bluuebunny/crossref_metadata_2025 huggingface dataset:
Avasimibe Dampens Cholangiocarcinoma Progression by Inhibiting FoxM1-AKR1C1 Signaling
Authors: Gao Yunshu , Xu Dongyun , Li Hongwei , Xu Jiahua , Pan Yating , Liao Xinyi , Qian Jianxin , Hu Yi , Yu Guanzhen
Published: May 2021

Avasimibe is a bioavailable acetyl-CoA acetyltransferase (ACAT) inhibitor and shows a good antitumor effect in various human solid tumors, but its therapeutic value in cholangiocarcinoma (CCA) and underlying mechanisms are largely unknown. In the study, we proved that avasimibe retard cell proliferation and tumor growth of CCAs and identified FoxM1/AKR1C1 axis as the potential novel targets of avasimibe. Aldo-keto reductase 1 family member C1 (AKR1C1) is gradually increased along with the disease progression and highly expressed in human CCAs. From survival analysis, AKR1C1 could be a vital predictor of tumor recurrence and prognostic factor. Enforced Forkhead box protein M1 (FoxM1) expression results in the upregulation of AKR1C1, whereas silencing FoxM1 do the opposite. FoxM1 directly binds to promoter of AKR1C1 and triggers its transcription, while FoxM1-binding site mutation decreases AKR1C1 promoter activity. Moreover, over-expressing exogenous FoxM1 reverses the growth retardation of CCA cells induced by avasimibe administration, while silencing AKR1C1 in FoxM1-overexpressing again retard cell growth. Furthermore, FoxM1 expression significantly correlates with the AKR1C1 expression in human CCA specimens. Our study demonstrates a novel positive regulatory between FoxM1 and AKR1C1 contributing cell growth and tumor progression of CCA and avasimibe may be an alternative therapeutic option for CCA by targeting this FoxM1/AKR1C1 signaling pathway.
A Prognostic DNA Damage Repair Genes Signature and Its Impact on Immune Cell Infiltration in Glioma
Authors: Wang Guohui , Zhou Huandi , Tian Lei , Yan Tianfang , Han Xuetao , Chen Pengyu , Li Haonan , Wang Wenyan , Xiao Zhiqing , Hou Liubing , Xue Xiaoying
Published: May 2021

Objective

Glioma is the most frequent type of malignant cerebral tumors. DNA damage repair genes (DDRGs) play a crucial role in the development of cancer. In this study, we constructed a DDRGs signature and investigated the potential mechanisms involved in this disease.

Methods

RNA sequence data, microarray data, and corresponding clinical information of gliomas were downloaded from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and Gene Expression Omnibus (GEO). Subsequently, we identified candidate genes by differential analysis and Cox regression analysis. The least absolute shrinkage and selection operator Cox regression model was utilized to construct a DDRGs signature using TCGA training dataset. According to this signature, patients with glioma were divided into low- and high-risk groups. The predictive ability of the signature was validated by prognostic analysis, receiver operating characteristic curves, principal component analysis, and stratification analysis in TCGA testing and CGGA verification datasets. CIBERSORT and single-sample gene set enrichment analysis (ssGSEA) were used to evaluate the immune microenvironment of glioma. Moreover, we conducted GSEA to determine the functions and pathways in the low- and high-risk groups. Finally, a nomogram was constructed by combining the signature and other clinical features.

Results

A total of 1,431 samples of glioma (592 from TCGA, 686 from the CGGA, and 153 from the GEO) and 23 samples of normal brain tissue from the GEO were analyzed in this study. There were 51 prognostic differentially expressed DDRGs. Additionally, five DDRGs (CDK4、HMGB2、WEE1、SMC3 and GADD45G) were selected to construct a DDRGs signature for glioma, stratifying patients into low- and high-risk groups. The survival analysis showed that the DDRGs signature could differentiate the outcome of the low- and high-risk groups, showing that high-risk gliomas were associated with shorter overall survival. The immune microenvironment analysis revealed that more immunosuppressive cells, such as tumor associated macrophages and regulatory T cells, were recruited in the high-risk group. GSEA also showed that high-risk glioma was correlated with the immune and extracellular matrix pathways.

Conclusion

The five DDRGs signature and its impact on the infiltration of immunosuppressive cells could precisely predict the prognosis and provide guidance on the treatment of glioma.
Primary Care Case Management of Febrile Children: Insights From the ePOCT Routine Care Cohort in Dar es Salaam, Tanzania
Authors: van de Maat Josephine , De Santis Olga , Luwanda Lameck , Tan Rainer , Keitel Kristina
Published: May 2021

Aim: To provide insight in the primary health care (PHC) case management of febrile children under-five in Dar es Salaam, and to identify areas for improving quality of care.

Methods: We used data from the routine care arm of the ePOCT trial, including children aged 2–59 months who presented with an acute febrile illness to two health centers in Dar es Salaam (2014–2016). The presenting complaint, anthropometrics, vital signs, test results, final diagnosis, and treatment were prospectively collected in all children. We used descriptive statistics to analyze the frequencies of diagnoses, adherence to diagnostics, and prescribed treatments.

Results: We included 547 children (47% male, median age 14 months). Most diagnoses were viral: upper respiratory tract infection (60%) and/or gastro-enteritis (18%). Vital signs and anthropometric measurements taken by research staff and urinary testing failed to influence treatment decisions. In total, 518/547 (95%) children received antibiotics, while 119/547 (22%) had an indication for antibiotics based on local guidelines. Antibiotic dosing was frequently out of range. Non-recommended treatments were common (29%), most often cough syrup and vitamins.

