bluuebunny/crossref_metadata_2025 huggingface dataset:
The Value of Dysregulated LncRNAs on Clinicopathology and Survival in Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis
Authors: Wang Juan , Han Xu , Yuan Ye , Gu Hao , Liao Xing , Jiang Miao
Published: April 2022

Background: There is growing evidence that a number of lncRNAs are involved in the pathogenesis of non-small-cell lung cancer (NSCLC). However, studies on lncRNA expression in NSCLC patients are far from conclusive. Therefore, we performed a systematic review of such studies to collect and examine the evidence on the potential role of lncRNAs in the development of NSCLC.

Methods: We systematically searched seven literature databases to identify all published studies that evaluated the expression of one or more lncRNAs in human samples with NSCLC (cases) and without NSCLC (controls) from January 1, 1995 to May 24, 2021. Quality assessment of studies was conducted by using the “Quality in Prognosis Studies” (QUIPS) tool, and the heterogeneity across studies was analyzed with the I-squared statistic and chi-square-based Q-tests. Either fixed or random-effect meta-analysis was performed to summarize effect size to investigate the association between lncRNA expression and overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and clinicopathological features. The R statistical software program was used to conduct standard meta-analysis.

Results: We finally obtained 48 studies with 5,211 patients included in this review after screening. Among the 48 lncRNAs, 38 lncRNAs were consistently upregulated, and 10 were deregulated in patients with NSCLC compared with the control groups. The upregulated lncRNAs were positively associated with histological type: study number (n) = 18, odds ratio (OR) = 0.78, 95% CI: 0.65–0.95 and OR = 1.30, 95% CI: 1.08–1.57, p < 0.01; TNM stages: n = 20, OR = 0.41, 95% CI: 0.29–0.57 and OR = 2.44, 95% CI: 1.73–3.44, p < 0.01; lymph node metastasis: n = 29, OR = 0.49, 95% CI: 0.34–0.71 and OR = 2.04, 95% CI: 1.40–2.96, p < 0.01; differentiation grade: n = 6, OR = 0.61, 95% CI: 0.38–0.99 and OR = 1.63, 95% CI: 1.01–2.64, p < 0.01; distant metastasis: n = 9, OR = 0.37, 95% CI: 0.26–0.53 and OR = 2.72, 95% CI: 1.90–3.90, p < 0.01; tumor size: n = 16, OR = 0.52, 95% CI: 0.43–0.64 and OR = 1.92, 95% CI: 1.57–2.34, p < 0.01; and overall survival [n = 38, hazard ratio (HR) = 1.79, 95% CI = 1.59–2.02, p < 0.01]. Especially, five upregulated lncRNAs (linc01234, ZEB1-AS1, linc00152, PVT1, and BANCR) were closely associated with TNM Ⅲa stage (n = 5, OR = 4.07, 95% CI: 2.63–6.28, p < 0.01). However, 10 deregulated lncRNAs were not significantly associated with the pathogenesis and overall survival in NSCLC in the meta-analysis (p ≥ 0.05).

Conclusion: This systematic review suggests that the upregulated lncRNAs could serve as biomarkers for predicting promising prognosis of NSCLC. The prognostic value of downregulated lncRNA in NSCLC needs to be further explored.

Systematic Review Registration: (http://www.crd.york.ac.uk/PROSPERO).identifier CRD42021240635.
SNP Discovery Using BSR-Seq Approach for Spot Blotch Resistance in Wheat (Triticum aestivum L.), an Essential Crop for Food Security
Authors: Saxesena Ravi Ranjan , Mishra Vinod Kumar , Chand Ramesh , Kumar Uttam , Chowdhury Apurba Kumar , Bhati Jyotika , Budhlakoti Neeraj , Joshi Arun Kumar
Published: April 2022

The pathogenic fungus, Bipolaris sorokiniana, that causes spot blotch (SB) disease of wheat, is a major production constraint in the Eastern Gangetic Plains of South Asia and other warm, humid regions of the world. A recombinant inbred line population was developed and phenotyped at three SB-prone locations in India. The single nucleotide polymorphism (SNP) for SB resistance was identified using a bulked segregant RNA-Seq-based approach, referred to as “BSR-Seq.” Transcriptome sequencing of the resistant parent (YS#24), the susceptible parent (YS#58), and their resistant and susceptible bulks yielded a total of 429.67 million raw reads. The bulk frequency ratio (BFR) of SNPs between the resistant and susceptible bulks was estimated, and selection of SNPs linked to resistance was done using sixfold enrichments in the corresponding bulks (BFR >6). With additional filtering criteria, the number of transcripts was further reduced to 506 with 1055 putative polymorphic SNPs distributed on 21 chromosomes of wheat. Based on SNP enrichment on chromosomal loci, five transcripts were found to be associated with SB resistance. Among the five SB resistance-associated transcripts, four were distributed on the 5B chromosome with putative 52 SNPs, whereas one transcript with eight SNPs was present on chromosome 3B. The SNPs linked to the trait were exposed to a tetra-primer ARMS-PCR assay, and an SNP-based allele-specific marker was identified for SB resistance. The in silico study of these five transcripts showed homology with pathogenesis-related genes; the metabolic pathway also exhibits similar results, suggesting their role in the plant defense mechanism.
Endometriosis-Associated Angiogenesis and Anti-angiogenic Therapy for Endometriosis
Authors: Chung Monica S. , Han Sang Jun
Published: April 2022

