bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of the Group of Pediatric Patients With Relapsing-Remitting Multiple Sclerosis: Data From the Czech National Registry
Authors: Vališ Martin , Pavelek Zbyšek , Novotný Michal , Klímová Blanka , Šarláková Jana , Halúsková Simona , Peterka Marek , Štětkárová Ivana , Štourač Pavel , Mareš Jan , Hradílek Pavel , Ampapa Radek , Vachová Marta , Recmanová Eva , Meluzínová Eva
Published: April 2022

Importance

Multiple sclerosis can also affect children. Approximately 3–10% of patients develop multiple sclerosis before the age of 16.

Objective

The aim of this analysis is to describe the characteristics of pediatric patients with multiple sclerosis who started their treatment with disease-modifying drugs in 2013–2020, with data obtained from the Czech National Registry of patients with multiple sclerosis.

Design and Setting

A method of retrospective analysis conducted with 134 pediatric patients with multiple sclerosis was used.

Results

The findings reveal that the mean age at the date of the introduction of the first disease-modifying drugs treatment is 15.89 years, and gender does not play any role. In addition, moderate (51.6%) and mild (45.2%) relapses are predominant in these young patients. Seventy five percent of patients will not experience a confirmed progression of the expanded disability status scale within 54.7 months from starting the treatment. Furthermore, the results confirm that the first-choice treatment is interferon beta-a and glatiramer acetate, which is common for adult patients. However, some factors, such as a low efficacy or a lack of tolerance may impact on treatment discontinuation in children.

Conclusion

More research should be performed on novel disease-modifying drugs for this target group.
Receptor-Interacting Protein Kinase 3 Inhibition Relieves Mechanical Allodynia and Suppresses NLRP3 Inflammasome and NF-κB in a Rat Model of Spinal Cord Injury
Authors: Xue Song , Cao Zhen-xin , Wang Jun-nan , Zhao Qing-xiang , Han Jie , Yang Wen-jie , Sun Tao
Published: April 2022

Background

Neuroinflammation is critical in developing and maintaining neuropathic pain after spinal cord injury (SCI). The receptor-interacting protein kinase 3 (RIPK3) has been shown to promote inflammatory response by exerting its non-necroptotic functions. In this study, we explored the involvement of RIPK3 in neuropathic pain after SCI.

Methods

Thoracic (T10) SCI rat model was conducted, and the mechanical threshold in rats was measured. The expressions of RIPK3, nod-like receptor family pyrin domain-containing protein 3 (NLRP3), caspase-1, and nuclear factor-κB (NF-κB) were measured with western blotting analysis or quantitative real-time polymerase chain reaction (qRT-PCR). Double immunofluorescence staining was used to explore the colabeled NLRP3 with NeuN, glial fibrillary acidic protein (GFAP), and ionized calcium-binding adapter molecule 1 (IBA1). In addition, enzyme-linked immunosorbent assay (ELISA) was applied to analyze the levels of proinflammatory factors interleukin 1 beta (IL-1β), interleukin 18 (IL-18), and tumor necrosis factor alpha (TNF-α).

Results

The expression of RIPK3 was elevated from postoperative days 7–21, which was consistent with the development of mechanical allodynia. Intrathecal administration of RIPK3 inhibitor GSK872 could alleviate the mechanical allodynia in SCI rats and reduce the expression levels of RIPK3. The activation of NLRP3 inflammasome and NF-κB was attenuated by GSK872 treatment. Furthermore, immunofluorescence suggested that NLRP3 had colocalization with glial cells and neurons in the L4–L6 spinal dorsal horns. In addition, GSK872 treatment reduced the production of inflammatory cytokines.

Conclusion

Our findings indicated that RIPK3 was an important facilitated factor for SCI-induced mechanical allodynia. RIPK3 inhibition might relieve mechanical allodynia by inhibiting NLRP3 inflammasome, NF-κB, and the associated inflammation.
Unrelenting Fear Under Stress: Neural Circuits and Mechanisms for the Immediate Extinction Deficit
Authors: Maren Stephen
Published: April 2022

Therapeutic interventions for disorders of fear and anxiety rely on behavioral approaches that reduce pathological fear memories. For example, learning that threat-predictive stimuli are no longer associated with aversive outcomes is central to the extinction of conditioned fear responses. Unfortunately, fear memories are durable, long-lasting, and resistant to extinction, particularly under high levels of stress. This is illustrated by the “immediate extinction deficit,” which is characterized by a poor long-term reduction of conditioned fear when extinction procedures are attempted within hours of fear conditioning. Here, I will review recent work that has provided new insight into the neural mechanisms underlying resistance to fear extinction. Emerging studies reveal that locus coeruleus norepinephrine modulates amygdala-prefrontal cortical circuits that are critical for extinction learning. These data suggest that stress-induced activation of brain neuromodulatory systems biases fear memory at the expense of extinction learning. Behavioral and pharmacological strategies to reduce stress in patients undergoing exposure therapy might improve therapeutic outcomes.
Association Between Dietary Fiber Intake and All-Cause and Cardiovascular Mortality in Middle Aged and Elderly Adults With Chronic Kidney Disease
Authors: Kwon Yu-Jin , Lee Hye Sun , Park Go Eun , Lee Ji-Won
Published: April 2022

Background and Aims

Despite accumulating evidence on the benefits of dietary fiber in the general population, there is a lack of representative data on mortality in patients with chronic kidney disease (CKD). This study examined the role of dietary fiber intake on all-cause and cardiovascular mortality in patients with CKD using representative Korean cohort data.