Conclusion: Our study points to challenges in using diagnostic test results, concerns regarding quality of antibiotic prescriptions, and frequent use of non-evidence-based complementary medicines in PHC in Tanzania. Larger studies on diagnostic and treatments processes in PHC in Tanzania are needed to inform effective solutions to support PHC workers in case management of children.
Coronavirus Disease 2019 in Children
Authors: Borrelli Melissa , Corcione Adele , Castellano Fabio , Fiori Nastro Francesca , Santamaria Francesca
Published: May 2021

Since its appearance in Wuhan in mid-December 2019, acute respiratory syndrome coronavirus 2 (SARS-CoV-2) related 19 coronavirus disease (COVID-19) has spread dramatically worldwide. It soon became apparent that the incidence of pediatric COVID-19 was much lower than the adult form. Morbidity in children is characterized by a variable clinical presentation and course. Symptoms are similar to those of other acute respiratory viral infections, the upper airways being more affected than the lower airways. Thus far, over 90% of children who tested positive for the virus presented mild or moderate symptoms and signs. Most children were asymptomatic, and only a few cases were severe, unlike in the adult population. Deaths have been rare and occurred mainly in children with underlying morbidity. Factors as reduced angiotensin-converting enzyme receptor expression, increased activation of the interferon-related innate immune response, and trained immunity have been implicated in the relative resistance to COVID-19 in children, however the underlying pathogenesis and mechanism of action remain to be established. While at the pandemic outbreak, mild respiratory manifestations were the most frequently described symptoms in children, subsequent reports suggested that the clinical course of COVID-19 is more complex than initially thought. Thanks to the experience acquired in adults, the diagnosis of pediatric SARS-CoV-2 infection has improved with time. Data on the treatment of children are sparse, however, several antiviral trials are ongoing. The purpose of this narrative review is to summarize current understanding of pediatric SARS-CoV-2 infection and provide more accurate information for healthcare workers and improve the care of patients.
Activation of AMP-Activated Protein Kinase-Sirtuin 1 Pathway Contributes to Salvianolic Acid A-Induced Browning of White Adipose Tissue in High-Fat Diet Fed Male Mice
Authors: Lai Jianfei , Qian Qianyu , Ding Qinchao , Zhou Li , Fu Ai , Du Zhongyan , Wang Cui , Song Zhenyuan , Li Songtao , Dou Xiaobing
Published: May 2021

Background: Salvianolic acid A (Sal A), a natural polyphenolic compound extracted from Radix Salvia miltiorrhiza (Danshen), exhibits exceptional pharmacological activities against cardiovascular diseases. While a few studies have reported anti-obesity properties of Sal A, the underlying mechanisms are largely unknown. Given the prevalence of obesity and promising potential of browning of white adipose tissue to combat obesity, recent research has focused on herbal ingredients that may promote browning and increase energy expenditure.

Purpose: The present study was designed to investigate the protective antiobesity mechanisms of Sal A, in part through white adipose browning.

Methods: Both high-fat diet (HFD)-induced obese (DIO) male mice model and fully differentiated C3H10T1/2 adipocytes from mouse embryo fibroblasts were employed in this study. Sal A (20 and 40 mg/kg) was administrated to DIO mice by intraperitoneal injection for 13-weeks. Molecular mechanisms mediating effects of Sal A were evaluated.

Resluts: Sal A treatment significantly attenuated HFD-induced weight gain and lipid accumulation in epididymal fat pad. Uncoupling protein 1 (UCP-1), a specialized thermogenic protein and marker for white adipocyte browning, was significantly induced by Sal A treatment in both white adipose tissues and cultured adipocytes. Further mechanistic investigations revealed that Sal A robustly reversed HFD-decreased AMP-activated protein kinase (AMPK) phosphorylation and sirtuin 1 (SIRT1) expression in mice. Genetically silencing either AMPK or SIRT1 using siRNA abolished UCP-1 upregulation by Sal A. AMPK silencing significantly blocked Sal A-increased SIRT1 expression, while SIRT1 silencing did not affect Sal A-upregulated phosphorylated-AMPK. These findings indicate that AMPK was involved in Sal A-increased SIRT1.

Conclusion: Sal A increases white adipose tissue browning in HFD-fed male mice and in cultured adipocytes. Thus, Sal is a potential natural therapeutic compound for treating and/or preventing obesity.
The Ethyl Acetate Extract From Celastrus orbiculatus Promotes Apoptosis of Gastric Cancer Cells Through Mitochondria Regulation by PHB
Authors: Tao Lide , Yin Zixin , Ni Tengyang , Chu Zewen , Hao Shihua , Wang Zeyu , Sunagawa Masataka , Wang Haibo , Liu Yanqing
Published: May 2021

Objective: To investigate the effect of ethyl acetate extract from Celastrus orbiculatus (COE) on gastric cancer cell apoptosis and reveal its underlying molecular mechanism. In addition, it was aimed to stablish a theoretical basis for the clinical application of Celastrus orbiculatus in the gastric cancer treatment.

Material and Methods: Western blot and RT-qPCR were used to detect mRNA and protein expression of PHB in gastric cancer and adjacent tissues. MTT method was used to detect the COE effect on the proliferation of AGS cells and to determine the 50% inhibitory concentration COE on these cells. COE effect on AGS apoptosis was evaluated by flow cytometry. Changes in apoptosis-related proteins expression in AGS cells were detected by western blot and changes in mitochondrial membrane potential were detected by JC-1 fluorescence staining. PHB expression was knocked down in AGS cells by lentiviral-mediated RNA interference. The COE antitumor effect was assessed in vivo using a subcutaneous transplantation tumor model in nude mice and in vivo fluorescence tracing technique in small animals.