Endometriosis is a known estrogen-dependent inflammatory disease affecting reproductive-aged women. Common symptoms include pelvic pain, dysmenorrhea, dyspareunia, heavy menstrual bleeding, and infertility. The exact etiology of endometriosis is largely unknown, and, thus, the diagnosis and treatment of endometriosis are challenging. A complex interplay of many molecular mechanisms is thought to aid in the progression of endometriosis, most notably angiogenesis. This mini-review examines our current knowledge of the molecular etiology of endometriosis-associated angiogenesis and discusses anti-angiogenic therapy, in the blockade of endometriosis-associated angiogenesis, as potential non-hormonal therapy for the treatment of endometriosis.
Training in Ultrasound to Determine Gestational Age (TUDA): Evaluation of a Novel Education Package to Teach Ultrasound-Naive Midwives Basic Obstetric Ultrasound in Malawi
Authors: Viner Alexandra C. , Membe-Gadama Gladys , Whyte Sonia , Kayambo Doris , Masamba Martha , Makwakwa Enita , Lissauer David , Stock Sarah J. , Norman Jane E. , Reynolds Rebecca M. , Magowan Brian , Freyne Bridget , Gadama Luis
Published: April 2022

Introduction

Although ultrasound to determine gestational age is fundamental to the optimum management of pregnancy and is recommended for all women by the World Health Organisation, it remains unavailable to many women in low-income countries where trained practitioners are scarce. This study aimed to evaluate a novel, context-specific education package to teach midwives basic obstetric ultrasound, including the determination of gestational age by measurement of fetal femur length.

Methods

The study was conducted across six sites in Malawi in January 2021. Following a virtual “training of the trainers”, local teams delivered a 10-day programme encompassing both didactic and “hands on” components. Matched pre and post course tests assessed participants' knowledge of key concepts, with Objective Structured Clinical Examinations used to evaluate practical skills. To achieve a pass, trainees were required to establish the gestational age to within ±7 days of an experienced practitioner and achieve an overall score of >65% on five consecutive occasions. A matched pre and post course survey explored participants' attitudes and confidence in performing ultrasound examinations.

Results

Of the 29 midwives who participated, 28 finished the programme and met the criteria specified to pass. 22 midwives completed the matched knowledge tests, with the mean (SD) score increasing from 10.2 (3.3) to 18 (2.5) after training (P <0.0001). Mean difference 7.9, 95% CI 6.5–9.2. Midwives passed 87% of the Observed Structured Clinical Examinations, establishing the gestational age to within ±7 days of an experienced practitioner in 89% of assessments. Beliefs regarding the importance of antenatal ultrasound increased post course (p = 0.02), as did confidence in performing ultrasound examinations (p <0.0001).

Conclusion

This study demonstrates not only that ultrasound-naive practitioners can be taught to perform basic obstetric ultrasound dating scans, confidently and competently, after 10 days of training, but also that local teams can be orientated to successfully deliver the programme virtually. Previous ultrasound training initiatives, while often more comprehensive in their syllabus, have been of considerably longer duration and this is likely to be a barrier to upscaling opportunities. We propose that this focused training increases the potential for widescale and sustainable implementation.
mtDNA-STING Axis Mediates Microglial Polarization via IRF3/NF-κB Signaling After Ischemic Stroke
Authors: Kong Lingqi , Li Wenyu , Chang E , Wang Wuxuan , Shen Nan , Xu Xiang , Wang Xinyue , Zhang Yan , Sun Wen , Hu Wei , Xu Pengfei , Liu Xinfeng
Published: April 2022

Neuroinflammation is initiated in response to ischemic stroke, and is usually characterized by microglial activation and polarization. Stimulator of interferon genes (STING) has been shown to play a critical role in anti-tumor immunity and inflammatory diseases. Nevertheless, the effect and underlying mechanisms of STING on microglial polarization after ischemic stroke remain unclarified. In this study, acute ischemic stroke was simulated using a model of middle cerebral artery occlusion (MCAO) at adult male C57BL/6 mice in vivo and the BV2 microglia oxygen-glucose deprivation/reperfusion (OGD/R) model in vitro. The specific STING inhibitor C-176 was administered intraperitoneally at 30min after MCAO. We found that the expression of microglial STING was increased following MCAO and OGD/R. Pharmacologic inhibition of STING with C-176 reduced the ischemia/reperfusion (I/R)-induced brain infarction, edema and neuronal injury. Moreover, blockade of STING improved neurological performance and cognitive function and attenuated neuronal degeneration in the hippocampus after MCAO. Mechanistically, both in vivo and in vitro, we delineated that STING could promote the polarization of microglia towards the M1 phenotype and restrain M2 microglia polarization via downstream pathways, including interferon regulatory factor 3 (IRF3) and nuclear factor-κB (NF-κB). In addition, mitochondrial DNA (mtDNA), which is released to microglial cytoplasm induced by I/R injury, could facilitate microglia towards M1 modality through STING signaling pathway. Treatment with C-176 abolished the detrimental effects of mtDNA on stroke outcomes. Taken together, these findings suggest that STING, activated by mtDNA, could polarize microglia to the M1 phenotype following MCAO. Inhibition of STING may serve as a potential therapeutic strategy to mitigate neuroinflammation after ischemic stroke.
HMG-Like DSP1 Mediates Immune Responses of the Western Flower Thrips (Frankliniella occidentalis) Against Beauveria bassiana, a Fungal Pathogen
Authors: Ahmed Shabbir , Roy Miltan Chandra , Choi Duyeol , Kim Yonggyun
Published: April 2022

