bluuebunny/crossref_metadata_2025 huggingface dataset:
Is Anti-NXP2 Autoantibody a Risk Factor for Calcinosis and Poor Outcome in Juvenile Dermatomyositis Patients? Case Series
Authors: Toplak Natasa , Pimpale Chavan Pallavi , Rosina Silvia , Dallos Tomas , Rotem Semo Oz , Aguiar Cassyanne L. , Khubchandani Raju , Ravelli Angelo , Patwardhan Anjali
Published: February 2022

Juvenile dermatomyositis (JDM) has a wide spectrum of clinical presentations. In the last decade, several myositis-specific antibodies have been identified in patients with JDM and connected with specific organ involvement or specific clinical picture. It has been published that the presence of anti-NXP2 autoantibodies presents a risk for calcinosis in patients with JDM. We aimed to investigate the prevalence of calcinosis and response to the treatment in JDM patients with anti-NXP2. In a retrospective, multinational, multicenter study, data on 26 JDM (19 F, 7 M) patients with positive anti-NXP2 were collected. The mean age at disease presentation was 6.5 years (SD 3.7), the median diagnosis delay was 4 months (range 0.5–27 months). Patients were divided into two groups (A and B) based on the presence of calcinosis, which occurred in 42% of anti-NXP2 positive JDM patients (group A). Four patients already had calcinosis at presentation, one developed calcinosis after 4 months, and 6 developed calcinosis later in the disease course (median 2 years, range 0.8–7.8). The differences in laboratory results were not statistically significant between the groups. The mean age at disease presentation (5.2/7.5 years) trended toward being younger in group A. Children with calcinosis were treated with several combinations of drugs. In four cases, rituximab and, in one case, anti-TNF alpha agents were used successfully. Disease outcome (by evaluation of the treating physician) was excellent in four, good in two, stable in two, and poor in three patients. None of the patients from group B had a poor disease outcome. In conclusion, JDM patients with anti-NXP2 are prone to develop calcinosis, especially if they present with the disease early, before 5 years of age. The development of calcinosis is associated with worse disease outcomes. The combination of several immunomodulatory drugs and biologic drugs can stop calcinosis progression; however, there are no evidence-based therapies for treating calcinosis in JDM patients.
Construction of a Non-Mutually Exclusive Decision Tree for Medication Recommendation of Chronic Heart Failure
Authors: Bai Yongyi , Yao Haishen , Jiang Xuehan , Bian Suyan , Zhou Jinghui , Sun Xingzhi , Hu Gang , Sun Lan , Xie Guotong , He Kunlun
Published: February 2022

Objective: Although guidelines have recommended standardized drug treatment for heart failure (HF), there are still many challenges in making the correct clinical decisions due to the complicated clinical situations of HF patients. Each patient would satisfy several recommendations, meaning the decision tree of HF treatment should be nonmutually exclusive, and the same patient would be allocated to several leaf nodes in the decision tree. In the current study, we aim to propose a way to ensemble a nonmutually exclusive decision tree for recommendation system for complicated diseases, such as HF.

Methods: The nonmutually exclusive decision tree was constructed via knowledge rules summarized from the HF clinical guidelines. Then similar patients were defined as those who followed the same pattern of leaf node allocation according to the decision tree. The frequent medication patterns for each similar patient were mined using the Apriori algorithms, and we also carried out the outcome prognosis analyses to show the capability for the evidence-based medication recommendations of our nonmutually exclusive decision tree.

Results: Based on a large database that included 29,689 patients with 84,705 admissions, we tested the framework for HF treatment recommendation. In the constructed decision tree, the HF treatment recommendations were grouped into two independent parts. The first part was recommendations for new cases, and the second part was recommendations when patients had different historical medication. There are 14 leaf nodes in our decision tree, and most of the leaf nodes had a guideline adherence of around 90%. We reported the top 10 popular similar patients, which accounted for 32.84% of the whole population. In addition, the multiple outcome prognosis analyses were carried out to assess the medications for one of the subgroups of similar patients. Our results showed even for the subgroup of the same similar patients that no one medication pattern would benefit all outcomes.

Conclusion: In the present study, the methodology to construct a nonmutually exclusive decision tree for medication recommendations for HF and its application in CDSS was proposed. Our framework is universal for most diseases and could be generally applied in developing the CDSS for treatment.
Bilobalide Exerts Anti-Inflammatory Effects on Chondrocytes Through the AMPK/SIRT1/mTOR Pathway to Attenuate ACLT-Induced Post-Traumatic Osteoarthritis in Rats
Authors: Ma Tianwen , Lv Liangyu , Yu Yue , Jia Lina , Song Xiaopeng , Xu XinYu , Li Ting , Sheng Xuanbo , Wang Haoran , Zhang Jiantao , Gao Li
Published: February 2022