Results: The clinical samples analysis results showed that the PHB expression in gastric cancer samples was significantly higher than in corresponding adjacent tissues. MTT results showed that the AGS cell proliferation was significantly inhibited. RT-qPCR and western blot results showed that COE can significantly inhibit the PHB mRNA and protein expression, respectively. Flow cytometry analysis showed that COE was able to significantly promote AGS cell apoptosis. Western blot results also indicated that apoptosis-related protein expression changed significantly; BCL-2 expression significantly reduced while the Caspase-3 and Bax expression significantly increased after COE treatment. JC-1 fluorescence staining results showed that COE changed the mitochondrial membrane potential and activated the mitochondrial apoptosis pathway. Furthermore, in vivo experiments results demonstrated that the growth of subcutaneous transplanted tumor was significantly inhibited by the PHB knockdown and by the COE intragastric administration.

Conclusion: COE can significantly promote apoptosis of human gastric cancer cells, which can be achieved by inhibiting PHB expression, thus altering the structure and function of mitochondria and activating the mitochondria apoptosis pathway. The antitumor effect of COE has also been proved in vivo.
Pharmacokinetics of Intraperitoneal Vancomycin and Amikacin in Automated Peritoneal Dialysis Patients With Peritonitis
Authors: Falbo dos Reis Pâmela , Barretti Pasqual , Marinho Laudilene , Balbi Andre Luís , Awdishu Linda , Ponce Daniela
Published: May 2021

Objective: The study aimed to evaluate the vancomycin and amikacin concentrations in serum and dialysate for automatic peritoneal dialysis (APD) patients.

Methods: A total of 558 serum and dialysate samples of 12 episodes of gram-positive and 18 episodes of gram-negative peritonitis were included to investigate the relationship between vancomycin and amikacin concentrations in serum and dialysate on the first and third days of treatment. Samples were analysed 30, 120 min, and 48 h after intraperitoneal administration of vancomycin in peritonitis caused by gram-positive agents and 30, 120 min, and 24 h after intraperitoneal administration of amikacin in peritonitis caused by gram-negative agents. Vancomycin was administered every 72 h and amikacin once a day. The target therapeutic concentration of amikacin was 25–35 mg/l at the peak moment and 4–8 mg/l at the trough moment; and after 48 h for vancomycin, 15–20 mg/l at the trough moment.

Results: For peritonitis caused by gram-negative agents, at the peak moment, therapeutic levels of amikacin were reached in dialysate in 80.7% of patients with evolution to cure and in 50% of patients evaluated as non-cure (p = 0.05). At the trough moment, only 38% were in therapeutic concentrations in the dialysate in the cure group and 42.8% in the non-cure group (p = 1). Peak plasma concentrations were subtherapeutic in 98.4% of the samples in the cure group and in 100% of the non-cure group. At the trough moment, therapeutic concentrations were present in 74.4% of the cure group and 71.4% of the non-cure group (p = 1). Regarding vancomycin and among gram-positive agents, therapeutic levels were reached at the peak moment in 94% of the cure group and 6% of the non-cure group (p = 0.007). After 48 h, 56.8% of the cure group had a therapeutic serum concentration whereas for the non-cure group it was only 33.3% (p = 0.39).

Conclusion: Despite a small sample size, we demonstrated peak dialysate amikacin level and peak serum vancomycin level correlates well with Gram-negative and Gram positve peritonitis cure, respectively. It is suggested to study the antibiotics pharmacodynamics for a better understanding of therapeutic success in a larger sample.
Pharmacological Screening of Viola odorata L. for Memory-Enhancing Effect via Modulation of Oxidative Stress and Inflammatory Biomarkers
Authors: Saleem Uzma , Hira Sundas , Anwar Fareeha , Shah Muhammad Ajmal , Bashir Samia , Baty Roua S. , Badr Reem H. , Blundell Renald , Batiha Gaber El-Saber , Ahmad Bashir
Published: May 2021

Purpose: Alzheimer disease (AD) is a progressive neurodegenerative disorder that is caused by neuroinflammation and oxidative stress. The present study aimed to characterize and then investigate the memory-enhancing potential of Viola odorata methanolic extract in lipopolysaccharide (LPS)–treated mice.

Methods:V. odorata characterization was done by using the GCMS technique. Neuroinflammation was induced by the intracerebroventricular administration of LPS at a dose of 12 µg. Animals were divided randomly into six groups (n = 10). Group I was normal control, which was given vehicle. Group II was disease control, which received LPS (12 µg) via the intracerebroventricular route. Group III was standard, which was administered with donepezil (3 µg) orally for 21 days. Groups IV–VI were the treatment groups, which were administered with the extract at 100, 200, and 400 mg/kg dose levels orally respectively for 21 days. Groups III–VI received LPS (12 µg) on the first day along with their treatments. During the treatment, the animals were assessed for memory retention by employing different behavioral paradigms namely elevated plus maze, passive avoidance, foot shock and open field. Various mediators [endogenous antioxidants, neurotransmitters, and acetylcholinesterase (AChE)] involved in the pathogenesis of AD were quantified by using the UV spectrophotometric method.

