bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of different cutting methods and additives on the fermentation quality and microbial community of Saccharum arundinaceum silage
Authors: Zheng Yulong , Li Mengxin , Xu Jinyi , Sun Hong , Cheng Qiming , Xie Yixiao , Wang Chunmei , Chen Chao , Li Ping
Published: September 2022

To develop a new high-yielding and polysaccharide-containing forage resource for livestock, the effects of different cutting methods and additives on Saccharum arundinaceum silage were evaluated. The wilted S. arundinaceum were chopped and knead-wired. The silages from each cutting method were treated with Lactobacillus plantarum (LP), cellulase (CE) and the combination of LP and CE (LP + CE) for 3, 7, 15, 30, and 60 days. Compared with the CK treatment, CE treatment exhibited better effects in the degradation of neutral detergent fiber (NDF), LP exhibited a better performance in preserving the content of dry matter (DM), and adding LP + CE significantly enhanced (P < 0.05) the contents of lactic acid (LA), crude protein (CP) and DM and significantly reduced (P < 0.05) the pH and NDF content during ensiling. In addition, both additives exerted a remarkable effect on the silage bacterial community (P < 0.05), with a dramatic increase in the Lactobacillus abundance and a decrease in the abundance of Enterobacter. Lactic acid bacteria (LAB) became the most dominant bacteria that affected the fermentation quality of LP and LP + CE silages. Meanwhile, chopped silages showed better fermentation quality and nutrient preservation and a higher abundance of LAB. Our research indicated that the chopped S. arundinaceum ensiling with LP + CE could exert a positive effect on LA fermentation and preservation of nutrient substances by shifting the bacterial community. In conclusion, S. arundinaceum can serve as a new silage resource for feed utilization by the ensiling method of LP + CE-chopped.
Association of THBS1 genetic variants and mRNA expression with the risks of ischemic stroke and long-term death after stroke
Authors: Chen Changying , Chen Xuemei , Yang Siyuan , Li Qingqing , Ren Zhanyun , Wang Lu , Jiang Yuzhang , Gu Xincheng , Liu Fangyuan , Mu Jialing , Liu Lihua , Wang Yi , Li Junrong , Yu Yanhua , Zhang Jun , Shen Chong
Published: September 2022

Background

Thrombospondin-1 (THBS1) derived from platelets and acted as a critical mediator of hemostasis promoting platelet activation in thrombus formation. The biological connection of genetic variants and mRNA expression of THBS1 with ischemic stroke (IS) warrants further validation with population-based evidence.

Objective

To evaluate the association of single nucleotide polymorphisms (SNPs) and mRNA expression of THBS1 with the risks of IS and long-term death after stroke.

Methods

A case-control study consisted of 4,584 IS patients recruited from five hospitals in Jiangsu, China, and 4,663 age-gender-matched controls free of IS. A cohort study enrolled 4,098 participants free of stroke and lasted from 2009 to 2022. Early collected 3158 IS patients aged between 35 and 80 years were followed up an average of 5.86-year to follow up their long-term death outcomes. Two tagSNPs of the THBS1 gene, rs2236471 and rs3743125, were genotyped in all subjects and THBS1 mRNA expression of peripheral leukocyte was measured using RT-qPCR in 314 IS cases and 314 controls.

Results

There is no significant difference in genotype and haplotype frequencies of rs2236741 and rs3743125 between IS cases and controls (all P > 0.05). Furthermore, the cohort studies did not observe significant associations between THBS1 variants and the risk of IS incidence or long-term death after IS (all P > 0.05). The THBS1 mRNA expression level (2–ΔΔCT) in IS cases was approximately equal to that in controls (1.01 vs. 0.99, P = 0.833). In addition, THBS1 mRNA expression had no significant association with all-cause death, stroke death, and IS death of IS patients (all P > 0.05).

Conclusion

Therefore, our study suggested that there is no significant association of THBS1 polymorphisms and mRNA expression level with the risk of IS and long-term death after IS.
Early life stress is associated with the default mode and fronto-limbic network connectivity among young adults
Authors: Ilomäki Miro , Lindblom Jallu , Salmela Viljami , Flykt Marjo , Vänskä Mervi , Salmi Juha , Tolonen Tuija , Alho Kimmo , Punamäki Raija-Leena , Wikman Patrik
Published: September 2022

Exposure to early life stress (ELS) is associated with a variety of detrimental psychological and neurodevelopmental effects. Importantly, ELS has been associated with regional alterations and aberrant connectivity in the structure and functioning of brain regions involved in emotion processing and self-regulation, creating vulnerability to mental health problems. However, longitudinal research regarding the impact of ELS on functional connectivity between brain regions in the default mode network (DMN) and fronto-limbic network (FLN), both implicated in emotion-related processes, is relatively scarce. Neuroimaging research on ELS has mostly focused on single nodes or bi-nodal connectivity instead of functional networks. We examined how ELS is associated with connectivity patterns within the DMN and FLN during rest in early adulthood. The participants (n= 86; 47 females) in the current functional magnetic resonance imaging (fMRI) study were young adults (18–21 years old) whose families had participated in a longitudinal study since pregnancy. ELS was assessed both prospectively (parental reports of family relationship problems and mental health problems during pregnancy and infancy) and retrospectively (self-reported adverse childhood experiences). Inter-subject representational similarity analysis (IS-RSA) and multivariate distance matrix regression (MDMR) were used to analyze the association between ELS and the chosen networks. The IS-RSA results suggested that prospective ELS was associated with complex alterations within the DMN, and that retrospective ELS was associated with alterations in the FLN. MDMR results, in turn, suggested that that retrospective ELS was associated with DMN connectivity. Mean connectivity of the DMN was also associated with retrospective ELS. Analyses further showed that ELS-related alterations in the FLN were associated with increased connectivity between the prefrontal and limbic regions, and between different prefrontal regions. These results suggest that exposure to ELS in infancy might have long-lasting influences on functional brain connectivity that persist until early adulthood. Our results also speak for the importance of differentiating prospective and retrospective assessment methods to understand the specific neurodevelopmental effects of ELS.
Dissociating motor impairment from five-choice serial reaction time task performance in a mouse model of Angelman syndrome
Authors: Negrón-Moreno Paola N. , Diep David T. , Guoynes Caleigh D. , Sidorov Michael S.
Published: September 2022