Methods

The study included 3,892 participants with estimated glomerular filtration rates <60 mL/min/1.73 m2 from the Korean Genome and Epidemiology Study. Mortality status was followed by data linkage with national data sources. Nutritional status was assessed using a validated food frequency questionnaire. Dietary fiber was categorized into quintiles (Q). A multivariable Cox proportional hazards regression model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cardiovascular mortality.

Results

The average daily fiber intake of patients with CKD was 5.1 g/day. During the 10.1-year follow-up period, 602 (149 cardiovascular) deaths were documented. The HR (95% CI) for all-cause mortality in the highest quintile compared with that in the lowest quintile was 0.63 (0.46–0.87) after adjusting for age, sex, BMI, smoking, alcohol intake, exercise, total calorie intake, hypertension, diabetes, and dyslipidemia (P = 0.005). The HR (95% CI) for cardiovascular mortality in the highest quintile compared with that in the lowest quintile was 0.56 (0.29–1.08) after adjusting for same confounders (P = 0.082).

Conclusion

In conclusion, we observed an inverse association between dietary fiber intake and all-cause mortality in CKD patients. Small increments in fiber intake reduced the risk of all-cause mortality by 37%. This finding highlights the need for inexpensive but important dietary modification strategies for encouraging fiber intake in the Korean CKD population.
Nutrient Content, Organoleptic Quality, and Shelf Life of Sagon Substitute From Lindur (Bruguiera gymnorrhiza L.) and Soybean Flour (Glycine max L.), as an Alternative Emergency Food
Authors: Afifah Diana Nur , Ningrum Yesi Pratama Aprilia , Syahidah Tazkiah , Nuryanto Nuryanto , Ayustaningwarno Fitriyono , Sugianto Denny Nugroho
Published: April 2022

Lindur (Bruguiera gymnorrhiza L.) fruit as a mangrove species has not been widely developed. However, the combination of lindur fruit functional food with soybean flour has high carbohydrates and protein potential to serve as an additional food product in emergency conditions. Therefore, this study aims to evaluate the nutritional content, dietary fiber, organoleptic quality, and sagon shelf-life estimation of lindur and soybean flour, in accordance with emergency food quality requirements. The shelf life was determined using the Accelerated Shelf-life Testing (ASLT) method with the Arrhenius equation, where the sample was stored in an incubator at a temperature of 27, 37, as well as 47°C for 30 days, and the water content, peroxide number, and free fatty acid content were tested every 5 days. In addition, formulation P1 comprising 45% lindur flour and 35% soybean flour was discovered to be the best formulation, with a composition of 251.5 kcal/bar of energy, 6.3 g of fat, 4.4 g of protein, 30 g of carbohydrates, 15.79% dietary fiber, 1.84% ash content, and 4.03% water content. Therefore, the nutritional content of sagon substitution for lindur flour is in accordance with the emergency food quality requirements, except for the protein content. Also, the P2 sagon sample’s shelf life was estimated to be 37 days in polypropylene plastic packaging at a room temperature of 27°C.
RNA-Binding Protein COL14A1, TNS1, NUSAP1 and YWHAE Are Valid Biomarkers to Predict Peritoneal Metastasis in Gastric Cancer
Authors: Jiang Yue , Chen Fangfang , Ren Xunshan , Yang Yu , Luo Jiajun , Yuan Jingwen , Yuan Jingping , Tong Qiang
Published: April 2022

Gastric cancer (GC) is the third leading cause of tumor related mortality worldwide. Peritoneal metastasis (PM) occurs in more than half of advanced GC patients, leading to poor prognosis. Therefore, the GSE62254 cohort was used to construct a signature consisting of four RNA-binding proteins (RBP) to predict the possibility of PM in GC patients. Then, ROC curves were plotted followed by calculation of AUCs, showing that the signature had a similar predictive accuracy compared with the TNM staging system. Importantly, the capability of prediction was enhanced by combining the classifier and TNM staging. In order to validate the expression of the four RBPs in GC tissues with and without PM, immunohistochemistry was further performed on samples from 108 patients. The differential expression of COL14A1, TNS1, NUSAP1 and YWHAE was in accordance with the emergence of PM. Afterwards, we produced Kaplan–Meier curves according to the signature and differential expression of the RBPs in patients. Finally, CCK-8 assays were performed to verify the effect on cell proliferation, finding that COL14A1 and TNS1 promoted cell proliferation, while NUSAP1 and YWHAE led to suppressed cell proliferation. In conclusion, the four-RBP-based signature, combined with TNM staging, has the potential to predict risk of PM in GC.
Effects of Biofilm Nano-Composite Drugs OMVs-MSN-5-FU on Cervical Lymph Node Metastases From Oral Squamous Cell Carcinoma
Authors: Huang Jian , Wu Zhiyuan , Xu Junwu
Published: April 2022