Although osteoarthritis (OA) significantly affects the quality of life of the elderly, there is still no effective treatment strategy. The standardized Ginkgo biloba L. extract preparation has been shown to have a wide range of therapeutic effects. Bilobalide, a unique ingredient of Ginkgo biloba, has anti-inflammatory and antioxidant pharmacological properties, but its mechanism of action on OA remains unknown. In this study, we investigated the effects of bilobalide on the development of OA through in vivo and in vitro experiments, as well as its potential anti-inflammatory mechanisms. The in vitro experiments demonstrated that bilobalide significantly inhibited the production of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and matrix metalloproteinase 13 (MMP13) in ATDC5 chondrocytes induced by Interleukin-1β (IL-1β). At the molecular level, bilobalide induced chondrocyte autophagy by activating the AMPK/SIRT1/mTOR signaling pathway, which increased the expression of autophagy-related Atg genes, up-regulated the expression of LC3 protein, and reduced the expression of the p62 protein. In vivo, bilobalide exerted significant anti-inflammatory and anti-extracellular matrix (ECM) degradation effects in a rat model of post-traumatic OA (PTOA) induced by anterior cruciate ligament transection (ACLT). Bilobalide could relieve joint pain in PTOA rats, inhibit the expression of iNOS and COX-2 protein in cartilage via the AMPK/SIRT1/mTOR pathway, and reduce the level of ECM degradation biomarkers in serum. In conclusion, bilobalide exhibits vigorous anti-inflammatory activity, presenting it as an interesting potential therapeutic agent for OA.
Platinum Nanoparticles in Biomedicine: Preparation, Anti-Cancer Activity, and Drug Delivery Vehicles
Authors: Abed Atena , Derakhshan Maryam , Karimi Merat , Shirazinia Matin , Mahjoubin-Tehran Maryam , Homayonfal Mina , Hamblin Michael R , Mirzaei Seyed Abbas , Soleimanpour Hamidreza , Dehghani Sadegh , Dehkordi Farnaz Farzaneh , Mirzaei Hamed
Published: February 2022

Cancer is the main cause of morbidity and mortality worldwide, excluding infectious disease. Because of their lack of specificity in chemotherapy agents are used for cancer treatment, these agents have severe systemic side effects, and gradually lose their therapeutic effects because most cancers become multidrug resistant. Platinum nanoparticles (PtNPs) are relatively new agents that are being tested in cancer therapy. This review covers the various methods for the preparation and physicochemical characterization of PtNPs. PtNPs have been shown to possess some intrinsic anticancer activity, probably due to their antioxidant action, which slows tumor growth. Targeting ligands can be attached to functionalized metal PtNPs to improve their tumor targeting ability. PtNPs-based therapeutic systems can enable the controlled release of drugs, to improve the efficiency and reduce the side effects of cancer therapy. Pt-based materials play a key role in clinical research. Thus, the diagnostic and medical industries are exploring the possibility of using PtNPs as a next-generation anticancer therapeutic agent. Although, biologically prepared nanomaterials exhibit high efficacy with low concentrations, several factors still need to be considered for clinical use of PtNPs such as the source of raw materials, stability, solubility, the method of production, biodistribution, accumulation, controlled release, cell-specific targeting, and toxicological issues to human beings. The development of PtNPs as an anticancer agent is one of the most valuable approaches for cancer treatment. The future of PtNPs in biomedical applications holds great promise, especially in the area of disease diagnosis, early detection, cellular and deep tissue imaging, drug/gene delivery, as well as multifunctional therapeutics.
Adverse Drug Reactions with Drugs Used in Multiple Sclerosis: An Analysis from the Italian Pharmacovigilance Database
Authors: Barbieri Maria Antonietta , Sorbara Emanuela Elisa , Battaglia Alessandro , Cicala Giuseppe , Rizzo Vincenzo , Spina Edoardo , Cutroneo Paola Maria
Published: February 2022

Given the importance of inflammation at the onset of multiple sclerosis (MS), therapy is mainly based on the use of anti-inflammatory drugs including disease modifying therapies (DMTs). Considering the recent approval of some DMTs, pharmacovigilance becomes a fundamental tool for the acquisition of new safety data. The aim of the study was to analyze adverse drug reactions (ADRs) related to the use of drugs approved for MS. All national publicly-available aggregated ADR reports recorded from 2002 to 2020 into the Reports of Adverse Reactions of Medicines (RAM) system and all complete Sicilian data reported into the Italian spontaneous reporting system (SRS) database having as suspected drugs interferon β-1a (IFN β-1a), interferon β-1b (IFN β-1b), peginterferon β-1a (PEG-IFN β-1a), glatiramer acetate (GA), natalizumab (NTZ), fingolimod (FNG), teriflunomide (TRF), dimethyl fumarate (DMF), alemtuzumab (Alem), ocrelizumab (OCZ), or cladribine (Cladr), were collected. Descriptive analyses of national, publicly-available aggregated data and full-access regional data were performed to assess demographic characteristics and drug-related variables followed by a more in-depth analysis of all Sicilian ADRs with a case-by-case assessment and a disproportionality analysis of unexpected ADRs. A total of 13,880 national reports have been collected from 2002 to 2020: they were mainly not serious ADRs (67.9% vs. 26.1%) and related to females (71.7% vs. 26.3%) in the age group 18–65 years (76.5%). The most reported ADRs were general and administration site conditions (n = 6,565; 47.3%), followed by nervous (n = 3,090; 22.3%), skin (n = 2,763; 19.9%) and blood disorders (n = 2,180; 15.7%). Some unexpected Sicilian ADRs were shown, including dyslipidemia for FNG (n = 10; ROR 28.5, CI 14.3–59.6), NTZ (n = 5; 10.3, 4.1–25.8), and IFN β-1a (n = 4; 8.7, 3.1–24.1), abortion and alopecia for NTZ (n = 9; 208.1, 73.4–590.1; n = 3; 4.9, 1.5–15.7), and vitamin D deficiency for GA (n = 3; 121.2, 30.9–475.3). Moreover, breast cancer with DMF (n = 4, 62.8, 20.5–191.9) and hypothyroidism with Cladr (n = 3; 89.2, 25.9–307.5) were also unexpected. The reporting of drugs-related ADRs in MS were mostly reported in the literature, but some unknown ADRs were also found. However, further studies are necessary to increase the awareness about the safety profiles of new drugs on the market.
Ca2+-Permeable Channels/Ca2+ Signaling in the Regulation of Ileal Na+/Gln Co-Transport in Mice
Authors: Chu Fenglan , Wan Hanxing , Xiao Weidong , Dong Hui , Lü Muhan
Published: February 2022