Angelman syndrome (AS) is a single-gene neurodevelopmental disorder associated with cognitive and motor impairment, seizures, lack of speech, and disrupted sleep. AS is caused by loss-of-function mutations in the UBE3A gene, and approaches to reinstate functional UBE3A are currently in clinical trials in children. Behavioral testing in a mouse model of AS (Ube3am–/p+) represents an important tool to assess the effectiveness of current and future treatments preclinically. Existing behavioral tests effectively model motor impairments, but not cognitive impairments, in Ube3am–/p+ mice. Here we tested the hypothesis that the 5-choice serial reaction time task (5CSRTT) can be used to assess cognitive behaviors in Ube3am–/p+ mice. Ube3am–/p+ mice had more omissions during 5CSRTT training than wild-type littermate controls, but also showed impaired motor function including open field hypoactivity and delays in eating pellet rewards. Motor impairments thus presented an important confound for interpreting this group difference in omissions. We report that despite hypoactivity during habituation, Ube3am–/p+ mice had normal response latencies to retrieve rewards during 5CSRTT training. We also accounted for delays in eating pellet rewards by assessing omissions solely on trials where eating delays would not impact results. Thus, the increase in omissions in Ube3am–/p+ mice is likely not caused by concurrent motor impairments. This work underscores the importance of considering how known motor impairments in Ube3am–/p+ mice may affect behavioral performance in other domains. Our results also provide guidance on how to design a 5CSRTT protocol that is best suited for future studies in Ube3a mutants.
Epigenetic regulation of GABAergic differentiation in the developing brain
Authors: Gao Juanmei , Luo Yuhao , Lu Yufang , Wu Xiaohua , Chen Peiyao , Zhang Xinyu , Han Lu , Qiu Mengsheng , Shen Wanhua
Published: September 2022

In the vertebrate brain, GABAergic cell development and neurotransmission are important for the establishment of neural circuits. Various intrinsic and extrinsic factors have been identified to affect GABAergic neurogenesis. However, little is known about the epigenetic control of GABAergic differentiation in the developing brain. Here, we report that the number of GABAergic neurons dynamically changes during the early tectal development in the Xenopus brain. The percentage of GABAergic neurons is relatively unchanged during the early stages from stage 40 to 46 but significantly decreased from stage 46 to 48 tadpoles. Interestingly, the histone acetylation of H3K9 is developmentally decreased from stage 42 to 48 (about 3.5 days). Chronic application of valproate acid (VPA), a broad-spectrum histone deacetylase (HDAC) inhibitor, at stage 46 for 48 h increases the acetylation of H3K9 and the number of GABAergic cells in the optic tectum. VPA treatment also reduces apoptotic cells. Electrophysiological recordings show that a VPA induces an increase in the frequency of mIPSCs and no changes in the amplitude. Behavioral studies reveal that VPA decreases swimming activity and visually guided avoidance behavior. These findings extend our understanding of histone modification in the GABAergic differentiation and neurotransmission during early brain development.
Axonal α7* nicotinic acetylcholine receptors modulate glutamatergic signaling and synaptic vesicle organization in ventral hippocampal projections
Authors: Zhong Chongbo , Akmentin Wendy , Role Lorna W. , Talmage David A.
Published: September 2022

Modulation of the release of glutamate by activation of presynaptic nicotinic acetylcholine receptors (nAChRs) is one of the most prevalent mechanism of nicotinic facilitation of glutamatergic transmission in cortico-limbic circuits. By imaging gene chimeric co-cultures from mouse, we examined the role of α7* nAChRs mediated cholinergic modulation of glutamate release and synaptic vesicle organization in ventral hippocampal projections. We directly visualized exogenous and endogenous cholinergic facilitation of glutamate release in this specialized preparation of circuits in vitro. Disrupting α7* nAChRs mediated cholinergic signaling genetically or pharmacologically diminished cholinergic facilitation of glutamate release at presynaptic terminals. Alteration of α7* nAChRs mediated cholinergic signaling along glutamatergic axons also decreased functional synaptic vesicle clustering to presynaptic terminals. These findings suggest that presynaptic α7* nAChRs contribute to cholinergic modulation of glutamate release and synaptic vesicle organization.
Efficient Temporal Coding in the Early Visual System: Existing Evidence and Future Directions
Authors: Price Byron H. , Gavornik Jeffrey P.
Published: September 2022