This work was developed to the effects of biofilm composite nano-drug delivery system (OMVs-MSN-5-FU) on lymph node metastasis from oral squamous cell carcinoma. Mesoporous silica nanoparticles loaded with 5-FU (MSN-5-FU) were prepared first. Subsequently, the outer membrane vesicles (OMV) of Escherichia coli were collected to wrap MSN-5-FU, and then OMVs-MSN-5-FU was prepared. It was then immersed in artificial gastric juice and artificial intestinal juice to explore the drug release rate. Next, the effects of different concentrations of the nano-drug delivery systems on the proliferation activity of oral squamous carcinoma cell line KOSC-2 cl3-43 were analyzed. Tumor-bearing nude mice models were prepared by injecting human tongue squamous cell carcinoma cells Tca8113 into BALB/c-nu nude mice. They were injected with the OMVs-MSN-5-FU nano drug carrier system, and peri-carcinoma tissue and cervical lymph node tissue were harvested to observe morphological changes by Hematoxylin – eosin (HE) staining. The scanning electron microscope (SEM) results showed that all MSN, MSN-5-FU, OMV, and OMV-MSN-5-FU were spherical and uniformly distributed, with particle sizes of about 60nm, 80nm, 90nm, and 140nm, respectively. Among them, OMV had a directional core-shell structure. The cumulative drug release rates of artificial gastric juice in 48 hours were 61.2 ± 2.3% and 26.5 ± 3.1%, respectively. The 48 hours cumulative drug release rates of artificial intestinal juice were 70.5 ± 6.3% and 32.1 ± 3.8%, respectively. The cumulative release of MSN-5-FU was always higher than OMV-MSN-5-FU. The cumulative release of MSN-5-FU was always higher than OMV-MSN-5-FU. After injection of OMVS-MSN-5-FU, the number of cancer cells was significantly reduced and cervical lymph node metastasis was significantly controlled. HE staining results showed that OMVS-MSN-5-FU injection reduced the number of stained cells. Dense lymphocytes were clearly observed in the cortex of neck lymphocytes. The OMVs-MSN-5-FU drug delivery system can slow down the drug release rate, significantly inhibit the proliferation activity of oral squamous cancer cells, and control the metastasis of cancer cells to cervical lymph nodes.
Dysfunction of Inflammatory Pathways and Their Relationship With Psychological Factors in Adult Female Patients With Eating Disorders
Authors: Caso Javier R. , MacDowell Karina S. , Soto Marta , Ruiz-Guerrero Francisco , Carrasco-Díaz Álvaro , Leza Juan C. , Carrasco José L. , Díaz-Marsá Marina
Published: April 2022

The attempts to clarify the origin of eating disorders (ED) have not been completely successful and their etiopathogenesis remains unknown. Current research shows an activation of the immune response in neuropsychiatric diseases, including ED. We aimed to investigate immune response parameters in patients with ED and to identify psychological factors influencing the inflammatory response. The relationship between inflammation markers and impulsivity and affective symptomatology was explored as well. Thirty-four adult female patients with current diagnosis of ED, none of them under psychopharmacological treatment (excluding benzodiazepines), were included in this study. Patients were compared with a healthy control group of fifteen adult females. The levels of inflammatory markers and indicators of oxidative/nitrosative stress were evaluated in plasma and/or in peripheral blood mononuclear cells (PBMCs). Subjects were assessed by means of different ED evaluation tools. Additionally, the Barratt Impulsiveness Scale, the Montgomery-Asberg Depression Rating Scale and the Hamilton Anxiety Rating Scale were also employed. Patients with ED shown increased plasma levels of the pro-inflammatory nuclear factor kappa B (NFκB) and the cytokine tumor necrosis factor-alpha (TNF-α), among other factors and an increment in the oxidative/nitrosative stress as well as increased glucocorticoid receptor (GR) expression levels in their PBMCs. Moreover, the inflammatory prostaglandin E2 (PGE2) correlated with impulsiveness and the anti-inflammatory prostaglandin J2 (15d-PGJ2) correlated with depressive symptomatology. Our results point towards a relationship between the immune response and impulsiveness and between the immune response and depressive symptomatology in female adult patients with ED.
A Review on the Ethnopharmacology and Phytochemistry of the Neotropical Sages (Salvia Subgenus Calosphace; Lamiaceae) Emphasizing Mexican Species
Authors: Ortiz-Mendoza Nancy , Aguirre-Hernández Eva , Fragoso-Martínez Itzi , González-Trujano María Eva , Basurto-Peña Francisco A. , Martínez-Gordillo Martha J.
Published: April 2022

Salvia is the most diverse genus within the mint family (Lamiaceae), many of its species are well-known due to their medicinal and culinary uses. Most of the ethnopharmacological and phytochemical studies on Salvia are centred on species from the European and Asian clades. However, studies about the most diverse clade, the Neotropical sages (Salvia subgenus Calosphace; 587 spp.), are relatively scarce. This review aims to compile the information on the traditional medicinal uses, pharmacological and phytochemistry properties of the Neotropical sages. To do so, we carried out a comprehensive review of the articles available in different online databases published from the past to 2022 (i.e., PubMed, Scopus, and Web of Science, among others) and summarized the information in tables. To uncover phylogenetic patterns in the distribution of four different groups of metabolites (mono-, sesqui-, di-, and triterpenes), we generated presence-absence matrices and plotted the tip states over a dated phylogeny of Salvia. We found several studies involving Mexican species of Salvia, but only a few about taxa from other diversity centres. The main traditional uses of the Mexican species of Calosphace are medicinal and ceremonial. In traditional medicine 56 species are used to treat diseases from 17 categories according to the WHO, plus cultural-bound syndromes. Pharmacological studies reveal a wide range of biological properties (e.g., antinociceptive, anti-inflammatory, anxiolytic, cytotoxic, and antidiabetic, etc.) found in extracts and isolated compounds of 38 Neotropical sages. From extracts of these species, at least 109 compounds have been isolated, identified and evaluated pharmacologically; 73 of these compounds are clerodanes, 21 abietanes, six flavonoids, five sesquiterpenoids, and four triterpenoids. The most characteristic metabolites found in the Neotropical sages are the diterpenes, particularly clerodanes (e.g., Amarisolide A, Tilifodiolide), that are found almost exclusively in this group. The Neotropical sages are a promising resource in the production of herbal medication, but studies that corroborate the properties that have been attributed to them in traditional medicine are scarce. Research of these metabolites guided by the phylogenies is recommended, since closely related species tend to share the presence of similar compounds and thus similar medicinal properties.
Induced Cell Cycle Arrest in Triple-Negative Breast Cancer by Combined Treatment of Itraconazole and Rapamycin
Authors: Wu Hua-Tao , Li Chun-Lan , Fang Ze-Xuan , Chen Wen-Jia , Lin Wen-Ting , Liu Jing
Published: April 2022

