bluuebunny/crossref_metadata_2025 huggingface dataset:
Subinhibitory Concentrations of Clinically-Relevant Antimicrobials Affect Resistance-Nodulation-Division Family Promoter Activity in Acinetobacter baumannii
Authors: Prieto Martin Gil Sonia , Tajuelo Ana , López-Siles Mireia , McConnell Michael J.
Published: December 2021

Efflux pumps contribute to multidrug resistance in Acinetobacter baumannii due to their ability to expel a wide variety of structurally unrelated compounds. This study aimed to characterize the effect of subinhibitory concentrations of clinically-relevant antibiotics and disinfectants on the promoter activity of members of the Resistance-Nodulation-Division (RND) family in A. baumannii. The promoter regions from three RND efflux pumps (AdeABC, AdeFGH and AdeIJK) and the AdeRS regulatory system from three different A. baumannii strains (ATCC 17961, ATCC 17978, and ATCC 19606) were cloned into a luciferase reporter system (pLPV1Z). Promoter activity was quantitatively assessed in both exponential and stationary phase cultures after exposure to subinhibitory concentrations of four antibiotics from different classes (rifampicin, meropenem, tigecycline and colistin) and two disinfectants (ethanol and chlorhexidine). Subinhibitory concentrations of the compounds tested had variable effects on promoter activity that were highly dependent on the A. baumannii strain, the compound tested and the growth phase. Fold changes in AdeABC promoter activity ranged from 1.97 to 113.7, in AdeFGH from −5.6 to 1.13, in AdeIJK from −2.5 to 2, and in AdeRS from −36.2 to −1.32. Taken together, these results indicate that subinhibitory concentrations of clinically-relevant antibiotics and disinfectants affect the promoter activity of RND family members in A. baumannii in a strain and growth phase dependent manner. These results may have important implications for the treatment of infections caused by A. baumannii.
Influence of Tissue Type on the Bacterial Diversity and Community in Pork Bacon
Authors: Gong Wenjuan , Zhu Yan , Shi XiXiong , Zhang Weibing , Wen PengCheng
Published: December 2021

In current study, bacterial diversity and community in different tissues of pork bacon were determined using high-throughput sequencing. In total, six phyla and 111 bacterial genera were identified. Among them, three dominant genera (Staphylococcus, Acinetobacter, and Macrococcus) were shared by all bacon samples. The linear discriminant analysis showed that 24 bacterial taxa significantly differentiated between the tissues. Results of non-metric Multidimensional Scaling and redundancy analysis showed that physicochemical characteristics of the tissue prominently structured the bacterial communities. Network analysis also illustrated that tissue type was an important factor impacting the bacterial interactions in different types of tissue. The results of current study can add valuable insights to the traditional homemade pork bacon.
A Thermodynamic Model for Interpreting Tryptophan Excitation-Energy-Dependent Fluorescence Spectra Provides Insight Into Protein Conformational Sampling and Stability
Authors: Kwok A , Camacho IS , Winter S , Knight M , Meade RM , Van der Kamp MW , Turner A , O’Hara J , Mason JM , Jones AR , Arcus VL , Pudney CR
Published: December 2021

It is now over 30 years since Demchenko and Ladokhin first posited the potential of the tryptophan red edge excitation shift (REES) effect to capture information on protein molecular dynamics. While there have been many key efforts in the intervening years, a biophysical thermodynamic model to quantify the relationship between the REES effect and protein flexibility has been lacking. Without such a model the full potential of the REES effect cannot be realized. Here, we present a thermodynamic model of the tryptophan REES effect that captures information on protein conformational flexibility, even with proteins containing multiple tryptophan residues. Our study incorporates exemplars at every scale, from tryptophan in solution, single tryptophan peptides, to multitryptophan proteins, with examples including a structurally disordered peptide, de novo designed enzyme, human regulatory protein, therapeutic monoclonal antibodies in active commercial development, and a mesophilic and hyperthermophilic enzyme. Combined, our model and data suggest a route forward for the experimental measurement of the protein REES effect and point to the potential for integrating biomolecular simulation with experimental data to yield novel insights.
Application of Artificial Intelligence Modeling Technology Based on Fluid Biopsy to Diagnose Alzheimer’s Disease
Authors: Sh Yuan , Liu Benliang , Zhang Jianhu , Zhou Ying , Hu Zhiyuan , Zhang Xiuli
Published: December 2021

Background: There are no obvious clinical signs and symptoms in the early stages of Alzheimer’s disease (AD), and most patients usually have mild cognitive impairment (MCI) before diagnosis. Therefore, early diagnosis of AD is very critical. This paper mainly discusses the blood biomarkers of AD patients and uses machine learning methods to study the changes of blood transcriptome during the development of AD and to search for potential blood biomarkers for AD.

Methods: Individualized blood mRNA expression data of 711 patients were downloaded from the GEO database, including the control group (CON) (238 patients), MCI (189 patients), and AD (284 patients). Firstly, we analyzed the subcellular localization, protein types and enrichment pathways of the differentially expressed mRNAs in each group, and established an artificial intelligence individualized diagnostic model. Furthermore, the XCell tool was used to analyze the blood mRNA expression data and obtain blood cell composition and quantitative data. Ratio characteristics were established for mRNA and XCell data. Feature engineering operations such as collinearity and importance analysis were performed on all features to obtain the best feature solicitation. Finally, four machine learning algorithms, including linear support vector machine (SVM), Adaboost, random forest and artificial neural network, were used to model the optimal feature combinations and evaluate their classification performance in the test set.