Results: Extract-treated groups showed a remarkable improvement in cognitive impairment in all behavioral paradigms. Oxidative stress biomarkers, that is, superoxide dismutase, catalase, and glutathione were raised dose-dependently in the treatment groups with a dose-dependent decrease in the malonaldehyde and AChE levels in the brains of the treated animals. The treatment groups showed decreased levels of inflammatory biomarkers, that is, tumor necrosis factor–alpha, nuclear factor kappa light-chain enhancer of activated β-cells, and cyclo-oxygenase, which supports the therapeutic effectiveness of the treatment.

Conclusion: Based on behavioral, oxidative stress biomarker, and neuroinflammatory data, it is concluded that V. odorata possesses memory-enhancing activity and may prove a beneficial role in the management of AD.
Cell-Free Biological Approach for Corneal Stromal Wound Healing
Authors: Jhanji Vishal , Billig Isabelle , Yam Gary Hin-Fai
Published: May 2021

Corneal opacification is the fourth most common cause of blindness globally behind cataracts, glaucoma, and age-related macular degeneration. The standard treatment of serious corneal scarring is corneal transplantation. Though it is effective for restoring vision, the treatment outcome is not optimal, due to limitations such as long-term graft survival, lifelong use of immunosuppressants, and a loss of corneal strength. Regulation of corneal stromal wound healing, along with inhibition or downregulation of corneal scarring is a promising approach to prevent corneal opacification. Pharmacological approaches have been suggested, however these are fraught with side effects. Tissue healing is an intricate process that involves cell death, proliferation, differentiation, and remodeling of the extracellular matrix. Current research on stromal wound healing is focused on corneal characteristics such as the immune response, angiogenesis, and cell signaling. Indeed, promising new technologies with the potential to modulate wound healing are under development. In this review, we provide an overview of cell-free strategies and some approaches under development that have the potential to control stromal fibrosis and scarring, especially in the context of early intervention.
Based on Plasma Metabonomics and Network Pharmacology Exploring the Therapeutic Mechanism of Gynura procumbens on Type 2 Diabetes
Authors: Guo Wenjing , Ouyang Hui , Liu Mi , Wu Jiahui , He Xiao , Yang Shilin , He Mingzhen , Feng Yulin
Published: May 2021

Gynura procumbens (GP) is a perennial herbal medicine and food homologous plant, which has been reported to have a good hypoglycemic effect. However, its active components and underlying mechanism of action are not clear. Here, we aimed to confirm the effects of GP on type 2 diabetes (T2DM) from several different aspects. We used UPLC/Q-TOF MS to analyze the metabolic patterns, which included blood samples of clinical subjects and db/db mice to screen for serum metabolic markers and metabolic pathways. We also used network pharmacology to study GP targets in the treatment of T2DM. Data from endogenous metabolites in plasma showed that two common pathways, including glycerol phosphate metabolism and retinol metabolism, were identified in plasma samples of the groups. Finally, Western blot analysis was used to verify the expression of proteins in the PI3K/AKT and AGE–RAGE signaling pathways. The protein expression of AKT, eNOS, iNS, and MAPK was significantly upregulated, and the expression of caspase-8 and caspase-3 was significantly downregulated. Thus, our findings indicated that GP could alleviate insulin resistance by regulating biometabolic markers and key proteins in the PI3K/AKT and AGE–RAGE signaling pathways to treat T2DM.
Comprehensive Review of Phytochemical Constituents, Pharmacological Properties, and Clinical Applications of Prunus mume
Authors: Gong Xue-Peng , Tang Ying , Song Yuan-Yuan , Du Guang , Li Juan
Published: May 2021

Prunus mumeis one of the most ancient medicinal herbs and health foods commonly used in Asian countries. It is widely used as a constituent of many medicinal preparations and as a food ingredient for its beneficial health effects. In this review, we retrieved reports from PubMed, embase, Scopus, and SciFinder databases, to collect extensive scientific evidence on the phytochemical constituents, pharmacological properties, and clinical applications ofPrunus mume. The literature review revealed that approximately 192 compounds have been isolated from different parts of the plant, and their molecular structures have been identified. The pharmacological properties of the plant, including anti-diabetic, liver-protective, antitumor, antimicrobial, antioxidant, and anti-inflammatory activities, as well as their underlying mechanisms, have been clarified byin vitroandin vivostudies. Clinical studies, although very limited, have been highlighted in this review to provide a reference for further exploration on therapeutic applications of the plant.
Multimodal Analgesia With Long-Acting Dinalbuphine Sebacate Plus Transversus Abdominis Plane Block for Perioperative Pain Management in Bariatric Surgery: A Case Report
Authors: Liu Shih-Yuan , Ho Yi-Hong , Wong Chih-Shung
Published: May 2021

Laparoscopic bariatric surgery is increasingly performed in morbidly obese patients. However, post-surgical pain is common and is usually managed with classical opioids such as morphine and fentanyl. Further, morbidly obese patients are predisposed to opioid-related side effects, especially post-operative nausea and vomiting (PONV), and respiratory depression. Obstructive sleep apnea in morbidly obese patients even predisposes them to respiratory depression. Thus, reducing opioid consumption is important. Multimodal analgesia (MMA) provides optimal perioperative analgesia while minimizing opioid consumption. Studies have shown that MMA strategy can provide sufficient pain relief in bariatric surgery with enhanced recovery. There are very few reports on the use of dinalbuphine sebacate (DS), a newly introduced non-controlled opioid medication with long-lasting analgesic effects. DS has a different mechanism of action from that of morphine or fentanyl and is non-addictive, with minimal side effects. It has been successfully used in laparoscopic cholecystectomy in our previous study. We present a case of a new MMA protocol with DS on a 46-year-old morbidly obese female patient who underwent laparoscopic sleeve gastrectomy. The MMA protocol included ultrasound-guided intramuscular DS injection plus transversus abdominis plane (TAP) block and other analgesics; it achieved good perioperative analgesia with opioid-sparing effect and enhanced patient’s recovery with no pain in the following 4 months.
Therapeutic Applications of Functional Nanomaterials for Prostatitis
Authors: Liu Chun-Ping , Chen Zi-De , Ye Zi-Yan , He Dong-Yue , Dang Yue , Li Zhe-Wei , Wang Lei , Ren Miao , Fan Zhi-Jin , Liu Hong-Xing
Published: May 2021