Triple-negative breast cancer (TNBC) is the aggressive molecular type of breast carcinoma, with a high metastasis/relapse incidence and cancer-related death rate, due to lack of specific therapeutic targets in the clinic. Exploring potential therapeutic targets or developing novel therapeutic strategies are the focus of intense research to improve the survival and life quality of patients with TNBC. The current study focused on drugs targeting the mTOR signaling pathway by investigating the potential utilization of itraconazole (ITZ) combined with rapamycin in the treatment of TNBC. CCK-8, colony formation and transwell assays were conducted to evaluate the effect of ITZ with rapamycin in combination on MDA-MB-231 and BT-549 TNBC cells. Synergistic inhibition was found in terms of proliferation and motility of TNBC cells. However, apoptosis was not enhanced by the combined treatment of ITZ and rapamycin. Flow cytometry analysis showed that ITZ and/or rapamycin arrested cells in G0/G1 phase and prevented G1/S phase transition. Reduced cyclin D1 protein levels were consistent with G0/G1 phase arrest, especially when resulting from the combination of ITZ with rapamycin. In conclusion, the combination of ITZ with rapamycin is a promising therapeutic strategy for patients with TNBC through synergistically arresting cells in the G0/G1 phase of the cell cycle, rather than inducing apoptosis.
Effects of Montelukast on Arsenic-Induced Epithelial-Mesenchymal Transition and the Role of Reactive Oxygen Species Production in Human Bronchial Epithelial Cells
Authors: Chen Huang-Chi , Chiou Hsin-Ying Clair , Tsai Mei-Lan , Chen Szu-Chia , Lin Ming-Hong , Chuang Tzu-Chun , Hung Chih-Hsing , Kuo Chao-Hung
Published: April 2022

Background: Epithelial-mesenchymal transition (EMT) of airway lung epithelial cells is considered a major driver of fibrosis and airway remodeling. Arsenic exposure is well known to cause the malignant transformation of cells, including those in the lung. Accumulating studies have shown that arsenic exposure is associated with chronic pulmonary diseases. However, clinical treatment for arsenic-induced pulmonary damage has not been well investigated.

Materials and Methods: The therapeutic effects of montelukast and its combination with fluticasone on sodium arsenite-induced EMT changes in normal human bronchial cells were investigated. The cell migration ability was evaluated by Transwell and wound healing assays. EMT marker expression was determined by immunoblotting. Furthermore, the role of reactive oxygen species (ROS) generation in arsenic-induced EMT and the effect of montelukast on this process were determined by ROS inhibitor treatment and ROS measurement, respectively.

Results: Montelukast was effective at reducing arsenic-induced cell migration and mesenchymal protein (fibronectin, MMP-2, N-cadherin, β-catenin, and SMAD2/3) expression. Arsenic-induced ROS production was attenuated by pretreatment with montelukast. Treatment with the ROS inhibitor N-acetyl cysteine reduced arsenic-induced NF-kB phosphorylation and the mesenchymal protein expression, indicating that ROS production is critical for arsenic-induced EMT. In addition, combined treatment with montelukast and fluticasone reversed the inhibitory effects of montelukast on cell migration. The expression of fibronectin, MMP-2 induced by arsenic was further enhanced by the combination treatment compared with montelukast treatment only.

Conclusion: This study demonstrated that montelukast is effective at reducing arsenic-induced EMT in human bronchial epithelial cells. Through the inhibition of arsenic-induced ROS generation and NF-kB activation, which is critical for arsenic-induced EMT, montelukast inhibited arsenic-induced cell migration and the expression of extracellular matrix proteins and several EMT-regulating transcription factors. The combination of fluticasone with montelukast reversed the inhibitory effect of montelukast on arsenic-induced EMT. This study provides therapeutic strategies and mechanisms for arsenic-induced pulmonary epithelial damage.
Rhynchophylline Regulates Calcium Homeostasis by Antagonizing Ryanodine Receptor 2 Phosphorylation to Improve Diabetic Cardiomyopathy
Authors: Liu Jiao , Zhao Yating , Zhu Yufang , Wang Yan , Liu Xiaoshuang , Nie Xiaobo , Zhao Jing , Wang Wei , Cheng Jie
Published: April 2022