Western flower thrips, Frankliella occidentalis, is a serious pest by directly infesting host crops. It can also give indirect damage to host crops by transmitting a plant virus called tomato spotted wilt virus. A fungal pathogen, Beauveria bassiana, can infect thrips. It has been used as a biopesticide. However, little is known on the defense of thrips against this fungal pathogen. This study assessed the defense of thrips against the fungal infection with respect to immunity by analyzing immune-associated genes of F. occidentalis in both larvae and adults. Immunity-associated genes of western flower thrips were selected from three immunity steps: nonself recognition, mediation, and immune responses. For the pathogen recognition step, dorsal switch protein 1 (DSP1) was chosen. For the immune mediation step, phospholipase A2 (PLA2) and prostaglandin E2 synthase were also selected. For the step of immune responses, two phenoloxidases (PO) genes and four proPO-activating peptidase genes involved in melanization against pathogens were chosen. Dual oxidase gene involved in the production of reactive oxygen species and four antimicrobial peptide genes for executing humoral immune responses were selected. All immunity-associated genes were inducible to the fungal infection. Their expression levels were induced higher in adults than in larvae by the fungal infections. However, inhibitor treatments specific to DSP1 or PLA2 significantly suppressed the inducible expression of these immune-associated genes, leading to significant enhancement of fungal pathogenicity. These results suggest that immunity is essential for thrips to defend against B. bassiana, in which DSP1 and eicosanoids play a crucial role in eliciting immune responses.
Exposure of Larvae to Sublethal Thiacloprid Delays Bee Development and Affects Transcriptional Responses of Newly Emerged Honey Bees
Authors: Li Bin , Ke Li , Li Ai-Rui , Diao Qing-Yun , Wang Qiang , Liu Yong-Jun
Published: April 2022

Understanding the cause of honey bee (Apis mellifera) population decline has attracted immense attention worldwide in recent years. Exposure to neonicotinoid pesticides is considered one of the most probable factors due to the physiological and behavioral damage they cause to honey bees. However, the influence of thiacloprid, a relatively less toxic cyanogen-substituted form of neonicotinoid, on honey bee (Apis mellifera L.) development is not well studied. The toxicity of sublethal thiacloprid to larvae, pupae, and emerging honey bees was assessed under laboratory conditions. We found that thiacloprid reduced the survival rate of larvae and pupae, and delayed the development of bees which led to lower bodyweight and size. Furthermore, we identified differentially expressed genes involved in metabolism and immunity though RNA-sequencing of newly-emerged adult bees. GO enrichment analysis identified genes involved in metabolism, catalytic activity, and transporter activity. KEGG pathway analysis indicated that thiacloprid induced up-regulation of genes related to glutathione metabolism and Toll-like receptor signaling pathway. Overall, our results suggest that chronic sublethal thiacloprid can affect honey bee colonies by reducing survival and delaying bee development.
High-Resolution Reconstruction of Dissolved Oxygen Levels in the Baltic Sea With Bivalves – a Multi-Species Comparison (Arctica islandica, Astarte borealis, Astarte elliptica)
Authors: Schöne Bernd R. , Huang Xizhi , Jantschke Anne , Mertz-Kraus Regina , Zettler Michael L.
Published: April 2022

An increasing area of shallow-marine benthic habitats, specifically in the Baltic Sea, is affected by seasonal oxygen depletion. To place the current spread of oxygen deficiency into context and quantify the contribution of anthropogenic ecosystem perturbation to this development, high-resolution archives for the pre-instrumental era are needed. As recently demonstrated, shells of the bivalve mollusk, Arctica islandica fulfil this task with molar Mn/Cashell ratios as proxies for dissolved oxygen (DO) levels in the water column. Since the ocean quahog is inhomogeneously distributed in the Baltic Sea and may not be present in museum collections or found throughout sedimentary sequences, the present study evaluated whether two other common bivalves, Astarte elliptica and Astarte borealis can be used interchangeably or alternatively as proxy DO recorders. Once mathematically resampled and corrected for shell growth rate-related kinetic effects and (some) vital effects, Mn/Cashell data of all three species (age ten onward in A. islandica) were statistically significantly (p < 0.0001) linearly and inversely correlated to DO concentration in the free water column above seafloor (r = –0.66 to –0.75, corresponding to 43 to 56% explained variability). A. elliptica may provide slightly more precise DO data (1σ error of ±1.5 mL/L) than A. islandica or A. borealis ( ± 1.6 mL/L), but has a shorter lifespan. Both Astarte species show a stronger correlation with DO than A. islandica, because their biomineralization seems to be less severely hampered by oxygen and salinity stress. In turn, A. islandica grows faster resulting in less time-averaged data. During youth, the ocean quahog typically incorporates a disproportionately large amount of manganese into its shell, possibly because food intake occurs directly at the sediment-water interface where Mn-rich porewater diffuses out of the sediment. With increasing age, however, A. islandica seems to generate a gradually stronger inhaling water current and takes in a larger proportion of water farther away from the fluffy layer. As demonstrated here, all three studied species can be used as DO archives, though species-specific limitations should be kept in mind.
Comparison of Corneal Optical Quality After SMILE, Wavefront-Optimized LASIK and Topography-Guided LASIK for Myopia and Myopic Astigmatism
Authors: Zhang Yu , Sun Xiaoxiao , Chen Yueguo
Published: April 2022