Results: Through feature engineering screening, the best feature collection was obtained. Moreover, the artificial intelligence individualized diagnosis model established based on this method achieved a classification accuracy of 91.59% in the test set. The area under curve (AUC) of CON, MCI, and AD were 0.9746, 0.9536, and 0.9807, respectively.

Conclusion: The results of cell homeostasis analysis suggested that the homeostasis of Natural killer T cell (NKT) might be related to AD, and the homeostasis of Granulocyte macrophage progenitor (GMP) might be one of the reasons for AD.
Clinical Efficacy and Safety of Lacosamide as an Adjunctive Treatment in Adults With Refractory Epilepsy
Authors: Hou Liyan , Peng Bingjie , Zhang Defu , Yang Jingjing , Wang Ying , Tong Li , Li Sheng , Wang Qingshan , Zhao Jie
Published: December 2021

Background: Lacosamide (LCM), a novel AED (antiepileptic drug), was used as an adjunctive treatment in patients with partial-onset seizures or without secondary generalization. However, no meta-analysis was performed to evaluate the efficacy of LCM as an adjunctive treatment in post-marketing clinical studies.

Aims: To assess the safety and efficacy of LCM as an adjunctive treatment in adults with refractory epilepsy, a systematic review and meta-analysis of randomized controlled trials (RCTs) and real-world studies were performed.

Methods: All studies were identified from electronic databases. Both RCTs and observational prospective studies were included. Primary outcomes included responder rate, adverse effects (AEs) and withdraw rate. The pooled rates (PR) with their corresponding 95% confidence intervals (CI) were calculated. Publication bias was assessed with Begg's or Egger's tests.

Results: Total 16 studies (3,191 patients) including 5 RCTs and 11 real-word studies were enrolled. The pooled 50% responder rate and seizure-free rate were 48% (95% CI: 0.42, 0.54) and 9% (95% CI: 0.06, 0.11) in all studies, respectively. Subgroup analysis showed that the pooled 50% responder rate were 53% (95% CI: 0.44, 0.62) from observational studies and 38% (95% CI: 0.35, 0.42) from RCTs, respectively; the pooled seizure-free rate were 13% (95% CI: 0.09, 0.18) from observational studies and 4% (95% CI: 0.06, 0.11) from RCTs, respectively. Similar incidence of AEs were reported in real-world studies (0.57, 95% CI: 0.43, 0.72) and RCTs (0.59, 95% CI: 0.42–0.76). Finally, a total of 13% (95%CI: 0.09, 0.16) and 13% (95% CI: 0.08, 0.16) of all patients prescribed with LCM was withdrawn in RCTs and real-world studies, respectively, due to the occurrence of AEs. Furthermore, similar to the 50% responder rate, seizure-free rate, incidence of AEs and withdraw rate were reported at 6-month or at least 12-month of LCM adjunction. Publication bias was not detected in these studies.

Conclusions: Our results revealed that LCM adjunctive therapy even with long-term treatment was efficacious and well tolerated in adults with refractory epilepsy.
Associations of Monocytes and the Monocyte/High-Density Lipoprotein Ratio With Extracranial and Intracranial Atherosclerotic Stenosis
Authors: Liu Zhu , Fan Qingli , Wu Shizheng , Lei Yancheng
Published: December 2021

Background: Although the monocyte/high-density lipoprotein ratio (MHR) has been shown to be a potential marker of inflammatory of cardiovascular and cerebrovascular diseases, there are few studies on its relationships with the degree of intracranial and extracranial atherosclerotic stenosis and the stenosis distribution.

Methods: In total, 271 patients were admitted for digital subtraction angiography (DSA) examination and were classified into a non-stenosis group and a stenosis group. (1) The two groups were compared and the arteries were categorized according to the degree of intracranial or extracranial atherosclerotic stenosis (if ≥two branches were stenotic, the artery with the most severe stenosis was used). (2) Clinical baseline data and laboratory indexes of patients grouped according to stenosis location (intracranial vs. extracranial) were collected.

Results: (1) MHR × 102 [odds ratio (OR) = 1.119, p < 0.001], age (OR = 1.057, p = 0.007), and lymphocyte count (OR = 0.273, p = 0.002) significantly affected the presence of cerebral atherosclerotic stenosis, with an MHR area of 0.82 under the receiver operating characteristic (ROC) curve (AUC) and an optimal diagnostic value of 0.486. Analyses of the moderate, mild, and severe stenosis groups showed that MHR × 102 (OR = 1.07, p < 0.001) significantly affected the severity of stenosis in patients. (2) In the analysis of stenosis at different sites, the rate of extracranial artery stenosis in patients who smoked (OR = 3.86, p = 0.023) and had a reduced lymphocyte level (OR = 0.202, p = 0.001) was remarkably greater than that in patients who smoked (OR = 3.86, p = 0.023). With increasing age, the rate of extracranial artery stenosis raised sharply. With the increase in the MHR level, the stenosis rate of each group was highly greater than that of the non-stenosis group.

Conclusion: The MHR has a predictive value for the diagnosis of extracranial and intracranial atherosclerotic stenosis and is correlated with the degree and distribution of stenosis.