Oral glutamine (Gln) has been widely used in gastrointestinal (GI) clinical practice, but it is unclear if Ca2+ regulates intestinal Gln transport, although both of them are essential nutrients for mammals. Chambers were used to determine Gln (25 mM)-induced Isc through Na+/Gln co-transporters in the small intestine in the absence or the presence of selective activators or blockers of ion channels and transporters. Luminal but not serosal application of Gln induced marked intestinal Isc, especially in the distal ileum. Lowering luminal Na+ almost abolished the Gln-induced ileal Isc, in which the calcium-sensitive receptor (CaSR) activation were not involved. Ca2+ removal from both luminal and serosal sides of the ileum significantly reduced Gln- Isc. Blocking either luminal Ca2+ entry via the voltage-gated calcium channels (VGCC) or endoplasmic reticulum (ER) release via inositol 1,4,5-triphosphate receptor (IP3R) and ryanodine receptor (RyR) attenuated the Gln-induced ileal Isc, Likewise, blocking serosal Ca2+ entry via the store-operated Ca2+ entry (SOCE), TRPV1/2 channels, and Na+/Ca2+ exchangers (NCX) attenuated the Gln-induced ileal Isc. In contrast, activating TRPV1/2 channels enhanced the Gln-induced ileal Isc. We concluded that Ca2+ signaling is critical for intestinal Gln transport, and multiple plasma membrane Ca2+-permeable channels and transporters play roles in this process. The Ca2+ regulation of ileal Na+/Gln transport expands our understanding of intestinal nutrient uptake and may be significant in GI health and disease.
Impact of Fluoxetine Treatment and Folic Acid Supplementation on the Mammary Gland Transcriptome During Peak Lactation
Authors: Sheftel Celeste M. , Liu Lihe , Field Sena L. , Weaver Samantha R. , Vezina Chad M. , Peñagaricano Francisco , Hernandez Laura L.
Published: February 2022

Serotonin is a key regulator of mammary gland homeostasis during lactation. Selective serotonin reuptake inhibitors (SSRIs) are commonly used to treat peripartum depression, but also modulates mammary gland serotonin concentrations and signaling in part through DNA methylation. The objective of this study was to determine mouse mammary transcriptome changes in response to the SSRI fluoxetine and how methyl donor supplementation, achieved by folic acid supplementation, affected the transcriptome. Female C57BL/6J mice were fed either breeder diet (containing 4 mg/kg folic acid) or supplemented diet (containing 24 mg/kg folic acid) beginning 2 weeks prior to mating, then on embryonic day 13 mice were injected daily with either saline or 20 mg/kg fluoxetine. Mammary glands were harvested at peak lactation, lactation day 10, for transcriptomic analysis. Fluoxetine but not folic acid altered circulating serotonin and calcium concentrations, and folic acid reduced mammary serotonin concentrations, however only fluoxetine altered genes in the mammary transcriptome. Fluoxetine treatment altered fifty-six genes. Elovl6 was the most significantly altered gene by fluoxetine treatment along with gene pathways involving fatty acid homeostasis, PPARγ, and adipogenesis, which are critical for milk fat synthesis. Enriched pathways in the mammary gland by fluoxetine revealed pathways including calcium signaling, serotonin receptors, milk proteins, and cellular response to cytokine stimulus which are important for lactation. Although folic acid did not impact specific genes, a less stringent pathway analysis revealed more diffuse effects where folic acid enriched pathways involving negative regulation of gene expression as expected, but additionally enriched pathways involving serotonin, glycolysis, and lactalbumin which are critical for lactation. In conclusion, peripartal SSRI use and folic acid supplementation altered critical genes related to milk synthesis and mammary gland function that are important to a successful lactation. However, folic acid supplementation did not reverse changes in the mammary gland transcriptome altered by peripartal SSRI treatment.
Canagliflozin Prevents Lipid Accumulation, Mitochondrial Dysfunction, and Gut Microbiota Dysbiosis in Mice With Diabetic Cardiovascular Disease
Authors: Wang Xueliang , Wang Zhe , Liu Di , Jiang Hao , Cai Chao , Li Guoyun , Yu Guangli
Published: February 2022