Purpose

To compare visual outcomes and corneal optical quality after small incision lenticule extraction (SMILE), wavefront-optimized (WFO) FS-LASIK, and topography-guided customized ablation treatment (TCAT) FS-LASIK for myopia.

Methods

This prospective case-series study included 283 eyes of 283 myopic patients who underwent SMILE or FS-LASIK. There were 102, 100, and 81 eyes in the SMILE group, WFO group and TCAT group, respectively. The tomography system (Sirius) was used to measure corneal aberrations and optical quality.

Results

At postoperative 1 and 6 months, there were no significant differences in uncorrected distance visual acuity and corrected distance visual acuity among the three groups (P > 0.05). Postoperative manifest refractive spherical equivalent was similar among the groups (P > 0.05). There was statistically significant difference in cylinder at 1 month among the three groups, with the highest mean value in TCAT group (P < 0.05). The corneal optical path difference, root mean square of corneal astigmatism and strehl ratio were the most superior in the TCAT group at postoperative 1 and 6 months (P < 0.05).

Conclusion

SMILE, WFO FS-LASIK, and TCAT FS-LASIK provided similar visual results. The corneal visual quality after TCAT FS-LASIK was the best.
Induction of Filopodia During Cytomegalovirus Entry Into Human Iris Stromal Cells
Authors: Chang Kenneth , Majmudar Hardik , Tandon Ritesh , Volin Michael V. , Tiwari Vaibhav
Published: April 2022

Many viruses exploit thin projections of filopodia for cell entry and cell-to-cell spread. Using primary cultures of human iris stromal (HIS) cells derived from human eye donors, we report a significant increase in filopodia formation during human cytomegalovirus (HCMV) infection. Using confocal microscopy, we observed a large number of virions being frequently associated along the filopodia prior to cell infection. Depolymerization of actin filaments resulted in a significant inhibition of HCMV entry into HIS cell. Our results further revealed that the transient expression of HCMV envelope glycoprotein B (gB) triggers the induction of the filopodial system. Since gB is known to bind the diverse chains of heparan sulfate (HS), a comparative study was performed to evaluate the gB-mediated filopodial induction in cells expressing either wild-type HS and/or 3-O sulfated HS (3-OS HS). We found that cells co-expressing HCMV gB together with the 3-O sulfotranseferase-3 (3-OST-3) enzyme had a much higher and robust filopodia induction compared to cells co-expressing gB with wild-type HS. The above results were further verified by pre-treating HIS cells with anti-3-OS HS (G2) peptide and/or heparinase-I before challenging with HCMV infection, which resulted in a significant loss in the filopodial counts as well as decreased viral infectivity. Taken together, our findings highlight that HCMV entry into HIS cells actively modulates the actin cytoskeleton via coordinated actions possibly between gB and the 3-OS HS receptor to influence viral infectivity.
Identifying Mild Alzheimer's Disease With First 30-Min 11C-PiB PET Scan
Authors: Shen Chushu , Wang Zhenguo , Chen Hongzhao , Bai Yan , Li Xiaochen , Liang Dong , Liu Xin , Zheng Hairong , Wang Meiyun , Yang Yongfeng , Wang Haifeng , Sun Tao
Published: April 2022

Introduction

11C-labeled Pittsburgh compound B (11C-PiB) PET imaging can provide information for the diagnosis of Alzheimer's disease (AD) by quantifying the binding of PiB to β-amyloid deposition in the brain. Quantification index, such as standardized uptake value ratio (SUVR) and distribution volume ratio (DVR), has been exploited to effectively distinguish between healthy and subjects with AD. However, these measures require a long wait/scan time, as well as the selection of an optimal reference region. In this study, we propose an alternate measure named amyloid quantification index (AQI), which can be obtained with the first 30-min scan without the selection of the reference region.

