bluuebunny/crossref_metadata_2025 huggingface dataset:
Pediatric acute liver failure: An experience of a pediatric intensive care unit from resource limited settings
Authors: Amatya Puja , Kapalavai Sudeep Kumar , Deep Akash , Sankaranarayanan Srinivas , Krupanandan Ravikumar , Sadasivam Kalaimaran , Ramachandran Bala
Published: September 2022

Introduction

Pediatric acute liver failure is a rare and serious disease. Though liver transplantation is considered as the established treatment option for patients who are unlikely to recover with medical management, however, with the advancement of medical care there has been an increase in spontaneous regeneration of liver, obviating the need for liver transplantation. We identified the etiologies, outcome and prognostic factors of acute liver failure and the validity of the existing liver transplantation criteria to predict the outcome of pediatric acute liver failure.

Materials and methods

This was a retrospective study done from January 2014 to December 2019 in a tertiary pediatric critical care unit in South India. All children aged between 1 month to 18 years admitted with acute liver failure were enrolled.

Results

Of 125 children with acute liver failure, the main etiologies were infections (32%), indeterminate (23%), paracetamol toxicity (21%), metabolic (13%) and others (11%). Dengue was the most common infection (55%). The median pediatric logistic organ dysfunction score at admission was 12 (4–27). Of 125 patients, 63.2% (n = 79) had spontaneous regeneration which was higher in paracetamol induced (92.3%) compared to non-paracetamol induced acute liver failure (55.5%). Only two patients underwent liver transplantation and 35% died. Peak alanine transaminase and use of inotropes significantly predicted the outcome of disease. Of 38 children meeting King's College Hospital criteria for liver transplantation, 57.9% had spontaneous regeneration and 36.8% died. Of 74 children meeting INR > 4 criteria, 54% (n = 40) had spontaneous regeneration and 43.2% died. INR >4 criteria was more sensitive than King's College Hospital criteria for predicting the need for liver transplantation.

Conclusion

Pediatric acute liver failure is caused by varied etiologies and infections were the commonest cause. Despite having a seriously ill cohort of patients, medical management resulted in spontaneous regeneration in the majority of children with acute liver failure. The use of inotropes, advanced hepatic encephalopathy, and peak alanine transaminase were predictors of poor outcome in children with acute liver failure and these patients could be considered for liver transplantation as available. Therefore, we may need to develop better predictors of pediatric acute liver failure in resource limited settings.
Experimental and clinical progress of in utero hematopoietic cell transplantation therapy for congenital disorders
Authors: Shi Chunyu , Pan Lu , Hu Zheng
Published: September 2022

In utero hematopoietic cell transplantation (IUHCT) is considered a potentially efficient therapeutic approach with relatively few side effects, compared to adult hematopoietic cell transplantation, for various hematological genetic disorders. The principle of IUHCT has been extensively studied in rodent models and in some large animals with close evolutionary similarities to human beings. However, IUHCT has only been used to rebuild human T cell immunity in certain patients with inherent immunodeficiencies. This review will first summarize the animal models utilized for IUHCT investigations and describe the associated outcomes. Recent advances and potential barriers for successful IUHCT are discussed, followed by possible strategies to overcome these barriers experimentally. Lastly, we will outline the progress made towards utilizing IUHCT to treat inherent disorders for patients, list out associated limitations and propose feasible means to promote the efficacy of IUHCT clinically.
Therapeutic potential of tucidinostat, a subtype-selective HDAC inhibitor, in cancer treatment
Authors: Sun Yichen , Hong Jing Han , Ning Zhiqiang , Pan Desi , Fu Xin , Lu Xianping , Tan Jing
Published: September 2022

Histone deacetylase (HDAC) is one of the most characterized epigenetic modifiers, modulating chromatin structure and gene expression, which plays an important role in cell cycle, differentiation and apoptosis. Dysregulation of HDAC promotes cancer progression, thus inhibitors targeting HDACs have evidently shown therapeutic efficacy in multiple cancers. Tucidinostat (formerly known as chidamide), a novel subtype-selective HDAC inhibitor, inhibits Class I HDAC1, HDAC2, HDAC3, as well as Class IIb HDAC10. Tucidinostat is approved in relapsed or refractory (R/R) peripheral T-cell lymphoma (PTCL), advanced breast cancer and R/R adult T-cell leukemia-lymphoma (ATLL). Compared with other HDAC inhibitors, tucidinostat shows notable antitumor activity, remarkable synergistic effect with immunotherapy, and manageable toxicity. Here, we comprehensively summarize recent advances in tucidinostat as both monotherapy and a regimen of combination therapy in both hematological and solid malignancies in clinic. Further studies will endeavor to identify more combination strategies with tucidinostat and to identify specific clinical biomarkers to predict the therapeutic effect.
Reduced activity of adenylyl cyclase 1 attenuates morphine induced hyperalgesia and inflammatory pain in mice
Authors: Johnson Kayla , Doucette Alexis , Edwards Alexis , Verdi Aleeya , McFarland Ryan , Hulke Shelby , Fowler Amanda , Watts Val J. , Klein Amanda H.
Published: September 2022

