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Background: Sarcopenia, common in the elderly, often linked to chronic diseases, correlates with inflammation.The association between SII and mortality in sarcopenia patients is underexplored, this study investigates this relationship in a U.S. adult cohort., Methods: We analyzed 1999-2018 NHANES data, focusing on 2,974 adults with sarcopenia. Mortality outcomes were determined by linking to National Death Index (NDI) records up to December 31, 2019. Using a weighted sampling design, participants were grouped into three groups by the Systemic Immune-Inflammation Index (SII). We used Cox regression models, adjusting for demographic and clinical variables, to explore SII's association with all-cause and cause-specific mortality in sarcopenia, performing sensitivity analyses for robustness., Results: Over a median follow-up of 9.2 years, 829 deaths occurred. Kaplan-Meier analysis showed significant survival differences across SII groups. The highest SII group showed higher hazard ratios (HRs) for all-cause and cause-specific mortality in both crude and adjusted models. The highest SII group had a higher HR for all-cause(1.57, 1.25-1.98), cardiovascular(1.61, 1.00-2.58), cancer(2.13, 1.32-3.44), and respiratory disease mortality(3.21, 1.66-6.19) in fully adjusted models. Subgroup analyses revealed SII's association with all-cause mortality across various demographics, including age, gender, and presence of diabetes or cardiovascular disease. Sensitivity analyses, excluding participants with cardiovascular diseases, those who died within two years of follow-up, or those under 45 years of age, largely reflected these results, with the highest SII group consistently demonstrating higher HRs for all types of mortality in both unadjusted and adjusted models., Conclusion: Our study is the first to demonstrate a significant relationship between SII and increased mortality risks in a sarcopenia population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zeng, Qin, Shi, Mu, Huang, Yang, Liu, An and Li.)

Pyrrolizidine alkaloids (PAs) are naturally occurring secondary metabolites of plants. To date, more than 660 types of PAs have been identified from an estimated 6000 plants, and approximately 120 of these PAs are hepatotoxic. As a result of PAs being found in spices, herbal teas, honey, and milk, PAs are considered contaminants in foods, posing a potential risk to human health. Here, we summarize the chemical structure, toxic effects, levels, and regulation of PAs in different countries to provide a better understanding of their toxicity and risk assessment. With recent research on the risk assessment of PAs, this review also discusses the challenges facing this field, aiming to provide a scientific basis for PA toxicity research and safety assessment.

Gut played a potent role in onset and progression of metabolic disorders, presenting an exciting direction for diabetes prevention. Here, the anti-diabetic effects of White hyacinth bean polysaccharides (WHBP) were observed, including the reduction of blood glucose levels and improvement of intestinal impairment in type 2 diabetes mellitus (T2DM) rats. Further data concerning intestinal protection suggested that WHBP restored intestinal barrier, as evidenced by inhibition of intestinal pathological damage, up-regulation of Zonula occluden-1 expression and manipulation of the redox system in T2DM rats. Moreover, WHBP-mediated anti-diabetic effects were in parallel with the adjustment of changes in gut microbiota composition of T2DM rats. Meanwhile, hypersecretion of corticotropin-releasing hormone, adrenocorticotropic hormone, and corticosterone levels, which were critical coordinators of the hypothalamic-pituitary-adrenal (HPA) axis, were suppressed in T2DM rats exposed to WHBP, indicating that WHBP-mediated health benefits were referring to regulate brain feedback in reduction of HPA axis. Concomitantly, further suggested and expanded on gut-brain communication by data of microbial metabolites short-chain fatty acids, mediators of gut-brain interactions, were remarkably raised in cecum contents of T2DM rats subjected to WHBP. Collectively, WHBP performed anti-diabetic effects were associated with control of microbiota-gut-brain axis implicated in intestinal barrier, HPA axis, gut microbiota and their metabolites., 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 © 2023 Elsevier B.V. All rights reserved.)

Objective To systematically analyze the current status of outcomes reporting in clinical trials on treating stasis acute mastitis with Traditional Chinese Medicine breast massage.Methods We searched CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, Embase, Cochrane library, JBI, CINAHL, PsycINFO, Clinical Trials Registry Platform portal, Clinical Trials Registry, Australian New Zealand Clinical Trials Registry, Center Watch Registry from inception to May 15, 2022 to find randomized controlled trials, non-randomized controlled trials, case series and cohort studies which reported the outcomes of stasis acute mastitis managed with Traditional Chinese Medicine breast massage, with search terms of mastitis, acute mastitis, lactation mastitis, puerperal mastitis, breast problem, breast engorgement, milk stasis, blocked ducked, breast pain, breast massage, and acupoint massage. Outcomes and the measurement schemes (measurement methods, timing of assessing outcome, frequency of assessing outcome, measurers) were extracted from the included studies. We used the Management of Otitis Media with Effusion in Children with Cleft Palate (MOMENT) to assess the quality of each study, then categorized outcomes derived from the included studies into different domains according to the Outcome Measures in Rheumatology Arthritis Clinic Trials (OMERACT) Filter 2.1 framework.Results We identified 85 clinical trials, in which 54 different outcomes were reported. A total of 81.2% (69/85) of studies were assessed as medium quality with a mean score of 2.6, and 18.8% (16/85) as low quality with a mean score of 0.9. These outcomes were organized in three core areas. Lump size (89.4%, 76/85) was the most frequently reported outcome, followed by breast pain (69.4%, 59/85) and milk excretion (68.2%, 58/85). Five methods were used to assess lump size and four methods to assess breast pain.Conclusions The outcomes reported in clinical trials regarding stasis acute mastitis treated by Traditional Chinese Medicine breast massage are heterogeneous. Developing a core outcome set to achieve consistent standards for reporting outcomes and modalities for validation of the outcomes is clearly warranted.

Nodular goiter has become increasingly prevalent in recent years. Clinically, there has been a burgeoning interest in nodular goiter due to the risk of progression to thyroid cancer. This review aims to provide a comprehensive summary of the mechanisms underlying the therapeutic effect of Chinese medicine (CM) in nodular goiter. Articles were systematically retrieved from databases, including PubMed, Web of Science and China National Knowledge Infrastructure. New evidence showed that CM exhibited multi-pathway and multi-target characteristics in the treatment of nodular goiter, involving hypothalamus-pituitary-thyroid axis, oxidative stress, blood rheology, cell proliferation, apoptosis, and autophagy, especially inhibition of cell proliferation and promotion of cell apoptosis, involving multiple signal pathways and a variety of cytokines. This review provides a scientific basis for the therapeutic use of CM against nodular goiter. Nonetheless, future studies are warranted to identify more regulatory genes and pathways to provide new approaches for the treatment of nodular goiter., (© 2022. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Trees of Engelhardia are important components of subtropical and tropical forests in South-eastern Asia with great ecological and economic values. However, phylogenetic relationships within Engelhardioideae (Juglandaceae) remains obscure. In this study, we report the first complete chloroplast genome sequences of Engelhardia sensu stricto , Engelhardia hainanensis Chen, a rare species endemic in southern China. Its complete chloroplast genome is 161,574 bp in length, with a typical quadripartite structure that includes a large single-copy region of 91,158 bp, a small single-copy region of 18,790 bp, and its GC content is 35.8%. A total of 128 genes were identified, including 83 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. Furthermore, a phylogenetic tree of Juglandaceae was constructed based the complete chloroplast genome sequence, which strongly support the three-subfamily classification system in Juglandaceae, and E. hainanensis was resolved sister to two Alfaropsis species. This study provides valuable genomic information for the species identification and phylogenetic study of Juglandaceae., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Kobresia species are common in meadows on the Qinghai-Tibet Plateau. They are important food resources for local livestock, and serve a critical foundation for ecosystem integration. Genetic resources of Kobresia species are scarce. Here, we generated a chromosome-level genome assembly for K. myosuroides (Cyperaceae), using PacBio long-reads, Illumina short-reads, and Hi-C technology. The final assembly had a total size of 399.9 Mb with a contig N50 value of 11.9 Mb. The Hi-C result supported a 29 pseudomolecules model which was in consistent with cytological results. A total of 185.5 Mb (44.89% of the genome) transposable elements were detected, and 26,748 protein-coding genes were predicted. Comparative analysis revealed that Kobresia plants have experienced recent diversification events during the late Miocene to Pliocene. Karyotypes analysis indicated that the fission and fusion of chromosomes have been a major driver of speciation, which complied with the lack of whole-genome duplication (WGD) in K. myosuroides genome. Generally, this high-quality reference genome provides insights into the evolution of alpine sedges, and may be helpful to endemic forage improvement and alpine ecosystem preservation., (© The Author(s) 2022. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.)

