bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein Diversity and Immune Specificity of Hemocyanin From Shrimp Litopenaeus vannamei
Authors: Zhao Xianliang , Qiao Jie , Zhang Pei , Zhang Zehui , Aweya Jude Juventus , Chen Xiaohan , Zhao Yongzhen , Zhang Yueling 
Published: December 2021

Hemocyanin is an important non-specific innate immune defense molecule with phenoloxidase, antiviral, antibacterial, hemolytic, and antitumor activities. To better understand the mechanism of functional diversity, proteomics approach was applied to characterize hemocyanin (HMC) expression profiles from Litopenaeus vannamei. At first, hemocyanin was purified by Sephadex G-100 and DEAE-cellulose (DE-52) columns from shrimp serum, and 34 protein spots were identified as HMC on the 2-DE gels. Furthermore, we found that 9 HMC spots about 75 or 77 kDa were regulated by Streptococcus agalactiae and Vibrio parahaemolyticus infection at 6, 12, and 24 h. In addition, 6 different pathogen-binding HMC fractions, viz., HMC-Mix, HMC-Vp, HMC-Va, HMC-Vf, HMC-Ec, and HMC-Sa, showed different agglutinative and antibacterial activities. Moreover, lectin-blotting analysis showed significant differences in glycosylation level among HMC isomers and bacteria-binding HMC fractions. Particularly, the agglutinative activities of the HMC fractions were almost completely abolished when HMC was deglycosylated by O-glycosidase, which suggest that O-linked sugar chains of HMC played important roles in the innate immune recognition. Our findings demonstrated for the first time that L. vannamei HMC had molecular diversity in protein level, which is closely associated with its ability to recognize diverse pathogens, whereas glycan modification probably contributed to HMC’s diversity and multiple immune activities.
The Effects of Differentially-Expressed Homeobox Family Genes on the Prognosis and HOXC6 on Immune Microenvironment Orchestration in Colorectal Cancer
Authors: Qi Lina , Ye Chenyang , Zhang Ding , Bai Rui , Zheng Shu , Hu Wangxiong , Yuan Ying 
Published: December 2021

BackgroundThe homeobox (HOX) gene family encodes highly conserved transcription factors, that play important roles in the morphogenesis and embryonic development of vertebrates. Mammals have four similar HOX gene clusters, HOXA, HOXB, HOXC, and HOXD, which are located on chromosomes 7, 17,12 and 2 and consist of 38 genes. Some of these genes were found to be significantly related to a variety of tumors; however, it remains unknown whether abnormal expression of the HOX gene family affects prognosis and the tumor microenvironment (TME) reshaping in colorectal cancer (CRC). Therefore, we conducted this systematic exploration to provide additional information for the above questions.MethodsRNA sequencing data from The Cancer Genome Atlas (TCGA) and mRNA expression data from Gene Expression Omnibus (GEO) combined with online tumor analysis databases (UALCAN, TIMER, PrognoScan) were utilized to explore the relationship among abnormal expression of HOX family genes, prognosis and the tumor immune microenvironment in CRC.Results1. Differential expression and prognosis analysis: 24 genes were significantly differentially expressed in CRC compared to adjacent normal tissues, and seven upregulated genes were significantly associated with poor survival. Among these seven genes, univariate and multivariate Cox regression analysis revealed that only high expression of HOXC6 significantly contributed to poor prognosis; 2. The influence of overexpressed HOXC6 on the pathway and TME: High HOXC6 expression was significantly related to the cytokine pathway and expression of T cell attraction chemokines, the infiltration ratio of immune cells, expression of immune checkpoint markers, tumor mutation burden (TMB) scores and microsatellite instability-high (MSI-H) scores; 3. Stratified analysis based on stages: In stage IV, HOXC6 overexpression had no significant impact on TMB, MSI-H, infiltration ratio of immune cells and response prediction of immune checkpoint blockers (ICBs), which contributed to significantly poor overall survival (OS).ConclusionSeven differentially expressed HOX family genes had significantly worse prognoses. Among them, overexpressed HOXC6 contributed the most to poor OS. High expression of HOXC6 was significantly associated with high immunogenicity in nonmetastatic CRC. Further research on HOXC6 is therefore worthwhile to provide potential alternatives in CRC immunotherapy.
Structural Lesion Progression of the Sacroiliac Joint and Clinical Features in axSpA During TNFi Reduction: A Retrospective Cohort Study
Authors: Mo Qian , Dong Yuanji , Ye Cong , Zhong Jixin , Cai Shaozhe , Wang Min , Dong Lingli 
Published: December 2021

