bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-omics analysis reveals GABAergic dysfunction after traumatic brainstem injury in rats
Authors: Su Qin , Chen Qianling , Li Zhigang , Zhao Jian , Li Lingyue , Xu Luyao , Yang Bin , Liu Chao 
Published: November 2022

BackgroundTraumatic brainstem injury (TBSI) is one of the forms of brain injury and has a very high mortality rate. Understanding the molecular mechanism of injury can provide additional information for clinical treatment.Materials and methodsIn this study, we detected transcriptome, proteomics, and metabolome expression changes in the brainstem of TBSI rats, and comprehensively analyzed the underlying mechanisms of TBSI.ResultsAfter TBSI, there was significant diffuse axonal injury (DAI) in the brainstem of rats. A total of 579 genes, 70 proteins, and 183 metabolites showed significant changes in brainstem tissue. Through molecular function and pathway analysis, the differentially expressed genes, proteins, and metabolites of TBSI were mainly attributed to neural signal regulation, inflammation, neuroprotection, and immune system. In addition, a comprehensive analysis of transcripts, proteins, and metabolites showed that the genes, proteins, and metabolic pathways regulated in the brainstem after TBSI were involved in neuroactive ligand-receptor interaction. A variety of GCPR-regulated pathways were affected, especially GAGA’s corresponding receptors GABAA, GABAB, GABAC, and transporter GAT that were inhibited to varying degrees.ConclusionThis study provides insights into the development of a rapid diagnostic kit and making treatment strategies for TBSI.
Maternal melatonin treatment rescues endocrine, inflammatory, and transcriptional deregulation in the adult rat female offspring from gestational chronodisruption
Authors: Mendez Natalia , Halabi Diego , Salazar-Petres Esteban Roberto , Vergara Karina , Corvalan Fernando , Richter Hans G. , Bastidas Carla , Bascur Pía , Ehrenfeld Pamela , Seron-Ferre Maria , Torres-Farfan Claudia 
Published: November 2022

IntroductionGestational chronodisruption impact maternal circadian rhythms, inhibiting the nocturnal increase of melatonin, a critical hormone that contributes to maternal changes adaptation, entrains circadian rhythms, and prepares the fetus for birth and successful health in adulthood. In rats, we know that gestational chronodisruption by maternal chronic photoperiod shifting (CPS) impaired maternal melatonin levels and resulted in long-term metabolic and cardiovascular effects in adult male offspring. Here, we investigated the consequences of CPS on mother and adult female offspring and explored the effects of melatonin maternal supplementation. Also, we tested whether maternal melatonin administration during gestational chronodisruption rescues maternal circadian rhythms, pregnancy outcomes, and transcriptional functions in adult female offspring.MethodsFemale rats raised and maintained in photoperiod 12:12 light: dark were mated and separated into three groups: (a) Control photoperiod 12:12 (LD); (b) CPS photoperiod; and (c) CPS+Mel mothers supplemented with melatonin in the drinking water throughout gestation. In the mother, we evaluated maternal circadian rhythms by telemetry and pregnancy outcomes, in the long-term, we study adult female offspring by evaluating endocrine and inflammatory markers and the mRNA expression of functional genes involved in adrenal, cardiac, and renal function.ResultsIn the mothers, CPS disrupted circadian rhythms of locomotor activity, body temperature, and heart rate and increased gestational length by almost 12-h and birth weight by 12%, all of which were rescued by maternal melatonin administration. In the female offspring, we found blunted day/night differences in circulating levels of melatonin and corticosterone, abnormal patterns of pro-inflammatory cytokines Interleukin-1a (IL1a), Interleukin-6 (IL6), and Interleukin-10 (IL10); and differential expression in 18 out of 24 adrenal, cardiac, and renal mRNAs evaluated.ConclusionMaternal melatonin contributed to maintaining the maternal circadian rhythms in mothers exposed to CPS, and the re-establishing the expression of 60% of the altered mRNAs to control levels in the female offspring. Although we did not analyze the effects on kidney, adrenal, and heart physiology, our results reinforce the idea that altered maternal circadian rhythms, resulting from exposure to light at night, should be a mechanism involved in the programming of Non-Communicable Diseases.
Directional prefrontal-thalamic information flow is selectively required during spatial working memory retrieval
Authors: Wang Jia , Zhang Shengnan , Liu Tiaotiao , Zheng Xuyuan , Tian Xin , Bai Wenwen 
Published: November 2022