Methods

11C-labeled Pittsburgh compound B PET scan data were obtained from the public dataset “OASIS-3”. A total of 60 mild subjects with AD and 60 healthy controls were included, with 50 used for training and 10 used for testing in each group. The proposed measure AQI combines information of clearance rate and mid-phase PIB retention in featured brain regions from the first 30-min scan. For each subject in the training set, AQI, SUVR, and DVR were calculated and used for classification by the logistic regression classifier. The receiver operating characteristic (ROC) analysis was performed to evaluate the performance of these measures. Accuracy, sensitivity, and specificity were reported. The Kruskal–Wallis test and effect size were also performed and evaluated for all measures. Then, the performance of three measures was further validated on the testing set using the same method. The correlations between these measures and clinical MMSE and CDR-SOB scores were analyzed.

Results

The Kruskal–Wallis test suggested that AQI, SUVR, and DVR can all differentiate between the healthy and subjects with mild AD (p < 0.001). For the training set, ROC analysis showed that AQI achieved the best classification performance with an accuracy rate of 0.93, higher than 0.88 for SUVR and 0.89 for DVR. The effect size of AQI, SUVR, and DVR were 2.35, 2.12, and 2.06, respectively, indicating that AQI was the most effective among these measures. For the testing set, all three measures achieved less superior performance, while AQI still performed the best with the highest accuracy of 0.85. Some false-negative cases with below-threshold SUVR and DVR values were correctly identified using AQI. All three measures showed significant and comparable correlations with clinical scores (p < 0.01).

Conclusion

Amyloid quantification index combines early-phase kinetic information and a certain degree of β-amyloid deposition, and can provide a better differentiating performance using the data from the first 30-min dynamic scan. Moreover, it was shown that clinically indistinguishable AD cases regarding PiB retention potentially can be correctly identified.
The Effect of Constraint-Induced Movement Therapy Combined With Repetitive Transcranial Magnetic Stimulation on Hand Function in Preschool Children With Unilateral Cerebral Palsy: A Randomized Controlled Preliminary Study
Authors: Wu Qianwen , Peng Tingting , Liu Liru , Zeng Peishan , Xu Yunxian , Yang Xubo , Zhao Yiting , Fu Chaoqiong , Huang Shiya , Huang Yuan , Zhou Hongyu , Liu Yun , Tang Hongmei , He Lu , Xu Kaishou
Published: April 2022

Constraint-induced movement therapy (CIMT) combined with repetitive transcranial magnetic stimulation (rTMS) have shown great potential in improving function in schoolchildren with unilateral cerebral palsy attributed to perinatal stroke. However, the prospect of application in preschool children with unilateral cerebral palsy (UCP) attributed to various brain disorders remains unclear. In this prospective, assessor-blinded, randomized controlled study, 40 preschool children with UCP (aged 2.5–6 years) were randomized to receive 10 days of CIMT combined with active or sham rTMS. Assessments were performed at baseline, 2 weeks, and 6 months post-intervention to investigate upper limb extremity, social life ability, and perceived changes by parents and motor-evoked potentials. Overall, 35 participants completed the trial. The CIMT plus active stimulation group had greater gains in the affected hand function (range of motion, accuracy, and fluency) than the CIMT plus sham stimulation group (P < 0.05), but there was no significant difference in muscular tone, social life ability, and perceived changes by parents between the two groups (P > 0.05). In addition, there was no significant difference in hand function between children with and without motor-evoked potential (P > 0.05). No participants reported severe adverse events during the study session. In short, the treatment of CIMT combined with rTMS is safe and feasible for preschool children with UCP attributed to various brain disorders. Randomized controlled studies with large samples and long-term effects are warranted.
Quantitative Structural Brain Magnetic Resonance Imaging Analyses: Methodological Overview and Application to Rett Syndrome
Authors: Shiohama Tadashi , Tsujimura Keita
Published: April 2022

Congenital genetic disorders often present with neurological manifestations such as neurodevelopmental disorders, motor developmental retardation, epilepsy, and involuntary movement. Through qualitative morphometric evaluation of neuroimaging studies, remarkable structural abnormalities, such as lissencephaly, polymicrogyria, white matter lesions, and cortical tubers, have been identified in these disorders, while no structural abnormalities were identified in clinical settings in a large population. Recent advances in data analysis programs have led to significant progress in the quantitative analysis of anatomical structural magnetic resonance imaging (MRI) and diffusion-weighted MRI tractography, and these approaches have been used to investigate psychological and congenital genetic disorders. Evaluation of morphometric brain characteristics may contribute to the identification of neuroimaging biomarkers for early diagnosis and response evaluation in patients with congenital genetic diseases. This mini-review focuses on the methodologies and attempts employed to study Rett syndrome using quantitative structural brain MRI analyses, including voxel- and surface-based morphometry and diffusion-weighted MRI tractography. The mini-review aims to deepen our understanding of how neuroimaging studies are used to examine congenital genetic disorders.
Electroencephalogram Analysis of Magnetic Stimulation at Different Acupoints
Authors: Yin Ning , Wang Ao-Xiang , Wang Hai-Li
Published: April 2022