Diabetic cardiomyopathy (DCM) is a serious complication of diabetes that can lead to heart failure and death, for which there is no effective treatment. Rhynchophylline (Rhy) is the main effective component of the Chinese herbal medicine Uncaria rhynchophylla, which mainly acts on the cardiovascular and nervous systems. However, its role in protecting against DCM remains unexplored. The present study sought to reveal the mechanism of Rhy in improving type 2 diabetes mellitus (T2DM) myocardial lesions from the perspective of regulating calcium homeostasis in cardiomyocytes. We prepared a mouse model of T2DM using a high-fat diet combined with low doses of streptozotocin. The T2DM mice were given 40 mg/kg of Rhy for 8 weeks. The results showed that Rhy can attenuate cardiac pathological changes, slow down the heart rate, decrease serum cardiac enzyme levels, reduce cardiomyocyte apoptosis, enhance cardiomyocyte contractility, and raise the calcium transient amplitude in T2DM mice. Further, Rhy downregulated the phosphorylation level of ryanodine receptor 2, upregulated the phosphorylation level of phospholamban, protected mitochondrial structure and function, and increased adenosine triphosphate levels in the cardiac tissue of T2DM mice. Our results demonstrated that Rhy may protect against myocardial damage in T2DM mice and promote cardiomyocyte contraction, and its mechanism of action seems to be related to the regulation of intracellular calcium homeostasis.
Geometrical Aspect of Compressibility Critical Exponent
Authors: Yu J. S. , Du W. K. , Liu Q. H.
Published: April 2022

Critical exponent γ ⪰ 1.1 characterizes the behavior of the mechanical compressibility of a real fluid when the temperature approaches the critical one. It results in zero Gaussian curvature of the local shape of the critical point on the thermodynamic equation of state surface, which imposes a new constraint upon the construction of the potential equation of state of the real fluid from the empirical data. All known empirical equations of the state suffer from a weakness that the Gaussian curvature of the critical point is negative definite instead of zero.
Coherent Control of Perfect Optical Vortex Through Four-Wave Mixing in an Asymmetric Semiconductor Double Quantum Well
Authors: Deng Xu , Shui Tao , Yang Wen-Xing
Published: April 2022

A scheme for the coherent control of perfect optical vortex (POV) in an asymmetric semiconductor double quantum well (SDQW) nanostructure is proposed by exploiting the tunneling-induced highly efficient four-wave mixing (FWM). The orbital angular momentum (OAM) is completely transferred from a unique POV mode to the generated FWM field. Using experimentally achievable parameters, we identify the conditions under which resonant tunneling allows us to improve the quality of the vortex FWM field and engineer helical phase wave front beyond what is achievable in the absence of resonant tunneling. Furthermore, we find that the intensity and phase patterns of the vortex FWM field are sensitive to the detuning of the probe field but rather robust against the detuning of the coupling field. Subsequently, we perform the coaxial interference between the vortex FWM field and a same-frequency POV beam and show interesting interference properties, which allow us to measure the topological charge of the output POV beam. Our result may find potential applications in quantum technologies based on POV in solids.
Effects of Hypoxia–Hyperoxia Preconditioning on Indicators of Muscle Damage After Acute Resistance Exercise in Male Athletes
Authors: Chen Peng-Wen , Hsu Chi-Chieh , Lai Li-Fan , Chi Chung-Pu , Yu Szu-Hsien
Published: April 2022

Purpose

The purpose of this study was to investigate the effects of acute repeated hypoxia–hyperoxia preconditioning on resistance exercise (RE)-induced muscle damage in male athletes.

Methods

Eleven young male athletes participated in this randomized double-blind counter-balanced crossover study, and were divided into Normoxia (N) and Hypoxia–Hyperoxia (HH) trials. Subjects of the respective trials were supplied with normoxic (FiO2 = 0.21), or alternating hypoxic/hyperoxic air (FiO2 = 0.10/0.99, 5 min each) for 60 min. Thirty minutes after preconditioning, subjects performed acute bouts of RE consisting of bench press, deadlift, and squats. Each exercise included 6 sets of 10 repetitions at 75% one-repetition maximum (1RM) with 2 min rest between sets. After a 2-week washout period, subjects changed trials and completed the same study procedure after the alternate preconditioning. Muscle soreness, maximal voluntary contraction (MVC), and circulating biochemical markers were tested before preconditioning (baseline) and during recovery at 0, 24, and 48 h after exercise.

Results

Acute RE significantly increased levels of muscle soreness, creatine kinase (CK) and myoglobin (Mb), and decreased levels of peak knee extension torque in the N trial. Muscle soreness, CK, and Mb levels of the HH trial were significantly lower than that of the N trial after exercise. Interestingly, interleukin-6 (IL-6) levels of the HH trial increased significantly 0 h after exercise compared to baseline and were significantly higher than that of the N trial 0 and 24 h after exercise. However, no significant differences of thiobarbituric acid reactive substances (TBARS), cortisol, testosterone, peak torque, and average power levels were found between N and HH trials during recovery.

Conclusion

Our data suggest that pre-exercise treatment of alternating hypoxic/hyperoxic air could attenuate muscle damage and pain after acute RE, but has no effect on muscle strength recovery in young male athletes.
In Transgenic Erythropoietin Deficient Mice, an Increase in Respiratory Response to Hypercapnia Parallels Abnormal Distribution of CO2/H+-Activated Cells in the Medulla Oblongata
Authors: Jeton Florine , Perrin-Terrin Anne-Sophie , Yegen Celine-Hivda , Marchant Dominique , Richalet Jean-Paul , Pichon Aurélien , Boncoeur Emilie , Bodineau Laurence , Voituron Nicolas
Published: April 2022