Opioid tolerance, opioid-induced hyperalgesia during repeated opioid administration, and chronic pain are associated with upregulation of adenylyl cyclase activity. The objective of this study was to test the hypothesis that a reduction in adenylyl cyclase 1 (AC1) activity or expression would attenuate morphine tolerance and hypersensitivity, and inflammatory pain using murine models. To investigate opioid tolerance and opioid-induced hyperalgesia, mice were subjected to twice daily treatments of saline or morphine using either a static (15 mg/kg, 5 days) or an escalating tolerance paradigm (10–40 mg/kg, 4 days). Systemic treatment with an AC1 inhibitor, ST03437 (2.5–10 mg/kg, IP), reduced morphine-induced hyperalgesia in mice. Lumbar intrathecal administration of a viral vector incorporating a short-hairpin RNA targeting Adcy1 reduced morphine-induced hypersensitivity compared to control mice. In contrast, acute morphine antinociception, along with thermal paw withdrawal latencies, motor performance, exploration in an open field test, and burrowing behaviors were not affected by intrathecal Adcy1 knockdown. Knockdown of Adcy1 by intrathecal injection also decreased inflammatory mechanical hyperalgesia and increased burrowing and nesting activity after intraplantar administration of Complete Freund’s Adjuvant (CFA) one-week post-injection.
Effectiveness of red yeast rice on carotid atherosclerosis: A systematic review and meta-analysis
Authors: Wang Shuai , Chen Yue , Wang Rui , Ma Bailing , Wang Zhenzhen , Tang Guanguang , Wang Siyu , He Yi , Qu Liping
Published: September 2022

While several studies have demonstrated the preventive and therapeutic effects of red yeast rice (RYR), a traditional Chinese medicine, on carotid atherosclerosis through the reduction of low-density lipoprotein cholesterol (LDL-C) level and other risk factors, the evidence remains inconsistent. This study aimed to further evaluate the effects of RYR in carotid atherosclerosis. Several databases were searched for original trials of RYR for the treatment of carotid atherosclerosis that reported plaque indicators. Carotid plaque area (AREA), carotid plaque score (SCORE), and intima-media thickness (IMT) were set as the primary outcomes, while lipid profile and safety indicators were set as the secondary outcomes. Meta-analyses were performed on the randomized controlled trials (RCTs) using Comprehensive Meta-analysis software. Heterogeneity was evaluated using the I2 index and Q statistic. Subgroup, sensitivity, and dose-effect analyses were conducted. Twenty RCTs with 2217 patients were included. Compared to the control group, AREA (SMD = −0.855, 95%CI: −1.259 to −0.451, p < 0.001), IMT (SMD = −0.588, 95%CI: −0.792 to −0.384, p < 0.001), SCORE (SMD = −0.708, 95%CI: −1.135 to −0.282, p = 0.001), LDL-C (SMD = −0.938, 95%CI: −1.375 to −0.502, p < 0.001), triglyceride (SMD = −0.766, 95%CI: −0.980 to −0.551, p < 0.001), and total cholesterol (SMD = −0.858, 95%CI: −1.254 to −0.462, p < 0.001) were significantly decreased and HDL-C (SMD = 0.389, 95%CI: 0.044–0.733, p = 0.027) was significantly increased following RYR therapy. The indicators for safety were not significant and did not differ between the two groups (p > 0.050). Heterogeneities mainly existed for the treatment time or control group setting. Most results showed no changes in the sensitivity analysis. Dose-effect relationships were observed for all indicators except for TC and HDL-C. We concluded that RYR therapy showed considerable efficacy and an acceptable safety profile for the treatment of carotid atherosclerosis in the Chinese population.
Effect of safranal on the response of cancer cells to topoisomerase I inhibitors: Does sequence matter?
Authors: Lozon Lama , Saleh Ekram , Menon Varsha , Ramadan Wafaa S. , Amin Amr , El-Awady Raafat
Published: September 2022

Lung and colorectal cancers are among the leading causes of death from cancer worldwide. Although topotecan (TPT), a topoisomerase1 inhibitor, is a first- and second-line drug for lung and colon cancers, the development of drug resistance and toxicity still remain as a major obstacle to chemotherapeutic success. Accumulating evidence indicates increased efficacy and reduced toxicity of chemotherapeutic agents upon combining them with natural products. We aimed to investigate the possible interaction of safranal (SAF), a natural compound obtained from Crocus sativus stigma, with TPT when used in different sequences in colon and lung cancer cell lines. The growth inhibitory effect of the proposed combination given in different sequences was assessed using the colony formation assay. The comet assay, cell cycle distribution, Annexin-V staining, and expression of proteins involved in DNA damage/repair were utilized to understand the mechanism underlying the effect of the combination. SAF enhanced the growth inhibitory effects of TPT particularly when it was added to the cells prior to TPT. This combination increased the double-strand break induction and dysregulated the DNA repair machinery, particularly the tyrosyl-DNA phosphodiesterase 1 enzyme. In addition, the SAF + TPT combination increased the fraction of cells arrested at the G2/M checkpoint as well as enhanced the induction of apoptosis. The current study highlights the status of SAF as a natural product sensitizing the lung and colon cancer cells to the cytotoxic effects of the anticancer drug TPT. In addition, it emphasizes the importance of sequence-dependent interaction which can affect the overall outcome.
KangPiLao decoction modulates cognitive and emotional disorders in rats with central fatigue through the GABA/Glu pathway
Authors: Xu Yifei , Lian Yajun , Li Jie , Zhang Yifei , Liu Yan , Wang Xuejiao , Ma Jie , Li Feng
Published: September 2022

Background: Central fatigue (CF) is a subjective sense of tiredness associated with cognitive and memory disorders, accompanied by reduced physical endurance and negative emotions, such as anxiety and depression. Disease progression and prognosis with regards to CF have been unfavorable and possibly contribute to dementia, schizophrenia, and other diseases. Additionally, effective treatments for CF are lacking. KangPiLao decoction (KPLD) has been widely applied in clinical treatment and is composed of six Chinese herbal medicines, some of which have confirmed anti-fatigue effects. While glutamic acid (Glu) is the main excitatory transmitter in the central nervous system (CNS), gamma-aminobutyric acid (GABA) is the major inhibitory transmitter. Both are involved in emotional, cognitive, and memory functions. This research was designed to explore how KPLD regulates cognitive and emotional disorders in rats with CF and to identify the relationship between the regulatory effect and the GABA/Glu pathway.

