 Xiaohua Tao,3 Hao Cheng,4,&ast; Yi Tang3,&ast; 1Department of Dermatology, People’s Hospital of Tiantai County, Zhejiang University, Taizhou, People’s Republic of China; 2School of Public Health, Hangzhou Normal University, Zhejiang University, Hangzhou, People’s Republic of China; 3Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Zhejiang University Hangzhou 310014 People’s Republic of China; 4Department of Dermatology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Tang, Center for Plastic & Reconstructive Surgery, Department of Dermatology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Zhejiang University, 158 Shangtang Road, Xiacheng District, Hangzhou, 310014, People’s Republic of China, Tel +86-13968076453, Fax +86-0571-85335800, Email tangyi@hmc.edu.cn Hao Cheng, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, Zhejiang, 310016, People’s Republic of China, Tel +86-13588706943, Fax +86-571-86006975, Email chenghao1@zju.edu.cnPurpose: To investigate the expression of Plasmacytoid Dendritic Cells (pDCs) and TLR7/9-MyD88-IRAKs pathway in chronic eczema lesions.Patients and Methods: Lesional tissues and the surrounding healthy tissues were collected from 25 individuals with chronic eczema, and immunohistochemistry was used to detect and comparatively analyze the expression profile of CD123, CD2AP, toll-like receptor 7 (TLR7), toll-like receptor 9 (TLR9) along with interleukin-1 receptor-associated kinase 1 (IRAK1) and interferon regulatory factor 7 (IRF7) in signaling pathways.Results: The positive rates of CD2AP + pDC and CD123 + pDC in lesional tissues were significantly elevated compared to the surrounding healthy tissues (P < 0.05). They were distributed in both the epidermal and dermal layers of the lesional tissue, but the majority were in the dermal layer. The TLR7, TLR9, IRAK1 and IRF7 were more expressed in dermal layers of the lesional tissue with higher positive rates of expression compared to the surrounding healthy tissues (P < 0.05). IRAK1 and IRF7 were expressed in a small amount in the epidermal layer with higher positive rates of expression than in the surrounding healthy tissues (P < 0.05), while the positive rates of TLR7 and TLR9 expression in the epidermal layer were not statistically different from those in the surrounding healthy tissues (P > 0.05).Conclusion: PDC and TLR7/9-MyD88-IRAKs pathways are actively expressed in chronic eczema lesions and may be involved in pathogenesis and disease progression.Keywords: eczema, plasmacytoid dendritic cells, toll-like receptor 7, toll-like receptor 9, immunohistochemistry

Yuxun Wei,1– 4,&ast; Yumeng Wei,1– 4,&ast; Lin Sheng,1– 4 Jingwen Ma,1– 4 Zhilian Su,1– 4 Jie Wen,1– 4 Lanmei Li,5 Qiang Jia,2,6 Huiyang Liu,1– 4 Hui Si,2,4 Linjin Xiong,1– 4 Jinglin Chen,1– 4 Ju Cheng,3,4 Ying Zuo,2,7 Hongru Yang,8 Ling Zhao2– 4 1Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, People’s Republic of China; 2Key Laboratory of Medical Electrophysiology, Ministry of Education, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University; Luzhou, Sichuan, People’s Republic of China; 3Central Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 4Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 5Nanchong Key Laboratory of Individualized Drug Therapy, Department of Pharmacy, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 6Ethics Committee Office, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 7Department of Comprehensive Medicine, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 8Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Zhao, Key Laboratory of Medical Electrophysiology, Ministry of Education, Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China, Tel/Fax +86 830 3160093, Email zhaoling-998@163.com Hongru Yang, Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China, Tel/Fax +86 830 8585668, Email yanghongru801@126.comPurpose: The present study aimed to construct a co-loading platform encapsulating curcumin and paclitaxel at ratios of 2:1– 80:1 (w/w) designated “CU-PTX-LNP” and explored the synergistic effects of CU-PTX at different composite proportions on liver cancer cells using the combination index (CI) method.Methods: The CU lipid nanoplatform (CU-LNP) formulation was optimized via single-factor and orthogonal experiments. Various concentrations of PTX were added to the optimal formulation of CU-LNP to generate CU-PTX-LNP and the nanoplatform characterized via differential scanning calorimetry (DSC), transmission electron microscope (TEM), X-ray diffraction (XRD), zeta potential, polydispersity index (PDI), and size analyses. The cumulative release, stability, and cytotoxicity of CU-PTX-LNP in LO2, HepG2, and SMMC-7221 cells were assessed in vitro, followed by safety investigation and pharmacokinetic studies in vivo. The anti-tumor activity of CU-PTX-LNP was also evaluated using nude mice.Results: CU-PTX-LNP formulations containing CU:PTX at a range of proportions (2:1– 80:1; w/w) appeared as uniformly dispersed nanosized spherical particles with high entrapment efficiency (EE> 90%), sustained release and long-lasting stability. Data from in vitro cytotoxicity assays showed a decrease in the IC50 value of PTX of CU-PTX-LNP (by 5.47– 332.7 times in HepG2 and 4.29– 143.21 times in SMMC-7221 cells) compared to free PTX. In vivo, CU-PTX-LNP displayed excellent biosafety, significant anti-tumor benefits and enhanced pharmacokinetic behavior with longer mean residence time (MRT(0-t); CU: 4.31-fold, PTX: 4.61-fold) and half-life (t1/2z; CU: 1.83-fold, PTX: 2.28-fold) relative to free drugs.Conclusion: The newly designed CU-PTX-LNP platform may serve as a viable technological support system for the successful production of CU-PTX composite preparations.Keywords: curcumin, paclitaxel, lipid nano platform, synergistic effect