Background: Ubiquilin 2 (UBQLN2) is an adaptor of ubiquitinated proteins and the proteasome. The potential role of UBQLN2 in carcinogenesis has been demonstrated. However, its role in modulating the radiosensitivity of cancer is not clear. Here, we explored the radiosensitizing effect of silencing UBQLN2 on esophageal squamous cell carcinoma (ESCC) and its mechanisms., Methods: We analyzed the prognostic role of UBQLN2 in the ESCC patient cohort from the Cancer Genomic Atlas (TCGA) database and our hospital. We also conducted a series of experiments in vivo and in vitro to investigate the effect of silencing UBQLN2 on ESCC radiosensitivity and its mechanisms., Results: UBQLN2 is highly expressed in ESCC tissues and positively correlated with poor overall survival (OS). The knockdown of UBQLN2 dramatically increased the radiosensitivity of ESCC cells. Mechanically, UBQLN2 suppression substantially upregulated p38 mitogen-activated protein kinases (MAPK). The p38 MAPK inhibitor SB203580 could reverse the radiation-enhancing effect induced by UBQLN2 knockdown. The direct interaction between UBQLN2 and p38 MAPK was confirmed by co-immunoprecipitation (CO-IP) assay. Furthermore, silencing UBQLN2 also inhibited the expression of phosphorylated DNA-dependent protein kinase catalytic subunit (p-DNA-PKcs) after irradiation. Finally, the xenografted tumor experiment confirmed the radiosensitizing effect of silencing UBQLN2 on ESCC in vivo., Conclusion: Our results suggest that silencing UBQLN2 enhances the radiosensitivity of ESCC by activating p38 MAPK, and UBQLN2 may be a potential target to enhance the radiosensitivity of ESCC., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2023 Jia-Lin Wang et al.)

Background: Establish a CT-based diagnostic radiomic model for AIDS complicated with pulmonary cryptococcosis and evaluate the diagnostic efficacy of this model., Methods: This retrospective study enrolled 98 AIDS patients with pulmonary cryptococcosis and 103 AIDS patients with other infections or neoplastic lesions, comprising a total of 699 lesions. Patients were randomly divided into a training group and test group at a ratio of 2.75:1. Features from all lesions, cavity lesions and solid nodule lesions were extracted, and two kinds of radiomic models (6 types) were established. ROC curves were drawn, and the sensitivity and specificity were calculated to compare the SVM model and LR model, radiologists' empirical diagnoses and the combination of these empirical diagnoses with the radiomic model., Results: The AUCs of senior radiologist for all lesions and cavity lesions were lower than those of the SVM and LR models. The diagnostic efficacy of primary radiologist was lower than that of both of the other model types. The diagnostic efficacy of the LR model was relatively stable, with the highest diagnostic efficiency of the 3 model/radiologist groups. The AUCs of intermediate radiologist in combination with the LR radiomic model for all lesions, nodular lesions and cavity lesions were 0.88, 0.84, and 0.9, respectively, which were the highest among all models and radiologists., Conclusions: The CT-based radiomic LR model of AIDS-associated pulmonary cryptococcosis exhibits good diagnostic performance, which was similar to that of senior radiologists and higher than that of the primary radiologist. With the help of a radiomic model, radiologists can achieve improved diagnostic accuracy compared to that when only an empirical diagnosis is used., (© 2022. The Author(s).)

Liquid submerged fermentation is an effective strategy to achieve large-scale production of active ingredients by macrofungi, and controlling mycelium morphology is a key factor restricting the development of this technology. Mining for superior morphological regulatory factors and elucidation of their regulatory mechanisms are vital for the further development of macrofungal fermentation technology. In this study, microparticles were used to control the morphology of Paraisaria dubia (P. dubia) in submerged fermentation, and the underlying regulatory mechanisms were revealed by transcriptomic. The relative frequency of S-type pellet diameter increased significantly from 7.14 to 88.31%, and biomass increased 1.54 times when 15 g/L talc was added. Transcriptome analysis showed that the morphological regulation of filamentous fungi was a complex biological process, which involved signal transduction, mycelium polar growth, cell wall synthesis and cell division, etc. It also showed a positive impact on the basic and secondary metabolism of P. dubia. We provided a theoretical basis for controlling the mycelium morphology of P. dubia in submerged fermentation, which will promote the development of macrofungal fermentation technology., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To analyze the current status of social support for middle-aged and older adults with multimorbidity and to explore the correlation between different dimensions of social support and multimorbidity and the related outcomes on the basis of China Health and Retirement Longitudinal Study (CHARLS) 2015 survey data so as to reveal the complex social background of multimorbidity and the impact of social support on multimorbidity., Methods: A total of 9168 valid samples, with an average age of 59.60 years, were included in the study. Using the social support-related variables of the respondents, we conducted factor analysis and constructed regression models of common factors of social support and multimorbidity-related outcomes, intending to analyze the impact of common factors of social support on multimorbidity in the middle-aged and older adults., Results: The multimorbidity of middle-aged and older adults in China was related to multiple factors of social support, and the differences were statistically significant. Logistic regression showed that social support in the form of activity/recreational facilities and medical resources was a protective factor of multimorbidity, that family emotional support and economic support had a positive effect on life satisfaction of comorbid patients, and that social support in the form of education, social life and housing conditions was negatively correlated with catastrophic medical expenditure of the comorbid population ( P <0.05)., Conclusion: Social support for middle-aged and older adults in China is unevenly distributed. Social support in the form of activity/recreational facilities and medical resources may reduce the risks of multimorbidity among middle-aged and older adults. Good family economic and emotional support can improve the life satisfaction of middle-aged and older adults with multimorbidity. Social support in the form of education, social life and housing conditions may reduce the risk of catastrophic medical expenditure in middle-aged and older adults with multimorbidity., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Characterizing genetic diversity and structure and identifying conservation units are both crucial for the conservation and management of threatened species. The development of high-throughput sequencing technology provides exciting opportunities for conservation genetics. Here, we employed the powerful SuperGBS method to identify 33, 758 high-quality single-nucleotide polymorphisms (SNP) from 134 individuals of a critically endangered montane shrub endemic to North China, Lonicera oblata . A low level of genetic diversity and a high degree of genetic differentiation among populations were observed based on the SNP data. Both principal component and phylogenetic analyses detected seven clusters, which correspond exactly to the seven geographic populations. Under the optimal K = 7, Admixture suggested the combination of the two small and geographically neighboring populations in the Taihang Mountains, Dongling Mountains, and Lijiazhuang, while the division of the big population of Jiankou Great Wall in the Yan Mountains into two clusters. High population genetic diversity and a large number of private alleles were detected in the four large populations, while low diversity and non-private alleles were observed for the remaining three small populations, implying the importance of these large populations as conservation units in priority. Demographic history inference suggested two drastic contractions of population size events that occurred after the Middle Pleistocene Transition and the Last Glacial Maximum, respectively. Combining our previous ecological niche modeling results with the present genomic data, there was a possible presence of glacial refugia in the Taihang and Yan Mountains, North China. This study provides valuable data for the conservation and management of L. oblata and broadens the understanding of the high biodiversity in the Taihang and Yan Mountains., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mu, Wu, Shen, Tong, Lei, Xia and Ning.)