Objective: In the clinic, some patients with axial spondyloarthritis (axSpA) have to reduce tumor necrosis factor inhibitor (TNFi) for various reasons. However, there are few studies about how to balance the relapse and TNFi reduction. Here we retrospectively analyzed the structural progression of the sacroiliac joint (SIJ) and clinical features in axSpA during TNFi reduction.Methods: A total of 108 patients with axSpA who followed up for 2 years and completed at least baseline, 12-month, and 24-month MRI scans of SIJ were divided into the tapering group (n = 63) and withdrawal group (n = 45) according to whether TNFi was stopped. We divided 2 years into five intervals, calculating the average dose quotient (DQ) for each of 540 intervals from 108 patients. By using generalized estimation equations with inverse probability of treatment weighting, we investigated the unbiased effects of average DQ on structural progression and treatment response.Results: The disease activity (such as Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP, and ASDAS-ESR) and relapse rate were lower in the tapering group at 12 and 24 months (p &lt; 0.05). Δerosion (β = −0.0100, p = 0.00026) and Δthe Spondyloarthritis Research Consortium of Canada (SPARCC; β = −0.0959, p &lt; 0.0001) were negatively correlated with average DQ. The average DQ 30 (74.8%, 80.0%) or 41.6 (76.5%, 83%) was best to discriminate the status of treatment response or the status of bone marrow edema, but considering operability, the average DQ 25 (78.0%, 63.3%) was also acceptable especially for patients with HLA-B27 negative and non-severe fat metaplasia.Conclusion: Complete TNFi withdrawal was not recommended. Our study provided a referable strategy (tapering then maintained the average DQ over 30 or even 25) for patients who need TNFi reduction. Higher dose usage of TNFi was associated with a slower erosion progression of SIJ.
New Trends and Most Promising Therapeutic Strategies for Epilepsy Treatment
Authors: Riva Antonella , Golda Alice , Balagura Ganna , Amadori Elisabetta , Vari Maria Stella , Piccolo Gianluca , Iacomino Michele , Lattanzi Simona , Salpietro Vincenzo , Minetti Carlo , Striano Pasquale 
Published: December 2021

Background: Despite the wide availability of novel anti-seizure medications (ASMs), 30% of patients with epilepsy retain persistent seizures with a significant burden in comorbidity and an increased risk of premature death. This review aims to discuss the therapeutic strategies, both pharmacological and non-, which are currently in the pipeline.Methods: PubMed, Scopus, and EMBASE databases were screened for experimental and clinical studies, meta-analysis, and structured reviews published between January 2018 and September 2021. The terms “epilepsy,” “treatment” or “therapy,” and “novel” were used to filter the results.Conclusions: The common feature linking all the novel therapeutic approaches is the spasmodic rush toward precision medicine, aiming at holistically evaluating patients, and treating them accordingly as a whole. Toward this goal, different forms of intervention may be embraced, starting from the choice of the most suitable drug according to the type of epilepsy of an individual or expected adverse effects, to the outstanding field of gene therapy. Moreover, innovative insights come from in-vitro and in-vivo studies on the role of inflammation and stem cells in the brain. Further studies on both efficacy and safety are needed, with the challenge to mature evidence into reliable assets, ameliorating the symptoms of patients, and answering the challenges of this disease.
Distinctive Mediating Effects of Subcortical Structure Changes on the Relationships Between Amyloid or Vascular Changes and Cognitive Decline
Authors: Jung Na-Yeon , Shin Jeong-Hyeon , Kim Hee Jin , Jang Hyemin , Moon Seung Hwan , Kim Seung Joo , Kim Yeshin , Cho Soo Hyun , Kim Ko Woon , Kim Jun Pyo , Jung Young Hee , Kim Sung Tae , Kim Eun-Joo , Na Duk L. , Vogel Jacob W. , Lee Sangjin , Seong Joon-Kyung , Seo Sang Won 
Published: December 2021