Trial Registration: Clinical Medical Research Center Project of Qinghai Province (2017-SF-L1). Qinghai Provincial Health Commission Project (Grant #2020-wjzdx-29).
Case Report: Long-Term Suppression of Paroxysmal Kinesigenic Dyskinesia After Bilateral Thalamotomy
Authors: Murakami Masato , Horisawa Shiro , Azuma Kenko , Akagawa Hiroyuki , Nonaka Taku , Kawamata Takakazu , Taira Takaomi
Published: December 2021

Background:Paroxysmal kinesigenic dyskinesia (PKD) is a movement disorder characterized by transient dyskinetic movements, including dystonia, chorea, or both, triggered by sudden voluntary movements. Carbamazepine and other antiepileptic drugs (AEDs) are widely used in the treatment of PKD, and they provide complete remission in 80–90% of medically treated patients. However, the adverse effects of AEDs include drowsiness and dizziness, which interfere with patients' daily lives. For those with poor compatibility with AEDs, other treatment approaches are warranted.

Case Report:A 19-year-old man presented to our institute with right hand and foot dyskinesia. He had a significant family history of PKD; his uncle, grandfather, and grandfather's brother had PKD. The patient first experienced paroxysmal involuntary left hand and toe flexion with left forearm pronation triggered by sudden voluntary movements at the age of 14. Carbamazepine (100 mg/day) was prescribed, which led to a significant reduction in the frequency of attacks. However, carbamazepine induced drowsiness, which significantly interfered with his daily life, especially school life. He underwent right-sided ventro-oral (Vo) thalamotomy at the age of 15, which resulted in complete resolution of PKD attacks immediately after the surgery. Four months after the thalamotomy, he developed right elbow, hand, and toe flexion. He underwent left-sided Vo thalamotomy at the age of 19. Immediately after the surgery, the PKD attacks resolved completely. However, mild dysarthria developed, which spontaneously resolved within three months. Left-sided PKD attacks never developed six years after the right Vo thalamotomy, and right-sided PKD attacks never developed two years after the left Vo thalamotomy without medication.

Conclusion:The present case showed long-term suppression of bilateral PKDs after bilateral thalamotomy, which led to drug-free conditions.
Cost-Effectiveness of Adjuvant Immunotherapy With Cytokine-Induced Killer Cell for Hepatocellular Carcinoma Based on a Randomized Controlled Trial and Real-World Data
Authors: Cho Jeong-Yeon , Kwon Sun-Hong , Lee Eui-Kyung , Lee Jeong-Hoon , Kim Hye-Lin
Published: December 2021

Background

Studies using data from randomized controlled trials (RCTs) and real-world data (RWD) have suggested that adjuvant cytokine-induced killer (CIK) cell immunotherapy after curative treatment for hepatocellular carcinoma (HCC) prolongs recurrence-free survival (RFS) and overall survival (OS). However, the cost-effectiveness of CIK cell immunotherapy as an adjuvant therapy for HCC compared to no adjuvant therapy is uncertain.

Methods

We constructed a partitioned survival model to compare the expected costs, life-year (LY), and quality-adjusted life-year (QALY) of a hypothetical population of 10,000 patients between CIK cell immunotherapy and no adjuvant therapy groups. Patients with HCC aged 55 years who underwent a potentially curative treatment were simulated with the model over a 20-year time horizon, from a healthcare system perspective. To model the effectiveness, we used OS and RFS data from RCTs and RWD. We estimated the incremental cost-effectiveness ratios (ICERs) and performed extensive sensitivity analyses.

Results

Based on the RCT data, the CIK cell immunotherapy incrementally incurred a cost of $61,813, 2.07 LYs, and 1.87 QALYs per patient compared to no adjuvant therapy, and the estimated ICER was $33,077/QALY. Being less than the willingness-to-pay threshold of $50,000/QALY, CIK cell immunotherapy was cost-effective. Using the RWD, the ICER was estimated as $25,107/QALY, which is lower than that obtained using RCT. The time horizon and cost of productivity loss were the most influential factors on the ICER.

Conclusion

We showed that receiving adjuvant CIK cell immunotherapy was more cost-effective than no adjuvant therapy in patients with HCC who underwent a potentially curative treatment, attributed to prolonged survival, reduced recurrence of HCC, and better prognosis of recurrence. Receiving CIK cell immunotherapy may be more cost-effective in real-world clinical practice.
Reinvestigating Tumor–Ventricle Relationship of Craniopharyngiomas With Predominantly Ventricular Involvement: An Endoscopic Endonasal Series Based on Histopathological Assessment
Authors: Fan Jun , Liu Yi , Wang Chaohu , Feng Zhanpeng , Pan Jun , Peng Yuping , Peng Junxiang , Bao Yun , Nie Jing , Qiu Binghui , Qi Songtao
Published: December 2021

Objective

Craniopharyngiomas (CPs) predominantly involving the third ventricle were commonly termed “intraventricular” lesions. The aim of this study was to clarify the anatomical relationship between the tumor and the third ventricle by both surgical and histological investigation.

Methods

A retrospective review of primarily resected CPs by endoscopic endonasal surgery was performed. CPs with predominantly ventricular involvement were selected for study inclusion by preoperative imaging. The surgical procedure of each case was reviewed. The wholly removed tumor specimens were histologically analyzed, in all cases, to investigate the tumor–third ventricle relationship using hematoxylin and eosin, immunochemical, and immunofluorescence staining.