IntroductionSpatial working memory is a kind of short-term memory that allows temporarily storing and manipulating spatial information. Evidence suggests that spatial working memory is processed through three distinctive phases: Encoding, maintenance, and retrieval. Though the medial prefrontal cortex (mPFC) and mediodorsal thalamus (MD) are involved in memory retrieval, how the functional interactions and information transfer between mPFC and MD remains largely unclear.MethodsWe recorded local field potentials (LFPs) from mPFC and MD while mice performed a spatial working memory task in T-maze. The temporal dynamics of functional interactions and bidirectional information flow between mPFC and MD was quantitatively assessed by using directed transfer function.ResultsOur results showed a significantly elevated information flow from mPFC to MD, varied in time and frequency (theta in particular), accompanying successful memory retrieval.DiscussionElevated theta information flow, a feature that was absent on error trials, indicates an important role of the directional information transfer from mPFC to MD for memory retrieval.
Muscle mass loss is associated with physical dysfunction in patients with early rheumatoid arthritis
Authors: Pan Jie , Zou Yao-Wei , Zhu Ying-Ying , Lin Jian-Zi , Wu Tao , Yang Ze-Hong , Zhang Xue-Pei , Zhang Qian , Zheng Hu-Wei , He Xiao-Ling , Cheng Wan-Mei , Ma Jian-Da , Dai Lie 
Published: November 2022

BackgroundMuscle mass loss is common in long-standing rheumatoid arthritis (RA). The aim was to explore the prevalence and effects of RA disease characteristics in patients with early RA.MethodsThis cross-sectional study was carried out based on a Chinese RA cohort and control subjects. The body composition (BC) was assessed using bioelectric impedance analysis. Myopenia was defined by an appendicular skeletal muscle mass index of ≤ 7.0 kg/m2 in men and ≤ 5.7 kg/m2 in women. Physical dysfunction was defined as a health assessment questionnaire disability index &gt; 1. Propensity score matching was performed to balance age and gender differences among patients with early RA (disease duration ≤ 12 months) and established RA, and controls (with 1:3:3 matching).ResultsIn total, 2017 controls and 1,008 patients with RA were recruited for this study. Among the patients with RA, there were 190 (18.8%) patients with early RA, with a median disease duration of 7 (4, 11) months. The matched patients with early RA (n = 160) showed a higher prevalence of myopenia than the matched controls (41.3 vs. 15.8%, P &lt; 0.0167), but no difference was found in the matched patients with established RA (41.3 vs. 50.4%, P &gt; 0.0167). Compared with the patients with established RA, the patients with early RA exhibited higher disease activity scores [disease activity score in 28 joints with four variables including C-reactive protein (DAS28-CRP): median 4.76 vs. 3.93, P &lt; 0.001] and a higher prevalence of physical dysfunction (26.3 vs. 19.4%, P = 0.035). In the patients with early RA, patients with myopenia showed a higher prevalence of physical dysfunction than those without myopenia (41.3 vs. 15.5%, P &lt; 0.001), among which walking and common daily activities were the most involved subdimensions. Multivariate logistic regression analysis showed that DAS28-CRP was positively associated with myopenia [adjusted odds ratio (AOR) 1.558, 95% CI (1.138–2.132)], and myopenia [AOR 2.983, 95% CI (1.192–7.465)] was independently associated with physical dysfunction in the patients with early RA.ConclusionOur data indicate the importance of early detection of muscle involvement in the early stage of RA and imply the significance of early aggressive control of disease activity for the prevention of myopenia and physical dysfunction in patients with early RA. Our study provides a new perspective on RA management.
PSMD2 promotes the progression of bladder cancer and is correlated with immune infiltration
Authors: Wang Song , Wang He , Zhu Shaoxing , Wang Zongping 
Published: November 2022