Objective: We investigated the mediation effects of subcortical volume change in the relationship of amyloid beta (Aβ) and lacune with cognitive function in patients with mild cognitive impairment (MCI).Methods: We prospectively recruited 101 patients with MCI who were followed up with neuropsychological tests, MRI, or Pittsburgh compound B (PiB) PET for 3 years. The mediation effect of subcortical structure on the association of PiB or lacunes with cognitive function was analyzed using mixed effects models.Results: Volume changes in the amygdala and hippocampus partially mediated the effect of PiB changes on memory function (direct effect = −0.168/−0.175, indirect effect = −0.081/−0.077 for amygdala/hippocampus) and completely mediated the effect of PiB changes on clinical dementia rating scale sum of the box (CDR-SOB) (indirect effect = 0.082/0.116 for amygdala/hippocampus). Volume changes in the thalamus completely mediated the effect of lacune on memory, frontal executive functions, and CDR-SOB (indirect effect = −0.037, −0.056, and 0.047, respectively).Conclusions: Our findings provide a better understanding of the distinct role of subcortical structures in the mediation of the relationships of amyloid or vascular changes with a decline in specific cognitive domains.
Pre-conceptional Maternal Vitamin B12 Supplementation Improves Offspring Neurodevelopment at 2 Years of Age: PRIYA Trial
Authors: D'souza Naomi , Behere Rishikesh V. , Patni Bindu , Deshpande Madhavi , Bhat Dattatray , Bhalerao Aboli , Sonawane Swapnali , Shah Rohan , Ladkat Rasika , Yajnik Pallavi , Bandyopadhyay Souvik K. , Kumaran Kalyanaraman , Fall Caroline , Yajnik Chittaranjan S. 
Published: December 2021

Background: The first thousand days window does not include the pre-conceptional period. Maternal pre-conceptional health has a profound influence on early embryonic development (implantation, gastrulation, placentation etc). Nutrition provided by B-complex vitamins is important for fetal growth, especially neural development. We report effects of a maternal pre-conceptional vitamin B12 and multi micronutrient (MMN) supplementation on offspring neurodevelopmental performance.Methods: In the Pune Rural Intervention in Young Adolescents trial (PRIYA), adolescents (N = 557, 266 females) were provided with vitamin B12 (2 μg/day) with or without multiple micronutrients, or a placebo, from preconception until delivery. All groups received mandatory iron and folic acid. We used the Bayley's Scale of Infant Development (BSID-III) at 24–42 months of age to investigate effects on offspring neurodevelopment.Results: Participants had similar baseline B12 levels. The levels improved in the B12 supplemented groups during pre-conception and pregnancy (28 weeks gestation), and were reflected in higher cord blood holotranscobalamin (holo-TC) levels compared to the placebo group. Neurodevelopmental outcomes in the B12 alone group (n = 21) were better than the placebo (n = 27) in cognition (p = 0.044) and language (p = 0.020) domains (adjusted for maternal baseline B12 levels). There was no difference in neurodevelopmental outcomes between the B12 + MMN (n = 26) and placebo group. Cord blood Brain Derived Neurotrophic Factor (BDNF) levels were highest in the B12 alone group, though not significant.Conclusion: Pre-conceptional vitamin B12 supplementation improved maternal B12 status and offspring neurodevelopment at 2 years of age. The usefulness of cord BDNF as a marker of brain development needs further investigation. Our results highlight the importance of intervening during pre-conception.
Five Constituents Contributed to the Psoraleae Fructus-Induced Hepatotoxicity via Mitochondrial Dysfunction and Apoptosis
Authors: Guo Zhaojuan , Li Pin , Wang Chunguo , Kang Qianjun , Tu Can , Jiang Bingqian , Zhang Jingxuan , Wang Weiling , Wang Ting 
Published: December 2021

Backgrounds: Psoraleae Fructus (PF)-induced hepatotoxicity has been reported in clinical and animal experiments. However, the hepatotoxic constituents and mechanisms underlying PF-induced toxicity have remained unclear. Therefore, this study explored the potentially toxic PF components and revealed their relative mechanisms.Methods: The hepatotoxicity of PF water (PFW) and ethanol (PFE) extracts was compared using Kunming mice. The different compositions between PFW and PFE, which were considered toxic compositions, were identified using the UHPLC-Q-Exactive MS method. Then, L02 and HepG2 cell lines were used to evaluate the toxicity of these compositions. Cell viability and apoptosis were determined through the Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. An automatic biochemical analyzer detected the aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). Lastly, we used high-content screening (HCS) to determine the levels of reactive oxygen species (ROS), lipid, and mitochondrial membrane potential (MMP).Results: The ethanol extraction process aggravated the hepatotoxicity of PF, causing more severe injuries. The content of psoralen, isopsoralen, bavachin, psoralidin, bavachinin, neobavaisoflavone, and bakuchiol was higher in the PFE than PFW. Bavachin, psoralidin, bavachinin, neobavaisoflavone, and bakuchiol induced cell apoptosis and the AST, ALT, and ALP leakages. Furthermore, these five constituents increased intracellular lipid accumulation and ROS levels but decreased the MMP level.Conclusion: The ethanol extraction process could induce severe PF hepatotoxicity. Bavachin, psoralidin, bavachinin, neobavaisoflavone, and bakuchiol are the main hepatotoxic ingredients. This mechanism could be associated with oxidative stress and mitochondrial damage-mediated apoptosis. Taken together, this study provides a basis for the clinical application of PF that formulates and improves its herbal standards.
Guanxinkang Decoction Attenuates the Inflammation in Atherosclerosis by Regulating Efferocytosis and MAPKs Signaling Pathway in LDLR−/− Mice and RAW264.7 Cells
Authors: Zhang Yifan , Ding Jie , Wang Yiru , Feng Xiaoteng , Du Min , Liu Ping 
Published: December 2021