Results

Twenty-six primary CPs predominantly involving the third ventricle were selected from our series of 223 CPs treated by endoscopic endonasal surgery between January 2017 and March 2021. Gross-total resection was achieved in 24 (92.3%) of 26 patients, with achievement of near-total resection in the remaining patients. A circumferential layer of stretched third ventricle floor was identified surrounding the tumor capsule, which could be peeled off easily from the ventricle floor remnants at most areas of the plane of tumor attachment. Some portions of the tumor capsule tightly adhered to the third ventricle floor were removed together with the floor. A breach of various size was observed at the third ventricle floor after tumor removal in most cases, the floor remaining intact in only two cases (7.7%). Histological examination on marked portions of tumor capsule showed that the pia mater was frequently detected at most of the tumor–brain interface, except at the antero-frontal border of tumor contacting with the third ventricle floor. At this point, a layer of gliosis with various thickness was observed between the tumor and the neural tissue of the third ventricle floor.

Conclusion

CPs with predominantly ventricular involvement should be considered as lesions with an extraventricular, epi-pia topography rather than “intraventricular” or “subpial” topography. Accurate understanding of the relationship between the third ventricle and such tumors would predict the circumferential cleavage plane of dissection, and remind neurosurgeons of performing dissection along the safe surgical plane to achieve total tumoral resection with minimizing hypothalamic damage.
Comparison of Four Lymph Node Stage Methods for Predicting the Prognosis of Distal Cholangiocarcinoma Patients After Surgery
Authors: Huang Xiuyi , Niu Xiaoya , You Zhen , Long Youlin , Luo Fan , Ye Hui
Published: December 2021

Background

The metastatic status of regional lymph nodes is an effective risk factor for the prognosis of distal cholangiocarcinoma (dCCA). But existing lymph node staging is not accurate enough and is susceptible to interference. This study aims to explore the predictive ability of the log odds of positive lymph nodes (LODDS) staging system of dCCA compared with existing lymph node staging systems.

Methods

A total of 928 dCCA patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database as the training cohort, and 207 dCCA patients from West China Hospital who underwent surgery were reviewed as the validation cohort. The least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression were conducted to identify the most meaningful factors relevant to prognosis. The performance of four lymph node stage systems was compared by a model-based approach.

Result

Age at diagnosis, pathological grade, American Joint Committee on Cancer (AJCC) tumor 7th T stage, tumor size, radiotherapy, chemotherapy, and lymph node stage system were independent prognostic factors. The model with the LODDS system had a better model fit with the highest C-index (0.679) and 1-/3-/5- area under the receiver operating characteristic curve (AUC) (0.739/0.671/0.658) as well as the lowest Akaike information criterion (AIC) (5,020.52). External validation results from 207 dCCA patients showed a C-index of 0.647 and 1-/3-/5-AUC of 0.740/0.683/0.589. Compared with the lymph node ratio (LNR), AJCC 8th N system, and 7th N system, the 5-year net reclassification improvement (NRI) of the LODDS system was 0.030 (95% CI: −0.079 to 0.147), 0.042 (95% CI: −0.062 to 0.139), and 0.040 (95% CI: −0.057 to 0.146), respectively. The integrated discrimination improvement (IDI) of LODDS improved compared with the LNR model (0.016; 95% CI: −0.001 to 0.036), AJCC 8th N system (0.020; 95% CI: 0.003–0.037), and AJCC 7th N system (0.019; 95% CI: 0.002–0.036). Decision curve analysis (DCA) also shows a greater net benefit of LODDS. In lymph node-negative patients, LODDS reveals a positive linear relationship with the hazard ratio (HR). The stage capacity of LODDS in a subgroup analysis stratified by examined lymph node number (ELNN) was consistent.

Conclusions

The LODDS lymph node stage system has superior predictive performance as compared with the LNR, AJCC 7th, and 8th lymph node stage systems. Meanwhile, LODDS has a more detailed staging ability and good stability.
Effects of Different Molecular Weight Polysaccharides From Dendrobium officinale Kimura & Migo on Human Colorectal Cancer and Transcriptome Analysis of Differentially Expressed Genes
Authors: Tao Shengchang , Ren Zhiyao , Yang Zerui , Duan Shuna , Wan Zhongxian , Huang Jiahui , Liu Chenxing , Wei Gang
Published: December 2021

We investigated the antitumor effects of four fractions of Dendrobium officinale Kimura & Migo (D. officinale) polysaccharides with different molecular weights (Mw), Astragalus membranaceus polysaccharides (APS) and Lentinus edodes polysaccharides (LNT) on colorectal cancer (CRC) using a zebrafish xenograft model. Transcriptome sequencing was performed to further explore the possible antitumor mechanisms of D. officinale polysaccharides. Fractions of D. officinale polysaccharides, LNT, and APS could significantly inhibit the growth of HT-29 cells in a zebrafish xenograft model. One fraction of D. officinale polysaccharides called DOPW-1 (Mw of 389.98 kDa) exhibited the strongest tumor inhibition. Compared with the control group, RNA-seq revealed that the DOPW-1–treated experimental group had 119 differentially expressed genes (DEGs), of which 45 had upregulated expression and 74 had downregulated expression. Analyses using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes suggested that the pathway “apoptosis-multiple species” was the most significantly enriched. Our data indicated that 1) fractions of D. officinale polysaccharides of Mw 389.98 kDa were most suitable against CRC; 2) DOPW-1 could be developed into a clinical agent against CRC; and 3) an apoptosis pathway is important for DOPW-1 to inhibit the proliferation of HT-29 cells.
Contextualising the Perceptions of Pharmacists Practicing Clinical Pharmacy in South Africa—Do We Practice what We Preach?
Authors: Bronkhorst Elmien , Schellack Natalie , Gous Andries G. S.
Published: December 2021