Erythropoietin (Epo) and its receptor are expressed in central respiratory areas. We hypothesized that chronic Epo deficiency alters functioning of central respiratory areas and thus the respiratory adaptation to hypercapnia. The hypercapnic ventilatory response (HcVR) was evaluated by whole body plethysmography in wild type (WT) and Epo deficient (Epo-TAgh) adult male mice under 4%CO2. Epo-TAgh mice showed a larger HcVR than WT mice because of an increase in both respiratory frequency and tidal volume, whereas WT mice only increased their tidal volume. A functional histological approach revealed changes in CO2/H+-activated cells between Epo-TAgh and WT mice. First, Epo-TAgh mice showed a smaller increase under hypercapnia in c-FOS-positive number of cells in the retrotrapezoid nucleus/parafacial respiratory group than WT, and this, independently of changes in the number of PHOX2B-expressing cells. Second, we did not observe in Epo-TAgh mice the hypercapnic increase in c-FOS-positive number of cells in the nucleus of the solitary tract present in WT mice. Finally, whereas hypercapnia did not induce an increase in the c-FOS-positive number of cells in medullary raphe nuclei in WT mice, chronic Epo deficiency leads to raphe pallidus and magnus nuclei activation by hyperacpnia, with a significant part of c-FOS positive cells displaying an immunoreactivity for serotonin in the raphe pallidus nucleus. All of these results suggest that chronic Epo-deficiency affects both the pattern of ventilatory response to hypercapnia and associated medullary respiratory network at adult stage with an increase in the sensitivity of 5-HT and non-5-HT neurons of the raphe medullary nuclei leading to stimulation of fR for moderate level of CO2.
Bilateral Interactions in the Mouse Dorsal Inferior Colliculus Enhance the Ipsilateral Neuronal Responses and Binaural Hearing
Authors: Liu Yun , Li Yan , Peng Yunyi , Yu Haipeng , Xiao Zhongju
Published: April 2022

The inferior colliculus (IC) is a critical centre for the binaural processing of auditory information. However, previous studies have mainly focused on the central nucleus of the inferior colliculus (ICC), and less is known about the dorsal nucleus of the inferior colliculus (ICD). Here, we first examined the characteristics of the neuronal responses in the mouse ICD and compared them with those in the inferior colliculus under binaural and monaural conditions using in vivo loose-patch recordings. ICD neurons exhibited stronger responses to ipsilateral sound stimulation and better binaural summation than those of ICC neurons, which indicated a role for the ICD in binaural hearing integration. According to the abundant interactions between bilateral ICDs detected using retrograde virus tracing, we further studied the effect of unilateral ICD silencing on the contralateral ICD. After lidocaine was applied, the responses of some ICD neurons (13/26), especially those to ipsilateral auditory stimuli, decreased. Using whole-cell recording and optogenetic methods, we investigated the underlying neuronal circuits and synaptic mechanisms of binaural auditory information processing in the ICD. The unilateral ICD provides both excitatory and inhibitory projections to the opposite ICD, and the advantaged excitatory inputs may be responsible for the enhanced ipsilateral responses and binaural summation of ICD neurons. Based on these results, the contralateral ICD might modulate the ipsilateral responses of the neurons and binaural hearing.
The Na+/H+ Exchanger 3 in the Intestines and the Proximal Tubule of the Kidney: Localization, Physiological Function, and Key Roles in Angiotensin II-Induced Hypertension
Authors: Nwia Sarah M. , Li Xiao Chun , Leite Ana Paula de Oliveira , Hassan Rumana , Zhuo Jia Long
Published: April 2022

The sodium (Na+)/hydrogen (H+) exchanger 3 (NHE3) is one of the most important Na+/H+antiporters in the small intestines of the gastrointestinal tract and the proximal tubules of the kidney. The roles of NHE3 in the regulation of intracellular pH and acid–base balance have been well established in cellular physiology usingin vitrotechniques. Localized primarily on the apical membranes in small intestines and proximal tubules, the key action of NHE3 is to facilitate the entry of luminal Na+and the extrusion of intracellular H+from intestinal and proximal tubule tubular epithelial cells. NHE3 is, directly and indirectly, responsible for absorbing the majority of ingested Na+from small and large intestines and reabsorbing >50% of filtered Na+in the proximal tubules of the kidney. However, the roles of NHE3 in the regulation of proximal tubular Na+transport in the integrative physiological settings and its contributions to the basal blood pressure regulation and angiotensin II (Ang II)-induced hypertension have not been well studied previously due to the lack of suitable animal models. Recently, novel genetically modified mouse models with whole-body, kidney-specific, or proximal tubule-specific deletion of NHE3 have been generated by us and others to determine the critical roles and underlying mechanisms of NHE3 in maintaining basal body salt and fluid balance, blood pressure homeostasis, and the development of Ang II-induced hypertension at the whole-body, kidney, or proximal tubule levels. The objective of this invited article is to review, update, and discuss recent findings on the critical roles of intestinal and proximal tubule NHE3 in maintaining basal blood pressure homeostasis and their potential therapeutic implications in the development of angiotensin II (Ang II)-dependent hypertension.
Stable Isotope Fractionation of Metals and Metalloids in Plants: A Review
Authors: Wiggenhauser Matthias , Moore Rebekah E. T. , Wang Peng , Bienert Gerd Patrick , Laursen Kristian Holst , Blotevogel Simon
Published: April 2022