Type 2 diabetes mellitus (T2DM) is associated with cardiovascular disease (CVD) and sodium glucose cotransporter 2 inhibitors, as oral medications for T2DM treatment have shown the potential to improve vascular dysfunction. The aim of this study was to evaluate the ability of canagliflozin (Cana) to relieve CVD in T2DM mice and its possible action mechanism. Mice with diabetic CVD was conducted by a high-fat diet for 24 weeks, followed by oral gavaging with metformin (200 mg/kg/day) or Cana (50 mg/kg/day) for 6 weeks. The result demonstrated that Cana reduced serum lipid accumulation, and decreased the arteriosclerosis index and atherogenic index of plasma. In addition, Cana treatment reduced the circulating markers of inflammation. More importantly, Cana improved cardiac mitochondrial homeostasis and relieved oxidative stress. Moreover, Cana treatment alleviated the myocardial injury with decreasing levels of serous soluble cluster of differentiation 40 ligand and cardiac troponin I. Thus, cardiovascular abnormality was relieved by suppressing fibrosis and basement membrane thickening, while elevating the cluster of differentiation 31 expression level. Importantly, Cana increased the ratio of gut bacteria Firmicutes/Bacteroidetes and the relative abundance of Alistipes, Olsenella, and Alloprevotella, while it decreased the abundance of Mucispirillum, Helicobacter, and Proteobacteria at various taxonomic levels in mice with diabetic CVD. In short, Cana treatment altered the colonic microbiota composition close to the normal level, which was related with blood lipid, inflammation, and oxidative stress, and might play a vital role in CVD. In general, the improvements in the gut microbiota and myocardial mitochondrial homeostasis may represent the mechanism of Cana on CVD treatment.
A Comparative Study of the Antihypertensive and Cardioprotective Potentials of Hot and Cold Aqueous Extracts of Hibiscus sabdariffa L. in Relation to Their Metabolic Profiles
Authors: Salem Mohamed A. , Ezzat Shahira M. , Ahmed Kawkab A. , Alseekh Saleh , Fernie Alisdair R. , Essam Reham M.
Published: February 2022

Ethnopharmacological relevance: Since ancient times, Hibiscus sabdariffa L. calyces have been used as a folk remedy for the treatment of hypertension. However, it is questionable as to whether there is a difference in the antihypertensive activity of the hot or cold aqueous extracts.

Aim of the study: We designed this study to specify the best method for water extraction of the antihypertensive metabolites of H. sabdariffa and to confirm their in vivo antihypertensive capabilities.

Materials and methods: The powdered dried calyces of H. sabdariffa were independently extracted with cold and hot water. A comparative study was performed between the cold and hot aqueous extracts of H. sabdariffa based on evaluation of the in vitro renin and angiotensin-converting enzyme (ACE) inhibition activities. Additionally, both extracts were subjected to an in vivo study for the evaluation of their antihypertensive activities in L-Nw-Nitro arginine methyl ester (L-NAME)–induced hypertensive rats. Further, a metabolomics study was also performed for both extracts to identify their chemical constituents.

Results: The cold and hot extracts significantly reduced the angiotensin II, ACE, and aldosterone levels in the plasma. Furthermore, in the myocardium and aorta, decreased iNOS (inducible nitric oxide synthase) levels and elevated eNOS (endothelial nitric oxide synthase), as well as the rise in plasma NO levels, were reported with both extracts, but better results were displayed with the hot extract, leading to a potential antihypertensive effect. Additionally, the cold and hot Hibiscus extracts induced a cardioprotective effect through reducing necrosis, inflammation, and vacuolization that results from the induction of hypertension, an effect that was more prominent with the hot extract. Moreover, a comprehensive metabolomics approach using ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC–MS/MS) was able to trace the metabolites in each extraction.

Conclusion: The extracts showed different anthocyanin and phenolic compounds, but the hot extract showed higher contents of specific phenolics to which the superior antihypertensive and cardioprotective activities could be related.
Unraveling the Proteomic Landscape of Intestinal Epithelial Cell-Derived Exosomes in Mice
Authors: Ding Zhenyu , Zhang Cuiyu , Zhang Baokun , Li Qin
Published: February 2022

Purpose

This study aimed to identify the biological functions of small intestine intestinal epithelial cell derived exosomes (IEC-Exos) and further distinguished the difference proteins in IEC-Exos between ileum and jejunum related to function of the digestive system and occurrence of several diseases.

Materials and Methods

IECs of Male C57BL/6J mice were isolated. IEC-Exos were extracted from jejunum and ileum epithelial cell culture fluid by ultracentrifugation. In addition, isobaric tags for relative and absolute quantitation (iTRAQ) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to detect IEC-Exo proteins and conduct biological information analysis.

Results

The results showed that compared with jejunum IEC-Exos from ileum IEC-Exos, there were 393 up-regulated proteins and 346 down-regulated proteins. IECs-Exos, especially derived from jejunum, were rich in angiotensin-converting enzyme 2 (ACE2). The highly expressed proteins from ileum IEC-Exos were mostly enriched in genetic information processing pathways, which mainly mediate the processes of bile acid transport, protein synthesis and processing modification. In contrast, the highly expressed proteins from jejunum IEC-Exos were mainly enriched in metabolic pathways involved in sugar, fatty acid, amino acid, drug, and bone metabolism, etc. The differentially expressed proteins between ileum and jejunum IEC-Exos were not only related to the function of the digestive system but also closely related to the occurrence of infectious diseases, endocrine diseases and osteoarthritis, etc.

Conclusion

IEC-Exos there were many differentially expressed proteins between ileum and jejunum, which played different roles in regulating intestinal biological functions. ACE2, the main host cell receptor of SARS-CoV-2, was highly expressed in IEC-Exos, which indicated that IEC-Exos may be a potential route of SARS-CoV-2 infection.
Ecophysiological Responses of the Lesser Mealworm Alphitobius diaperinus Exposed to Desiccating Conditions
Authors: Engell Dahl Julie , Renault David
Published: February 2022