The National Department of Health published their Quality Standards for Healthcare Establishments in South Africa and introduced the National Health Insurance, with the pilot phase that commenced in 2012. The system requires an adequate supply of pharmaceutical personnel and the direct involvement of clinical pharmacists throughout the medication-use process to ensure continuity of care, minimised risk with increasing improvement of patient outcomes. The study aimed to provide insight into the pressing issues of clinical pharmacy practice in South Africa, and sets out to contextualise the current profile of the pharmacist performing clinical functions. The study used a quantitative, explorative, cross-sectional design. The population included pharmacists from private and public tertiary hospitals. A questionnaire was administered, using Typeform™. Ethics approval was obtained from Sefako Makgatho Health Sciences University, National Department of Health and Private Healthcare groups. Categorical data were summarised using frequency counts and percentages; continuous data were summarised by mean values and standard deviations. The sample size included 70 pharmacists practicing clinical pharmacy (private sector n = 59; public sector n = 11). Most participants hold a BPharm degree (busy with MPharm qualification) (64%; n = 70). No statistical significance was found between participants in private and public practice. Most pharmacist agreed (32% (private); n = 59) and strongly agreed (45% (public); n = 11) to have sufficient training to perform pharmaceutical care. The majority respondents felt that interventions made by the pharmacist improved the rational use of medicine (47% (private); 55% (public). Pharmacist interventions influence prescribing patterns (42% (private); 64% (public); and reduce polypharmacy (41% (private); 55% (public). The clinical functions mostly performed were evaluation of prescriptions (private 90%; public 82%), while the top logistical function is daily ordering of medication (40.7%; private), and checking of ward stock (36%; public). Although not all pharmacists appointed in South Africa has completed the MPharm degree in clinical pharmacy, the pharmacists at ward level perform numerous clinical functions, even if only for a small part of their workday. This paper sets the way to standardise practices of clinical pharmacy in South Africa, with a reflection on the differences in practice in different institutions.
Centella asiatica (L.) Urb. Prevents Hypertension and Protects the Heart in Chronic Nitric Oxide Deficiency Rat Model
Authors: Bunaim Mohd Khairulanwar , Kamisah Yusof , Mohd Mustazil Mohd Noor , Fadhlullah Zuhair Japar Sidik , Juliana Abdul Hamid , Muhammad Norliza
Published: December 2021

Background: Hypertension is a major risk factor for cardiovascular disease (CVD), which is the number one cause of global mortality. The potential use of natural products to alleviate high blood pressure has been demonstrated to exert a cardioprotective effect. Centella asiatica (L.) Urb. belongs to the plant family Apiaceae (Umbelliferae). It contains a high amount of triterpenoid and flavonoid that have antioxidant properties and are involved in the renin-angiotensin-aldosterone system which is an important hormonal system for blood pressure regulation.

Objective: This study aimed to investigate the effects of C. asiatica ethanolic extract on blood pressure and heart in a hypertensive rat model, which was induced using oral N(G)-nitro-l-arginine methyl ester (l-NAME).

Methods: Male Sprague-Dawley rats were divided into five groups and were given different treatments for 8 weeks. Group 1 only received deionized water. Groups 2, 4, and 5 were given l-NAME (40 mg/kg, orally). Groups 4 and 5 concurrently received C. asiatica extract (500 mg/kg, orally) and captopril (5 mg/kg, orally), respectively. Group 3 only received C. asiatica extract (500 mg/kg body weight, orally). Systolic blood pressure (SBP) was measured at weeks 0, 4, and 8, while serum nitric oxide (NO) was measured at weeks 0 and 8. At necropsy, cardiac and aortic malondialdehyde (MDA) contents, cardiac angiotensin-converting enzyme (ACE) activity, and serum level of brain natriuretic peptide (BNP) were measured.

Results: After 8 weeks, the administrations of C. asiatica extract and captopril showed significant (p < 0.05) effects on preventing the elevation of SBP, reducing the serum nitric oxide level, as well as increasing the cardiac and aortic MDA content, cardiac ACE activity, and serum brain natriuretic peptide level.

Conclusion:C. asiatica extract can prevent the development of hypertension and cardiac damage induced by l-NAME, and these effects were comparable to captopril.
Oxytocin Protects Against Isoproterenol-Induced Cardiac Hypertrophy by Inhibiting PI3K/AKT Pathway via a lncRNA GAS5/miR-375-3p/KLF4-Dependent Mechanism
Authors: Yang Yuqiao , Wang Zhuoran , Yao Mengran , Xiong Wei , Wang Jun , Fang Yu , Yang Wei , Jiang Haixia , Song Ning , Liu Lan , Qian Jinqiao
Published: December 2021