While it is universally accepted that the brain makes predictions, there is little agreement about how this is accomplished and under which conditions. Accurate prediction requires neural circuits to learn and store spatiotemporal patterns observed in the natural environment, but it is not obvious how such information should be stored, or encoded. Information theory provides a mathematical formalism that can be used to measure the efficiency and utility of different coding schemes for data transfer and storage. This theory shows that codes become efficient when they remove predictable, redundant spatial and temporal information. Efficient coding has been used to understand retinal computations and may also be relevant to understanding more complicated temporal processing in visual cortex. However, the literature on efficient coding in cortex is varied and can be confusing since the same terms are used to mean different things in different experimental and theoretical contexts. In this work, we attempt to provide a clear summary of the theoretical relationship between efficient coding and temporal prediction, and review evidence that efficient coding principles explain computations in the retina. We then apply the same framework to computations occurring in early visuocortical areas, arguing that data from rodents is largely consistent with the predictions of this model. Finally, we review and respond to criticisms of efficient coding and suggest ways that this theory might be used to design future experiments, with particular focus on understanding the extent to which neural circuits make predictions from efficient representations of environmental statistics.
Outcome of CPAP Titration for Moderate-to-Severe OSA Under Drug-Induced Sleep Endoscopy: A Randomized Controlled Crossover Trial
Authors: Wang Tsai-Yu , Huang Yu-Chen , Lin Ting-Yu , Ni Yung-Lun , Lo Yu-Lun
Published: September 2022

Background

The titration pressure of continuous positive airway pressure (CPAP) is important in patients with obstructive sleep apnea (OSA). This study aimed to understand the difference between drug-induced sleep endoscopy (DISE)-guided CPAP titration and conventional sleep center (CSC) CPAP titration in patients with OSA.

Methods

In this randomized, controlled, and single-blind crossover trial, we compared the effects of 1-month CPAP treatment in patients with OSA with either DISE-guided CPAP titration or CSC CPAP titration. Twenty-four patients with OSA were recruited for the study. All patients underwent polysomnography, DISE-guided CPAP titration, and accommodation. Initially, patients were randomly assigned to receive either DISE-guided CPAP titration or CSC CPAP treatment for the first month. They were then switched to other treatments in the second month. The Epworth sleepiness scale (ESS) score was recorded at baseline, 1 and 2 months.

Results

The upper limit of the pressure of DISE-guided titration and CSC CPAP titration was not significantly different (13.9 ± 0.7 vs. 13.5 ± 0.5 cm H2O; P = 0.92). The residual apnea-hypopnea index and compliance were also not significantly different between the groups. ESS score significantly improved from baseline to 1 month after CPAP treatment in both groups. Both epiglottis (anterior-posterior collapse) and tongue base collapse were significantly associated with 95% CPAP pressure (P = 0.031 and 0.038, respectively). After multivariate regression analyses, the epiglottis (anterior-posterior collapse) was an independent factor for 95% CPAP pressure. The incidence rate of bradycardia was 58.3%, which is a safety concern for DISE. Despite the high incidence of bradycardia, all patients with bradycardia recovered with proper management.

Conclusion

Both modalities were comparable in terms of establishing the pressure settings required to treat patients. Further large-scale studies are required to confirm these results.

Trial registration

https://clinicaltrials.gov/, NCT03523013.
An interactive web-based programme on relapse management for people with multiple sclerosis (POWER@MS2) - development, feasibility, and pilot testing of a complex intervention
Authors: Wenzel Lisa , Heesen Christoph , Peper Julia , Grentzenberg Kristina , Faßhauer Edeltraud , Scheiderbauer Jutta , Thale Frithjof , Meyer Björn , Köpke Sascha , Rahn Anne Christin
Published: September 2022

Introduction

Despite the lack of high-quality evidence regarding its long-term effectiveness, intravenous corticosteroid therapy is recommended as the standard treatment of acute multiple sclerosis relapses in Germany. High financial expenses and the equivalent effectiveness of oral corticosteroid therapy contrast with this trend. There is an urgent need to provide patients with evidence-based and comprehensible information on relapse management and to actively involve patients in relapse treatment decisions. Web-based decision support on relapse management could be an effective measure to empower people with multiple sclerosis making informed treatment decisions.

Objectives

To develop a web-based programme on relapse management for people with multiple sclerosis and evaluate the feasibility and acceptability of the intervention.

Methods

The study followed the first two phases of the UK Medical Research Council Framework for complex interventions. The first phase involved the development of an interactive web-based programme on relapse management. The second phase focused on the feasibility and pilot testing of the programme with people with multiple sclerosis and experts with a professional background in multiple sclerosis. Data was obtained using questionnaires with closed- and open-ended questions as well as qualitative semi-structured telephone interviews. Quantitative data was analyzed descriptively, whereas qualitative data was clustered by topic.

Results

Feasibility of the intervention programme was tested with 10 people with multiple sclerosis and 10 experts. Feasibility testing indicated good practicability and acceptance of the content. After revision, the programme was piloted with seven people with multiple sclerosis and three experts. The results showed good acceptance in both groups. Based on the feedback, a final revision was performed.