Fanghui Li,1,2,&ast; Dongze Li,1,&ast; Jing Yu,1 Yu Jia,3 Jirui Wen,4 Wentao Li,2 Yao Tong,2 Jiang Wu,4 Zhi Wan,1 Yu Cao,1 Qing Zhang,2 Rui Zeng1,2 1Department of Emergency Medicine, Laboratory of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Cardiology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 3Department of General Practice and National Clinical Research Center for Geriatrics, International Medical Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 4Deep Underground Space Medical Center, West China Hospital, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rui Zeng; Qing Zhang, Department of Cardiology, West China Hospital, Sichuan University, 37 Guoxue Road, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-28-85423248, Fax +86-28-85582944, Email zengrui_0524@126.com; qzhang2000cn@163.comBackground: The plasma lipidome profile is likely to improve risk stratification in patients with acute coronary syndrome (ACS) and predict cardiovascular events for secondary disease prevention. Ceramides are involved in the initiation or acceleration of several key pathophysiological processes in atherosclerosis. This study evaluated whether plasma ceramide levels at admission was associated with one-year mortality in patients with ACS.Methods: In total, 826 patients with ACS from a prospective multicenter study for early evaluation of acute chest pain were enrolled. High-performance liquid chromatography with tandem mass spectrometry (LC/MS) was used to measure the plasma levels of eleven ceramides (C16–C26). The primary outcome was all-cause mortality, and the secondary outcome was cardiac mortality during the one-year follow-up. The relationship between the ceramide levels and mortality was evaluated by Cox regression analysis. The receiver operating characteristic (ROC) curve was established to evaluate discrimination of ceramides.Results: Eighty-eight (10.7%) patients died after a 12-month follow-up. Five ceramides (C16:0, C18:0, C20:0, C24:1 and C24:2) and their ratios to Cer(d18:1/24:0) were independently associated with the risk of all-cause death and cardiac death. Combining the Global Registry of Acute Coronary Events (GRACE) score with ceramides and their ratios to Cer(d18:1/24:0) had areas under ROC curves ranging from 0.778– 0.804 (P< 0.001) for all-cause mortality, which was greater than that of the GRACE score alone.Conclusion: Measurements of long-chain ceramides and very-long-chain ceramides may help in identifying a high risk of mortality beyond traditional assessment tools in patients with ACS.Trial Registration: clinicaltrials.gov, identifier: NCT04122573.Keywords: ceramide, acute coronary syndrome, mortality, high-performance liquid chromatography with tandem mass spectrometry

Manganese dust generated during the production of ferroalloys contains iron and zinc oxides together with other minor oxides. Pure manganese compounds can be recovered from the leaching solution of the manganese dust by removing the impure ions. In this work, sulfuric acid and ferrous sulfate were employed as leaching and reducing agents for the manganese oxides in the dust. First, the leaching conditions for complete dissolution of the manganese oxides were investigated by varying the concentration of sulfuric acid and ferrous sulfate, and pulp density. Second, after oxidizing Fe(II) to Fe(III) by hydrogen peroxide, Fe(III) was removed from the solution by three stages of counter current extraction with D2EHPA. Third, Zn(II) was removed by two stages of cross current extraction with Cyanex 272. Stripping conditions for Fe(III) and Zn(II) were determined from the respective loaded organics. Fourth, Mn(OH)2 was precipitated from the raffinate by adjusting the pH of the solution to 10 with NaOH solution. The MnSO4 crystals with 99.5% purity were recovered by crystallization from the sulfuric acid solutions after the precipitates of Mn(OH)2 were dissolved. A comparison of the cost of the chemicals used to recover MnO2 and MnSO4 indicated that the current process was much more economical.

The rate, frequency and extent of forest disturbances decreased in China over 1986–2020 probably due to forest protection policies, but while they intensified in the southeast, they weakened in the northeast, according to 30 m resolution Landsat satellite data

BackgroundExercise has been reported as an effective intervention for Parkinson's disease. However, there is still debate on the what kinds of exercises prior to choosing. This study aimed to compare and rank the different exercises that effectively enhance postural balance in Parkinson's disease patients by quantifying the information gleaned from randomized controlled trials (RCTs).MethodsWe conducted a comprehensive database search, including PubMed, Cochrane Library, Embase, Web of Science, and PsycINFO. The included studies were evaluated for methodological quality by the Cochrane Risk of Bias tool.ResultsThe RCTs were collected between the earliest available date and March 2023. Sixty RCTs were included and the total sample size used in the study was 3,537. Thirty-five studies were defined as low risk of bias, twenty-one studies as medium risk of bias, and four studies as high risk of bias. The network meta-analysis results showed that exergaming exercise can significantly improve patients' Timed-Up-and-Go time (SUCRA = 91.5%). Dance can significantly enhance patients' Berg Balance Scale (surface under the cumulative ranking curve, SUCRA = 81.3%), and rhythmical auditory exercise can significantly improve patients' Mini-Balance Evaluation Systems Test score (SUCRA = 95.6%).ConclusionCompared with other exercises, exergaming exercise, Dance, and rhythmical auditory exercise showed superior efficacy in improving postural balance among Parkinson's disease patients.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier: CRD42023411918.

In cold pulse experiments in J-TEXT, the ion transport shows similar non-local response as the electron transport channel. Very fast ion temperature decreases are observed in the edge, while the ion temperature in the core promptly begin to rise after the injection of cold pulse. Moreover, the cutoff density is also found for the ion non-local effect. The experimental observed density fluctuation in a high frequency ranging from 500 kHz to 2 MHz is obviously reduced in the whole plasma region during non-local transport phase.