Cardiac hypertrophy is caused by cardiac volume or pressure overload conditions and ultimately leads to contractile dysfunction and heart failure. Oxytocin (OT), an endocrine nonapeptide, has been identified as a cardiovascular homeostatic hormone with anti-hypertrophic effects. However, the underlying mechanism remains elusive. In this study, we aimed to investigate the role and mechanism of OT in cardiac hypertrophy. The rats with cardiac hypertrophy induced by isoproterenol (ISO) were treated with or without oxytocin. Cardiac functional parameters were analyzed by echocardiography. The changes in cell surface area were observed using wheat germ agglutinin (WGA) or immunofluorescence staining. The expressions of cardiac hypertrophy markers (B-Natriuretic Peptide, BNP and β-myosin heavy chain, β-MHC), long non-coding RNA Growth (LcRNA) Arrest-Specific transcript 5 (lncRNA GAS5), miR-375-3p, and Kruppel-like factor 4 (Klf4) were detected by qRT-PCR. KLF4 protein and PI3K/AKT pathway related proteins were detected by Western blot. The interactions among lncRNA GAS5, miR-375-3p, and Klf4 were verified by dual-luciferase reporter assays. The findings showed that OT significantly attenuated cardiac hypertrophy, increased expressions of lncRNA GAS5 and KLF4, and decreased miR-375-3p expression. In vitro studies demonstrated that either knock-down of lncRNA GAS5 or Klf4, or over-expression of miR-375-3p blunted the anti-hypertrophic effects of OT. Moreover, down-regulation of lncRNA GAS5 promoted the expression of miR-375-3p and inhibited KLF4 expression. Similarly, over-expression of miR-375-3p decreased the expression of KLF4. Dual-luciferase reporter assays validated that lncRNA GAS5 could sponge miR-375-3p and Klf4 was a direct target gene of miR-375-3p. In addition, OT could inactivate PI3K/AKT pathway. The functional rescue experiments further identified OT regulated PI3K/AKT pathway through lncRNA GAS5/miR-375-3p/KLF4 axis. In summary, our study demonstrates that OT ameliorates cardiac hypertrophy by inhibiting PI3K/AKT pathway via lncRNA GAS5/miR-375-3p/KLF4 axis.
Identification of High Nitrogen Use Efficiency Phenotype in Rice (Oryza sativa L.) Through Entire Growth Duration by Unmanned Aerial Vehicle Multispectral Imagery
Authors: Liang Ting , Duan Bo , Luo Xiaoyun , Ma Yi , Yuan Zhengqing , Zhu Renshan , Peng Yi , Gong Yan , Fang Shenghui , Wu Xianting
Published: December 2021

Identification of high Nitrogen Use Efficiency (NUE) phenotypes has been a long-standing challenge in breeding rice and sustainable agriculture to reduce the costs of nitrogen (N) fertilizers. There are two main challenges: (1) high NUE genetic sources are biologically scarce and (2) on the technical side, few easy, non-destructive, and reliable methodologies are available to evaluate plant N variations through the entire growth duration (GD). To overcome the challenges, we captured a unique higher NUE phenotype in rice as a dynamic time-series N variation curve through the entire GD analysis by canopy reflectance data collected by Unmanned Aerial Vehicle Remote Sensing Platform (UAV-RSP) for the first time. LY9348 was a high NUE rice variety with high Nitrogen Uptake Efficiency (NUpE) and high Nitrogen Utilization Efficiency (NUtE) shown in nitrogen dosage field analysis. Its canopy nitrogen content (CNC) was analyzed by the high-throughput UAV-RSP to screen two mixed categories (51 versus 42 varieties) selected from representative higher NUE indica rice collections. Five Vegetation Indices (VIs) were compared, and the Normalized Difference Red Edge Index (NDRE) showed the highest correlation with CNC (r = 0.80). Six key developmental stages of rice varieties were compared from transplantation to maturation, and the high NUE phenotype of LY9348 was shown as a dynamic N accumulation curve, where it was moderately high during the vegetative developmental stages but considerably higher in the reproductive developmental stages with a slower reduction rate. CNC curves of different rice varieties were analyzed to construct two non-linear regression models between N% or N% × leaf area index (LAI) with NDRE separately. Both models could determine the specific phenotype with the coefficient of determination (R2) above 0.61 (Model I) and 0.86 (Model II). Parameters influencing the correlation accuracy between NDRE and N% were found to be better by removing the tillering stage data, separating the short and long GD varieties for the analysis and adding canopy structures, such as LAI, into consideration. The high NUE phenotype of LY9348 could be traced and reidentified across different years, locations, and genetic germplasm groups. Therefore, an effective and reliable high-throughput method was proposed for assisting the selection of the high NUE breeding phenotype.
Abscisic Acid Improves Linoleic Acid Accumulation Possibly by Promoting Expression of EgFAD2 and Other Fatty Acid Biosynthesis Genes in Oil Palm Mesocarp
Authors: Shi Peng , Hua Wei , Htwe Yin Min , Zhang Dapeng , Li Jun , Wang Yong
Published: December 2021