In order to improve predictions of the impacts of climate change on insects, this study aimed to uncover how exposure to dry conditions can affect the biology of the invasive pest beetle Alphitobius diaperinus in terms of longevity, activity, water content, metabolic profiles, and fecundity. We measured desiccation resistance in adults of A. diaperinus by recording the time the beetles could survive desiccation stress. We found that the species was highly desiccation resistant, with about 50% of the insects exposed to desiccation being able to survive for 30 days, and some individuals even survived for up to 50 days at 10% ± 2 relative humidity. There was no evidence of active upregulation of sugars or other metabolites which the beetles could have used to better tolerate desiccation. Food deprivation affected both control (food deprivation, no desiccation) and treatment (food deprivation, desiccation) groups, as their metabolic phenotypes changed similarly after 1 week of treatment. Also, the activity of beetles from both control and desiccation treatments was similarly increased 2 weeks after the experiment had started. Even if there were no changes in the metabolic phenotypes of the insects experiencing desiccating conditions, beetles exposed to desiccation for 8 days had a significantly reduced reproductive output as compared with control insects. This result indicated a physiological cost of drought resistance or repair of stress-incurred damages. The exact nature of that effect (e.g., direct or indirect physiological costs) has not yet been described for tenebrionid beetles and should be investigated in future studies.
Adipose-Derived Extracellular Vesicles: Systemic Messengers and Metabolic Regulators in Health and Disease
Authors: Bond Simon T. , Calkin Anna C. , Drew Brian G.
Published: February 2022

Adipose tissue is comprised of a heterogeneous population of cells that co-operate to perform diverse physiological roles including endocrine-related functions. The endocrine role of adipose tissue enables it to communicate nutritional and health cues to other organs, such as the liver, muscle, and brain, in order to regulate appetite and whole body metabolism. Adipose tissue dysfunction, which is often observed in obesity, is associated with changes in the adipose secretome, which can subsequently contribute to disease pathology. Indeed, secreted bioactive factors released from adipose tissue contribute to metabolic homeostasis and likely play a causal role in disease; however, what constitutes the entirety of the adipose tissue secretome is still poorly understood. Recent advances in nanotechnology have advanced this field substantially and have led to the identification of small, secreted particles known as extracellular vesicles (EVs). These small nano-sized lipid envelopes are released by most cell types and are capable of systemically delivering bioactive molecules, such as nucleic acids, proteins, and lipids. EVs interact with target cells to deliver specific cargo that can then elicit effects in various tissues throughout the body. Adipose tissue has recently been shown to secrete EVs that can communicate with the periphery to maintain metabolic homeostasis, or under certain pathological conditions, drive disease. In this review, we discuss the current landscape of adipose tissue-derived EVs, with a focus on their role in the regulation of metabolic homeostasis and disease pathology.
Storage-Induced Micro-Erythrocytes Can Be Quantified and Sorted by Flow Cytometry
Authors: Marin Mickaël , Peltier Sandy , Hadjou Youcef , Georgeault Sonia , Dussiot Michaël , Roussel Camille , Hermine Olivier , Roingeard Philippe , Buffet Pierre A. , Amireault Pascal
Published: February 2022

Refrigerated storage of red cell concentrates before transfusion is associated with progressive alterations of red blood cells (RBC). Small RBC (type III echinocytes, sphero-echinocytes, and spherocytes) defined as storage-induced micro-erythrocytes (SME) appear during pretransfusion storage. SME accumulate with variable intensity from donor to donor, are cleared rapidly after transfusion, and their proportion correlates with transfusion recovery. They can be rapidly and objectively quantified using imaging flow cytometry (IFC). Quantifying SME using flow cytometry would further facilitate a physiologically relevant quality control of red cell concentrates. RBC stored in blood bank conditions were stained with a carboxyfluorescein succinimidyl ester (CFSE) dye and incubated at 37°C. CFSE intensity was assessed by flow cytometry and RBC morphology evaluated by IFC. We observed the accumulation of a CFSEhigh RBC subpopulation by flow cytometry that accounted for 3.3 and 47.2% at day 3 and 42 of storage, respectively. IFC brightfield images showed that this CFSEhigh subpopulation mostly contains SME while the CFSElow subpopulation mostly contains type I and II echinocytes and discocytes. Similar numbers of SME were quantified by IFC (based on projected surface area) and by flow cytometry (based on CFSE intensity). IFC and scanning electron microscopy showed that ≥95% pure subpopulations of CFSEhigh and CFSElow RBC were obtained by flow cytometry-based sorting. SME can now be quantified using a common fluorescent dye and a standard flow cytometer. The staining protocol enables specific sorting of SME, a useful tool to further characterize this RBC subpopulation targeted for premature clearance after transfusion.
Spinal Reflex Control of Arterial Blood Pressure: The Role of TRP Channels and Their Endogenous Eicosanoid Modulators
Authors: Minic Zeljka , O’Leary Donal S. , Reynolds Christian A.
Published: February 2022

The spinal cord is an important integrative center for blood pressure control. Spinal sensory fibers send projections to sympathetic preganglionic neurons of the thoracic spinal cord and drive sympathetically-mediated increases in blood pressure. While these reflexes responses occur in able-bodied individuals, they are exaggerated following interruption of descending control – such as occurs following spinal cord injury. Similar reflex control of blood pressure may exist in disease states, other than spinal cord injury, where there is altered input to sympathetic preganglionic neurons. This review primarily focuses on mechanisms wherein visceral afferent information travelingviaspinal nerves influences sympathetic nerve activity and blood pressure. There is an abundance of evidence for the widespread presence of this spinal reflex arch originating from virtually every visceral organ and thus having a substantial role in blood pressure control. Additionally, this review highlights specific endogenous eicosanoid species, which modulate the activity of afferent fibers involved in this reflex, through their interactions with transient receptor potential (TRP) cation channels.
Aerially Applied Zinc Oxide Nanoparticle Affects Reproductive Components and Seed Quality in Fully Grown Bean Plants (Phaseolus vulgaris L.)
Authors: Salehi Hajar , Chehregani Rad Abdolkarim , Sharifan Hamidreza , Raza Ali , Varshney Rajeev K.
Published: February 2022