Prostatitis is a common disease in adult males, with characteristics of a poor treatment response and easy recurrence, which seriously affects the patient’s quality of life. The prostate is located deep in the pelvic cavity, and thus a traditional infusion or other treatment methods are unable to easily act directly on the prostate, leading to poor therapeutic effects. Therefore, the development of new diagnostic and treatment strategies has become a research hotspot in the field of prostatitis treatment. In recent years, nanomaterials have been widely used in the diagnosis and treatment of various infectious diseases. Nanotechnology is a promising tool for 1) the accurate diagnosis of diseases; 2) improving the targeting of drug delivery systems; 3) intelligent, controlled drug release; and 4) multimode collaborative treatment, which is expected to be applied in the diagnosis and treatment of prostatitis. Nanotechnology is attracting attention in the diagnosis, prevention and treatment of prostatitis. However, as a new research area, systematic reviews on the application of nanomaterials in the diagnosis and treatment of prostatitis are still lacking. In this mini-review, we will highlight the treatment approaches for and challenges associated with prostatitis and describe the advantages of functional nanoparticles in improving treatment effectiveness and overcoming side effects.
Linear Behavior of the Phase Lifetime in Frequency-Domain Fluorescence Lifetime Imaging of FRET Constructs
Authors: Sumetsky Daniel , Jiang James Y. , Ayad Marina A. , Mahon Timothy , Menaesse Audrey , Cararo-Lopes Marina M. , Patel Mihir V. , Firestein Bonnie L. , Boustany Nada N.
Published: May 2021

We utilize a cost-effective frequency-domain fluorescence lifetime imaging microscope to measure the phase lifetime of mTFP1 in mTFP1-mVenus fluorescence resonance energy transfer (FRET) constructs relevant to the VinTS molecular tension probe. Our data were collected at 15 modulation frequencies ω/2π selected between 14 and 70 MHz. The lifetime of mTFP1 was τD = 3.11 ± 0.02 ns in the absence of acceptor. For modulation frequencies, ω, such that (ω · τD) < 1.1, the phase lifetime of mTFP1in the presence of acceptor (mVenus), τϕDA, was directly related to the amplitude-weighted lifetime τaveDA inferred from the known FRET efficiency (EFRETtrue) of the constructs. A linear fit to a plot of (ω·τϕDA) vs. (ω·τaveDA) yielded a slope of 0.79 ± 0.05 and intercept of 0.095 ± 0.029 (R2 = 0.952). Thus, our results suggest that a linear relationship exists between the apparent EFRETapp based on the measured phase lifetime and EFRETtrue for frequencies such that (ω · τD) < 1.1. We had previously reported a similar relationship between EFRETapp and EFRETtrue at 42 MHz. Our current results provide additional evidence in support of this observation, but further investigation is still required to fully characterize these results. A direct relationship between τϕDAand τaveDA has the potential to simplify significantly data acquisition and interpretation in fluorescence lifetime measurements of FRET constructs.
Measuring Law Over Time: A Network Analytical Framework with an Application to Statutes and Regulations in the United States and Germany
Authors: Coupette Corinna , Beckedorf Janis , Hartung Dirk , Bommarito Michael , Katz Daniel Martin
Published: May 2021

How do complex social systems evolve in the modern world? This question lies at the heart of social physics, and network analysis has proven critical in providing answers to it. In recent years, network analysis has also been used to gain a quantitative understanding of law as a complex adaptive system, but most research has focused on legal documents of a single type, and there exists no unified framework for quantitative legal document analysis using network analytical tools. Against this background, we present a comprehensive framework for analyzing legal documents as multi-dimensional, dynamic document networks. We demonstrate the utility of this framework by applying it to an original dataset of statutes and regulations from two different countries, the United States and Germany, spanning more than twenty years (1998–2019). Our framework provides tools for assessing the size and connectivity of the legal system as viewed through the lens of specific document collections as well as for tracking the evolution of individual legal documents over time. Implementing the framework for our dataset, we find that at the federal level, the United States legal system is increasingly dominated by regulations, whereas the German legal system remains governed by statutes. This holds regardless of whether we measure the systems at the macro, the meso, or the micro level.
Chronic E-Cigarette Aerosol Inhalation Alters the Immune State of the Lungs and Increases ACE2 Expression, Raising Concern for Altered Response and Susceptibility to SARS-CoV-2
Authors: Masso-Silva Jorge A. , Moshensky Alexander , Shin John , Olay Jarod , Nilaad Sedtavut , Advani Ira , Bojanowski Christine M. , Crotty Shane , Li Wei Tse , Ongkeko Weg M. , Singla Sunit , Crotty Alexander Laura E.
Published: May 2021