Abscisic acid plays an important role in fruit development. However, the effect of ABA on fatty acid biosynthesis in oil palm is still unknown. In this study, ABA treatments (CK, A1–A4) were applied to oil palm fruit at 16 WAP (weeks after pollination), and fatty acids in the mesocarp at 24 WAP were analyzed by GC-MS. Results showed that linoleic acid content under treatment A2 (20 μM ABA) was significantly higher (slightly increased by 8.33%) than the control. Therefore, mesocarp samples of A2, and the control at 16, 20, and 24 WAP was sampled for RNA-Seq. KEGG pathway enrichment analysis showed that 43 genes were differentially expressed in the fatty acid biosynthesis pathway, of which expression of EgFAD2 (unigene 105050201) under 20 μM ABA treatment was 1.84-fold higher than in the control at 20 WAP. Further sequence analysis found that unigene 105050201 had more ABA-responsive elements (ABRE), complete conserved domains, and a C-terminal signaling motif among two FAD2 copies. Furthermore, WGCNA and correlation analysis showed co-expression of EgFAD2 (unigene 105050201) with transcription factors (TFs) (WRI1, AP2-EREBP, bZIP, bHLH, C2C2-Dof, MYB, NAC, and WRKY), ABA signaling genes (PYR, PP2C, SnRK, and ABI5), and other genes involved in fatty acid biosynthesis (FATA, FATB, LACS, SAD, Oleosins, and so on). These results indicated that ABA treatment promoted the expression of FAD2 and other genes involved in fatty acid biosynthesis, which possibly resulted in the accumulation of linoleic acid. This study will be helpful for understanding the possible mechanisms through which ABA affects fatty acid biosynthesis and their accumulation in the mesocarp of oil palm.
Global Profiling of N-Glycoproteins and N-Glycans in the Diatom Phaeodactylum tricornutum
Authors: Xie Xihui , Du Hong , Chen Jichen , Aslam Muhammad , Wang Wanna , Chen Weizhou , Li Ping , Du Hua , Liu Xiaojuan
Published: December 2021

N-glycosylation is an important posttranslational modification in all eukaryotes, but little is known about the N-glycoproteins and N-glycans in microalgae. Here, N-glycoproteomic and N-glycomic approaches were used to unveil the N-glycoproteins and N-glycans in the model diatom Phaeodactylum tricornutum. In total, 863 different N-glycopeptides corresponding to 639 N-glycoproteins were identified from P. tricornutum. These N-glycoproteins participated in a variety of important metabolic pathways in P. tricornutum. Twelve proteins participating in the N-glycosylation pathway were identified as N-glycoproteins, indicating that the N-glycosylation of these proteins might be important for the protein N-glycosylation pathway. Subsequently, 69 N-glycans corresponding to 59 N-glycoproteins were identified and classified into high mannose and hybrid type N-glycans. High mannose type N-glycans contained four different classes, such as Man-5, Man-7, Man-9, and Man-10 with a terminal glucose residue. Hybrid type N-glycan harbored Man-4 with a terminal GlcNAc residue. The identification of N-glycosylation on nascent proteins expanded our understanding of this modification at a N-glycoproteomic scale, the analysis of N-glycan structures updated the N-glycan database in microalgae. The results obtained from this study facilitate the elucidation of the precise function of these N-glycoproteins and are beneficial for future designing the microalga to produce the functional humanized biopharmaceutical N-glycoproteins for the clinical therapeutics.
Water-Use Efficiency of Co-occurring Sky-Island Pine Species in the North American Great Basin
Authors: Liu Xinsheng , Ziaco Emanuele , Biondi Franco
Published: December 2021

Water-use efficiency (WUE), weighing the balance between plant transpiration and growth, is a key characteristic of ecosystem functioning and a component of tree drought resistance. Seasonal dynamics of tree-level WUE and its connections with drought variability have not been previously explored in sky-island montane forests. We investigated whole-tree transpiration and stem growth of bristlecone (Pinus longaeva) and limber pine (Pinus flexilis) within a high-elevation stand in central-eastern Nevada, United States, using sub-hourly measurements over 5 years (2013–2017). A moderate drought was generally observed early in the growing season, whereas interannual variability of summer rains determined drought levels between years, i.e., reducing drought stress in 2013–2014 while enhancing it in 2015–2017. Transpiration and basal area increment (BAI) of both pines were coupled throughout June–July, resulting in a high but relatively constant early season WUE. In contrast, both pines showed high interannual plasticity in late-season WUE, with a predominant role of stem growth in driving WUE. Overall, bristlecone pine was characterized by a lower WUE compared to limber pine. Dry or wet episodes in the late growing season overrode species differences. Our results suggested thresholds of vapor pressure deficit and soil moisture that would lead to opposite responses of WUE to late-season dry or wet conditions. These findings provide novel insights and clarify potential mechanisms modulating tree-level WUE in sky-island ecosystems of semi-arid regions, thereby helping land managers to design appropriate science-based strategies and reduce uncertainties associated with the impact of future climatic changes.
Tracing the Growth, Gaps, and Characteristics in Positive Education Science: A Long-Term, Large-Scale Review of the Field
Authors: Waters Lea , Loton Daniel
Published: December 2021

This large-scale quantitative review used publication data to track the presence of positive education terms over a 100+ year period across 35 psychology journals and education journals utilizing two analytical methods. First, computer-generated linguistic word count analysis identified that positive education terms have shown small but steady growth in psychology and education research for more than a century. From 1904 to 2016, positive education terms have risen consistently, with increases in 1952, 1982, 2010, and 2014 to over 4, 5, 6, and 7 percent, respectively. Four new terms were present in the top 20 most prevalent terms following the official launch of positive education in 2009: well-being, satisfaction, motivat*, and engag* (note: terms ending with an asterisk are word stems). Three terms also increased in rank order prevalence from 2009 onwards: emotion*; health; and goal*. The second analytical method involved in-depth human coding of a subset of positive education abstracts (n=2,805) by a team of five researchers1to identify trends pertaining to how positive education research has been conducted in terms of paradigms, designs, methods, tools, samples, and settings from 1950 to 2016. College students and students in secondary school make up the most common samples, with little research in the early childhood years. Quantitative, cross-sectional studies using self-report surveys have been the most common design and method used over the past six decades, suggesting room for growth in qualitative methods and the need for greater longitudinal and intervention designs. The human coding was also used to classify positive education variables into broader categories of research. Nine categories were identified: positive functioning; well-being; ill-being; strengths; agency; connection and belonging; identity and personality; school climate and outcomes; and demographics. By tracking positive education science over time, the current paper allows researchers to take stock of the field, identify gaps, outline areas of growth, and pursue fruitful topics for future research.
Effects of L1 Transfer Are Profound, Yet Native-Like Processing Strategy Is Attainable: Evidence From Advanced Learners’ Production of Complex L2 Chinese Structures
Authors: Wu Fuyun , Lyu Jun , Sheng Yanan
Published: December 2021