Long noncoding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) is nuclear-located and transcribed from chromatin 11. To date, little is known about the cellular functions and regulatory mechanisms of NEAT1 in prostate cancer (PCa). In this study, whole-genome RNA sequencing data were downloaded from TCGA and GEO databases. Biological information was used to analyze the different expressions of NEAT1. In situ hybridization (ISH) was performed to detect the expression of NEAT1 in PCa and paracarcinoma clinical samples. Then, NEAT1 was knocked down in PC3 cells through lentiviral infection with a plasmid construct. Bioinformatics and integrative analytical approaches were utilized to identify the relationships of NEAT1 with specific cancer-related gene sets. Cell proliferation assay and colony formation assay were performed to evaluate the cell proliferative ability. Glycolysis stress test, metabolism assay, and infiltrating T-cell function analysis were implemented to assess the changes in metabolism and immune microenvironment of PCa. We found that the expression of NEAT1 was higher in PCa than in non-neoplastic tissues. The cell proliferative capability of PCa cells was significantly reduced in the NEAT1 knockdown group. PCR array and bioinformatics analysis revealed that the enrichment of acidic substance-related gene sets was associated with NEAT1 expression. NEAT1 depletion inhibited PCa cell aerobic glycolysis accompanied by the reduction of lactate levels in the medium. Further, we found that lactate dehydrogenase A (LDHA) expression was positively regulated by NEAT1. At last, co-culture systems indicated that NEAT1 or LDHA knockdown promoted the secretion of CD8+ T-lymphocyte factors, including TNF-α, IFN-γ, and Granzyme B, and enhanced the antitumor effects.

Background: Plants in cliff habitats may evolve specific reproductive strategies to cope with harsh environments, and unraveling these reproductive characteristics can improve our understanding of survival strategies and lithophyte evolution. This understanding is especially important for efforts to protect rare and endemic plants. Here, we investigated the reproductive biology of Lonicera oblata, an endangered lithophytic shrub that is scattered in highly fragmented and isolated cliff habitats of the Taihang and Yan mountains in North China., Results: Flowers of L. oblata are herkogamous and protandrous, characteristics that can prevent autogamy at the single-flower level, and insects are necessary for pollination. The outcrossing index, pollen/ovule ratio, and the results of hand pollination were measured and all revealed a mixed mating system for L. oblata, that combines cross-fertilization and partial self-fertilization. The floral traits of L. oblata of zygomorphic and brightly yellowish corolla, heavy fragrance, and rich nectar, suggest an entomophilous pollination system. Sweat bees were observed as the most effective pollinators but their visiting frequencies were not high. Pollen limitation may limit the reproductive success of L. oblata., Conclusions: We determined the reproductive characteristics of L. oblata, a critically endangered species endemic to cliffs in North China, providing insight into its endangerment and suggesting conservation strategies. L. oblata has highly pollinator-dependent self-fertilization as part of a mixed mating system. Floral features such as low-flowering synchrony, asynchronous anthers dehiscence, and high duration of stigma receptivity, improve pollination efficiency in the case of low pollinator service. Our work provides reference information to understand the survival strategies and conservation of L. oblata and other lithophytes., (© 2022. The Author(s).)

Background: Polysaccharides are important active ingredients in Ophiocordyceps gracilis with many physiological functions. It can be obtained from the submerged fermentation by the anamorph (Paraisaria dubia) of Ophiocordyceps gracilis. However, it was found that the mycelial pellets of Paraisaria dubia were dense and increased in volume in the process of fermentation, and the center of the pellets was autolysis due to the lack of nutrient delivery, which extremely reduced the yield of polysaccharides. Therefore, it is necessary to excavate a fermentation strategy based on morphological regulation for Paraisaria dubia to promote polysaccharides accumulation., Results: In this study, we developed a method for enhancing polysaccharides production by Paraisaria dubia using microparticle enhanced technology, talc microparticle as morphological inducer, and investigated the enhancement mechanisms by transcriptomics. The optimal size and dose of talc were found to be 2000 mesh and 15 g/L, which resulted in a high polysaccharides yield. It was found that the efficient synthesis of polysaccharides requires an appropriate mycelial morphology through morphological analysis of mycelial pellets. And, the polysaccharides synthesis was found to mainly rely on the ABC transporter-dependent pathway revealed by transcriptomics. This method was also showed excellent robustness in 5-L bioreactor, the maximum yields of intracellular polysaccharide and exopolysaccharides were 83.23 ± 1.4 and 518.50 ± 4.1 mg/L, respectively. And, the fermented polysaccharides were stable and showed excellent biological activity., Conclusions: This study provides a feasible strategy for the efficient preparation of cordyceps polysaccharides via submerged fermentation with talc microparticles, which may also be applicable to similar macrofungi., (© 2021. The Author(s).)

Background: Populations of natural killer cells lacking CD56 expression [CD56 neg natural killer (NK) cells] have been demonstrated to expand during human immunodeficiency virus (HIV)-1 infection. However, their phenotypic and functional characteristics have not been systematically analyzed, and their roles during disease progression remain poorly understood., Methods: In this study, 84 donors, namely 34 treatment-naïve HIV-1-infected patients (TNs), 29 HIV-1-infected patients with successful antiretroviral therapy (ARTs), and 21 healthy controls (HCs), were enrolled. The phenotypic and functional characteristics of CD56 neg NK cells were analyzed using single-cell RNA-sequencing (scRNA-seq) and flow cytometry. A potential link between the characteristics of CD56 neg NK cells and the clinical parameters associated with HIV-1 disease progression was examined., Results: The frequency of the CD56 neg NK cell population was significantly increased in TNs, which could be partially rescued by ART. Flow cytometry analyses revealed that CD56 neg NK cells were characterized by high expression of CD39, TIGIT, CD95, and Ki67 compared to CD56 dim NK cells. In vitro assays revealed reduced IFN-γ and TNF-α secretion, as well as decreased expression of granzyme B and perforin in CD56 neg NK cells. In line with the data obtained by flow cytometry, scRNA-seq analysis further demonstrated impaired cytotoxic activities of CD56 neg NK cells. Notably, a negative correlation was observed between CD39, CD95, and Ki67 expression levels in CD56 neg NK cells and CD4 + T cell counts., Conclusions: The results presented in this study indicate that the CD56 neg NK cell population expanded in HIV-1-infected individuals is dysfunctional and closely correlates with HIV-1 disease progression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cao, Zhang, Wan, Li, Mu, Guo, Zhou, Shen, Zhang, Fan, Jiao, Xu, Zhou, Yuan, Wang, Wang and Song.)