Conclusion

Feasibility and pilot testing indicated good user-friendliness, acceptance, and practicability of the programme. The programme is currently evaluated in a randomized controlled trial (Registration Number on ClinicalTrials.gov: NCT04233970). It is expected that the programme will have a positive impact on patients' relapse management and strengthen their autonomy and participation.
Longitudinal investigation of the factor structure of the Parkinson's disease activities of daily living, interference and dependence instrument
Authors: Sirbu Cristian , Saxby Brian K. , McNamara Cynthia W. , Deal Linda S.
Published: September 2022

The Parkinson's Disease Activities of Daily Living, Interference, and Dependence Instrument© (PD-AID) is a patient-reported outcome (PRO) instrument, recently developed to assess the clinical benefit of Parkinson's Disease (PD) treatment. The PD-AID consists of morning and evening assessments, administered daily. To benefit from the full set of the repeated observations over time, analytic approaches that account for both within- and between-individual variability are required. The current study aimed to employ the advantages of exploratory Multilevel Factor Analysis (MFA) on data collected from 93 participants with moderate to advanced PD, currently using and responding to Levodopa (L-Dopa), who completed the PD-AID twice daily as part of a prospective, non-intervention, observational study for ~28 days. Average daily completion rates were comparable for the Morning and the Evening PD-AID (78% and 74%, respectively). The intraclass correlation coefficients for the Morning and Evening PD-AID items were in the range of 0.70–0.90, with an average of 0.81 for the Morning PD-AID items and 0.83 for the Evening PD-AID items, suggesting that most variability (81%–83%) in responses was due to between-individual variability. For the Morning PD-AID, one factor (including nine out of 10 Morning PD-AID items) emerged at the between-individual level and four factors (core physical actions, basic self-care activities, feeding, and interference & dependence) at the within-individual level. For the Evening PD-AID, there were four between-individual factors (basic activities of daily living ADLs, life interference, impact on planning, and emotional consequences) and five within-individual factors (basic ADLs, toileting, life interference, medication planning, and emotional impact). The factors had high reliability.
Sex-related differences in spontaneous intracerebral hemorrhage outcomes: A prognostic study based on 111,112 medical records
Authors: Zhao Jieyi , Zhang Tao , Wan Hongli , Yu Yang , Wen Jin , Wang Xiaoyu
Published: September 2022

Objective

To identify sex-related differences in the outcome of hospitalized patients with spontaneous intracerebral hemorrhage (SICH), and to identify potential causal pathways between sex and SICH outcome.

Methods

A total of 111,112 medical records of in-hospital patients with SICH were collected. Data- and expert-driven techniques were applied, such as a multivariate logistic regression model and causal mediation analysis. These analyses were used to determine the confounders and mediators, estimate the true effect of sex on the SICH outcome, and estimate the average causal mediation effect for each mediator.

Results

(1) Failure (disability or death) rates in women with SICH were significantly lower than in men with SICH. On the day of discharge, the odds ratio (OR) of failure between women and men was 0.9137 [95% confidence interval (CI), 0.8879–0.9402], while the odds ratio at 90 days post-discharge was 0.9353 (95% confidence interval, 0.9121–0.9591). (2) The sex-related difference in SICH outcome decreased with increasing age and disappeared after 75 years. (3) Deep coma, brainstem hemorrhage, and an infratentorial hemorrhage volume of >10 ml accounted for 62.76% (p < 0.001), 33.46% (p < 0.001), and 11.56% (p < 0.001) of the overall effect on the day of discharge, and for 52.28% (p < 0.001), 27.65% (p < 0.001), and 10.86% (p < 0.001) of the overall effect at the 90-day post-discharge.

Conclusion

Men have a higher failure risk than women, which may be partially mediated by a higher risk for deep coma, brainstem hemorrhage, and an infratentorial hemorrhage volume of >10 ml. Future work should explore the biological mechanisms underlying this difference.
Activation of human spinal locomotor circuitry using transvertebral magnetic stimulation
Authors: Kawai Kazutake , Tazoe Toshiki , Yanai Toshimasa , Kanosue Kazuyuki , Nishimura Yukio
Published: September 2022

Transvertebral magnetic stimulation (TVMS) of the human lumbar spinal cord can evoke bilateral rhythmic leg movements, as in walking, supposedly through the activation of spinal locomotor neural circuitry. However, an appropriate stimulus intensity that can effectively drive the human spinal locomotor circuitry to evoke walking-like movements has not been determined. To address this issue, TVMS was delivered over an intervertebral space of the lumbar cord (L1–L3) at different stimulus intensities (10–70% of maximum stimulator output) in healthy human adults. In a stimulus intensity-dependent manner, TVMS evoked two major patterns of rhythmic leg movements in which the left-right movement cycles were coordinated with different phase relationships: hopping-like movements, in which both legs moved in the same direction in phase, and walking-like movements, in which both legs moved alternatively in anti-phase; uncategorized movements were also observed which could not be categorized as either movement type. Even at the same stimulation site, the stimulus-evoked rhythmic movements changed from hopping-like movements to walking-like movements as stimulus intensity was increased. Different leg muscle activation patterns were engaged in the induction of the hopping- and walking-like movements. The magnitude of the evoked hopping- and walking-like movements was positively correlated with stimulus intensity. The human spinal neural circuitry required a higher intensity of magnetic stimulation to produce walking-like leg movements than to produce hopping-like movements. These results suggest that TVMS activates distinct neural modules in the human spinal cord to generate hopping- and walking-like movements.
Unraveling the Role of Thyroid Hormones in Seasonal Neuroplasticity in European Starlings (Sturnus vulgaris)
Authors: Orije Jasmien E. M. J. , Raymaekers Sander R. , Majumdar Gaurav , De Groof Geert , Jonckers Elisabeth , Ball Gregory F. , Verhoye Marleen , Darras Veerle M. , Van der Linden Annemie
Published: September 2022