English as a verb-medial language has a short-before-long preference, whereas Korean and Japanese as verb-final languages show a long-before-short preference. In second language (L2) research, little is known regarding how L1 processing strategies affect the ultimate attainment of target structures. Existing work has shown that native speakers of Chinese strongly prefer to utter demonstrative-classifier (DCL) phrases first in subject-extracted relatives (DCL-SR-N) and DCLs second in object-extracted relatives (OR-DCL-N). But it remains unknown whether L2 learners with typologically different language backgrounds are able to acquire native-like strategies, and how they deviate from native speakers or even among themselves. Using a phrase-assembly task, we investigated advanced L2-Chinese learners whose L1s were English, Korean, and Japanese, because English lacks individual classifiers and has postnominal relative clause (RC), whereas Korean and Japanese have individual classifiers and prenominal RCs. Results showed that the English and Korean groups deviated from the native controls’ asymmetric pattern, but the Japanese group approximated native-like performance. Furthermore, compared to the English group, the Korean and Japanese groups favored the DCL-second configuration in SRs and ORs. No differences were found between the Korean and Japanese groups. Overall, our findings suggest that L1 processing strategies play an overarching role in L2 acquisition of asymmetric positioning of DCLs in Chinese RCs.
Delineating the Relationships Between Motor, Cognitive-Executive and Psychiatric Symptoms in Female FMR1 Premutation Carriers
Authors: Hocking Darren R. , Loesch Danuta Z. , Stimpson Paige , Tassone Flora , Atkinson Anna , Storey Elsdon
Published: December 2021

Introduction: Premutation expansions (55–200 CGG repeats) of the Fragile X Mental Retardation 1 (FMR1) gene on the X chromosome are associated with a range of clinical features. Apart from the most severe - Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) - where the most typical white matter changes affect cerebellar peduncles, more subtle changes may include impairment of executive functioning, affective disorders and/or subtle motor changes. Here we aimed to examine whether performance in selected components of executive functioning is associated with subclinical psychiatric symptoms in non-FXTAS, adult females carrying the FMR1 premutation.

Methods and Sample: A total of 47 female premutation carriers (sub-symptomatic for FXTAS) of wide age range (26–77 years; M = 50.3; SD = 10.9) were assessed using standard neuropsychological tests, three motor rating scales and self-reported measures of psychiatric symptoms using the Symptom Checklist-90-Revised (SCL-90-R).

Results: After adjusting for age and educational level where appropriate, both non-verbal reasoning and response inhibition as assessed on the Stroop task (i.e., the ability to resolve cognitive interference) were associated with a range of primary psychiatric symptom dimensions, and response inhibition uniquely predicted some primary symptoms and global psychiatric features. Importantly, lower scores (worse performance) in response inhibition were also strongly correlated with higher (worse) scores on standard motor rating scales for tremor-ataxia and for parkinsonism.

Conclusion: These results provide evidence for the importance of response inhibition in the manifestation of psychiatric symptoms and subtle tremor-ataxia motor features, suggestive of the presence of early cerebellar changes in female premutation carriers.
Association of VEGF With Antianhedonic Effects of Repeated-Dose Intravenous Ketamine in Treatment-Refractory Depression
Authors: Zheng Wei , Gu Li-Mei , Zhou Yan-Ling , Wang Cheng-Yu , Lan Xiao-Feng , Zhang Bin , Shi Hai-Shan , Wang Dan-Feng , Ning Yu-Ping
Published: December 2021

Objectives: To first explore the role of plasma vascular endothelial growth factor (VEGF) concentrations in ketamine's antianhedonic effects, focusing on Chinese patients with treatment-refractory depression (TRD).

Methods: Seventy-eight patients with treatment-refractory major depressive disorder (MDD) or bipolar disorder (BD) were treated with six ketamine infusions (0.5 mg/kg). Levels of anhedonia were measured using the Montgomery–Åsberg Depression Rating Scale (MADRS) anhedonia item at baseline, day 13 and 26. Plasma VEGF concentrations were examined at the same time points as the MADRS.

Results: Despite a significant reduction in anhedonia symptoms in individuals with treatment-refractory MDD (n = 59) or BD (n = 19) after they received repeated-dose ketamine infusions (p < 0.05), no significant changes in plasma VEGF concentrations were found at day 13 when compared to baseline (p > 0.05). The alteration of plasma VEGF concentrations did not differ between antianhedonic responders and non-responders at days 13 and 26 (all ps > 0.05). Additionally, no significant correlations were observed between the antianhedonic response to ketamine and plasma VEGF concentrations (all ps > 0.05).

Conclusion: This preliminary study suggests that the antianhedonic effects of ketamine are not mediated by VEGF.