Magnetic stimulation has some similarities with acupuncture, and it has broad application prospects because of its non-invasiveness and easy quantification. This paper combines magnetic stimulation technology with electroencephalography to analyze the time-frequency and the brain functional network results elicited by magnetic stimulation at different acupoints. This paper hopes to observe the different effects of stimulating different acupoints on the brain from the perspective of EEG. The EEG signals during magnetic stimulation at ST36, ST40, and GB37 were recorded, respectively. The time-frequency results showed that the magnetic stimulation at ST36 and ST40 on the Foot Yangming Stomach Meridian increased the energy in the left parietal lobe and the right central region, and the energy increased mainly in the theta and alpha bands. However, during the magnetic stimulation at GB37 on the Foot Shaoyang Gallbladder Meridian, the energy in the central region and the frontal lobe increased, and the energy increased mainly in the delta, theta, and alpha bands. Moreover, the energy in the right parietal lobe decreased during magnetic stimulation at GB37. The results of brain functional network were also consistent with time-frequency results. The brain network connections of GB37 stimulation in the central region were significantly less than that of ST36 and ST40 (p < 0.01). In addition, the connections between central region and frontal lobe and the connections between central region and parietal lobe of GB37 stimulation were significantly different from that of ST36 and ST40 (p < 0.01). The above results indicate that ST36 and ST40 on the same meridian have similar effects on the brain, while GB37 on the other meridian has completely different effects from ST36 and ST40. The results of this paper explain the reason why stimulating ST36 and ST40 can treat similar diseases from the perspective of EEG, and also explain that stimulating GB37 has significantly different effects on the brain from that of ST36 and ST40.
Metabolic and Cardiovascular Benefits of Apple and Apple-Derived Products: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Kim Sun Jo , Anh Nguyen Hoang , Jung Cheol Woon , Long Nguyen Phuoc , Park Seongoh , Cho Young Hyun , Yoon Young Cheol , Lee Eun Goo , Kim Mina , Son Eui Young , Kim Tae Ha , Deng Yingqian , Lim Johan , Kwon Sung Won
Published: April 2022

Background

Quantitative evidence of the metabolic and cardiovascular effects of apples (Malus domestica) is lacking in interventional studies. This study aimed to summarize the available evidence of the beneficial effects of apples and apple-derived products (ADPs) on metabolic and cardiovascular markers.

Methods

Peer-reviewed randomized controlled trials (RCTs) were identified from four databases on May 3, 2021 and regularly updated until the end of May 2021. Demographic characteristics, intervention types, and evaluation parameters were extracted. A meta-analysis on the mean difference of change scores was conducted on commonly presented outcomes in the RCTs.

Results

The metabolic and cardiovascular effects of diverse regimens, including whole apple, apple extract, and apple juice, were examined in 18 eligible RCTs. Nine common evaluation outcomes were eventually introduced to the meta-analysis, including total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride, glucose, insulin, C-reactive protein, and systolic/diastolic blood pressures. The levels of TC (−2.69 mg/dL; 95% CI: −5.43, 0.04 mg/dL) and LDL (−2.80 mg/dL; 95% CI: −5.78, 0.17 mg/dL) showed a non-significant decreasing tendency after at least a week of apple consumption. Further subgroup analysis, particularly, a comparison with placebo as a control, showed a significant reduction in TC and LDL levels. When stratified by the baseline level, subjects with high TC and LDL level were shown to have more benefits from the apple intake. Intriguingly, apple and ADPs significantly reduced HDL levels to a small extent (−1.04 mg/dL; 95% CI: −1.79, −0.29 mg/dL). The other markers were mostly unaffected by the intervention.

Conclusion

Our investigation revealed that apples could improve blood cholesterol levels.

Systematic Review Registration

[https://www.crd.york.ac.uk/prospero/], identifier [CRD42020215977].
Characterization of Chelation and Absorption of Calcium by a Mytilus edulis Derived Osteogenic Peptide
Authors: Xu Zhe , Han Shiying , Chen Hui , Zhu Zhixuan , Han Lingyu , Dong Xiufang , Du Ming , Li Tingting
Published: April 2022

In a previous study, the peptide LGKDQVRT, which was identified by enzymatic hydrolysis, released during the proteolysis of Mytilus edulis, had potential osteogenic activity. In this study, the octapeptide LGKDQVRT was able to spontaneously bind calcium in a 1:1 stoichiometric ratio, and the calcium-binding site likely involves calcium and amino acid VAL6 in the LGKDQVRT peptide to form a metal-donor to metal acceptor complex. The peptide LGKDQVRT has the activity of promoting the proliferation and differentiation of osteoblasts. The results of this study suggest that hydrolyzed peptides from Mytilus edulis protein can be used as a dietary supplement to improve calcium absorption and prevent osteoporosis.
Metabolomics Analysis of Morchella sp. From Different Geographical Origins of China Using UPLC-Q-TOF-MS
Authors: Dong Hui , Zhao Xiaoyan , Cai Min , Gu Haotian , E Hengchao , Li Xiaobei , Zhang Yanmei , Lu Huan , Zhou Changyan
Published: April 2022