Methods: The compounds comprising KPLD were analyzed using high-performance liquid chromatography-mass spectrometry. Sixty Wistar rats were randomly divided into six groups. The modified multiple platform method was used to induce CF. Cognitive, emotional, and fatigue states were evaluated by performing behavioral tests (Morris water maze [MWM], open-field test [OFT], and grip strength test). Histomorphology, western blotting, immunohistochemistry, and RT-qPCR were performed to investigate protein and mRNA expression levels in the hippocampus and prefrontal cortexes involved in the GABA/Glu pathway.

Results: Rats with CF exhibited impaired spatial cognition and increased negative emotions in the MWM and OFT. KPLD enabled the improvement of these symptoms, especially in the high-concentration group. Western blotting and RT-qPCR demonstrated that the expression of GABAARα1, GABAARγ2, GABABR1, and GAD67 in rats with CF was higher, whereas GAT-1 and NMDAR2B were lower in the hippocampus and prefrontal cortex. KPLD decreased the expression of GABAARα1, GABABR1, GABAARγ2, and GAD67 in the hippocampus and prefrontal cortex and enhanced the expression of NR2B in the prefrontal cortex.

Conclusion: KPLD significantly improved cognitive and emotional disorders in rats with CF by regulating the GABA/Glu pathway. Overall, KPLD may be a promising candidate for developing a drug for treating CF.
Efficacy and safety of a Chinese herbal formula Maxing Ganshi Decoction in children with community-acquired pneumonia: A randomized, double-blind, placebo-controlled, multicenter trial
Authors: Zheng Yujiao , Shi Changren , Han Yaowei , Li Xinmin , Dong Lijing , Li Yan , Chen Hui , Wang Yushui , Li Jinsong , Liu Geli , Ma Rong , Lian Fengmei , Tong Xiaolin
Published: September 2022

Background: As one of the most commonly used Chinese medicine formula in the manage of respiratory diseases, Maxing Ganshi Decoction (MGD) has been demonstrated to improve the clinical symptoms of pneumonia. To evaluate the efficacy and safety of MGD in treating children with community-acquired pneumonia (CAP), we conducted the clinical trial.

Methods: A randomized, double-blind, placebo-controlled, multicenter trial was conducted in 3 study sites in Tianjin, China. MDG or placebo were randomly given to patients aged 3–6 years with onset of CAP within 48 h. Changes in disease efficacy during the study period (which was measured as recovery, significant effect, improvement and no effect) was evaluated as the primary outcome. Time from enrollment to fever resolution was assessed as the secondary outcome. The adverse event was analyzed as safety evaluation.

Results: A total of 71 patients (36 in MGD and 35 in placebo) were randomized and completed the whole study. The patient demographics and other characteristics at baseline were similar between the 2 groups (p > 0.05). After 10 days of intervention, the proportion of recovered and significant effective patients was increased significantly in the MGD group (34.85% [95% CI, 12.44%–57.26%]; p < 0.05) compared with the control group. Besides, the symptom score of the MGD group was lowered significantly (p < 0.001). The estimated time to fever resolution in the MGD group was also reduced compared with the control group (p < 0.05). During the whole study, no side effects were observed in both MGD and control groups.

Conclusion: MGD was effective in improving disease efficacy, clinical symptoms and reducing time to fever resolution in patients with childhood CAP, which suggested that MGD may be used as an alternative therapy in the treatment of childhood CAP.

Clinical Trial Registration: http://www.chictr.org.cn/showproj.aspx?proj=5612, identifier 13003955.
Performance of a pharmaceutical services regionalization strategy policy in Minas Gerais, Brazil: Pre-post analysis from ERAF project
Authors: Luz Tatiana Chama Borges , Castro Ana Karine Sarvel de , Marques Isabela Cristina , Cota Betania Barros , Alves Jèssica de Castro , Law Michael Robert
Published: September 2022

Background: In 2016, the Brazilian state of Minas Gerais (∼20 million people), implemented the ERAF policy (“Regionalization Strategy of Pharmaceutical Services”) in an effort to improve medicine procurement and distribution within primary care. We evaluated the impact of the policy on three main goals: price reductions, volume increases, and expansion of therapeutic options.

Methods: We analyzed the procurement data from the Integrated System of Management of Pharmaceutical Services database in 2012 and 2018. We estimated the volume, drug mix, and expenditure indicators for all major therapeutic classes, and, in detail, for cardiovascular and nervous system drugs. We evaluated the expenditure drivers using decomposition analyses.

Results: Overall, the expenditure increased by 14.5%, drug mix almost doubled, while the volume decreased by a third. Cardiovascular and neurological system drugs followed similar patterns. Decomposition analyses showed that prices and drug mix had positive effects while the volume had negative effects, resulting in an overall increase in expenditure.