This work critically reviews stable isotope fractionation of essential (B, Mg, K, Ca, Fe, Ni, Cu, Zn, Mo), beneficial (Si), and non-essential (Cd, Tl) metals and metalloids in plants. The review (i) provides basic principles and methodologies for non-traditional isotope analyses, (ii) compiles isotope fractionation for uptake and translocation for each element and connects them to physiological processes, and (iii) interlinks knowledge from different elements to identify common and contrasting drivers of isotope fractionation. Different biological and physico-chemical processes drive isotope fractionation in plants. During uptake, Ca and Mg fractionate through root apoplast adsorption, Si through diffusion during membrane passage, Fe and Cu through reduction prior to membrane transport in strategy I plants, and Zn, Cu, and Cd through membrane transport. During translocation and utilization, isotopes fractionate through precipitation into insoluble forms, such as phytoliths (Si) or oxalate (Ca), structural binding to cell walls (Ca), and membrane transport and binding to soluble organic ligands (Zn, Cd). These processes can lead to similar (Cu, Fe) and opposing (Ca vs. Mg, Zn vs. Cd) isotope fractionation patterns of chemically similar elements in plants. Isotope fractionation in plants is influenced by biotic factors, such as phenological stages and plant genetics, as well as abiotic factors. Different nutrient supply induced shifts in isotope fractionation patterns for Mg, Cu, and Zn, suggesting that isotope process tracing can be used as a tool to detect and quantify different uptake pathways in response to abiotic stresses. However, the interpretation of isotope fractionation in plants is challenging because many isotope fractionation factors associated with specific processes are unknown and experiments are often exploratory. To overcome these limitations, fundamental geochemical research should expand the database of isotope fractionation factors and disentangle kinetic and equilibrium fractionation. In addition, plant growth studies should further shift toward hypothesis-driven experiments, for example, by integrating contrasting nutrient supplies, using established model plants, genetic approaches, and by combining isotope analyses with complementary speciation techniques. To fully exploit the potential of isotope process tracing in plants, the interdisciplinary expertise of plant and isotope geochemical scientists is required.
Transcriptomic Analysis of Cadmium Stressed Tamarix hispida Revealed Novel Transcripts and the Importance of Abscisic Acid Network
Authors: Wang Pei-Long , Lei Xiao-Jin , Wang Yuan-Yuan , Liu Bai-chao , Wang Dan-ni , Liu Zhong-Yuan , Gao Cai-Qiu
Published: April 2022

Cadmium (Cd) pollution is widely detected in soil and has been recognized as a major environmental problem. Tamarix hispida is a woody halophyte, which can form natural forest on the desert and soil with 0.5 to 1% salt content, making it an ideal plant for the research on response to abiotic stresses. However, no systematic study has investigated the molecular mechanism of Cd tolerance in T. hispida. In the study, RNA-seq technique was applied to analyze the transcriptomic changes in T. hispida treated with 150 μmol L–1 CdCl2 for 24, 48, and 72 h compared with control. In total, 72,764 unigenes exhibited similar sequences in the Non-redundant nucleic acid database (NR database), while 36.3% of all these unigenes may be new transcripts. In addition, 6,778, 8,282, and 8,601 DEGs were detected at 24, 48, and 72 h, respectively. Functional annotation analysis indicated that many genes may be involved in Cd stress response, including ion bonding, signal transduction, stress sensing, hormone responses and ROS metabolism. A ThUGT gene from the abscisic acid (ABA) signaling pathway can enhance Cd resistance ability of T. hispida by regulating the production of ROS under Cd stress and inhibit absorption of Cd. The new transcriptome resources and data that we present in this study for T. hispida may facilitate investigation of molecular mechanisms governing Cd resistance.
Foliar Application of Spermidine Reduced the Negative Effects of Salt Stress on Oat Seedlings
Authors: Hai Xia , Mi Junzhen , Zhao Baoping , Zhang Biru , Zhao Zhou , Liu Jinghui
Published: April 2022

The effects of foliar application of spermidine (Spd) on the physiological aspects of salt-stressed oat seedlings were studied under greenhouse conditions. At the seedling stage, the salt-sensitive variety, namely, Caoyou 1 and the salt-tolerant variety, namely, Baiyan 2 were treated with 70 and 100 mM of salt, followed by the foliar application of 0.75 mM Spd or distilled water. Results showed that Spd application increased the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX), and reduced the rate of O2⋅– production and the accumulation of H2O2 and malondialdehyde (MDA). In addition, it increased the level of zeatin riboside (ZR) and the content of endogenous polyamines. The application of Spd increased the contents of soluble sugar, soluble protein, and free proline and helped maintain the osmotic balance of oat leaves. At the same time, foliar Spd treatment helped in maintaining the ion nutrition balance. Specifically, it reduced the content of Na+ and thereby stabilized the ratio of Na+/K+, Na+/Ca2+, and Na+/Mg2+. The effects of Spd application were more obvious for the salt-sensitive cultivar Caoyou 1 and under the lighter 70 mM salt stress.
A Spatial-Temporal Analysis of Cellular Biopolymers on Leaf Blight-Infected Tea Plants Using Confocal Raman Microspectroscopy
Authors: Sanaeifar Alireza , Ye Dapeng , Li Xiaoli , Luo Liubin , Tang Yu , He Yong
Published: April 2022