Thyroid hormones clearly play a role in the seasonal regulation of reproduction, but any role they might play in song behavior and the associated seasonal neuroplasticity in songbirds remains to be elucidated. To pursue this question, we first established seasonal patterns in the expression of thyroid hormone regulating genes in male European starlings employing in situ hybridization methods. Thyroid hormone transporter LAT1 expression in the song nucleus HVC was elevated during the photosensitive phase, pointing toward an active role of thyroid hormones during this window of possible neuroplasticity. In contrast, DIO3 expression was high in HVC during the photostimulated phase, limiting the possible effect of thyroid hormones to maintain song stability during the breeding season. Next, we studied the effect of hypothyroidism on song behavior and neuroplasticity using in vivo MRI. Both under natural conditions as with methimazole treatment, circulating thyroid hormone levels decreased during the photosensitive period, which coincided with the onset of neuroplasticity. This inverse relationship between thyroid hormones and neuroplasticity was further demonstrated by the negative correlation between plasma T3 and the microstructural changes in several song control nuclei and cerebellum. Furthermore, maintaining hypothyroidism during the photostimulated period inhibited the increase in testosterone, confirming the role of thyroid hormones in activating the hypothalamic–pituitary–gonadal (HPG) axis. The lack of high testosterone levels influenced the song behavior of hypothyroid starlings, while the lack of high plasma T4 during photostimulation affected the myelination of several tracts. Potentially, a global reduction of circulating thyroid hormones during the photosensitive period is necessary to lift the brake on neuroplasticity imposed by the photorefractory period, whereas local fine-tuning of thyroid hormone concentrations through LAT1 could activate underlying neuroplasticity mechanisms. Whereas, an increase in circulating T4 during the photostimulated period potentially influences the myelination of several white matter tracts, which stabilizes the neuroplastic changes. Given the complexity of thyroid hormone effects, this study is a steppingstone to disentangle the influence of thyroid hormones on seasonal neuroplasticity.
Topographic organization of the human caudate functional connectivity and age-related changes with resting-state fMRI
Authors: O'Rawe Jonathan F. , Leung Hoi-Chung
Published: September 2022

The striatum is postulated to play a central role in gating cortical processing during goal-oriented behavior. While many human neuroimaging studies have treated the striatum as an undivided whole or several homogeneous compartments, some recent studies showed that its circuitry is topographically organized and has more complex relations with the cortical networks than previously assumed. Here, we took a gradient functional connectivity mapping approach that utilizes the entire anatomical space of the caudate nucleus to examine the organization of its functional relationship with the rest of the brain and how its topographic mapping changes with age. We defined the topography of the caudate functional connectivity using three publicly available resting-state fMRI datasets. We replicated and extended previous findings. First, we found two stable gradients of caudate connectivity patterns along its medial-lateral (M-L) and anterior-posterior (A-P) axes, supporting findings from previous tract-tracing studies of non-human primates that there are at least two main organizational principles within the caudate nucleus. Second, unlike previous emphasis of the A-P topology, we showed that the differential connectivity patterns along the M-L gradient of caudate are more clearly organized with the large-scale neural networks; such that brain networks associated with internal vs. external orienting behavior are respectively more closely linked to the medial vs. lateral extent of the caudate. Third, the caudate's M-L organization showed greater age-related reduction in integrity, which was further associated with age-related changes in behavioral measures of executive functions. In sum, our analysis confirmed a sometimes overlooked M-L functional connectivity gradient within the caudate nucleus, with its lateral longitudinal zone more closely linked to the frontoparietal cortical circuits and age-related changes in cognitive control. These findings provide a more precise mapping of the human caudate functional connectivity, both in terms of the gradient organization with cortical networks and age-related changes in such organization.
Development and optimization of NIRS prediction models for simultaneous multi-trait assessment in diverse cowpea germplasm
Authors: Padhi Siddhant Ranjan , John Racheal , Bartwal Arti , Tripathi Kuldeep , Gupta Kavita , Wankhede Dhammaprakash Pandhari , Mishra Gyan Prakash , Kumar Sanjeev , Rana Jai Chand , Riar Amritbir , Bhardwaj Rakesh
Published: September 2022

Cowpea (Vigna unguiculata(L.) Walp.) is one such legume that can facilitate achieving sustainable nutrition and climate change goals. Assessing nutritional traits conventionally can be laborious and time-consuming. NIRS is a technique used to rapidly determine biochemical parameters for large germplasm. NIRS prediction models were developed to assess protein, starch, TDF, phenols, and phytic acid based on MPLS regression. Higher RSQexternalvalues such as 0.903, 0.997, 0.901, 0.706, and 0.955 were obtained for protein, starch, TDF, phenols, and phytic acid respectively. Models for all the traits displayed RPD values of >2.5 except phenols and low SEP indicating the excellent prediction of models. For all the traits worked,p-value ≥ 0.05 implied the accuracy and reliability score >0.8 (except phenol) ensured the applicability of the models. These prediction models will facilitate high throughput screening of large cowpea germplasm in a non-destructive way and the selection of desirable chemotypes in any genetic background with huge application in cowpea crop improvement programs across the world.
Effects of Proteins and Mineral Ions on the Physicochemical Properties of 1,3-Dioleoyl-2-Palmitoylglycerol Emulsion to Mimic a Liquid Infant Formula
Authors: Wang Qi , Xu Yuxi , Liu Yanchen , Qian Fang , Mu Guangqing , Zhu Xuemei
Published: September 2022