Conclusion: Our findings suggest that the ERAF policy cannot be considered effective as it has not fulfilled its intended purposes so far. Strategies to address the identified problems and to build a platform for a more sustainable long-lasting policy should be put in place by the government.
Study on the mechanism of American ginseng extract for treating type 2 diabetes mellitus based on metabolomics
Authors: Liu Tiantian , Wang Dan , Zhou Xinfeng , Song Jiayin , Yang Zijun , Shi Chang , Li Rongshan , Zhang Yanwen , Zhang Jun , Yan Jiuxing , Zhu Xuehui , Li Ying , Gong Min , Wang Chongzhi , Yuan Chunsu , Cui Yan , Wu Xiaohui
Published: September 2022

American ginseng extract (AGE) is an efficient and low-toxic adjuvant for type 2 diabetes mellitus (T2DM). However, the metabolic mechanisms of AGE against T2DM remain unknown. In this study, a rat model of T2DM was created and administered for 28 days. Their biological (body weight and serum biochemical indicators) and pathological (pancreatic sections stained with HE) information were collected for further pharmacodynamic evaluation. Moreover, an ultra-performance liquid chromatography–mass spectrometry–based (UHPLC–MS/MS–based) untargeted metabolomics method was used to identify potential biomarkers of serum samples from all rats and related metabolic pathways. The results indicated that body weight, fasting blood glucose (FBG), fasting blood insulin (FINS), blood triglyceride concentration (TG), high-density lipoprotein cholesterol (HDL-C), insulin resistance index (HOMA-IR) and insulin sensitivity index (ISI), and impaired islet cells were significantly improved after the high dose of AGE (H_AGE) and metformin treatment. Metabolomics analysis identified 101 potential biomarkers among which 94 metabolites had an obvious callback. These potential biomarkers were mainly enriched in nine metabolic pathways linked to amino acid metabolism and lipid metabolism. Tryptophan metabolism and glutathione metabolism, as differential metabolic pathways between AGE and metformin for treating T2DM, were further explored. Further analysis of the aforementioned results suggested that the anti-T2DM effect of AGE was closely associated with inflammation, oxidative stress, endothelial dysfunction, dyslipidemia, immune response, insulin resistance, insulin secretion, and T2DM-related complications. This study can provide powerful support for the systematic exploration of the mechanism of AGE against T2DM and a basis for the clinical diagnosis of T2DM.
Mechanism of hydroxysafflor yellow A on acute liver injury based on transcriptomics
Authors: Hou Xiangmei , Zhang Ziying , Ma Yuehong , Jin Rong , Yi Bing , Yang Dongdong , Ma Lijie
Published: September 2022

Objective: To investigate how Hydroxysafflor yellow A (HSYA) effects acute liver injury (ALI) and what transcriptional regulatory mechanisms it may employ.

Methods: Rats were randomly divided into five groups (n = 10): Control, Model, HSYA-L, HSYA-M, and HSYA-H. In the control and model groups, rats were intraperitoneally injected with equivalent normal saline, while in the HSYA groups, they were also injected with different amounts of HSYA (10, 20, and 40 mg/kg/day) once daily for eight consecutive days. One hour following the last injection, the control group was injected into the abdominal cavity with 0.1 ml/100 g of peanut oil, and the other four groups got the same amount of a peanut oil solution containing 50% CCl4. Liver indexes were detected in rats after dissection, and hematoxylin and eosin (HE) dyeing was utilized to determine HSYA’s impact on the liver of model rats. In addition, with RNA-Sequencing (RNA-Seq) technology and quantitative real-time PCR (qRT-PCR), differentially expressed genes (DEGs) were discovered and validated. Furthermore, we detected the contents of anti-superoxide anion (anti-O2−) and hydrogen peroxide (H2O2), and verified three inflammatory genes (Icam1, Bcl2a1, and Ptgs2) in the NF-kB pathway by qRT-PCR.

Results: Relative to the control and HSYA groups, in the model group, we found 1111 DEGs that were up-/down-regulated, six of these genes were verified by qRT-PCR, including Tymp, Fabp7, Serpina3c, Gpnmb, Il1r1, and Creld2, indicated that these genes were obviously involved in the regulation of HSYA in ALI model. Membrane rafts, membrane microdomains, inflammatory response, regulation of cytokine production, monooxygenase activity, and iron ion binding were significantly enriched in GO analysis. KEGG analysis revealed that DEGs were primarily enriched for PPAR, retinol metabolism, NF-kB signaling pathways, etc. Last but not least, compared with the control group, the anti-O2− content was substantially decreased, the H2O2 content and inflammatory genes (Icam1, Bcl2a1, and Ptgs2) levels were considerably elevated in the model group. Compared with the model group, the anti-O2− content was substantially increased, the H2O2 content and inflammatory genes (Icam1, Bcl2a1, and Ptgs2) levels were substantially decreased in the HSYA group (p < 0.05).

Conclusion: HSYA could improve liver function, inhibit oxidative stress and inflammation, and improve the degree of liver tissue damage. The RNA-Seq results further verified that HSYA has the typical characteristics of numerous targets and multiple pathway. Protecting the liver from damage by regulating the expression of Tymp, Fabp7, Serpina3c, Gpnmb, Il1r1, Creld2, and the PPAR, retinol metabolism, NF-kappa B signaling pathways.
Neferine alleviates chronic stress-induced depression by regulating monoamine neurotransmitter secretion and gut microbiota structure
Authors: Dong Zaiquan , Xie Qinglian , Xu Feiyu , Shen Xiaoling , Hao Yanni , Li Jin , Xu Haizhen , Peng Qiang , Kuang Weihong
Published: September 2022