The development of reproductive components in plant species is susceptible to environmental stresses. The extensive application of zinc oxide nanoparticles (nZnO) in various agro-industrial processes has jeopardized the performance and functionality of plants. To understand the response of the developmental (gametogenesis and sporogenesis) processes to nanoparticles (NPs) exposure, the aerial application of nZnO and their ionic counterpart of ZnSO4 at four different levels were examined on bean plants (Phaseolus vulgaris) before the flowering stage. To evaluate the mentioned processes, briefly, flowers in multiple sizes were fixed in paraffin, followed by sectioning and optical analysis. The possibility of alteration in reproductive cells was thoroughly analyzed using both light and electron microscopes. Overall, our results revealed the histological defects in male and female reproductive systems of mature plants depend on NPs levels. Furthermore, NPs caused tapetum abnormalities, aberrations in carbohydrate accumulation, and apoptosis. The nZnO induced abnormal alterations right after meiosis and partly hindered the microspore development, leading to infertile pollens. The seed yield and dry weight were reduced to 70 and 82% at 2,000 mg L–1 nZnO foliar exposure, respectively. The sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis pattern showed the increased expression of two proteins at the molecular weight of 28 and 42 kDa at various concentrations of nZnO and ZnSO4. Overall, our results provided novel insights into the negative effect of nano-scaled Zn on the differential mechanism involved in the reproductive stage of the plants compared with salt form.
Triploid Hybrid Vigor in Above-Ground Growth and Methane Fermentation Efficiency of Energy Willow
Authors: Dudits Dénes , Cseri András , Török Katalin , Sass László , Zombori Zoltán , Ferenc Györgyi , Poór Péter , Borbély Péter , Czékus Zalán , Vankova Radomira , Dobrev Petre , Szántó Judit , Bagi Zoltán , Kovács Kornél L.
Published: February 2022

Hybrid vigor and polyploidy are genetic events widely utilized to increase the productivity of crops. Given that bioenergy usage needs to be expanded, we investigated triploid hybrid vigor in terms of the biology of biomass-related willow traits and their relevance to the control of biomethane production. To produce triploid hybrid genotypes, we crossed two female diploid Swedish cultivars (Inger, Tordis) with two male autotetraploid willow (Salix viminalis) variants (PP-E7, PP-E15). Field studies at two locations and in two successive years recorded considerable midparent heterosis (MPH%) in early shoot length that ranged between 11.14 and 68.85% and in the growth rate between 34.12 and 97.18%. The three triploid hybrids (THs) developed larger leaves than their parental cultivars, and the MPH% for their CO2 assimilation rate varied between 0.84 and 25.30%. The impact of hybrid vigor on the concentrations of plant hormones in these TH genotypes reflected essentially different hormonal statuses that depended preferentially on maternal parents. Hybrid vigor was evinced by an elevated concentration of jasmonic acid in shoot meristems of all the three THs (MPH:29.73; 67.08; 91.91%). Heterosis in auxin-type hormones, such as indole-3-acetic acid (MPH:207.49%), phenylacetic acid (MPH:223.51%), and salicylic acid (MPH:27.72%) and benzoic acid (MPH:85.75%), was detectable in the shoots of TH21/2 plants. These hormones also accumulated in their maternal Inger plants. Heterosis in cytokinin-type hormones characterized the shoots of TH3/12 and TH17/17 genotypes having Tordis as their maternal parent. Unexpectedly, we detected abscisic acid as a positive factor in the growth of TH17/17 plants with negative MPH percentages in stomatal conductance and a lower CO2 assimilation rate. During anaerobic digestion, wood raw materials from the triploid willow hybrids that provided positive MPH% in biomethane yield (6.38 and 27.87%) showed negative MPH in their acid detergent lignin contents (from –8.01 to –14.36%). Altogether, these insights into controlling factors of above-ground growth parameters of willow genotypes support the utilization of triploid hybrid vigor in willow breeding to expand the cultivation of short rotation energy trees for renewable energy production.
The NAC Transcription Factor ANAC087 Induces Aerial Rosette Development and Leaf Senescence in Arabidopsis
Authors: Vargas-Hernández Brenda Yazmín , Núñez-Muñoz Leandro , Calderón-Pérez Berenice , Xoconostle-Cázares Beatriz , Ruiz-Medrano Roberto
Published: February 2022

CmNACP1 mRNA has been shown to move long distance through the phloem in Cucurbita maxima (pumpkin) and through a graft junction. Whereas the phloem transport of several different mRNAs has been documented in other systems as well, its function remains, for most of these RNAs, largely unknown. To gain insight into the possible role of these RNAs, we searched for the closest homologs of CmNACP1 in Arabidopsis, a model plant much more amenable for analysis. A phylogenetic approach using the predicted NAC domain indicated that ANAC059, ANAC092, ANAC079, ANAC100, ANAC046, and ANAC087 form a single clade with CmNACP1. In the present work, we analyzed the possible function of the ANAC087 gene in more detail. The promoter region of this gene directed expression in the vasculature, and also in trichomes, stem, apexes, and developing flowers which supports the notion that ANAC087 and CmNACP1 are orthologs. Overexpression of the ANAC087 gene induced increased branching in inflorescence stem, and also development of ectopic or aerial rosettes in T1 and T2 plants. Furthermore, overexpression of ANAC087 leads to accelerated leaf senescence in 44 days post-germination (dpg). Interestingly, a similar phenotype was observed in plants expressing the ANAC087 gene upstream region, also showing an increase in ANAC087 transcript levels. Finally, the results shown in this work indicate a role for ANAC087 in leaf senescence and also in rosette development.
Identification of Chilling Accumulation-Associated Genes for Litchi Flowering by Transcriptome-Based Genome-Wide Association Studies
Authors: Lu Xingyu , Lü Peitao , Liu Hao , Chen Houbin , Pan Xifen , Liu Pengxu , Feng Lei , Zhong Silin , Zhou Biyan
Published: February 2022