Subacute thyroiditis (SAT) is the most common self-limiting thyroid disease causing pain. The etiology of the disease remains unknown, but it is usually related to viral infection or allergic reaction after viral infection. SAT after vaccination is extremely rare. The patient had a fever of no clearly defined cause about 8 hours after receiving the first dose of a 0.5 mL 9-valent human papillomavirus vaccine (Gardasil 9). The highest temperature was 37.8 ℃, accompanied by a pain in the neck, fatigue and the increasing pain when swallowing. After the patient was admitted to the hospital, physical examination revealed Ⅱ° enlargement of the thyroid gland, which was hard and tender, and no vascular murmur was heard. There was no redness, swelling or ulceration at the vaccination site, and no obvious abnormalities were observed in other physical examinations. Laboratory findings were as follows: C-reactive protein, 25.20 mg/L; erythrocyte sedimentation rate, 55 mm/1 h; leukocyte, 4.94×10 9 L -1 ; thyrotropin, 0.137 mU/L; free thyroxine, 22.32 pmol/L; antithyroglobulin antibody, 69.18 IU/mL; anti-thyroid peroxidase antibody, 21.66 IU/mL. Thyroid ultrasonography showed diffuse enlargement of bilateral thyroid with uneven internal echo. The patient was diagnosed with SAT. After 5 days of treatment with ibuprofen, the patient no longer had low fever and the neck pain was relieved. The patient was followed up till now, and had completed the vaccination of the three-dose 9-valent human papillomavirus vaccine. The function of thyroid was found to be normal in follow-up visits, and SAT did not recur., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Neutrophils are characterized by their heterogeneity. They fight against pathogens and are involved in tissue injury repair and immune system regulation. Neutrophils have an extremely short life span in the peripheral blood and undergo aging after being released from the bone marrow. The over-aggregation of aged neutrophils is associated with phenotypical and functional changes. Here, we aimed to investigate the dynamics of neutrophil aging and its relationship with T cell exhaustion in HIV-1 infection, as they are not well understood. In this study, we enrolled 23 treatment naïve (TN) patients, 23 individuals that had received antiretroviral therapy (ART), and 21 healthy controls (HC). In these cohorts, we measured the degree of neutrophil aging, and its possible correlation with T cell dysfunction. In TN patients, peripheral neutrophils showed a more distinct aging phenotype and were over-activated compared to those in ART-treated patients. The degree of neutrophil aging was positively correlated with HIV-1 RNA viral load and negatively correlated with CD4+ T cell count. Moreover, aged neutrophils had impaired reactive oxygen species (ROS) production after lipopolysaccharide (LPS) stimulation, and were characterized by increased PD-L1 and arginase-1 expression in a time-dependent manner. Aged neutrophils demonstrated an increased inhibition of IFN-γ and TNF-α secretion by CD8+ T cell compared to non-aged neutrophils. The inhibition effect could be partially reversed by blocking PD-L1 and arginase-1 in vitro , and LPS was identified as an important activator of neutrophil aging. These results provide evidence that dampening neutrophil aging may provide a novel approach to recover T cell dysfunction in patients with HIV-1 infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Huang, Yang, Jiao, Zhang, Song, Zhang, Zhou, Yuan, Cao, Mu, Zhou, Li, Shi, Xu and Wang.)

As a digestive organ, the liver has the functions of metabolism, synthesis, and detoxification. It is also an immune organ and plays an important role in maintaining anti-infection, autoimmune stability, and anti-tumor. In particular, the liver has unique immunological advantages. Its immune cells can maintain the liver's immune homeostasis and participate in immunoregulation. A variety of immunotherapy is used in clinical trials for the treatment of difficult and critical liver diseases. This review mainly summarizes the recent clinical trials of immunotherapy in chronic hepatitis B, cirrhosis, hepatocellular carcinoma, and autoimmune liver disease.

The genus Lonicera (Caprifoliaceae) is of great economical significance. It has been taxonomically studied frequently in history, while phylogenetic relationships intra the genus are still obscure. Here, we reported the first species complete chloroplast genome sequence in the section Isoxylosteum , Lonicera angustifolia var. myrtillus . It is 156,222 bp in length, comprising a large single-copy (LSC) region of 89,838 bp, a small single-copy (SSC) region of 19,211 bp, and a pair of inverted repeats (IRs) of 23,509 bp. In L. angustifolia var. myrtillus chloroplast genome, a total of 114 functional genes were identified, with an overall GC content of 38.4%. The phylogenetic relationships of Lonicera based on maximum-likelihood (ML) showed that L. angustifolia var. myrtillus is most closely related to L. nervosa in section Isika . Our study contributes to the molecular phylogenetic studies of Lonicera and Caprifoliaceae., Competing Interests: No potential conflict interest was reported by the author(s)., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

The cosmopolitan family Solanaceae, which originated and first diversified in South America, is economically important. The tribe Hyoscyameae is one of the three clades in Solanaceae that occurs outside of the New World; Hyoscyameae genera are distributed mainly in Europe and Asia, and have centers of species diversity in the Qinghai-Tibet Plateau and adjacent regions. Although many phylogenetic studies have focused on Solanaceae, the phylogenetic relationships within the tribe Hyoscyameae and its biogeographic history remain obscure. In this study, we reconstructed the phylogeny of Hyoscyameae based on whole chloroplast genome data, and estimated lineage divergence times according to the newly reported fruit fossil from the Eocene Patagonia, Physalis infinemundi , the earliest known fossil of Solanaceae. We reconstructed a robust phylogeny of Hyoscyameae that reveals the berry fruit-type Atropa is sister to the six capsule-bearing genera (Hyoscyameae sensu stricto ), Atropanthe is sister to the clade ( Scopolia , Physochlaina , Przewalskia ), and together they are sister to the robustly supported Anisodus - Hyoscyamus clade. The stem age of Hyoscyameae was inferred to be in the Eocene (47.11 Ma, 95% HPD: 36.75-57.86 Ma), and the crown ages of Hyoscyameae sensu stricto were estimated as the early Miocene (22.52 Ma, 95% HPD: 15.19-30.53 Ma), which shows a close correlation with the rapid uplift of the Qinghai-Tibet Plateau at the Paleogene/Neogene boundary. Our results provide insights into the phylogenetic relationships and the history of the biogeographic diversification of the tribe Hyoscyameae, as well as plant diversification on the Qinghai-Tibet Plateau., Competing Interests: The authors declare no conflict of interest., (© 2021 Kunming Institute of Botany, Chinese Academy of Sciences. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

A series of 2-ethoxycarbonylthieno[2,3- b ]quinolines were synthesized in the bio-derived "green" solvent γ-valerolactone (GVL) and evaluated for their inhibitory activities against PTP1B, the representative compound 6a displayed an IC 50 value of 8.04 ± 0.71 μM with 4.34-fold preference over TCPTP. These results provided novel lead compounds for the design of inhibitors of PTP1B as well as other PTPs., Competing Interests: The authors have declared no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Background: Infection is common in acute-on-chronic liver failure (ACLF), which may worsen the clinical condition and prognosis. However, the characteristics of infection and its influence on prognosis in hepatitis B virus related ACLF (HBV-ACLF) as defined by the European Association for the Study of the Liver (EASL) have not been clarified. We aimed to investigate the characteristics of infection and its influence on mortality in patients with HBV-ACLF defined by EASL in China., Methods: We performed a retrospective cohort study in patients with HBV-ACLF defined by EASL in a single center from January 2015 to December 2017. These patients were divided into two groups with and without infection. The incidence, sites of infection, isolated strains, and risk factors associated with mortality were evaluated., Results: A total of 289 patients were included, among them 185 (64.0%) were diagnosed with an infection. The most common type of infection was pneumonia (55.7%), followed by spontaneous bacterial peritonitis (47.6%) and others. The gram-negative bacteria were the most frequent (58.3%). Patients with one, two, and three or more infection sites had a gradually increasing incidence of sepsis (P < 0.01), septic shock (P < 0.001), and ACLF-3 (P < 0.05). Also, patients with infection isolated one, two, and three or more strains showed a growing incidence of sepsis (P < 0.01) and septic shock (P < 0.001). Patients with infection showed a significantly higher 28-day mortality than those without (P < 0.01), especially in patients with ACLF-3. Infection was identified as an independent risk factor for 28-day mortality in all HBV-ACLF patients. Pneumonia and sepsis were identified as independent predictors of 28-day mortality for patients with infection., Conclusions: Infection is associated with severe clinical course and high mortality in HBV-ACLF defined by EASL. The increased number of infection sites or isolated strains was associated with the occurrence of sepsis and septic shock. Pneumonia and sepsis were independent predictors for mortality in HBV-ACLF patients with infection.