Conventional smoking is known to both increase susceptibility to infection and drive inflammation within the lungs. Recently, smokers have been found to be at higher risk of developing severe forms of coronavirus disease 2019 (COVID-19). E-cigarette aerosol inhalation (vaping) has been associated with several inflammatory lung disorders, including the recent e-cigarette or vaping product use-associated lung injury (EVALI) epidemic, and recent studies have suggested that vaping alters host susceptibility to pathogens such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To assess the impact of vaping on lung inflammatory pathways, including the angiotensin-converting enzyme 2 (ACE2) receptor known to be involved in SARS-CoV-2 infection, mice were exposed to e-cigarette aerosols for 60 min daily for 1–6 months and underwent gene expression analysis. Hierarchical clustering revealed extensive gene expression changes occurred in the lungs of both inbred C57BL/6 mice and outbred CD1 mice, with 2,933 gene expression changes in C57BL/6 mice, and 2,818 gene expression changes in CD1 mice (>abs 1.25-fold change). Particularly, large reductions in IgA and CD4 were identified, indicating impairment of host responses to pathogens via reductions in immunoglobulins and CD4 T cells. CD177, facmr, tlr9, fcgr1, and ccr2 were also reduced, consistent with diminished host defenses via decreased neutrophils and/or monocytes in the lungs. Gene set enrichment (GSE) plots demonstrated upregulation of gene expression related to cell activation specifically in neutrophils. As neutrophils are a potential driver of acute lung injury in COVID-19, increased neutrophil activation in the lungs suggests that vapers are at higher risk of developing more severe forms of COVID-19. The receptor through which SARS-CoV-2 infects host cells, ACE2, was found to have moderate upregulation in mice exposed to unflavored vape pens, and further upregulation (six-fold) with JUUL mint aerosol exposure. No changes were found in mice exposed to unflavored Mod device-generated aerosols. These findings suggest that specific vaping devices and components of e-liquids have an effect on ACE2 expression, thus potentially increasing susceptibility to SARS-CoV-2. In addition, exposure to e-cigarette aerosols both with and without nicotine led to alterations in eicosanoid lipid profiles within the BAL. These data demonstrate that chronic, daily inhalation of e-cigarette aerosols fundamentally alters the inflammatory and immune state of the lungs. Thus, e-cigarette vapers may be at higher risk of developing infections and inflammatory disorders of the lungs.
Community Trait Responses of Three Dominant Macrophytes to Variations in Flooding During 2011–2019 in a Yangtze River-Connected Floodplain Wetland (Dongting Lake, China)
Authors: Huang Ying , Chen Xin-Sheng , Li Feng , Hou Zhi-Yong , Li Xu , Zeng Jing , Deng Zheng-Miao , Zou Ye-Ai , Xie Yong-Hong
Published: May 2021

In lacustrine wetlands connected to rivers, the changes in flood regimes caused by hydrological projects lead to changes in the community traits of dominant macrophytes and, consequently, influence the structure and function of wetland vegetation. However, community trait responses of macrophytes to the timing and duration of flood disturbance have been rarely quantified. In 2011–2019, we investigated plant species diversity, density, and biomass in three dominant macrophyte communities (Carex brevicuspis C.B. Clarke, Miscanthus sacchariflorus (Maxim.) Hackel, and Polygonum hydropiper L.) through monthly field surveys in Dongting Lake wetlands. Partial least squares regressions were used to analyze how the variations in hydrological regimes affected plant community traits. Apparent inter-annual fluctuations in plant community traits were detected during 2011–2019. The species richness and Shannon index of diversity of Miscanthus and Polygonum communities increased, whereas the Shannon index of diversity of Carex community decreased. Variation in flooding had a greater effect on Polygonum and Carex community traits than on Miscanthus community traits. Flooding disturbed all plant communities, especially when the duration and timing varied. Shorter inundation periods caused the biomass of Miscanthus community to decline, and that of Carex and Polygonum communities to increase. Earlier flood recession caused the species richness and Shannon index of diversity of Polygonum and Miscanthus community to increase, and those of Carex community to decrease. These findings imply that shorter inundation durations and earlier flood recession generated by the operation of the Three Gorges Dam have changed the macrophyte growth pattern.
High Drying Temperature Accelerates Sunflower Seed Deterioration by Regulating the Fatty Acid Metabolism, Glycometabolism, and Abscisic Acid/Gibberellin Balance
Authors: Huang Yutao , Lu Min , Wu Huaping , Zhao Tiyuan , Wu Pin , Cao Dongdong
Published: May 2021

Sunflower seed storage is accompanied by the loss of seed vigor. Seed drying is a key link between seed harvest and seed storage; however, to date, the effect of seed drying on sunflower seed deterioration during storage remains unclear. The present study performed hot air drying for sunflower seeds with an initial moisture content of 30% to examine the manner in which drying temperature (35, 40, 45, 50, and 55°C) affects the drying performance and seed vigor following storage process (6 and 12 months). A drying temperature of 40°C was evidently safe for sunflower seeds, whereas the high drying temperatures (HTD, 45, 50, and 55°C) significantly lowered sunflower seed vigor by regulating the fatty acid metabolism, glycometabolism, and abscisic acid (ABA)/gibberellin (GA) balance. HDT significantly increased the seed damage rate and accelerated sunflower seed deterioration during natural and artificial aging process. Further biochemical analysis indicated that HDT significantly increased lipoxygenase and dioxygenase activities, leading to malonaldehyde and reactive oxygen species over-accumulation during storage. During early seed germination, HDT significantly inhibited fatty acid hydrolysis and glycometabolism by decreasing triacylglycerol lipase, CoA-SH oxidase, and invertase activities. Moreover, HDT remarkably increased ABA levels but reduced GA levels by regulating gene expressions and metabolic enzyme activities during early imbibitions. Cumulatively, the seed drying effect on sunflower seed vigor deterioration during the storage process may be strongly related to fatty acid oxidation and hydrolysis metabolism, toxic substance accumulation, and ABA/GA balance.
Effects of Organic Polymer Compound Material on K+ and Na+ Distribution and Physiological Characteristics of Cotton Under Saline and Alkaline Stresses
Authors: Wang Xiaoli , An Mengjie , Wang Kaiyong , Fan Hua , Shi Jiaohua , Chen Kuan
Published: May 2021