Proteins and minerals in infant formula not only serve as nutrients, but also have important effects on the physical and chemical stability of emulsions. In this study, calcium carbonate (0 or 9.08 mM) and potassium chloride (0 or 15.96 mM), as representatives of divalent and monovalent minerals, were added to 1,3-dioleoyl-2-palmitoylglycerol (OPO) emulsions in different ratios (10:0, 9:1, 6:4, 5:5, and 0:10) of whey protein isolate (WPI) and sodium caseinate (CN). The influence of proteins and minerals on emulsion stability was investigated by analyzing particle size, zeta potential, creaming index, rheological properties, storage stability, and lipid oxidation. 1,3-dioleoyl-2-palmitoylglycerol (OPO) emulsions could be destabilized by adding Ca2+, as shown by the increase in particle size index, creaming index, and the decrease in zeta potential magnitude. Divalent ions could affect the electrostatic interactions between lipid droplets and the interactive effects of ion surface adsorption. In addition, the effect of different protein ratios on the physical stability of emulsions was not significant under the same ion-type conditions. In terms of chemical stability, higher oxidized values were found in emulsions stabilized with only CN than in those containing WPI. Our study showed that protein ratios and minerals played an important role in the stability of OPO emulsions, which might provide a reference for the development and utilization of liquid infant formula.
Human amniotic membrane for myocutaneous dehiscence after a radical surgical treatment of vulvar cancer: A case report
Authors: Restaino Stefano , Paparcura Federico , Giorgiutti Cristina , Trojan Diletta , Montagner Giulia , Pengo Giancarlo , Pividore Grazia , Albanese Roberta , Rampino Emanuele , Dogareschi Teresa , Bove Tiziana , Titone Francesca , Trovò Marco , Garganese Giorgia , Parodi Pier Camillo , Scambia Giovanni , Driul Lorenza , Vizzielli Giuseppe
Published: September 2022

Background

The application of the amniotic membrane could have a favourable effect on tissue repair and regeneration. We report the first case of implant of an amniotic membrane in a patient affected by myo-cutaneous dehiscence, after a radical surgical treatment for vulvar cancer.

Methods

We describe a case of a 74-years-old patient affected by vulvar cancer. After radiotherapy, the patient underwent to an anterior pelvic exenteration with uretero-ileo-cutaneostomy by Wallace, bilateral pelvic lymphadenectomy, omental biopsies, omental flap, bilateral inguinal lymphadenectomy, resection of ulcerated left inguinal lesion, reconstruction with left gracilis muscle flap and locoregional V-Y advancement flap. The patient developed a myo-cutaneous dehiscence. Two months after the surgery, following an accurate curettage of the wound and negative pressure therapy, a patch of human amniotic membrane was implanted.

Results

The surgical procedure was easy, feasible and did not require long operating room times. No intraoperative or postoperative complications occurred. The results obtained were encouraging with a marked improvement in the surgical wound.

Conclusion

the use of amniotic membranes was safely and easily performed to promote the healing of complicated surgical wounds.
Case report: Successful treatment of a rare case of combined parathyroid adenoma, cervical bronchogenic cyst, and tracheal diverticulum with gasless endoscopic resection of neck masses via an axillary approach: A case report and literature review
Authors: Lu Dong-Ning , Zhang Wan-Chen , Zheng Chuan-Ming , Ge Ming-Hua , Xu Jia-Jie
Published: September 2022

Parathyroid adenoma (PA), one of the most common causes of hyperparathyroidism, generally involves a single parathyroid gland and is manifested as hyperparathyroidism. Bronchogenic cysts are rare congenital cystic lesions caused by a development malformation in bronchi during the embryonic period, which mostly occur in the lung and mediastinum, with an extremely low morbidity rate in the neck. A 27-year-old young female was found to suffer from hyperparathyroidism on routine physical examination, and further examination suggested a cystic lesion in the right inferior parathyroid area combined with a tracheal diverticulum. Therefore, she was initially diagnosed with cystic hyperplasia of the parathyroid glands complicated by a tracheal diverticulum. Gasless endoscopic resection of neck masses via an axillary approach was performed because of the high requirements for the surgical cosmetic effect of the patient. During the surgery, we observed that the preoperatively diagnosed cystic lesion was a combination of two masses, which were successfully resected under endoscopy. Based on the postoperative pathology and clinical features, the patient was eventually diagnosed with a rare case of triple diseases including PA, cervical bronchial cyst, and tracheal diverticulum. Now, the patient recovered well as per the follow-up with no signs of recurrence and was extremely satisfied with the cosmetic effect of the surgery.
Effects and mechanisms of natural alkaloids for prevention and treatment of osteoporosis
Authors: Lin Bingfeng , Xu Pingcui , Zheng Juan , Deng Xuehui , Ye Qitao , Huang Zhongping , Wang Nani
Published: September 2022