Litchi is an important Sapindaceae fruit tree. Flowering in litchi is triggered by low temperatures in autumn and winter. It can be divided into early-, medium-, and late-flowering phenotypes according to the time for floral induction. Early-flowering varieties need low chilling accumulation level for floral induction, whereas the late-flowering varieties require high chilling accumulation level. In the present study, RNA-Seq of 87 accessions was performed and transcriptome-based genome-wide association studies (GWAS) was used to identify candidate genes involved in chilling accumulation underlying the time for floral induction. A total of 98,155 high-quality single-nucleotide polymorphism (SNP) sites were obtained. A total of 1,411 significantly associated SNPs and 1,115 associated genes (AGs) were identified, of which 31 were flowering-related, 23 were hormone synthesis-related, and 27 were hormone signal transduction-related. Association analysis between the gene expression of the AGs and the flowering phenotypic data was carried out, and differentially expressed genes (DEGs) in a temperature-controlled experiment were obtained. As a result, 15 flowering-related candidate AGs (CAGs), 13 hormone synthesis-related CAGs, and 11 hormone signal transduction-related CAGs were further screened. The expression levels of the CAGs in the early-flowering accessions were different from those in the late-flowering ones, and also between the flowering trees and non-flowering trees. In a gradient chilling treatment, flowering rates of the trees and the CAGs expression were affected by the treatment. Our present work for the first time provided candidate genes for genetic regulation of flowering in litchi using transcriptome-based GWAS.
Transcriptomic and Metabolomic Analyses Reveal the Differential Regulatory Mechanisms of Compound Material on the Responses of Brassica campestris to Saline and Alkaline Stresses
Authors: Li Ziwei , An Mengjie , Hong Dashuang , Chang Doudou , Wang Kaiyong , Fan Hua
Published: February 2022

Oilseed rape not only has the function of improve saline and alkaline soils, but also alleviate the local feed shortage. However, medium- and high-degree soil salinization and alkalinization always inhibit the growth of oilseed rape. Studies have shown that compound material can improve the tolerance to saline and alkaline stress of crops, but the difference in the regulation mechanism of compound material on oilseed rape in saline and alkaline soils is not clear. This study explored the difference through determining the leaf ion contents, physiological indexes, transcriptomics, and metabolomics of oilseed rape in salinized soil (NaCl 8 g kg−1) and alkalinized soil (Na2CO3 8 g kg−1) at full flowering stage, respectively after the application of compound material. The results showed that in salinized and alkalinized soil, the compound material upregulated the genes related to the regulation of potassium ion transport, and changed the amino acid metabolic pathway, which reduced the contents of Na+, malondialdehyde (MDA), and relative conductivity (REC) in leaves, and increased the contents of K+ and Mg2+ and the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT). However, there were differences in the regulation mechanism of compound material in salinized and alkalinized soil. In salinized soil, the compound material improved the tolerance of oilseed rape to saline stress by upregulating transcription factors mannose-1-phosphate guanylyltransferase (GPMM) and Glutamine--fructose-6-phosphate transaminase (GFPT) and downregulating phosphomannomutase (PMM) to change nucleotide metabolism pathway and lipid metabolism pathway. In alkalized soil, the compound material improved the tolerance of oilseed rape to alkaline stress by upregulating transcription factors Phenylalanine ammonia lyase (PAL) to change the biosynthesis pathway of other secondary metabolites. Therefore, the compound material can improve the tolerance of oilseed rape to saline and alkaline stress by regulating the genetic adaptability and apparent plasticity, but the mechanisms were different. This study provides a practical method for the ecological environment restoration and the development of animal husbandry.
Highly Resolved Papilionoid Legume Phylogeny Based on Plastid Phylogenomics
Authors: Choi In-Su , Cardoso Domingos , de Queiroz Luciano P. , de Lima Haroldo C. , Lee Chaehee , Ruhlman Tracey A. , Jansen Robert K. , Wojciechowski Martin F.
Published: February 2022