Neferine (Nef) might possess anti-depressive properties; however, its therapeutic effects are yet to be elucidated. Therefore, in this study, we aimed to explore the anti-depressant property of Nef using a mouse model of chronic stress-induced depression. Fifteen depression-prone mice were randomly selected and divided into three groups, namely, the model, Nef, and fluoxetine (Flu) groups. We observed that in tail suspension and forced swimming tests, the Nef and Flu treatments significantly decreased the immobility time of the depressed mice, and increased their sucrose preference indices. Moreover, both Nef and Flu treatments induced significant increases in the levels of anti-depressant neurotransmitters, including dopamine (DA), serotonin (5-HT), and norepinephrine (NE), and also reduced pathological damage to the hippocampus of the depressed mice. Incidentally, Illumina MiSeq sequencing analysis demonstrated that the relative abundance of Lactobacillus in the intestinal microbiota of depressed mice was restored after Nef/Flu treatment. Moreover, colonic Lactobacillus abundance was positively correlated with the levels of DA, 5-HT, and NE in the hippocampus of the mice. In conclusion, Nef improved monoamine neurotransmitter secretion and modulated the intestinal flora structure, particularly the abundance of Lactobacillus. Hence, it showed considerable anti-depressant potential, and might be a prospective anti-depressant therapeutic agent.
Nicotine self-administration and ERK signaling are altered in RasGRF2 knockout mice
Authors: Morella Ilaria , Pohořalá Veronika , Calpe-López Claudia , Brambilla Riccardo , Spanagel Rainer , Bernardi Rick E.
Published: September 2022

Ras/Raf/MEK/ERK (Ras-ERK) signaling has been demonstrated to play a role in the effects of drugs of abuse such as cocaine and alcohol, but has not been extensively examined in nicotine-related reward behaviors. We examined the role of Ras Guanine Nucleotide Releasing Factor 2 (RasGRF2), an upstream mediator of the Ras-ERK signaling pathway, on nicotine self-administration (SA) in RasGRF2 KO and WT mice. We first demonstrated that acute nicotine exposure (0.4 mg/kg) resulted in an increase in phosphorylated ERK1/2 (pERK1/2) in the striatum, consistent with previous reports. We also demonstrated that increases in pERK1/2 resulting from acute (0.4 mg/kg) and repeated (0.4 mg/kg, 10 daily injections) exposure to nicotine in WT mice were not present in RasGRF2 KO mice, confirming that RasGRF2 at least partly regulates the activity of the Ras-ERK signaling pathway following nicotine exposure. We then performed intravenous nicotine SA (0.03 mg/kg/infusion for 10 days) in RasGRF2 KO and WT mice. Consistent with a previous report using cocaine SA, RasGRF2 KO mice demonstrated an increase in nicotine SA relative to WT controls. These findings suggest a role for RasGRF2 in the reinforcing effects of nicotine, and implicate the Ras-ERK signaling pathway as a common mediator of the response to drugs of abuse.
Salvia chinensia Benth induces autophagy in esophageal cancer cells via AMPK/ULK1 signaling pathway
Authors: Jia Lei , Lin Xin-Rong , Guo Wen-Yan , Huang Ming , Zhao Yang , Zhang Yu-Shuang , Li Jing
Published: September 2022

Salvia chinensia Benth (Shijianchuan in Chinese, SJC) has been used as a traditional anti-cancer herb. SJC showed good anti-esophageal cancer efficacy based on our clinical application. However, the current research on SJC is minimal, and its anti-cancer effect lacks scientific certification. This study aims to clarify the inhibitory effect of SJC on esophageal cancer and explore its underlying mechanism. Q-Orbitrap high-resolution LC/MS was used to identify the primary chemical constituents in SJC. Cell proliferation and colony formation assays showed that SJC could effectively inhibit the growth of esophageal tumor cells in vitro. To clarify its mechanism of action, proteomic and bioinformatic analyses were carried out by combining tandem mass labeling and two-dimensional liquid chromatography-mass spectrometry (LC-MS). Data are available via ProteomeXchange with identifier PXD035823. The results indicated that SJC could activate AMPK signaling pathway and effectively promote autophagy in esophageal cancer cells. Therefore, we further used western blotting to confirm that SJC activated autophagy in esophageal cancer cells through the AMPK/ULK1 signaling pathway. The results showed that P-AMPK and P-ULK1 were significantly up-regulated after the treatment with SJC. The ratio of autophagosomes marker proteins LC3II/I was significantly increased. In addition, the expression of the autophagy substrate protein P62 decreased with the degradation of autophagosomes. Using lentiviral transfection of fluorescent label SensGFP-StubRFP-LC3 protein and revalidation of LC3 expression before and after administration by laser confocal microscopy. Compared with the control group, the fluorescence expression of the SJC group was significantly enhanced, indicating that it promoted autophagy in esophageal cancer cells. Cell morphology and the formation of autophagosomes were observed by transmission electron microscopy. Our study shows that the tumor suppressor effect of SJC is related to promoting autophagy in esophageal tumor cells via the AMPK/ULK1 signaling pathway.
Characteristics analysis of compact cesium atomic clock with magnetic state selection
Authors: Chen Jiang , Wang Ji , Guo Lei , Yang Jun , Ma Pei , Huang Liangyu , Liu Zhidong
Published: September 2022