Natural alkaloids are polycyclic, nitrogen-containing, and basic compounds obtained from plants. In this review, the advances in bioactive alkaloids with respect to their chemical structures, herbal sources, and effects for the prevention and treatment of osteoporosis are discussed. Anti-osteoporosis alkaloids are classified into six categories based on the chemical structure, namely, isoquinoline alkaloids, quinolizidine alkaloids, piperidine alkaloids, indole alkaloids, pyrrolizidine alkaloids and steroidal alkaloids. They promote mesenchymal stem cells differentiation, improve osteoblast proliferation, stimulate osteoblast autophagy and suppress osteoclast formation. These natural alkaloids can regulate multiple signaling pathways, including interrupting the tumor necrosis factor receptor associated factor 6- receptor activator of nuclear factor kappa B interaction, inhibiting the nuclear factor kappa B pathway in osteoclasts, activating the p38 mitogen-activated protein kinases pathway in osteoblasts, and triggering the wingless and int-1 pathway in mesenchymal stem cells. This review provides evidence and support for novel drug and clinical treatment of osteoporosis using natural alkaloids.
Current status of iridium-based complexes against lung cancer
Authors: Yang Tongfu , Zhu Minghui , Jiang Ming , Yang Feng , Zhang Zhenlei
Published: September 2022

Lung cancer is one of the most common malignant tumors, with the highest mortality rate in the world, and its incidence is second only to breast cancer. It has posed a serious threat to human health. Cisplatin, a metal-based drug, is one of the most widely used chemotherapeutic agents for the treatment of various cancers. However, its clinical efficacy is seriously limited by numerous side effects and drug resistance. This has led to the exploration and development of other transition metal complexes for the treatment of malignant tumors. In recent years, iridium-based complexes have attracted extensive attention due to their potent anticancer activities, limited side effects, unique antitumor mechanisms, and rich optical properties, and are expected to be potential antitumor drugs. In this review, we summarize the recent progress of iridium complexes against lung cancer and introduce their anti-tumor mechanisms, including apoptosis, cycle arrest, inhibition of lung cancer cell migration, induction of immunogenic cell death, etc.
Artemisinin resistance and malaria elimination: Where are we now?
Authors: Hanboonkunupakarn Borimas , Tarning Joel , Pukrittayakamee Sasithon , Chotivanich Kesinee
Published: September 2022

The emergence of artemisinin resistance is a major obstacle to the global malaria eradication/elimination programs. Artemisinin is a very fast-acting antimalarial drug and is the most important drug in the treatment of severe and uncomplicated malaria. For the treatment of acute uncomplicated falciparum malaria, artemisinin derivatives are combined with long half-life partner drugs and widely used as artemisinin-based combination therapies (ACTs). Some ACTs have shown decreased efficacy in the Southeast Asian region. Fortunately, artemisinin has an excellent safety profile and resistant infections can still be treated successfully by modifying the ACT. This review describes the pharmacological properties of ACTs, mechanisms of artemisinin resistance and the potential changes needed in the treatment regimens to overcome resistance. The suggested ACT modifications are extension of the duration of the ACT course, alternating use of different ACT regimens, and addition of another antimalarial drug to the standard ACTs (Triple-ACT). Furthermore, a malaria vaccine (e.g., RTS,S vaccine) could be added to mass drug administration (MDA) campaigns to enhance the treatment efficacy and to prevent further artemisinin resistance development. This review concludes that artemisinin remains the most important antimalarial drug, despite the development of drug-resistant falciparum malaria.
Triptolide in the treatment of systemic lupus erythematosus - regulatory effects on miR-146a in B cell TLR7 signaling pathway in mice
Authors: Zhang Yi , Zhang FengQi , Gao YiNi , Wang MeiJiao , Gao Yan , Li HaiChang , Sun Jing , Wen ChengPing , Xie ZhiJun
Published: September 2022

Objective: To clarify the mechanism of triptolide (TP) in alleviating the conditions underlying SLE.

Methods: Eight-week-old MRL/lpr mice were randomly divided into a model group (n = 5), low-dose TP (TP-L) group (n = 5), and high-dose TP (TP-H) group (n = 5). Mice in these groups were gavaged with normal saline, low-dose TP solution, and high-dose TP solution for 8 weeks, respectively. The expression levels of anti-dsDNA, IgG, IgM, IgA, C3, C4, and CREA, BUN, ALT, AST, ALB, and ALP indexes in the serum of mice were detected. The proportion of CD19+CD138+B220− cells in the spleen and the pathological changes of kidney tissue in the mice were also evaluated. The possible signaling pathways and microRNA (miRNA) targets of TP in the treatment of SLE were analyzed using network pharmacology. The expressions of TLR7 mRNA and miR-146a in Raji cells (a B lymphocyte line) were detected using qPCR before and after intervention with a miR-146a inhibitor. The protein expression levels of TLR7, MyD88, p-IRAK1, and p-NF-κBp65 were detected using western blot analysis.

Results: TP could significantly decrease the levels of ds-DNA and IgG, alleviate pathological injury in renal tissue, and upregulate miR-146a expression in the B cells of MRL/lpr mice without obvious liver and kidney toxicity. Network pharmacology analysis showed that TP could mainly regulate the Toll-like receptor signaling pathway, and NF-κB signaling pathway, among others. miRNA target prediction suggested that TP could regulate miRNAs such as miR-146a. In vitro cell experiments further confirmed that TP could significantly upregulate miR-146a expression and downregulate the expression of TLR7 mRNA and protein levels TLR7, MyD88, p-IRAK1, and p-NF-κBp65. After intervention with a miR-146a inhibitor, TP had no obvious inhibitory effects on TLR7, MyD88, p-IRAK1, and p-NF-κBp65 expression.