The walnut family Juglandaceae was widely distributed in the Northern Hemisphere while several extant genera now exhibit intercontinental disjunctions. Recent progress in the systematics of Juglandaceae has greatly broadened our knowledge about its origin and evolution. However, there are still uncertainties about the intergeneric relationships within Juglandaceae, and discrepancies between fossil records and inferred divergence times for certain lineages were observed. In this study, well-resolved phylogenies of the Juglandaceae are reconstructed based on both the nuclear RAD-Seq and the whole chloroplast genome data. Our results support the Juglandoideae topology of (Hicoreae, (Platycaryeae, Juglandeae)) at the tribal level. Within Juglandeae, a discordant position of Pterocarya was detected between nuclear and plastid genome data, and a more likely topology (nuclear), (Juglans, (Pterocarya, Cyclocarya)), was discussed based on evidence from molecular data and fossil records. Based on carefully selected fossil calibrations, the divergence times of extant lineages were estimated and they corroborated well with fossil records (especially concerning Juglans and Pterocarya). Four sections within Juglans were strongly supported by the nuclear data. Within Juglans, the incongruent position of J. hopeiensis was recovered between the nuclear and plastid genomes. Yet the origin and evolutionary history of J. cinerea and J. hopeiensis are supported to be complicated and need further clarification. Integrative evidence from the fossil records, phylogeny and lineage divergence times shows that Juglandoideae originated in North America, and migrated to Eurasia via both the Bering and the North Atlantic land bridges. Our study shows the potential of integrative biogeographic studies for illuminating the evolutionary history of Juglandaceae., (Copyright © 2020 Elsevier Inc. All rights reserved.)

A 61-year-old Chinese woman was diagnosed as primary pulmonary adenocarcinoma of left superior lobe with epidermal growth factor receptor (EGFR) 19 del mutation positive. Treatment with icotinib was given, but her disease progressed after 6 months remission. CT-guide needle biopsy for the new lesion in inferior lobe of left lung demonstrated intrapulmonary metastasis, and EGFR gene panel by Amplification Refractory Mutation System Polymerase Chain Reaction (ARMS-PCR) confirmed EGFR T790M mutation. Treatment with osimertinib was initiated. After 2 months remission, the disease progressed. Re-biopsy was performed for the tumor in the inferior lobe of left lung, and ARMS-PCR demonstrated no other gene mutation except EGFR 19 del. Icotinib was re-challenged, but disease progressed continuously. Bevacizumab was added, and partial response was achieved after 2-cycle of combination therapy. The non-small cell lung cancer (NSCLC) in this case maintained EGFR activating mutation and lost EGFR T790M mutation was a genetic change after osimertinib treatment. This case suggests the re-challenge of the first-generation EGFR-TKIs combined with bevacizumab may overcome the tumor resistance and prolong survival of NSCLC patient.

Aim: The value of the peripheral blood lymphocyte subpopulation ratios and tumor diameter for prognosis in bladder cancer (BC) patients needs to be explored. Materials & methods: A total of 161 male BC patients and 68 male normal controls were retrospectively reviewed. The value of combining predictor consisted of both CD4 + CD25 + /CD4 + and computed tomography urography tumor diameter (CTU-D) on stage, overall survival (OS) and recurrence probability was analyzed by logistic regression, Kaplan-Meier method and log-rank test. Results: The combining predictor was a statistically independent risk for stage; dramatic differences in OS and recurrence probability were found between the combining predictor-high (cut-off point >0.08) and combining predictor-low groups (cut-off point ≤0.08). Conclusion: The combining predictor could be a significant predictor for advanced stage, OS and recurrence probability in male patients with BC.

Physochlaina is an important perennial herbaceous genus with significant medicinal value, while the phylogeny of Physochlaina and tribe Hyoscyameae is not well resolved yet. In this study, we report the complete chloroplast genome sequences of Ph. physaloides , its complete chloroplast genome is 156,413 bp in length, which is a typical quadripartite structure that includes a large single-copy region of 86,659 bp, a small single-copy region of 18,012 bp, and its GC content was 37.7%. A total of 132 genes were identified, including 87 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. Furthermore, a phylogenetic tree of the tribe Hyoscyameae was constructed based the complete chloroplast genome sequence, and a new topology of the tribe was obtained. This study provides valuable genetic information for the conservation and utilization of Ph. physaloides and also provide the potential for better understanding of the phylogeny of Hyoscyameae and Solanaceae., Competing Interests: The authors report no conflict of interest., (© 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Symphoricarpos orbiculatus is an important landscape and ornamental plant. In this study, we report the complete chloroplast genome sequences of S. orbiculatus . The complete chloroplast genome of S. orbiculatus was 156,044 bp in length. The genome has a typical quadripartite structure, including a large single-copy (LSC) region of 88,756 bp, a small single-copy (SSC) region of 19,130 bp, and two inverted repeat (IR) regions of 24,079 bp each. Overall, the GC content was 38.4%. In the genome, it was identified to comprise130 genes, including 85 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. This study provides valuable information for molecular phylogenetic study of Caprifoliaceae and is significant for variety development of Symphoricarpos ., Competing Interests: The authors report no conflict of interest., (© 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Lonicera oblata , a critically endangered species endemic to North China with about 30 wild individuals, has long been ignored for conservation since its publication because of little attention on its living situation. In this study, we characterized the complete chloroplast (cp) genome of L. oblata . The cp genome was 155,481 bp in length, included a large single-copy (LSC) region of 89,139 bp, a small single-copy (SSC) region of 18,676 bp, and two inverted repeat (IR) regions of 23,833 bp each. The genome contains 130 genes, including 85 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. Phylogenetic position of L. oblata was also investigated based on cp genome phylogeny of Lonicera representatives. This study is valuable for molecular phylogenetic study and conservation of Lonicera and related taxa., (© 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: As a large, prospective, multicenter study-based prognostic score for hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF), the Chinese group on the study of severe hepatitis B-acute-on-chronic liver failure score (COSSH-ACLFs), has been approved by some foreign scholars; however, its predictive value needs to be verified. This study investigated the predictive value of COSSH-ACLFs for short-term prognosis in Chinese patients with HBV-ACLF., Methods: This retrospective cohort study included 751 patients with HBV-ACLF admitted to the Fifth Medical Center of Chinese PLA General Hospital between January 2011 and December 2014. Spearman method was used to assess the correlation of COSSH-ACLFs with classical scores. Different COX multivariate regression models were used to confirm the relationship between COSSH-ACLFs and short-term prognosis in patients with HBV-ACLF, and stratified analysis was used to further verify the stability of this relationship. We compared the predictive powers of COSSH-ACLFs and other classical scores using area under the receiver operating characteristic curve (AUROC) and Z-test., Results: A total of 975 patients with HBV-ACLF were screened, and 751 were analyzed (623 male and 128 female). COSSH-ACLFs was the highest in patients with end-stage ACLF, followed by those with middle- and early-stage ACLF (H = 211.8, P < 0.001). In the fully adjusted model, COX multivariate regression analysis revealed that COSSH-ACLFs (as a continuous variable) was independently and positively correlated with mortality risk in patients with HBV-ACLF at 28 days (hazard ratio [HR]: 1.37 [1.22, 1.53], P < 0.001) and 90 days (HR: 1.43 [1.29, 1.58], P < 0.001). The same trend could be observed in the crude model and minimally adjusted model. The AUROCs of COSSH-ACLFs for 28-day and 90-day prognoses in patients with HBV-ACLF were 0.807 and 0.792, respectively, indicating a stronger predictive accuracy than those of classic models., Conclusions: COSSH-ACLFs, with a superior predictive accuracy compared with other classical scores, can strongly predict short-term prognosis in Chinese patients with HBV-ACLF.