This paper introduces a compact magnetic state-selection cesium atomic clock called LIP Cs-3000 and analyses its characteristics. The test results reveal that the ranges of the line width, peak-to-valley ratio and signal-to-noise ratio of Ramsey pattern are 340–410 Hz, 2–13 and 2,000–8,000 respectively. The corresponding distributions of these parameters are derived by using statistical methods. According to these results, some suggestions are put forward for the further development of the clock. It is also pointed out that the most important factor affecting the accuracy of LIP Cs-3000 atomic clock is the uncertainty of cavity phase shift. In addition, the method to estimate the lifetime of a clock has been proposed. In the end, the paper gives some environmental adaptability designs of the clock, which enable the clock to be used in complex environments.
Solutions of the Schrodinger equation of the shifted screened Kratzer potential and its thermodynamic functions using the extended Nikiforov–Uvarov method
Authors: Ibrahim Nuhu , Okorie Uduakobong Sunday , Sulaiman Nidhal , Rampho Gaotsiwe Joel , Ramantswana Morris
Published: September 2022

By employing the extended Nikiforov–Uvarov (ENU) method, we solved the radial Schrodinger equation with the shifted screened Kratzer potential model. The analytical expression of the energy eigenvalues and numerical results were determined for some selected diatomic molecule systems. Variations of the energy eigenvalues obtained with potential parameters and quantum numbers were discussed graphically. Also, variations of different thermodynamic properties with temperature and maximum vibration quantum numbers were discussed extensively. Our results correspond to the results obtained in the literatures. The shifting parameters contribute a great effect to the energy results obtained. It has also been established that there exists a critical temperature at specific entropy values for the selected diatomic molecule systems.
Overexpression of a ceramide synthase gene,GhCS1, inhibits fiber cell initiation and elongation by promoting the synthesis of ceramides containing dihydroxy LCB and VLCFA
Authors: Li Guiming , Wang Qiaoling , Meng Qian , Wang Guanhua , Xu Fan , Chen Qian , Liu Fang , Hu Yulin , Luo Ming
Published: September 2022

Cotton is an important natural fiber crop worldwide. Cotton fiber cell is regarded as an ideal material for studying the growth and development of plant cells. Sphingolipids are important components of biomembrane and bioactive molecules which participate in many processes such as plant growth, development regulation, stimulus sensing, and stress response. However, the functions of sphingolipids in the cotton fiber development are still unclear. In the present study, we identified a cotton ceramide synthase gene, GhCS1, which is predominantly expressed in fiber cell. The GhCS1 is located in the endoplasmic reticulum and has the conserved domains of ceramide synthase. Overexpression of GhCS1 gene inhibited both vegetative and reproductive growth in cotton. Importantly, the fiber cell initiation and elongation were severely inhibited when compared with control. Comparison of the sphingolipid profile in the 0-DPA (days past anthesis) ovule (with fiber cell) between control and transgenic cotton plants showed that the content of sphingosines (Sph) decreased significantly in transgenic ovules, whereas the content of phyto-sphingosines (Phyto-Sph) had no change. Meanwhile, the content of ceramide containing Sph and very-long-chain fatty acid (VLCFA) increased significantly in transgenic ovules, while ceramide containing Phyto-Sph and long-chain fatty acids (LCFA)/VLCFA significantly decreased. These results indicated that GhCS1 was a functional ceramide synthase, which preferentially used Sph and VLCFA as substrates and was different from the Arabidopsis ceramide synthase AtLOH1/AtLOH3, which preferentially used Phyto-Sph and VLCFA as substrates, and also different from AtLOH2, which preferentially used Sph and LCFA as substrates. It is suggested that GhCS1 might be a new ceramide synthase gene in the plant, play some roles in the development of fiber cells and cotton plants.
Using machine learning to link the influence of transferred Agrobacterium rhizogenes genes to the hormone profile and morphological traits in Centella asiatica hairy roots
Authors: Alcalde Miguel Angel , Müller Maren , Munné-Bosch Sergi , Landín Mariana , Gallego Pedro Pablo , Bonfill Mercedes , Palazon Javier , Hidalgo-Martinez Diego
Published: September 2022

Hairy roots are made after the integration of a small set of genes from Agrobacterium rhizogenes in the plant genome. Little is known about how this small set is linked to their hormone profile, which determines development, morphology, and levels of secondary metabolite production. We used C. asiatica hairy root line cultures to determine the putative links between the rol and aux gene expressions with morphological traits, a hormone profile, and centelloside production. The results obtained after 14 and 28 days of culture were processed via multivariate analysis and machine-learning processes such as random forest, supported vector machines, linear discriminant analysis, and neural networks. This allowed us to obtain models capable of discriminating highly productive root lines from their levels of genetic expression (rol and aux genes) or from their hormone profile. In total, 12 hormones were evaluated, resulting in 10 being satisfactorily detected. Within this set of hormones, abscisic acid (ABA) and cytokinin isopentenyl adenosine (IPA) were found to be critical in defining the morphological traits and centelloside content. The results showed that IPA brings more benefits to the biotechnological platform. Additionally, we determined the degree of influence of each of the evaluated genes on the individual hormone profile, finding that aux1 has a significant influence on the IPA profile, while the rol genes are closely linked to the ABA profile. Finally, we effectively verified the gene influence on these two specific hormones through feeding experiments that aimed to reverse the effect on root morphology and centelloside content.
Humanization and expression of IgG and IgM antibodies in plants as potential diagnostic reagents for Valley Fever
Authors: Jugler Collin , Grill Francisca J. , Eidenberger Lukas , Karr Timothy L. , Grys Thomas E. , Steinkellner Herta , Lake Douglas F. , Chen Qiang
Published: September 2022