The objective of the present study was to characterize the temporal and spatial variation of biopolymers in cells infected by the tea leaf blight using confocal Raman microspectroscopy. We investigated the biopolymers on serial sections of the infection part, and four sections corresponding to different stages of infection were obtained for analysis. Raman spectra extracted from four selected regions (circumscribing the vascular bundle) were analyzed in detail to enable a semi-quantitative comparison of biopolymers on a micron-scale. As the infection progressed, lignin and other phenolic compounds decreased in the vascular bundle, while they increased in both the walls of the bundle sheath cells as well as their intracellular components. The amount of cellulose and other polysaccharides increased in all parts as the infection developed. The variations in the content of lignin and cellulose in different tissues of an individual plant may be part of the reason for the plant’s disease resistance. Through wavelet-based data mining, two-dimensional chemical images of lignin, cellulose and all biopolymers were quantified by integrating the characteristic spectral bands ranging from 1,589 to 1,607 cm–1, 1,087 to 1,100 cm–1, and 2,980 to 2,995 cm–1, respectively. The chemical images were consistent with the results of the semi-quantitative analysis, which indicated that the distribution of lignin in vascular bundle became irregular in sections with severe infection, and a substantial quantity of lignin was detected in the cell wall and inside the bundle sheath cell. In serious infected sections, cellulose was accumulated in vascular bundles and distributed within bundle sheath cells. In addition, the distribution of all biopolymers showed that there was a tylose substance produced within the vascular bundles to prevent the further development of pathogens. Therefore, confocal Raman microspectroscopy can be used as a powerful approach for investigating the temporal and spatial variation of biopolymers within cells. Through this method, we can gain knowledge about a plant’s defense mechanisms against fungal pathogens.
Verticillium dahliae Secretes Small RNA to Target Host MIR157d and Retard Plant Floral Transition During Infection
Authors: Zhang Bo-Sen , Li Ying-Chao , Guo Hui-Shan , Zhao Jian-Hua
Published: April 2022

Bidirectional trans-kingdom RNA silencing [or RNA interference (RNAi)] plays a key role in plant-pathogen interactions. It has been shown that plant hosts export specific endogenous miRNAs into pathogens to inhibit their virulence, whereas pathogens deliver small RNAs (sRNAs) into plant cells to disturb host immunity. Here, we report a trans-kingdom fungal sRNA retarding host plant floral transition by targeting a miRNA precursor. From Arabidopsis plants infected with Verticillium dahliae, a soil-borne hemibiotrophic pathogenic fungus that causes wilt diseases in a wide range of plant hosts, we obtained a number of possible trans-kingdom V. dahliae sRNAs (VdsRNAs) by sequencing AGO1-immunoprecipitated sRNAs. Among these, a 24-nt VdsRNA derived from V. dahliae rRNA, VdrsR-1, was shown to be an actual trans-kingdom VdsRNA that targets the miR157d precursor MIR157d, resulting in increased rather than reduced miR157d accumulation in V. dahliae-infected plants. Consistent with the miR157 family in the regulation of vegetative and floral transitions by targeting SPL genes in several plant species, we detected two SPL genes, SPL13A/B, that were notably reduced in V. dahliae-infected and VdrsR-1-expressing plants compared with control plants. Furthermore, V. dahliae-infected and VdrsR-1-expressing plants also displayed delayed vegetative phase change and floral transition compared to control plants. Taken together, we disclosed a novel mode of action for a trans-kingdom fungal sRNA, VdrsR-1, which was secreted into host cells to modulate plant floral transition by employing the miR157d/SPL13A/B regulatory module, leading to prolonged host vegetative growth that would undoubtedly benefit fungal propagation.
Genomic Architecture and Evolution of the Cellulose synthase Gene Superfamily as Revealed by Phylogenomic Analysis
Authors: Pancaldi Francesco , van Loo Eibertus N. , Schranz M. Eric , Trindade Luisa M.
Published: April 2022

The Cellulose synthase superfamily synthesizes cellulose and different hemicellulosic polysaccharides in plant cell walls. While much has been discovered about the evolution and function of these genes, their genomic architecture and relationship with gene (sub-)functionalization and evolution remains unclear. By using 242 genomes covering plant evolution from green algae to eudicots, we performed a large-scale analysis of synteny, phylogenetic, and functional data of the CesA superfamily. Results revealed considerable gene copy number variation across species and gene families, and also two patterns – singletons vs. tandem arrays – in chromosomic gene arrangement. Synteny analysis revealed exceptional conservation of gene architecture across species, but also lineage-specific patterns across gene (sub-)families. Synteny patterns correlated with gene sub-functionalization into primary and secondary CesAs and distinct CslD functional isoforms. Furthermore, a genomic context shift of a group of cotton secondary CesAs was associated with peculiar properties of cotton fiber synthesis. Finally, phylogenetics suggested that primary CesA sequences appeared before the secondary CesAs, while phylogenomic analyses unveiled the genomic trace of the CslD duplication that initiated the CslF family. Our results describe in detail the genomic architecture of the CesA superfamily in plants, highlighting its crucial relevance for gene diversification and sub-functionalization, and for understanding their evolution.
LF-NMR/MRI Determination of Different 6-Benzylaminopurine Concentrations and Their Effects on Soybean Moisture
Authors: Gu Ying , Chen Yi , Yue Xia , Xiong Peng , Pan Dayu , Song Ping , Luo Bin
Published: April 2022

In this study, we aimed to clarify the distribution and dynamics of water in the Xudou 20 soybean cultivar post-germination after culturing plants with various concentrations of 6-benzylaminopurine (6-BA). Low-field nuclear magnetic resonance and magnetic resonance imaging (LF-NMR/MRI), as well as principal component analysis (PCA), were used for the investigation. Results showed that low concentrations of 6-BA promoted soybean germination and high concentrations inhibited soybean germination, with 5 mg/l of 6-BA producing the most optimal conditions for growth. Moreover, the T22 determination of weakly bound water increased with increasing 6-BA concentration, and the PCA effectively distinguished soybeans cultured at different 6-BA concentrations. This study provides a method for the rapid detection of 6-BA concentration in bean sprouts and provides theoretical support and bean sprout quality assessment.