IntroductionPSMD2 plays an oncogenic role in multiple human malignancies, while it is still unclear that the potential roles and underlying mechanisms of PSMD2 in BCa.MethodsThe RNA-seq from TCGA and GTEx database was utilized to preliminarily analyze the expression of PSMD2 in BCa tissues, qRT-PCR was adopted to verify the PSMD2 expression in BCa cell lines. Cox regression analyses were applied to assess the prognostic values of PSMD2 in BCa. GSEA analysis was used to explore the underlying mechanisms of PSMD2. In vitro assays such as wound healing and colony formation assays were applied to determine the carcinogenesis of PSMD2 in BCa. xCell and ssGSEA algorithms were applied to analyze the associations of PSMD2 with TIME.ResultsThe results revealed that in comparison with normal bladder tissues and cell line, PSMD2 was found to be significantly elevated in BCa tissues and cell lines. Elevated expression of PSMD2 can independently predict unfavorable OS for BCa patients. The PSMD2 expression and other clinicopathologic factors were combined to develop a nomogram, which can help to predict OS for BCa patients. GSEA analyses revealed that PSMD2 is correlated with the cell cycle, antigen processing and presentation, JAK-STAT signaling pathway, Toll like receptor signaling pathway, P53 and MAPK signaling pathway. Knockdown of PSMD2 could remarkably inhibit the wound healing and colony formation efficiency of BCa cells. xCell analysis revealed that overexpressed PSMD2 is positively related to the Th2 cells infiltrates and expression levels of immune escape markers, and negatively associated with the infiltrating levels of NK T cell and CD8+ T cell.DiscussionIn conclusion, overexpressed PSMD2 is tightly linked to the immune infiltrates and promotes the progression of BCa.
Feasibility, safety, and efficacy of circumferential spine stereotactic body radiotherapy
Authors: Dibs Khaled , Palmer Joshua D. , Prasad Rahul N. , Olausson Alexander , Bourekas Eric C. , Boulter Daniel , Ayan Ahmet S. , Cochran Eric , Marras William S. , Mageswaran Prasath , Thomas Evan , Grecula John , Guiou Michael , Soghrati Soheil , Tili Esmerina , Raval Raju R. , Mendel Ehud , Scharschmidt Thomas , Elder James B. , Lonser Russell , Chakravarti Arnab , Blakaj Dukagjin M. 
Published: November 2022

BackgroundWith advances in systemic therapy translating to improved survival in metastatic malignancies, spine metastases have become an increasingly common source of morbidity. Achieving durable local control (LC) for patients with circumferential epidural disease can be particularly challenging. Circumferential stereotactic body radiotherapy (SBRT) may offer improved LC for circumferential vertebral and/or epidural metastatic spinal disease, but prospective (and retrospective) data are extremely limited. We sought to evaluate the feasibility, toxicity, and cancer control outcomes with this novel approach to circumferential spinal disease.MethodsWe retrospectively identified all circumferential SBRT courses delivered between 2013 and 2019 at a tertiary care institution for post-operative or intact spine metastases. Radiotherapy was delivered to 14–27.5 Gy in one to five fractions. Feasibility was assessed by determining the proportion of plans for which ≥95% planning target volume (PTV) was coverable by ≥95% prescription dose. The primary endpoint was 1-year LC. Factors associated with increased likelihood of local failure (LF) were explored. Acute and chronic toxicity were assessed. Detailed dosimetric data were collected.ResultsFifty-eight patients receiving 64 circumferential SBRT courses were identified (median age 61, KPS ≥70, 57% men). With a median follow-up of 15 months, the 12-month local control was 85% (eight events). Five and three recurrences were in the epidural space and bone, respectively. On multivariate analysis, increased PTV and uncontrolled systemic disease were significantly associated with an increased likelihood of LF; ≥95% PTV was covered by ≥95% prescription dose in 94% of the cases. The rate of new or progressive vertebral compression fracture was 8%. There were no myelitis events or any grade 3+ acute or late toxicities.ConclusionsFor patients with circumferential disease, circumferential spine SBRT is feasible and may offer excellent LC without significant toxicity. A prospective evaluation of this approach is warranted.
Safety, pharmacokinetics, and pharmacodynamics of SHR7280, an oral gonadotropin-releasing hormone antagonist in healthy premenopausal women
Authors: Xu Yi , Hu Wei , Li Jian , Jiang Xin , Shi Ping , Shen Kai , Shen Yu , Ma Lingyu , Cao Yu 
Published: November 2022