Bladder cancer (BC) is a malignant tumor of urinary epithelium. Gemcitabine is an introduced treatment for BC and also has immunomodulatory function, but the immunoregulation mechanism is not clear. In this study, we found that gemcitabine-treated BC cell recruited more monocyte-myeloid-derived suppressed cells (M-MDSCs), which played a significant role in immune suppression and contributed to cancer progression. We found that this phenomenon was induced by Chemokine (C-C motif) ligand 2 (CCL2), an M-MDSCs recruitment related monomeric polypeptide. Gemcitabine treatment promotes the generation of CCL2 and CCL2 could attach to C-C chemokine receptor type 2 (CCR2) to recruit M-MDSCs. We used RS 504393, a selective CCR2 antagonist, to inhibit the recruitment of M-MDSCs. RS 504393 improved the prognosis by blocking chemotaxis of M-MDSCs, and this finding sheds lights on how to prevent and alleviate the side effects occurred on the gemcitabine-treated BC patients., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Biofilm formation is a critical determinant in the pathopoiesis of Pseudomonas aeruginosa It could significantly increase bacterial resistance to drugs and host defense. Thus, inhibition of biofilm matrix production could be regarded as a promising attempt to prevent colonization of P. aeruginosa and the subsequent infection. PpgL, a periplasmic gluconolactonase, has been reported to be involved in P. aeruginosa quorum-sensing (QS) system regulation. However, the detailed function and catalysis mechanism remain elusive. Here, the crystal structure of PpgL is described in the current study, along with biochemical analysis, revealing that PpgL is a typical β-propeller enzyme with unique metal-independent lactone hydrolysis activity. Consequently, comparative analysis of seven-bladed propeller lactone-catalyzing enzymes and mutagenesis studies identify the critical sites which contribute to the diverse catalytic and substrate recognition functions. In addition, the reduced biofilm formation and attenuated invasion phenotype resulting from deletion of ppgL confirm the importance of PpgL in P. aeruginosa pathogenesis. These results suggest that PpgL is a potential target for developing new agents against the diseases caused by P. aeruginosa ., (Copyright © 2019 American Society for Microbiology.)

MicroRNA (miR)‑26a‑5p and miR‑26b‑5p consistently play an antitumor role in many types of cancers, but the underlying mechanism remains unclear in bladder cancer (BC). In the present study, we found that, in BC tissues, the levels of miR‑26a‑5p and miR‑26b‑5p were lower than in paired normal tissues. The upregulation of miR‑26‑5p significantly inhibited the proliferation of BC cell lines (T24 and 5637). Bioinformatics analysis indicated that Programmed Cell Death 10 (PDCD10) was the downstream target gene of miR‑26a‑5p/miR‑26b‑5p, and this was ascertained by western blotting and quantitative real‑time reverse transcription PCR (RT‑qPCR). In addition, in the 3'‑UTR of PDCD10, the binding site was identified using a luciferase reporter assay. We determined that clinical BC tissues presented higher PDCD10 levels than adjacent normal tissues and that PDCD10 promoted proliferation of BC cell lines. Overexpression of miR‑26a‑5p/miR‑26b‑5p inhibited the stimulatory effect on proliferation of BC cells induced by PDCD10. In addition, in vivo experiments and clinical data revealed that the prognosis of BC patients with high expression of miR‑26a‑5p/miR‑26b‑5p and low expression of PDCD10 was better than that of patients with low miR‑26‑5p and high PDCD10 expression. These data revealed that miR‑26a‑5p and miR‑26b‑5p were pivotal regulators in BC progression by targeting the proliferation‑related protein, PDCD10. The miR‑26‑5p/PDCD10 interaction may provide important insight into the pathway of BC progression and present novel opportunities for future diagnosis and treatment strategies, especially for patients with high levels of PDCD10.

Bladder cancer (BC) is a disease arising from the malignant cells of the urinary bladder. Myeloid-derived suppressor cells (MDSCs) expand broadly and have strong immunosuppressive activities in the cancer microenvironment. Determining how to inhibit the negative effects of MDSCs requires immediate attention. In this study, we found that granulocytic-MDSCs (G-MDSCs), which constitute one of the two types of MDSCs, were significantly increased in BC tissues compared with those in the adjacent bladder tissues. There was a robust negative correlation between the G-MDSCs and the CD8 + T cells in the BC tissues. In this study, we attempted to identify pharmacological approaches to eliminate MDSCs and restore T cell anti-tumor activities. It is necessary to explore a method to eliminate the detrimental effects of MDSCs. Cisplatin, a chemotherapy medication used to treat BC, not only rapidly kills proliferating cancer cells but also affects the tumor immune microenvironment. However, the mechanism underlying this phenomenon is largely unknown. In this study, we found that Cisplatin directly inhibited the proliferation and induced the apoptosis of T24 cells (a BC cell line), as well as decreased the percentage of the G-MDSCs in the population of peripheral blood mononuclear cells (PBMCs), which restored the expansion of the CD8 + T cells. In the C3H/He mouse BC model, Cisplatin treatment inhibited the progression of BC and effectively decreased the proportion of G-MDSCs. These results suggest that Cisplatin treatment enhances the anti-tumor function of CD8 + T cells by decreasing G-MDSCs. This finding provides a new perspective for Cisplatin treatment to prevent the progression of BC, particularly in patients with abnormally high levels of G-MDSCs., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Research on the changes to knee structures in asymptomatic amateur ice hockey players (AAIHPs) has been limited. We aimed to assess the performance of the knees in AAIHPs using 3.0-T magnetic resonance imaging (MRI)., Methods: A total of 71 asymptomatic knees (32 AAIHPs and 39 age- and sex-matched controls) were imaged using a 3.0-T MRI scanner at the Affiliated Zhongshan Hospital of Dalian University in April 2017. Two experienced musculoskeletal radiologists were blinded to assess all MRI findings, including bursae around the knee, bone marrow edema (BME), meniscal signal changes, and articular cartilage and ligament damage. Any disagreements were resolved by a third professor of musculoskeletal radiology. Categorical variables were compared using the Chi-square test and continuous variables using the Student's t-test or Mann-Whitney U-test., Results: The most common finding was fluid-filled bursae surrounding the knee. In the AAIHP group, which totaled 32 knees and 416 bursae, 155 (37%) fluid-filled bursae were present. In the control group, there were a total of 39 knees and 507 bursae, and 91 (18%) fluid-filled bursae were present. There was a significant difference in the number of fluid-filled bursae between the two groups (P < 0.05). However, in AAIHPs, the prevalence of meniscal signal changes (16 knees, 50%) was higher than in the control group (2 knees, 5%; P < 0.001). Importantly, 15 of the 19 were grade II signals. Other changes were only found in AAIHPs. Articular cartilage lesions were detected in 47% of their knees, predominantly at the patellofemoral joint, and BME was found in 34% of their knees., Conclusion: The MRI findings of knees in AAIHPs mainly manifested as self-protection reaction, and proper ice hockey exercise could be advocated., Competing Interests: There are no conflicts of interest

Juglans species have considerable ecological and economic value worldwide. In China, Wenwan walnuts have been collected by aristocrats and noblemen for more than 2000 years. As a diversity center of Asian Juglans , five species are widely distributed in China. The most famous of these is Mahetao ( J. hopeiensis ), which is an uncharacterized species that is mostly cultivated. Wild J. hopeiensis individuals are very rare and are endemic to Hebei Province. Because of the minimal variations in previously used molecular markers and the heterogeneity between chloroplast and nuclear genomes, determining the phylogenetic relationships among the Juglans species has been challenging, and has hindered subsequent evolutionary inferences. In this study, we collected enough materials for both cultivated and wild Mahetao to construct well-resolved phylogenetic trees for Asian Juglans species. We used a high-throughput genome-wide restriction site-associated DNA sequencing method. Consequently, the identity of J. hopeiensis has been clearly resolved. Our results indicate that J. hopeiensis is a hybrid of J. regia and J. mandshurica . However, J. hopeiensis, J. regia and J. sigillata should be considered as a single species from section Juglans . Additionally, J. ailantifolia, J. cathayensis , and J. mandshurica likely represent one species from section Cardiocaryon according to morphological and molecular studies. These results are supported by population structure analysis and morphological comparison. We propose that J. hopeiensis trees growing in the wild should be conserved because of the economic value of their nuts. These trees may be of particular importance to impoverished communities. Furthermore, they may serve as a valuable genetic resource relevant for enhancing the production of edible walnuts. The 2b-RAD method is a viable option for future phylogenetic studies of Juglans species as well as other plant species.