The morel mushroom (Morchella sp.) is reputed as one of the most highly-prized edible fungi with mounting cultivated area as well as commercial popularity in China. To date, optimized methods specific for quality evaluation and constituent analysis of Morchella sp. are still non-available, impeding the healthy and sustainable development of this industry. Herein, an untargeted UPLC-Q-TOF-MS-based metabolomics approach was performed to characterize the metabolite profiles of morel samples from four distinct geographical origins of China, viz. Gansu, Guizhou, Liaoning, and Henan province. A total of 32 significantly different metabolites assigned to lipids (19), organic acids (9), amino acids (3), and ketones (1) were identified to distinguish the geographic-segregation samples amenable to multivariate analysis. These metabolites may serve as molecular markers indicative of specific regions. More importantly, the lipid, protein and amino acid metabolism were responsible for geographic differences as revealed by KEGG pathway enrichment analysis. Collectively, this study not only pioneered high-throughput methodology to evaluate quality of Morchella sp. and distinguish geographical origins in a sensitive, rapid and efficient manner, but also shed light on the potential link between physiochemical variation and geological origins from a metabolic perspective, which may be conducive to the advancement of edible fungi industry and establishment of food traceability system.
Maternal Folic Acid-Containing Supplement Use in Relation to Offspring Motor Function. A Prospective Study of 503 Mother-Child Dyads
Authors: Melfald Tveten Kine , Miodini Nilsen Roy , Dragesund Tove
Published: April 2022

Background

The preventive effect of maternal folic acid use on offspring neural tube defects is well-established. However, a putative link between supplement use and other neurodevelopmental outcome is inconsistent. The aim of this study was to examine the association of folic acid-containing supplement use before and during pregnancy with motor function in children aged 3–18 months.

Method

The study has a prospective cohort design including 503 mother-infant dyads. Motor function was measured by the Infant Motor Profile (IMP) and Ages and Stages Questionnaire Second Edition (ASQ-2). Associations between exposure and outcome were examined using linear regression analysis with robust standard error estimation.

Results

Offspring total IMP score was not associated with any maternal folic acid-containing supplement use when they were used during pregnancy only (adjusted β = 0.11 95% CI = −1.19, 1.40; p = 0.87) or when they were used both before and during pregnancy (adjusted β = 0.22 95% CI = −0.95, 1.40; p = 0.70). When examining the five domain scores separately, only the IMP domain adaptability showed some association with supplement use during pregnancy (adjusted β = 2.87; 95% CI = 0.08, 5.68; p = 0.04), but the strength of the association was weak. Further, supplement use was not associated with any of the two motor domains of ASQ-2.

Conclusion

Although no association between folic acid-containing supplement use and offspring motor function was found, the complexity of this topic and its potential mechanisms, requires further investigation. This research should include robust and accurate measures on maternal nutritional status along with thorough endpoint assessments.
Multisystemic Inflammatory Syndrome in Children From the South of Colombia: One Year of Experience
Authors: Pérez López Pilar , Carvajal Duque Darling , Salgado García Doris Martha , Vega Vega Martha Rocío , Ramos-Castaneda Jorge Andrés , Ardila Gómez Iván José , Romero Andrés Felipe
Published: April 2022

Background

Multisystemic inflammatory syndrome in children (MIS-C) is one of the most severe presentations of COVID-19 infection in pediatrics. Currently, we have few studies that describe the characteristics of this condition in Colombian children.

Objective

To describe the clinical and epidemiological characteristics of children hospitalized with MIS-C in Neiva, Colombia.

Methods

Observational follow-up study of a cohort of children with MIS-C for 12 months (May 15, 2020, to May 30, 2021) in two hospitals in the city of Neiva. Epidemiological data, clinical characteristics, laboratory characteristics, cardiological evaluation, treatment, and clinical outcomes were analyzed.

Results

We included 34 patients who met the diagnosis of MIS-C. The median age was 68 months. Some type of nutritional issue was observed by 43.75% of those under 5 years of age and by 27.78% of those over 5 years of age. Gastrointestinal symptoms were the most frequent, with vomiting, diarrhea, and abdominal pain being the most frequent by 79, 70, and 67%, respectively. By 77% of the patients, a history of SARS-COV-2 infection was documented through IgG. In the echocardiogram, 35.4% of the patients had systolic dysfunction, followed by coronary involvement by 35%.

Conclusion

This study describes a series of cases of children with MIS-C in Colombia. Gastrointestinal manifestations were predominant. Mortality was high in comparison to other countries but similar to that reported in Colombia. This fact was associated with relevant pathological background. More training is required for physicians in order to have a better understanding of the disease so as to have an early diagnosis and timely treatment.
Mechanism of Action of Shenerjiangzhi Formulation on Hyperlipidemia Induced by Consumption of a High-Fat Diet in Rats Using Network Pharmacology and Analyses of the Gut Microbiota
Authors: Zhang Shuang , Wang Yu , Lu Fang , Mohammed Shadi A. D. , Liu Hanxing , Ding Song , Liu Shu-min
Published: April 2022