Monoclonal antibodies (mAbs) are important proteins used in many life science applications, from diagnostics to therapeutics. High demand for mAbs for different applications urges the development of rapid and reliable recombinant production platforms. Plants provide a quick and inexpensive system for producing recombinant mAbs. Moreover, when paired with an established platform for mAb discovery, plants can easily be tailored to produce mAbs of different isotypes against the same target. Here, we demonstrate that a hybridoma-generated mouse mAb against chitinase 1 (CTS1), an antigen from Coccidioides spp., can be biologically engineered for use with serologic diagnostic test kits for coccidioidomycosis (Valley Fever) using plant expression. The original mouse IgG was modified and recombinantly produced in glycoengineered Nicotiana benthamiana plants via transient expression as IgG and IgM isotypes with human kappa, gamma, and mu constant regions. The two mAb isotypes produced in plants were shown to maintain target antigen recognition to CTS1 using similar reagents as the Food and Drug Administration (FDA)-approved Valley Fever diagnostic kits. As none of the currently approved kits provide antibody dilution controls, humanization of antibodies that bind to CTS1, a major component of the diagnostic antigen preparation, may provide a solution to the lack of consistently reactive antibody controls for Valley Fever diagnosis. Furthermore, our work provides a foundation for reproducible and consistent production of recombinant mAbs engineered to have a specific isotype for use in diagnostic assays.
RNA sequencing and weighted gene co-expression network analysis uncover the hub genes controlling cold tolerance in Helictotrichon virescens seedlings
Authors: Cheng Mingjun , Pan Zeyang , Cui Kuoshu , Zheng Junjun , Luo Xuan , Chen Youjun , Yang Tao , Wang Hui , Li Xiaofeng , Zhou Yang , Lei Xiong , Li Yingzheng , Zhang Ruizhen , Iqbal Muhammad Zafar , He Ruyu
Published: September 2022

Helictotrichon virescens is a perennial herbaceous plant with a life expectancy of about 10 years. It has high cold and heat resistance and can successfully survive over winter in the habitats with a temperature range of −25 to 25°C. Therefore, this study aimed to identify the key genes regulating low-temperature stress responses in H. virescens and analyze cold tolerant at molecular level. This study used RNA sequencing (RNA-Seq) and weighted gene co-expression network analysis (WGCNA) to identify the hub genes associated with cold tolerance in H. virescens. RT-PCR was conducted, homologous genes were identified, and related bioinformatics were analyzed to verify the identified hub genes. Moreover, WGCNA analysis showed that only the brown module had the highest correlation with the active-oxygen scavenging enzymes [peroxide (POD), superoxide dismutase (SOD), and catalase (CAT)]. The expression levels of three hub genes in the brown module (Cluster-37118.47362, cluster-37118.47713, and cluster-37118.66740) were significantly higher under low-temperature stress than those under control conditions. Furthermore, gene ontology (GO) and KEGG annotations showed that the three hub genes were mainly enriched in the metabolism pathways of sphingolipids, selenocompounds, glyoxylate, and dicarboxylate, carotenoids biosynthesis, and other biological pathways. The results of this study also showed that the subcellular localization prediction results showed that the cold tolerance hub genes were all localized to the plasma membrane. By constructing a protein interaction network, it was found that the hub gene Cluster-37118.66740 interacted with Sb09g003460.1 and Sb04g020180.1 proteins in Sorghum bicolor. By constructing phylogenetic trees of the four species of H. virescens, Sorghum bicolo, Oryza sativa Japonica, and Arabidopsis thaliana, the results showed that, the hub gene Cluster 37118.66740 (of H. virescens) and Os03g0340500 (of Oryza sativa Japonica) belonged to the same ancestral branch and were in the same subfamily. Thus, this study provides methodology and guidance to identify the cold tolerance genes for other herbage and their cold tolerant molecular mechanisms at molecular level.
Optimizing water and nitrogen productivity of wheat and triticale across diverse production environments to improve the sustainability of baked products
Authors: Tamagno Santiago , Pittelkow Cameron M. , Fohner George , Nelsen Taylor S. , Hegarty Joshua M. , Carter Claudia E. , Vang Teng , Lundy Mark E.
Published: September 2022

Wheat (Triticum aestivum L.) is a major global commodity and the primary source for baked products in agri-food supply chains. Consumers are increasingly demanding more nutritious food products with less environmental degradation, particularly related to water and fertilizer nitrogen (N) inputs. While triticale (× Triticosecale) is often referenced as having superior abiotic stress tolerance compared to wheat, few studies have compared crop productivity and resource use efficiencies under a range of N-and water-limited conditions. Because previous work has shown that blending wheat with triticale in a 40:60 ratio can yield acceptable and more nutritious baked products, we tested the hypothesis that increasing the use of triticale grain in the baking supply chain would reduce the environmental footprint for water and N fertilizer use. Using a dataset comprised of 37 site-years encompassing normal and stress-induced environments in California, we assessed yield, yield stability, and the efficiency of water and fertilizer N use for 67 and 17 commercial varieties of wheat and triticale, respectively. By identifying environments that favor one crop type over the other, we then quantified the sustainability implications of producing a mixed triticale-wheat flour at the regional scale. Results indicate that triticale outyielded wheat by 11% (p < 0.05) and 19% (p < 0.05) under average and N-limited conditions, respectively. However, wheat was 3% (p < 0.05) more productive in water-limited environments. Overall, triticale had greater yield stability and produced more grain per unit of water and N fertilizer inputs, especially in high-yielding environments. We estimate these differences could translate to regional N fertilizer savings (up to 555 Mg N or 166 CO2-eq kg ha−1) in a 40:60 blending scenario when wheat is sourced from water-limited and low-yielding fields and triticale from N-limited and high-yielding areas. Results suggest that optimizing the agronomic and environmental benefits of triticale would increase the overall resource use efficiency and sustainability of the agri-food system, although such a transition would require fundamental changes to the current system spanning producers, processors, and consumers.
Genome-wide identification and multiple abiotic stress transcript profiling of potassium transport gene homologs in Sorghum bicolor
Authors: Anil Kumar S. , Hima Kumari P. , Nagaraju Marka , Sudhakar Reddy Palakolanu , Durga Dheeraj T. , Mack Alexis , Katam Ramesh , Kavi Kishor P. B.
Published: September 2022