The present study is designed to explore the role of plasma cells in the change of protein C system (PCS) in ulcerative colitis (UC). Dextran sulfate sodium (DSS, 4% in concentration) was used to induce mouse UC model. The plasma cells and the type of immune complex in colon were observed by immunofluorescence. The amount and type of plasma cells separated from colonic mucosal lamina propria were detected by flow cytometry using anti-CD54 + CD38 + and IgA/M/G antibodies, respectively. After stimulation of macrophages by IgG type immune complex, TNF-α and IL-6 levels were evaluated by ELISA. After co-incubation of microvascular endothelial cells with TNF-α or IL-6, the expressions of endothelial protein C receptor (EPCR) and thrombomodulin (TM), and the activity of activated protein C (APC) were examined. As the results showed, the IgG type plasma cells infiltration and the quantity of IgG type immune complex were increased in DSS group in comparison with control group. After incubation with IgG type immune complex, the levels of TNF-α and IL-6 in the supernatant of macrophages were increased (P < 0.01) in a concentration-dependent manner. Meanwhile, after incubation with TNF-α or IL-6, the expressions of EPCR and TM in the microvascular endothelial cells were decreased (P < 0.05 or P < 0.01), while the activity of APC was reduced (P < 0.05 or P < 0.01). These results suggested that the quantity of IgG type plasma cells increases in UC and forms immune complexes, which affect the secretion of cytokines from macrophage, thereby affecting the function of endothelial cells and finally inhibiting PCS in UC. Therefore, plasma cell may be a novel target for the treatment of UC.

In this work, a unique D-amino acid oxidase reactor for enhanced enzymolysis efficiency is presented. A kind of magnetic polymer matrices, composed of iron oxide nanoparticles and porous polymer membrane (poly styrene-co-maleic anhydride), was prepared. With covalent bonding D-Amino acid oxidase on the surface of the matrices and characterization of scanning electron microscope and vibrating sample magnetometer, it demonstrated that the membrane enzyme reactor was successfully constructed. The enzymolysis efficiency of the enzyme reactor was evaluated and the apparent Michaelis-Menten constants of D-Amino acid oxidase were determined (K m was 1.10mM, V max was 23.8mMmin -1 ) by a chiral ligand exchange capillary electrophoresis protocol with methionine as the substrate. The results indicated that the enzyme reactor could exhibit good stability and excellent reusability. Importantly, because the enzyme and the substrate could be confined into the pores of the matrices, the enzyme reactor displayed the improved enzymolysis efficiency due to the confinement effect. Further, the prepared enzyme reactor was applied for D-Amino acid oxidase inhibitors screening. It has displayed that the proposed protocol could pave a new way for fabrication of novel porous polymer membrane based enzyme reactors to screen enzyme inhibitors., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The herbicide Quizalofop-P-ethyl (QpE) exerts toxic effects in fish, but limited information is currently available on its effects on the endocrine system. In the current study, adult zebrafish (Danio rerio) were exposed to different concentrations (0, 2, 20, 200μg/L) of QpE for 30days. In males, QpE exposure significantly increased plasma estradiol (E2) and vitellogenin (VTG) levels, concomitant with up-regulation of hepatic esr1 and vtg gene expression. In females, plasma sex hormone levels and VTG concentrations were not altered significantly, but an increased expression of hepatic esr1 in addition to decreased expression of hepatic vtg, esr2a and esr2b was observed. Marked histological lesions were also observed in the gonads of both males and females. Moreover, QpE exposure significantly increased transcriptional profiles of some genes in the HPG axis and liver in males, while the majority of these genes were down-regulated in females. Docking studies showed QpE forming stable interactions with the ligand-binding domain (LBD) of zebrafish ESR1 and ESR2a, suggesting QpE may bind to estrogen receptors (ESRs). This study for the first time reveals QpE as an endocrine-disrupting chemical (EDC) disrupting the zebrafish endocrine system in a sex-specific manner, whereby it increases estrogen axis activity in males and slightly decreases estrogen axis activity in females, which may be accounted for by QpE regulating steroidogenesis and/or activating ESR(s)., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Celastrus and Tripterygium species, which are used in traditional Chinese medicine, have attracted much attention due to their anti-tumor promoting and neuroprotective activities, in addition to their applications in autoimmune disorders. However, systematic relationships between them and among species are unclear, and it may disturb their further medicinal utilization. In the present study, the molecular analysis of combined chloroplast and nuclear markers of all Chinese Celastrus and Tripterygium was performed, and clear inter- and intra-genus relationships were presented. The result suggests that Tripterygium constitute a natural monophyletic clade within Celastrus with strong support value. Fruit and seed type are better than inflorescence in subgeneric classification. Chinese Celastrus are classified for three sections: Sect. Sempervirentes (Maxim.) CY Cheng & TC Kao, Sect. Lunatus XY Mu & ZX Zhang, sect. nov., and Sect. Ellipticus XY Mu & ZX Zhang, sect. nov. The phylogenetic data was consistent with their chemical components reported previously. Owing to the close relationship, several evergreen Celastrus species are recommended for chemical and pharmacological studies. Our results also provide reference for molecular identification of Chinese Celastrus and Tripterygium., Competing Interests: The authors have declared that no competing interests exist.

Long term peritoneal dialysis (PD) is often associated with peritoneal fibrosis. The aim of this study was to explore the effect of emodin on PD-related peritoneal fibrosis and its related cellular and molecular mechanism. PD-related peritoneal fibrosis rats and cultured rat peritoneal mesothelial cells were recruited in the experiment. PD-related peritoneal fibrosis was induced by intraperitoneal injection of lactate-buffered solution containing 4.25% glucose. The peritoneal equilibrium test (PET) was performed at the end of 2 weeks, 4 weeks, and 6 weeks, respectively. HE staining and Masson staining were used for histopathological evaluation. Enzyme linked immunosorbent assay (ELISA) was used to measure the plasma N-terminal procollagen III propeptide (PIIINP) level. Real-time PCR technique was used to detect the mRNA levels of Notch1, Jagged-1, and Hes-1 in peritoneal tissue. Western blot was applied to identify the protein levels of Notch1, Jagged-1, Hes-1, and Notch intracellular domain (NICD). In vitro, Notch1 overexpressing or knockdown rat peritoneal mesothelial cells were established and Western blot was used to examine the effect of emodin on the expressions of Hes-1 and Hey. Compared with the control group, HE staining revealed that PD rats suffered from decreasing in mesothelial cells, or detaching from surface of parietal peritoneum, accompanied by infiltration of inflammatory cells; Masson staining result showed thickened peritonea (P < 0.01), and the collagen deposition in the parietal peritoneum was increased; also, PIIINP level in plasma was elevated (P < 0.01). Treatment of the PD rats with emodin increased mesothelial cells in peritoneal tissue, and decreased the peritoneal thickness (P < 0.01), collagen depositions, as well as the plasma PIIINP level (P < 0.05). The expressions of Notch1, Jagged-1, Hes-1 and NICD in peritoneal tissue were also attenuated (P < 0.05 or P < 0.01). In cultured rat peritoneal mesothelial cells, compared with emodin group, emodin further inhibited the expressions of Hes-1 and Hey induced by Notch1-overexpression (P < 0.05), but not the expressions of Hes-1 and Hey induced by Notch1-knockdown (P > 0.05). Therefore, the activation of Notch pathway may be involved in the pathological process of PD-induced peritoneal fibrosis. Emodin may ameliorate the PD-related peritoneal fibrosis through inhibiting the activation of Notch pathway.