Background: Treatment with gonadotropin-releasing hormone (GnRH) antagonists is a powerful strategy to suppress gonadotropin activity in women with sex hormone-dependent disorders. Herein, we provide the safety, pharmacokinetics (PK), and pharmacodynamics (PD) profiles of SHR7280, an oral non-peptide GnRH antagonist in healthy premenopausal women.Methods: In this randomized, double-blinded, placebo-controlled, dose-ascending, phase 1 trial, healthy premenopausal women were randomized to receive SHR7280 or placebo orally. Four doses of SHR7280 (200, 300, 400, and 500 mg BID) were planned. Safety, PK, and PD parameters were evaluated.Results: SHR7280 presented tolerable toxicity and most adverse events were mild in severity. SHR7280 showed rapid onset of action (median Tmax ranged from 1.0 to 1.2 h for each dose), and plasma exposure was dose-dependent. PD results showed that SHR7280 300 mg BID and above suppressed estrogen concentration within the estradiol (E2) treatment window for endometriosis (20–50 pg/ml), inhibited the emergence of the peak of luteinizing hormone (LH) and the concentration of follicle stimulating hormone (FSH), and maintained the concentration of progesterone (P) in an anovulatory state (2 nmol/L).Conclusion: SHR7280 showed favorable safety, PK, and PD profiles in the dose range of 200–500 mg BID in healthy premenopausal women. This study supports the continued clinical development of SHR7280 as a GnRH antagonist for sex hormone-dependent disorders in women.Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT04554043, Identifier NCT04554043
Effects of different intermittent pneumatic compression stimuli on ankle dorsiflexion range of motion
Authors: Yanaoka Takuma , Numata Urara , Nagano Kanna , Kurosaka Shiho , Kawashima Hiroki 
Published: November 2022

Despite substantial evidence of the effectiveness of intermittent pneumatic compression (IPC) treatments for range of motion (ROM) improvement, little evidence is available regarding how different IPC stimuli affect ankle dorsiflexion (DF) ROM. This study aimed to investigate the effects of different IPC stimuli on the ankle DF ROM. Fourteen, university intermittent team sport male athletes (age: 21 ± 1 year, height: 1.74 ± 0.05 m, body mass: 70.9 ± 7.7 kg, body fat percentage: 14.2 ± 3.6%, body mass index: 23.5 ± 2.5 kg/m2; mean ± standard deviation) completed four experimental trials in a random order: 1) no compression with wearing IPC devices (SHAM), 2) the sequential compression at approximately 80 mmHg (SQUEE80), 3) the uniform compression at approximately 80 mmHg (BOOST80), and 4) the uniform compression at approximately 135 mmHg (BOOST135). For the experimental trials, the participants were initially at rest for 10 min and then assigned to either a 30-min SHAM, SQUEE80, BOOST80, or BOOST135. Participants rested for 20 min after IPC treatment. The Weight-Bearing Lunge Test (WBLT), popliteal artery blood flow, pressure-to-pain threshold (PPT), muscle hardness, heart rate variability, and perceived relaxation were measured before (Pre) and immediately after IPC treatment (Post-0) and 20 min after IPC treatment (Post-20), and the changes in all variables from Pre (Δ) were calculated. ΔWBLT performance, ΔPPT, and Δperceived relaxation in all IPC treatments were significantly higher than those in SHAM at Post-0 and Post-20 (p &lt; 0.05). ΔPopliteal artery blood flow in BOOST80 and BOOST135 was significantly higher than that in SHAM and SQUEE80 at Post-0 (p &lt; 0.05). ΔMuscle hardness and Δheart rate variability did not differ significantly between trials. In conclusion, IPC treatments, irrespective of applied pressure and mode of compression, increased ankle DF ROM. This resulted from decreased pain sensitivity (i.e., increased PPT). In addition, high inflation pressure and frequency did not provide additional benefits in increasing ankle DF ROM.
Evolutionary history of genus Coptis and its dynamic changes in the potential suitable distribution area
Authors: Wang Yiheng , Sun Jiahui , Qiao Ping , Wang Jingyi , Wang Mengli , Du Yongxi , Xiong Feng , Luo Jun , Yuan Qingjun , Dong Wenpan , Huang Luqi , Guo Lanping 
Published: November 2022

The genus Coptis belongs to the Ranunculaceae family, containing 15 recognized species highly diverse in morphology. It is a conspicuous taxon with special evolutionary position, distribution pattern and medicinal value, which makes it to be of great research and conservation significance. In order to better understand the evolutionary dynamics of Coptis and promote more practical conservation measures, we performed plastome sequencing and used the sequencing data in combination with worldwide occurrence data of Coptis to estimate genetic diversity and divergence times, rebuild biogeographic history and predict its potential suitable distribution area. The average nucleotide diversity of Coptis was 0.0067 and the hotspot regions with the highest hypermutation levels were located in the ycf1 gene. Coptis is most likely to have originated in North America and Japanese archipelago and has a typical Eastern Asian and North American disjunct distribution pattern, while the species diversity center is located in Mid-West China and Japan. The crown age of the genus is estimated at around 8.49 Mya. The most suitable climatic conditions for Coptis were as follows: precipitation of driest quarter &gt; 25.5 mm, annual precipitation &gt; 844.9 mm and annual mean temperature -3.1 to 19 °C. The global and China suitable area shows an upward trend in the future when emission of greenhouse gases is well controlled, but the area, especially in China, decreases significantly without greenhouse gas policy interventions. The results of this study provide a comprehensive insight into the Coptis evolutionary dynamics and will facilitate future conservation efforts.
Genome-wide analysis of the XTH gene family and functional analysis of DlXTH23.5/25 during early longan somatic embryogenesis
Authors: Ma Xiangwei , Chen Yan , Liu Mengyu , Xue Xiaodong , Zhang Xueying , Xu Luzhen , Lai Zhongxiong , Lin Yuling 
Published: November 2022