Potassium (K+) is the most abundant cation that plays a crucial role in various cellular processes in plants. Plants have developed an efficient mechanism for the acquisition of K+ when grown in K+ deficient or saline soils. A total of 47 K+ transport gene homologs (27 HAKs, 4 HKTs, 2 KEAs, 9 AKTs, 2 KATs, 2 TPCs, and 1 VDPC) have been identified in Sorghum bicolor. Of 47 homologs, 33 were identified as K+ transporters and the remaining 14 as K+ channels. Chromosome 2 has been found as the hotspot of K+ transporters with 9 genes. Phylogenetic analysis revealed the conservation of sorghum K+ transport genes akin to Oryza sativa. Analysis of regulatory elements indicates the key roles that K+ transport genes play under different biotic and abiotic stress conditions. Digital expression data of different developmental stages disclosed that expressions were higher in milk, flowering, and tillering stages. Expression levels of the genes SbHAK27 and SbKEA2 were higher during milk, SbHAK17, SbHAK11, SbHAK18, and SbHAK7 during flowering, SbHAK18, SbHAK10, and 23 other gene expressions were elevated during tillering inferring the important role that K+ transport genes play during plant growth and development. Differential transcript expression was observed in different tissues like root, stem, and leaf under abiotic stresses such as salt, drought, heat, and cold stresses. Collectively, the in-depth genome-wide analysis and differential transcript profiling of K+ transport genes elucidate their role in ion homeostasis and stress tolerance mechanisms.
Gibberellic acid promotes selenium accumulation in Cyphomandra betacea under selenium stress
Authors: Xu Yaxin , Zhang Lu , Wang Jin , Liang Dong , Xia Hui , Lv Xiulan , Deng Qunxian , Wang Xun , Luo Xian , Liao Ming’an , Lin Lijin
Published: September 2022

The selenium (Se) deficiency is threatening the human health, and the increase of Se content in food can prevent the Se deficiency of human body. To increase the Se content in fruit trees and alleviate the Se stress to fruit trees, the effects of gibberellic acid (GA) on the growth and Se accumulation in Cyphomandra betacea under Se stress were studied. Although GA increased the biomass of C. betacea, it did not significantly affect the root/shoot ratio. The root and shoot biomass had a quadratic polynomial regression relationship with the GA concentration. Furthermore, GA increased the photosynthetic pigment content, photosynthetic parameters, and antioxidant enzyme activity of C. betacea. GA also increased the Se content in C. betacea, peaking at 300 mg/L GA. For instance, GA (300 mg/L) increased the Se contents in roots and shoots of C. betacea by 70.31 and 22.02%, respectively, compared with the control. Moreover, the root Se and shoot Se contents had a quadratic polynomial regression relationship with the GA concentration. Correlation and gray relational analyses showed that the carotenoid, chlorophyll a, and chlorophyll b contents were closely related to the Se uptake in C. betacea under the GA application. These results show that GA (300 mg/L) can promote the growth and Se uptake of C. betacea under Se stress.
Comprehensive survey of transposon mPing insertion sites and transcriptome analysis for identifying candidate genes controlling high protein content of rice
Authors: Monden Yuki , Tanaka Hirona , Funakoshi Ryota , Sunayama Seiya , Yabe Kiyotaka , Kimoto Eri , Matsumiya Kentaro , Yoshikawa Takanori
Published: September 2022

Rice is the most important crop species in the world, being staple food of more than 80% of people in Asia. About 80% of rice grain is composed of carbohydrates (starch), with its protein content as low as 7–8%. Therefore, increasing the protein content of rice offers way to create a stable protein source that contributes to improving malnutrition and health problems worldwide. We detected two rice lines harboring a significantly higher protein content (namely, HP5-7 and HP7-5) in the EG4 population. The EG4 strain of rice is a unique material in that the transposon mPing has high transpositional activity and high copy numbers under natural conditions. Other research indicated that mPing is abundant in the gene-rich euchromatic regions, suggesting that mPing amplification should create new allelic variants, novel regulatory networks, and phenotypic changes in the EG4 population. Here, we aimed to identify the candidate genes and/or mPing insertion sites causing high protein content by comprehensively identifying the mPing insertion sites and carrying out an RNA-seq-based transcriptome analysis. By utilizing the next-generation sequencing (NGS)-based methods, ca. 570 mPing insertion sites were identified per line in the EG4 population. Our results also indicated that mPing apparently has a preference for inserting itself in the region near a gene, with 38 genes in total found to contain the mPing insertion in the HP lines, of which 21 and 17 genes were specific to HP5-7 and HP7-5, respectively. Transcriptome analysis revealed that most of the genes related to protein synthesis (encoding glutelin, prolamin, and globulin) were up-regulated in HP lines relative to the control line. Interestingly, the differentially expressed gene (DEG) analysis revealed that the expression levels of many genes related to photosynthesis decreased in both HP lines; this suggests the amount of starch may have decreased, indirectly contributing to the increased protein content. The high-protein lines studied here are expected to contribute to the development of high protein-content rice by introducing valuable phenotypic traits such as high and stable yield, disease resistance, and abundant nutrients.