Objective: To explore the relationship between umbilical cord blood brain-derived neurotrophic factor (BDNF) and neonatal neurobehavioral development in lead exposure infants., Methods: All infants and their mother were randomly selected during 2011 to 2012, subjects were selected according to the umbilical cord blood lead concentrations, which contcentration of lead was higher than 0.48 μmol/L were taken into high lead exposure group, about 60 subjects included. Comparing to the high lead exposure group, according to gender, weight, pregnant week, length and head circumferenece, the level of cord blood lead concentration under 0.48 μmol/L were taken into control group, 60 cases included. Lead content was determined by graphite furnace atomic absorption spectrometry. Neonatal behavioral neurological assessment (NBNA) was used to determine the development of neonatal neuronal behavior. The content of BDNF was detected by ELISA. Comparing the BDNF and the NBNA score between two groups, and linear correlation was given on analysis the correlation between lead concentration in cord blood and BDNF, BDNF and the NBNA score., Results: Lead content in high exposure group was (0.613±0.139) μmol/L, and higher than (0.336±0.142) μmol/L in low exposure group (t=3.21, P<0.001) . NBNA summary score (36.35±1.86), active muscle tension score (6.90±0.27) and general assessment score (5.93±0.32) in high exposure group were lower than those (38.13±0.96, 7.79±0.35, 6.00±0.00) in low exposure group (t values were 8.21, 10.23, 2.32, respectively, P values were <0.001, <0.001 and 0.037) . BDNF content in high exposure group which was (3.538±1.203) ng/ml was higher than low exposure group (2.464±0.918) ng/ml (t=7.60, P<0.001). The correlation analysis found that the cord blood BDNF content was negatively correlated with NBNA summary score, passive muscle tension and active muscle tone score (r was -0.27, -0.29, -0.30, respectively, P values were <0.001, respectively) ., Conclusion: Prenatal lead exposure results poor neonatal neurobehavioral development and cord blood BDNF was negatively correlated with neonatal neurodevelopment, may serve as a useful biomarker.

Background: Rapid advances in multislice computed tomography (MSCT) technology facilitate accurate clinical imaging. The newly developed 64-slice CT increases temporal and spatial resolution efficiently., Purpose: The purpose of this study is to evaluate the application of 64 slice spiral computed tomography (CT) on the imaging of the normal optics canal., Methods and Materials: 100 healthy adults were investigated using 64 slice spiral CT. The optics canal was scanned, reconstructed and examined., Results: Among the four walls of the optic canal, the medial wall is the longest one. The upper wall and outer wall are inferior to the medial wall while the inferior wall is the shortest one. All the data accomplished by the 64 slice CT was consistent with the results of previous reports using other methods., Conclusion: The results suggested that the 64 slice spiral CT could be a valuable and accurate method for measuring the length of optics canal walls.

Intracellular temperature has a fundamental effect on cellular events. Herein, a novel fluorescent polymer ratiometric nanothermometer has been developed based on transferrin protein-stabilized gold nanoclusters as the targeting and fluorescent ratiometric unit and the thermosensitve polymer as the temperature sensing unit. The resultant nanothermometer could feature a high and spontaneous uptake into the HeLa cells and the ratiometric temperature sensing over the physiological temperature range. Moreover, the precise temperature sensing for intracellular heat generation in HeLa cells following calcium ions stress has been achieved. This practical intracellular thermometry could eliminate the interference of the intracellular surrounding environment in cancer cells without a microinjection procedure, which is user-friendly. The prepared new nanothermometer can provide tools for unveiling the intrinsic relationship between the intracellular temperature and ion channel function.

A two-year field study with split plot design was conducted to investigate the effects of different soil tillage (conventional tillage, CT; deep tillage, DT; subsoil tillage, ST) and straw returning (all straw retention, AS; no straw returning, NS) on microorganism quantity, enzyme activities in soil and grain yield. The results showed that, deep or subsoil tillage and straw returning not only reduced the soil bulk density and promoted the content of organic carbon in soil, but increased the soil microbial quantity, soil enzyme activities and grain yield. Furthermore, such influences in maize season were greater than that in wheat season. Compared with CT+NS, DT+AS and ST+AS decreased the soil bulk density at 20-30 cm depth by 8.5% and 6.6%, increased the content of soil organic carbon by 14.8% and 12.4%, increased the microorganism quantity by 45.9% and 33.9%, increased the soil enzyme activities by 34.1% and 25.5%, increased the grain yield by 18.0% and 19.3%, respectively. No significant difference was observed between DT+AS and ST+AS. We concluded that retaining crop residue and deep or subsoil tillage improved soil microorganism quantity, enzyme activities and crop yield.

It is well known that maternal folate deficiency results in adverse pregnancy outcomes. In addition to aspects in embryonic development, maternal uterine receptivity and the decidualization of stromal cells is also very important for a successful pregnancy. In this study, we focused on endometrium decidualization and investigated whether apoptosis, which is essential for decidualization, was impaired. Flow cytometry and TUNEL detection revealed that apoptosis of mouse endometrium decidual cells was suppressed in the dietary folate-deficient group on Days 7 and 8 of pregnancy (Day 1 = vaginal plug) when decidua regression is initiated. The endometrium decidual tissue of the folate deficiency group expressed less Bax compared to the normal diet group while they had nearly equal expression of Bcl2 protein. Further examination revealed that the mitochondrial transmembrane potential (ΔΨm) decreased, and the fluorescence of diffuse cytoplasmic cytochrome c protein was detected using laser confocal microscopy in normal decidual cells. However, no corresponding changes were observed in the folate-deficient group. Western blotting analyses confirmed that more cytochrome c was released from mitochondria in normal decidual cells. Taken together, these results demonstrated that folate deficiency could inhibit apoptosis of decidual cells via the mitochondrial apoptosis pathway, thereby restraining decidualization of the endometrium and further impairing pregnancy.

The researches in the dynamic changes of the progress of HSCs aging are very limited and necessary. In this study, male C57BL/6 mice were divided into 5 groups by age. We found that the superoxide damage of HSPCs started to increase from the middle age (6 months old), with notably reduced antioxidation ability. In accordance with that, the senescence of HSPCs also started from the middle age, since the self-renewal and differentiation ability remarkably decreased, and senescence-associated markers SA-β-GAL increased in the 6-month-old and the older groups. Interestingly, the telomere length and telomerase activity increased to a certain degree in the 6-month-old group. It suggested an intrinsic spontaneous ability of HSPCs against aging. It may provide a theoretical and experimental foundation for better understanding the senescence progress of HSPCs. And the dynamic biological characteristics of HSPCs senescence may also contribute to the clinical optimal time for antiaging drug intervention.

Aims: PTBP3 overexpression inhibits the differentiation of leukemia cells; however, its effects on the differentiation and proliferation of solid cancer cells remain unclear. Thus, the impact of PTBP3 on the differentiation and proliferation of gastric cancer cells was investigated., Main Methods: PTBP3 expression was analyzed in normal and tumor tissues using immunohistochemistry. A xenograft model was established in nude mice by subcutaneous injection of untransfected human gastric cancer MKN45 cells or those expressing a control vector or PTBP3 siRNA. We analyzed the tumor inhibition rate, the expression of PTBP3, the PCNA-positive rate and the serum levels of CEA, CA199, CA125, LDH, ALP and γ-GT in different groups., Key Findings: The tumor weights in the PTBP3 siRNA group were significantly lower than that of the MKN45 cell control group (P<0.001). Immunohistochemistry analysis of PCNA expression revealed that it was markedly reduced after PTBP3 silencing. ELISAs showed that the serum levels of CEA and CA199 tumor markers as well as LDH and ALP were reduced after PTBP3 silencing. Transmission electron microscopy revealed that MKN45 cells expressing PTBP3 siRNA had reduced nuclear-to-cytoplasmic ratio and regular nuclei, suggesting differentiation., Significance: PTBP3 may promote proliferation and inhibit the differentiation of human gastric cancer MKN45 cells., (Copyright © 2014 Elsevier Inc. All rights reserved.)