Conclusion: TP may exert therapeutic effects on SLE by regulating miR-146a expression, inhibiting the TLR7/NF-κB signaling pathway, and affecting B cell activation.
Prediction of pyrotinib exposure based on physiologically-based pharmacokinetic model and endogenous biomarker
Authors: Zhang Miao , Yu Zhiheng , Yao Xueting , Lei Zihan , Zhao Kaijing , Wang Wenqian , Zhang Xue , Chen Xijing , Liu Dongyang
Published: September 2022

Pyrotinib, a novel irreversible epidermal growth factor receptor dual tyrosine kinase inhibitor, is mainly (about 90%) eliminated through cytochrome P450 (CYP) 3A mediated metabolism in vivo. Meanwhile, genotype is a key factor affecting pyrotinib clearance and 4β-hydroxycholesterol is an endogenous biomarker of CYP3A activity that can indirectly reflect the possible pyrotinib exposure. Thus, it is necessary to evaluate the clinical drug-drug interactions (DDI) between CYP3A perpetrators and pyrotinib, understand potential exposure in specific populations including liver impairment and geriatric populations, and explore the possible relationships among pyrotinib exposure, genotypes and endogenous biomarker. Physiologically-based pharmacokinetic (PBPK) model can be used to replace prospective DDI studies and evaluate external and internal factors that may influence system exposure. Herein, a basic PBPK model was firstly developed to evaluate the potential risk of pyrotinib coadministration with strong inhibitor and guide the clinical trial design. Subsequently, the mechanistic PBPK model was established and used to quantitatively estimate the potential DDI risk for other CYP3A modulators, understand the potential exposure of specific populations, including liver impairment and geriatric populations. Meanwhile, the possible relationships among pyrotinib exposure, genotypes and endogenous biomarker were explored. With the help of PBPK model, the DDI clinical trial of pyrotinib coadministration with strong inhibitor has been successfully completed, some DDI clinical trials may be waived based on the predicted results and clinical trials in specific populations can be reasonably designed. Moreover, the mutant genotypes of CYP3A4*18A and CYP3A5*3 were likely to have a limited influence on pyrotinib clearance, and the genotype-independent linear correlation coefficient between endogenous biomarker and system exposure was larger than 0.6. Therefore, based on the reliable predicted results and the linear correlations between pyrotinib exposure and endogenous biomarker, dosage adjustment of pyrotinib can be designed for clinical practice.
Simulation of the crosstalk between glucose and acetaminophen metabolism in a liver zonation model
Authors: Maeda Kazuhiro , Hagimori Shuta , Sugimoto Masahiro , Sakai Yasuyuki , Nishikawa Masaki
Published: September 2022

The liver metabolizes a variety of substances that sometimes interact and regulate each other. The modeling of a single cell or a single metabolic pathway does not represent the complexity of the organ, including metabolic zonation (heterogeneity of functions) along with liver sinusoids. Here, we integrated multiple metabolic pathways into a single numerical liver zonation model, including drug and glucose metabolism. The model simulated the time-course of metabolite concentrations by the combination of dynamic simulation and metabolic flux analysis and successfully reproduced metabolic zonation and localized hepatotoxicity induced by acetaminophen (APAP). Drug metabolism was affected by nutritional status as the glucuronidation reaction rate changed. Moreover, sensitivity analysis suggested that the reported metabolic characteristics of obese adults and healthy infants in glucose metabolism could be associated with the metabolic features of those in drug metabolism. High activities of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphate phosphatase in obese adults led to increased APAP oxidation by cytochrome P450 2E1. In contrast, the high activity of glycogen synthase and low activities of PEPCK and glycogen phosphorylase in healthy infants led to low glucuronidation and high sulfation rates of APAP. In summary, this model showed the effects of glucose metabolism on drug metabolism by integrating multiple pathways into a single liver metabolic zonation model.
Diode-pumped, actively Q-switched Nd,La:CaNb2O6 self-Raman laser at 1,174 nm
Authors: Zhuang Youyi , Mao Wenjie , Gong Xinghong , Jin Xinxin , Li Zhihong , Huang Yidong , Duan Yanmin
Published: September 2022

Diode end-pumped Nd,La:CaNb2O6 self-Raman laser with acousto-optic Q-switching was successfully demonstrated for the first Stokes wave generation at 1,174 nm. A 1.0 at.% Nd3+ and 1.0 at.% La3+-doped CaNb2O6 crystal in dimensions 3 × 3 × 14.3 mm3 was used as the self-Raman laser crystal. Doping 1 at.% La3+ ions into this crystal could subdue the fluorescence quenching caused by cross-relaxation between Nd3+ ions and finally improve the laser output performance. Under the incident pump power of 9.9 W, the first Stokes wave at 1,174 nm with a maximum output power up to 928 mW was obtained, with the diode to Stokes conversion efficiency of about 9.4%. The results show that the Nd,La:CaNb2O6 is also a promising self-Raman crystal for efficient fundamental and Raman laser operation.