Comprising 501 genera and around 14,000 species, Papilionoideae is not only the largest subfamily of Fabaceae (Leguminosae; legumes), but also one of the most extraordinarily diverse clades among angiosperms. Papilionoids are a major source of food and forage, are ecologically successful in all major biomes, and display dramatic variation in both floral architecture and plastid genome (plastome) structure. Plastid DNA-based phylogenetic analyses have greatly improved our understanding of relationships among the major groups of Papilionoideae, yet the backbone of the subfamily phylogeny remains unresolved. In this study, we sequenced and assembled 39 new plastomes that are covering key genera representing the morphological diversity in the subfamily. From 244 total taxa, we produced eight datasets for maximum likelihood (ML) analyses based on entire plastomes and/or concatenated sequences of 77 protein-coding sequences (CDS) and two datasets for multispecies coalescent (MSC) analyses based on individual gene trees. We additionally produced a combined nucleotide dataset comprising CDS plus matK gene sequences only, in which most papilionoid genera were sampled. A ML tree based on the entire plastome maximally supported all of the deep and most recent divergences of papilionoids (223 out of 236 nodes). The Swartzieae, ADA (Angylocalyceae, Dipterygeae, and Amburaneae), Cladrastis, Andira, and Exostyleae clades formed a grade to the remainder of the Papilionoideae, concordant with nine ML and two MSC trees. Phylogenetic relationships among the remaining five papilionoid lineages (Vataireoid, Dermatophyllum, Genistoid s.l., Dalbergioid s.l., and Baphieae + Non-Protein Amino Acid Accumulating or NPAAA clade) remained uncertain, because of insufficient support and/or conflicting relationships among trees. Our study fully resolved most of the deep nodes of Papilionoideae, however, some relationships require further exploration. More genome-scale data and rigorous analyses are needed to disentangle phylogenetic relationships among the five remaining lineages.
Experimental Climate Warming Reduces Floral Resources and Alters Insect Visitation and Wildflower Seed Set in a Cereal Agro-Ecosystem
Authors: Moss Ellen D. , Evans Darren M.
Published: February 2022

Declines in pollinating insects and wildflowers have been well documented in recent years. Climate change is an emerging threat to insect pollinators and their food plants, but little is known about how whole communities of interacting species will be affected or what impacts there may be on ecosystem services such as pollination. Using a novel open-air field experiment, we simulated an increase in temperature of 1.5°C and rainwater of 40% for two growing seasons to investigate how climate change may impact several within-field features of temperate arable agro-ecosystems: (1) wildflower floral resources; (2) insect visitation; (3) flower-visitor network structure; and (4) wildflower seed set. Experimental warming reduced total floral abundance by nearly 40%, and nectar volumes by over 60% for two species. The species richness of the visiting insects and flowering plants (dominated by annuals) were unaffected by warming, and while a negative impact on visitor abundance was observed, this effect appears to have been mediated by different community compositions between years. Warming increased the frequency of visits to flowers and the complexity of the flower-visitor interaction networks. Wildflower seed set was reduced in terms of seed number and/or weight in four of the five species examined. Increased rainwater did not ameliorate any of these effects. These findings demonstrate the adverse impacts that climate warming might have on annual wildflowers in arable systems and the pollinating insects that feed on them, highlighting several mechanisms that could drive changes in community composition over time. The results also reveal how cascading impacts within communities can accumulate to affect ecosystem functioning.
Quality of Life and Depressive Symptoms Among Peruvian University Students During the COVID-19 Pandemic
Authors: Figueroa-Quiñones Joel , Cjuno Julio , Machay-Pak Daniel , Ipanaqué-Zapata Miguel
Published: February 2022

Objective

To determine the factors associated with quality of life and depressive symptoms in Peruvian university students during the COVID-19 pandemic.

Methods

Multicentre study in 1,634 students recruited by convenience sampling. The quality of life (QoL) was assessed with the European Quality of Life-5 Dimensions at three levels (EQ-5D-3L) and depressive symptoms with the Patient Health Questionnaire-9 (PHQ-9). To assess factors associated with QoL and depressive symptoms, linear regressions and fitted regressions were used, with robust coefficients of variance information (β).

Results

A 345 (21.1%) reported problems in performing daily activities, 544 (33.3%) reported pain and discomfort, 772 (47.2%) were moderately/very anxious or depressed. Furthermore, 207 (12.7%) had moderate-severe and severe depressive symptoms. Men reported better QoL than women (β: 3.2; 95% CI: 1.1, 5.4; p = 0.004) and fewer depressive symptoms (β: −0.7; 95% CI: −1.3, −0.2; p = 0.011). Ayacucho’s residents had more depressive symptoms than Ancash’s residents (β: 0.8; 95% CI: 0.1, 1.5; p = 0.022) and Piura’s residents had fewer depressive symptoms than Ancash’s residents (β: −1.195% CI: −1.8, −0.3, p = 0.005). Students who left home during quarantine reported more depressive symptoms (β: 0.7, 95% CI: 0.2, 1.2, p = 0.006).

Conclusion

Problems performing daily activities, pain and discomfort, as well as mild to severe depressive symptoms were found in more than three-quarters of the sample. Authorities could consider depression care to improve quality of life in regions where high rates of infection occurred during the pandemic.
Age Difference in Roles of Perceived Social Support and Psychological Capital on Mental Health During COVID-19
Authors: Cao Shiyue , Zhu Yue , Li Pei , Zhang Wei , Ding Cody , Yang Dong
Published: February 2022

Due to the outbreak of the Coronavirus Disease-2019 (COVID-19) pandemic and consequent confinement measures, young people are vulnerable to mental health problems. The current study compared a group of 440 young adolescents (10–12 years) and a group of 330 emerging adults (18–25 years) to investigate the extent to which perceived social support and psychological capital (PsyCap) were differentially associated with mental health problems. Participants were asked to report their current psychosocial adaptation status during the COVID-19 pandemic, and data were collected via online questionnaires during a relatively severe period of COVID-19 in China. Results of the multi-group path analysis indicated that the effect of perceived social support on mental health problems was mediated by PsyCap for young adolescents, but not for emerging adults. These results were discussed with respect to the mechanism of how social support and PsyCap serve as protective mental health factors for youth in the context of the COVID-19 pandemic.