Guanxinkang decoction (GXK), a traditional Chinese medicinal drug, is used to treat cardiovascular disease. The aim of the study was to investigate the effects of GXK on inflammation in LDLR−/− mice and RAW264.7 cells. Fed with high fat diet for 12 weeks, the mice were randomly divided into six groups, then administered with oral 0.9% saline or GXK (7.24, 14.48, and 28.96 g/kg) or Atorvastatin (1.3 mg/kg) for 12 weeks. RAW 264.7 cells were induced with ox-LDL or ox-LDL plus different concentrations of GXK (1.25, 2.5, and 5 μg/ml), or ox-LDL plus GXK plus MAPKs activators. Serum lipid profiles and inflammatory cytokines were detected by ELISA, gene expression by RT-qPCR, plaque sizes by Oil Red O, α-SMA, caspase 3, NF-κB p65 and TNF-α production by immunofluorescence staining, and protein expression by Western Blot. The phagocytic ability of cells was determined by neutral red uptake assay. Efferocytosis-related proteins (AML, MERTK, TYRO3 and MFGE8) and MAPKs pathways were detected by Western Blot. Compared to mice fed with high fat diet, the mice with GXK showed lower cholesterol, triglyceride, low-density lipoprotein cholesterol, IL-1β, IL-6, and TNF-α, smaller plaque sizes, higher α-SMA, and lower caspase 3 and NF-κB p65 in aortic roots. RAW264.7 cells treated with ox-LDL plus GXK had lower IL-1β, IL-6, and TNF-α. GXK also increased the phagocytic ability of cells. High levels of AML, MERTK, TYRO3 and MFGE8, and decreased levels of iNOS, VCAM-1, LOX-1 and MCP-1, and phosphorylation of ERK1/2, JNK, p38, and NF-κB were detected in GXK-treated group. MAPKs activators reversed the effects of GXK in repressing inflammation and promoting phagocytosis. These results suggested that GXK could attenuate atherosclerosis and resolve inflammation via efferocytosis and MAPKs signaling pathways in LDLR−/− mice and RAW264.7 cells.
Gender Difference in the Relationship of Physical Activity and Subjective Happiness Among Chinese University Students
Authors: Jiang Wenning , Luo Jin , Guan Hannan 
Published: December 2021

Background: Gender makes a difference in health and physical activity (PA). This research aimed to identify the gender difference in the relationship of PA and subjective happiness among Chinese university students.Methods: A cross-sectional survey was conducted in Shanghai Jiao Tong University from July 7 to 17 in 2021, using an anonymous online self-report questionnaire. The questionnaire included the Chinese version of the International Physical Activity Questionnaire-Short Form (IPAQ-SF), the Subjective Happiness Scale (SHS), the Depression Anxiety Stress Scale-21(DASS-21). The demographic and health-related factors were also reported. Linear regression was carried out to identify the relationship of PA and subjective happiness.Findings: In total, 1,512 students (1,108 males and 404 females) from three comprehensive schools completed the survey. The SHS score was 17.20 ± 3.44, and it was 17.00 ± 3.23 in males, and 17.75 ± 3.93 in females, respectively (p &lt; 0.001). There was no gender difference in vigorous, moderate PA, or walk min/week, while female students had longer sedentary behavior hours/day than males. Male students scored higher in each subscale of DASS-21. After controlling for confounders, vigorous PA min/week (β = 0.002, p = 0.002) and sedentary behavior hours/day (β = 0.168, p = 0.005) were significantly positively associated with happiness in male students. In contrast, walk min/week (2= 0.002, p = 0.005) was significantly positively associated with happiness in female students.Interpretation: This research demonstrated a significant gender difference in the association between PA and happiness. Policymakers and college management should pay more attention to PA programs to promote students’ happiness and mental health status.
Perinatal Mental Health Problems in Rural China: The Role of Social Factors
Authors: Jiang Qi , Guo Yian , Zhang Evelyn , Cohen Nourya , Ohtori Mika , Sun Adrian , Dill Sarah-Eve , Singh Manpreet Kaur , She Xinshu , Medina Alexis , Rozelle Scott D. 
Published: December 2021