IntroductionXyloglucan endotransglucosylase (XET)/hydrolase (XTH) is a cell wall-modifying protein that affects cell expansion and loosening of the cell wall.ResultsThis study focused on the regulatory mechanism of DlXTH genes during early somatic embryogenesis (SE) and the heat stress response in longan. Mining of the available D. longan genome sequence yielded 25 putative XTH genes. Transcript profiles based on RNA sequencing (RNA-seq) data showed that most of the 17 detected DlXTH genes were highly expressed in the embryogenic callus (EC) (8) and globular embryo (GE) (8), and 13 of them responded significantly to heat stress. The assay for transposase-accessible chromatin sequencing (ATAC-seq) data analysis showed that in terms of chromatin accessibility, 22 of the 25 DlXTH genes were open during early SE, and most of the peak DlXTH genes with transcription differences during early SE were associated with high levels of H3K4me1. The most differentially expressed genes, DlXTH23.5 and DlXTH25, were selected for analysis. According to subcellular localization and quantitative real-time PCR (qRT-PCR) analysis, DlXTH23.5/25, which encode cell membrane-localized proteins, were expressed at the highest level in the GE and significantly responded to heat stress. Dual-luciferase assays and transient transformation showed that the transcription factors (TFs) DlWRKY31, DlERF1, and DlERF5 might bind to the DlXTH23.5/25 promoters to activate gene transcription. Transient overexpression of TFs and DlXTH23.5/25 induced XET activity in Nicotiana benthamiana leaves. Under heat stress in the longan EC, the XET activities and expression levels of TFs and DlXTH23.5/25 were significantly increased, and a high concentration of XET might inhibit longan SE.DiscussionsThus, the regulatory network composed of DlXTH23.5/25 and its related TFs may regulate early longan SE and participate in the regulatory pathway of longan under heat stress via cell wall repair through the action of XET.
Identification of key genes controlling soluble sugar and glucosinolate biosynthesis in Chinese cabbage by integrating metabolome and genome-wide transcriptome analysis
Authors: Wang Lixia , Zhang Shu , Li Jingjuan , Zhang Yihui , Zhou Dandan , Li Cheng , He Lilong , Li Huayin , Wang Fengde , Gao Jianwei 
Published: November 2022

IntroductionSoluble sugar and glucosinolate are essential components that determine the flavor of Chinese cabbage and consumer preferences. However, the underlying regulatory networks that modulate the biosynthesis of soluble sugar and glucosinolate in Chinese cabbage remain largely unknown.MethodsThe glucosinolate and carotene content in yellow inner-leaf Chinese cabbage were observed, followed by the combination of metabolome and transcriptome analysis to explore the metabolic basis of glucosinolate and soluble sugar.ResultsThis study observed high glucosinolate and carotene content in yellow inner-leaf Chinese cabbage, which showed a lower soluble sugar content. The differences between the yellow and the white inner-leaf Chinese cabbage were compared using the untargeted metabonomic and transcriptomic analyses in six cultivars of Chinese cabbage to explore the metabolic basis of glucosinolate and soluble sugar. Aliphatic glucosinolate and two soluble sugars (fructose and glucose) were the key metabolites that caused the difference in Chinese cabbage’s glucosinolate and soluble sugar. By integrating soluble sugar and glucosinolate-associated metabolism and transcriptome data, we indicated BraA05gAOP1 and BraA04gAOP4, BraA03gHT7 and BraA01gHT4 were the glucosinolates and soluble sugar biosynthesis structural genes. Moreover, BraA01gCHR11 and BraA07gSCL1 were two vital transcription factors that regulate soluble sugar and glucosinolate biosynthesis.DiscussionThese findings provide novel insights into glucosinolate and soluble sugar biosynthesis and a possible explanation for the significant difference in nutrients between yellow and white inner-leaf Chinese cabbage. Moreover, it will facilitate genetic modification to improve the Chinese cabbage’s nutritional and health values.