Soil salinization and alkalization greatly restrict crop growth and yield. In this study, NaCl (8 g kg−1) and Na2CO3 (8 g kg−1) were used to create saline stress and alkaline stress on cotton in pot cultivation in the field, and organic polymer compound material (OPCM) and stem girdling were applied before cotton sowing and at flowering and boll-forming stage, respectively, aiming to determine the effects of OPCM on K+ and Na+ absorption and transport and physiological characteristics of cotton leaf and root. The results showed that after applying the OPCM, the Na+ content in leaf of cotton under saline stress and alkaline stress were decreased by 7.72 and 6.49%, respectively, the K+/Na+ ratio in leaf were increased by 5.65 and 19.10%, respectively, the Na+ content in root were decreased by 9.57 and 0.53%, respectively, the K+/Na+ ratio in root were increased by 65.77 and 55.84%, respectively, and the transport coefficients of K+ and Na+ from leaf to root were increased by 39.59 and 21.38%, respectively. The activities of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD), and the relative electrical conductivity (REC) in cotton leaf were significantly increased, while the content of malondialdehyde (MDA) was decreased; but the changes in those in root were not significant. The boll weights were increased by 11.40 and 13.37%, respectively, compared with those for the control. After stem girdling, the application of OPCM still promoted the ion transport of cotton organs; moreover, the CAT activity in root was increased by 25.09% under saline stress, and the SOD activity in leaf and CAT in root were increased by 42.22 and 6.91%, respectively under alkaline stress. Therefore, OPCM can significantly change the transport of K+ and Na+ to maintain the K+ and Na+ homeostasis in leaf and root, and regulate physiological and biochemical indicators to alleviate the stress-induced damage. Besides, the regulation effect of OPCM on saline stress was better than that on alkaline stress.
Nepenthes × ventrata Transcriptome Profiling Reveals a Similarity Between the Evolutionary Origins of Carnivorous Traps and Floral Organs
Authors: Shchennikova Anna V. , Beletsky Alexey V. , Filyushin Mikhail A. , Slugina Maria A. , Gruzdev Eugeny V. , Mardanov Andrey V. , Kochieva Elena Z. , Ravin Nikolay V.
Published: May 2021

The emergence of the carnivory syndrome and traps in plants is one of the most intriguing questions in evolutionary biology. In the present study, we addressed it by comparative transcriptomics analysis of leaves and leaf-derived pitcher traps from a predatory plant Nepenthes ventricosa × Nepenthes alata. Pitchers were collected at three stages of development and a total of 12 transcriptomes were sequenced and assembled de novo. In comparison with leaves, pitchers at all developmental stages were found to be highly enriched with upregulated genes involved in stress response, specification of shoot apical meristem, biosynthesis of sucrose, wax/cutin, anthocyanins, and alkaloids, genes encoding digestive enzymes (proteases and oligosaccharide hydrolases), and flowering-related MADS-box genes. At the same time, photosynthesis-related genes in pitchers were transcriptionally downregulated. As the MADS-box genes are thought to be associated with the origin of flower organs from leaves, we suggest that Nepenthes species could have employed a similar pathway involving highly conserved MADS-domain transcription factors to develop a novel structure, pitcher-like trap, for capture and digestion of animal prey during the evolutionary transition to carnivory. The data obtained should clarify the molecular mechanisms of trap initiation and development and may contribute to solving the problem of its emergence in plants.
Using Spectral Reflectance to Estimate the Leaf Chlorophyll Content of Maize Inoculated With Arbuscular Mycorrhizal Fungi Under Water Stress
Authors: Sun Jinhua , Yang Liu , Yang Xitian , Wei Jie , Li Lantao , Guo Erhui , Kong Yuhua
Published: May 2021

Leaf chlorophyll content is an important indicator of the growth and photosynthesis of maize under water stress. The promotion of maize physiological growth by (AMF) has been studied. However, studies of the effects of AMF on the leaf chlorophyll content of maize under water stress as observed through spectral information are rare. In this study, a pot experiment was carried out to spectrally estimate the leaf chlorophyll content of maize subjected to different durations (20, 35, and 55 days); degrees of water stress (75%, 55% and 35% water supply) and two inoculation treatments (inoculation with Funneliformis mosseae and no inoculation). Three machine learning algorithms, including the back propagation (BP) method, least square support vector machine (LSSVM) and random forest (RF) method, were used to estimate the leaf chlorophyll content of maize. The results showed that AMF increased the leaf chlorophyll content, net photosynthetic rate (A), stomatal conductance (gs), transpiration rate (E), and water use efficiency (WUE) of maize but decreased the intercellular carbon dioxide concentration (Ci) of maize and atmospheric vapor pressure deficit (VPD) regardless of the water stress duration and degree. The first-order differential spectral data can better reflect the correlation between leaf chlorophyll content and spectrum of inoculated maize when compared with original spectral data. The BP model performed bestin modeling the maize leaf chlorophyll content, yielding the largest R2-values and smallest root mean square error (RMSE) values, regardless of stress duration. These results provide a reliable basis for the effective monitoring of the leaf chlorophyll content of maize under water stress.
Calcium Positively Mediates Blue Light-Induced Anthocyanin Accumulation in Hypocotyl of Soybean Sprouts
Authors: Hu Gang , Yue Xiaomeng , Song Jinxue , Xing Guipei , Chen Jun , Wang Haixia , Su Nana , Cui Jin
Published: May 2021