Background: Perinatal mental health is important for the well-being of the mother and child, so the relatively high prevalence of perinatal mental health problems in developing settings poses a pressing concern. However, most studies in these settings focus on the demographic factors associated with mental health problems, with very few examing social factors. Hence, this study examines the prevalence of the depressive, anxiety and stress symptoms among pregnant women and new mothers in rural China, and the associations between these mental health problems and social factors, including decision-making power, family conflicts, and social support.Methods: Cross-sectional data were collected from 1,027 women in their second trimester of pregnancy to 6 months postpartum in four low-income rural counties in Sichuan Province, China. Women were surveyed on symptoms of mental health problems using the Depression, Anxiety, and Stress Scale (DASS-21) and social risk factors. Multivariate logistic regression analyses were conducted to examine social risk factors associated with maternal mental health problems, with results reported as odds ratios (OR) and 95% confidence intervals (CI).Results: Among all respondents, 13% showed symptoms of depression, 18% showed symptoms of anxiety, 9% showed symptoms of stress, and 23% showed symptoms of any mental health problem. Decision-making power was negatively associated with showing symptoms of depression (OR = 0.71, CI: 0.60–0.83, p &lt; 0.001) and stress (OR = 0.76, CI: 0.63–0.90, p = 0.002). Family conflict was positively associated with depression (OR = 1.53, CI: 1.30–1.81, p &lt; 0.001), anxiety (OR = 1.34, CI: 1.15–1.56, p &lt; 0.001), and stress (OR = 1.68, CI: 1.41–2.00, p &lt; 0.001). In addition, social support was negatively associated with depression (OR = 0.56, CI: 0.46–0.69, p &lt; 0.001), anxiety (OR = 0.76, CI: 0.63–0.91, p = 0.002), and stress (OR = 0.66, CI: 0.53–0.84, p &lt; 0.001). Subgroup analyses revealed that more social risk factors were associated with symptoms of anxiety and stress among new mothers compared to pregnant women.Conclusion: Perinatal mental health problems are relatively prevalent among rural women in China and are strongly associated with social risk factors. Policies and programs should therefore promote individual coping methods, as well as target family and community members to improve the social conditions contributing to mental health problems among rural women.
Mediators for the Effect of Compassion Cultivating Training: A Longitudinal Path Analysis in a Randomized Controlled Trial Among Caregivers of People With Mental Illness
Authors: Hansen Nanja Holland , Fjorback Lone Overby , Frydenberg Morten , Juul Lise 
Published: December 2021

Background:There is a paucity of research on mediators of change, within compassion training programs. The aim was to investigate the mediators, of an 8-week compassion cultivation training (CCT) program, on the effect of psychological distress on caregivers of people with a mental illness.Method:Longitudinal path models in a randomized controlled trial (RCT). One hundred ninety-two participants were assessed for eligibility, and 161 participants were included into the trial and randomized. The main outcome was psychological distress measured by the Depression, Anxiety and Stress scale at 6 months. Mediators included self-compassion (SC), mindfulness (FM), emotion regulation (ER), emotion suppression (ES), and cognitive reappraisal (CR). Baseline, post, and 3- and 6-month follow-up measurements were collected.Results:The mediated effects for CCT are as follows: depression at 6 months: SC: −1.81 (95% CI: −3.31 to −0.31); FM: −1.98 (95% CI: −3.65 to −0.33); ER: −0.14 (95% CI: −1.31 to 1.02); anxiety at 6 months: SC: −0.71 (95% CI: −1.82 to 0.40); FM: −1.24 (95% CI: −2.39 to −0.09); ER: 0.18 (95% CI: −1.04 to 1.40); stress at 6 months: SC: −1.44 (95% CI: −2.84 to −0.05); FM: −2.17 (95% CI: −3.63 to −0.71); ER: −0.27 (95% CI: −1.51 to 0.98).Conclusion:Mindfulness and self-compassion are important components in reducing psychological distress experienced by informal caregivers of people with a mental illness. Results contribute to the knowledge about the underlying mechanisms of CCT.