Soybean sprouts are a flavorful microgreen that can be eaten all year round and are widely favored in Southeast Asia. In this study, the regulatory mechanism of calcium on anthocyanin biosynthesis in soybean sprouts under blue light was investigated. The results showed that blue light, with a short wavelength, effectively induced anthocyanin accumulation in the hypocotyl of soybean sprout cultivar “Dongnong 690.” Calcium supplementation further enhanced anthocyanin content, which was obviously inhibited by LaCl3 and neomycin treatment. Moreover, exogenous calcium changed the metabolism of anthocyanins, and seven anthocyanin compounds were detected. The trend of calcium fluorescence intensity in hypocotyl cells, as well as that of the inositol 1,4,5-trisphosphate and calmodulin content, was consistent with that of anthocyanins content. Specific spatial distribution patterns of calcium antimonate precipitation were observed in the ultrastructure of hypocotyl cells under different conditions. Furthermore, calcium application upregulated the expression of genes related to anthocyanin biosynthesis, and calcium inhibitors suppressed these genes. Finally, transcriptomics was performed to gain global insights into the molecular regulation mechanism of calcium-associated anthocyanin production. Genes from the flavonoid biosynthesis pathway were distinctly enriched among the differentially expressed genes, and weighted gene co-expression network analysis showed that two MYBs were related to the accumulation of anthocyanins. These results indicated that calcium released from apoplast and intracellular stores in specific spatial-temporal features promote blue light-induced anthocyanin accumulation by upregulation of the expression of genes related to anthocyanin synthesis of “Dongnong 690” hypocotyl. The findings deepen the understanding of the calcium regulation mechanism of blue light-induced anthocyanin accumulation in soybean sprouts, which will help growers produce high-quality foods beneficial for human health.
Flower Development in Cassava Is Feminized by Cytokinin, While Proliferation Is Stimulated by Anti-Ethylene and Pruning: Transcriptome Responses
Authors: Oluwasanya Deborah , Esan Olayemisi , Hyde Peter T. , Kulakow Peter , Setter Tim L.
Published: May 2021

Cassava, a tropical storage-root crop, is a major source of food security for millions in the tropics. Cassava breeding, however, is hindered by the poor development of flowers and a low ratio of female flowers to male flowers. To advance the understanding of the mechanistic factors regulating cassava flowering, combinations of plant growth regulators (PGRs) and pruning treatments were examined for their effectiveness in improving flower production and fruit set in field conditions. Pruning the fork-type branches, which arise at the shoot apex immediately below newly formed inflorescences, stimulated inflorescence and floral development. The anti-ethylene PGR silver thiosulfate (STS) also increased flower abundance. Both pruning and STS increased flower numbers while having minimal influence on sex ratios. In contrast, the cytokinin benzyladenine (BA) feminized flowers without increasing flower abundance. Combining pruning and STS treatments led to an additive increase in flower abundance; with the addition of BA, over 80% of flowers were females. This three-way treatment combination of pruning+STS+BA also led to an increase in fruit number. Transcriptomic analysis of gene expression in tissues of the apical region and developing inflorescence revealed that the enhancement of flower development by STS+BA was accompanied by downregulation of several genes associated with repression of flowering, including homologs of TEMPRANILLO1 (TEM1), GA receptor GID1b, and ABA signaling genes ABI1 and PP2CA. We conclude that flower-enhancing treatments with pruning, STS, and BA create widespread changes in the network of hormone signaling and regulatory factors beyond ethylene and cytokinin.
Sedentary Plant-Parasitic Nematodes Alter Auxin Homeostasis via Multiple Strategies
Authors: Oosterbeek Matthijs , Lozano-Torres Jose L. , Bakker Jaap , Goverse Aska
Published: May 2021

Sedentary endoparasites such as cyst and root-knot nematodes infect many important food crops and are major agro-economical pests worldwide. These plant-parasitic nematodes exploit endogenous molecular and physiological pathways in the roots of their host to establish unique feeding structures. These structures function as highly active transfer cells and metabolic sinks and are essential for the parasites’ growth and reproduction. Plant hormones like indole-3-acetic acid (IAA) are a fundamental component in the formation of these feeding complexes. However, their underlying molecular and biochemical mechanisms are still elusive despite recent advances in the field. This review presents a comprehensive overview of known functions of various auxins in plant-parasitic nematode infection sites, based on a systematic analysis of current literature. We evaluate multiple aspects involved in auxin homeostasis in plants, including anabolism, catabolism, transport, and signalling. From these analyses, a picture emerges that plant-parasitic nematodes have evolved multiple strategies to manipulate auxin homeostasis to establish a successful parasitic relationship with their host. Additionally, there appears to be a potential role for auxins other than IAA in plant-parasitic nematode infections that might be of interest to be further elucidated.