Shenerjiangzhi formulation (SEJZ) is a new traditional Chinese medicine formulation (patent number: CN110680850A). SEJZ contains Eleutherococcus senticosus (Rupr. and Maxim.), Maxim (Araliaceae; E. senticosus radix and rhizome), Lonicera japonica Thunb (Caprifoliaceae; Lonicera japonica branch, stem), Crataegus pinnatifida Bunge (Rosaceae; Crataegus pinnatifida fruit), and Auricularia auricula. SEJZ has been designed to treat hyperlipidemia. Despite the therapeutic benefits of SEJZ, its underlying mechanism of action is not known. We explored the efficacy of SEJZ against hyperlipidemia by integrating network pharmacology and 16S rRNA gene sequencing and elucidated its mechanism of action. First, SEJZ targets were found through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and from the literature. Hyperlipidemia-related therapeutic targets were obtained from GeneCards, Online Mendelian Inheritance in Man, and DrugBank databases. Then, Search Tool for the Retrieval of Interacting Genes/Proteins and Cytoscape were applied for the analyses and construction of a protein–protein interaction (PPI) network. The Kyoto Encyclopedia of Genes and Genomes database was employed to identify signaling pathways that were enriched. Second, the therapeutic effects of SEJZ against hyperlipidemia induced by consumption of a high-fat diet in rats were evaluated by measuring body weight changes and biochemical tests. SEJZ treatment was found to alleviate obesity and hyperlipidemia in rats. Finally, 16S rRNA gene sequencing showed that SEJZ could significantly increase the abundance of short-chain fatty acid-producing bacteria, restore the intestinal barrier, and maintain intestinal-flora homeostasis. Using PICRUSt2, six metabolic pathways were found to be consistent with the results of network pharmacology: “African trypanosomiasis”, “amoebiasis”, “arginine and proline metabolism”, “calcium signaling pathway”, “NOD-like receptor signaling pathway”, and “tryptophan metabolism”. These pathways might represent how SEJZ works against hyperlipidemia. Moreover, the “African trypanosomiasis pathway” had the highest association with core genes. These results aid understanding of how SEJZ works against dyslipidemia and provide a reference for further studies.
Comparative Efficacy and Safety of Advanced Intravitreal Therapeutic Agents for Noninfectious Uveitis: A Systematic Review and Network Meta-Analysis
Authors: Liao Weiting , Zhong Zhenyu , Su Guannan , Feng Xiaojie , Yang Peizeng
Published: April 2022

Background: To compare the efficacy and safety of advanced intravitreal therapeutic regimens, including a dexamethasone implant at 350 and 700 μg; a fluocinolone acetonide (FA) implant, 0.2 µg/day, 0.59 and 2.1 mg; intravitreal bevacizumab, 1.25 mg; intravitreal ranibizumab, 0.5 mg; intravitreal triamcinolone acetonide (IVTA), 2 and 4 mg; and standard of care (SOC, systemic therapy) for noninfectious uveitis.

Methods: We searched the Cochrane Library database, EMBASE, Medline, clinicaltrials.gov until April 2021 with 13 RCTs (1806 participants) identified and conducted a pairwise and Bayesian network meta-analysis with random effects.

Results: No specific regimen showed a statistically significant advantage or disadvantage to another treatment regimen with regard to efficacy. However, the FA implant, 0.59 mg was associated with a higher risk of cataract (RR 4.41, 95% CI 1.51–13.13) and raise in intraocular pressure (IOP) (RR 2.53 95% CI 1.14–6.25) compared with SOC at 24 months. IVTA, 4 mg at 6 months was associated with lower risk of IOP rising compared with FA implant, 0.2 µg/day at 36 months (RR 3.43 95% CI 1.12–11.35).

Conclusion: No intravitreal therapeutic regimens showed a significant advantage or disadvantage with regard to efficacy. However, SOC was associated with lower risk of side effects compared with FA implants. IVTA, 4 mg, might be the best choice with lowest risk of IOP rising.

Systematic Review Registration:clinicaltrials.gov, identifier CRD42020172953
Network Pharmacology-Based Strategy to Identify the Pharmacological Mechanisms of Pulsatilla Decoction against Crohn’s Disease
Authors: Liu Jinguo , Zhang Lu , Wang Zhaojun , Chen Shanshan , Feng Shuyan , He Yujin , Zhang Shuo
Published: April 2022

Purpose: To explore pharmacological mechanisms of Pulsatilla decoction (PD) against Crohn’s disease (CD) via network pharmacology analysis followed by experimental validation.

Methods: Public databases were searched to identify bioactive compounds and related targets of PD as well as related genes in patients with CD. Analyses using the drug–compound–target–disease network, the protein–protein interaction (PPI) network, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to predict the core targets and pathways of PD against CD. Colon tissue resected from patients with CD and tissue samples from a mouse model of CD fibrosis treated with PD were assessed to verify the major targets of PD in CD predicted by network pharmacologic analysis.

Results: A search of the targets of bioactive compounds in PD and targets in CD identified 134 intersection targets. The target HSP90AA1, which was common to the drug–compound–target–disease and PPI networks, was used to simulate molecular docking with the corresponding bioactive compound. GO and KEGG enrichment analyses showed that multiple targets in the antifibrotic pathway were enriched and could be experimentally validated in CD patients and in a mouse model of CD fibrosis. Assays of colon tissues from CD patients showed that intestinal fibrosis was greater in stenoses than in nonstenoses, with upregulation of p-AKT, AKT, p-mTOR, mTOR, p-ERK1/2, ERK1/2, p-PKC, and PKC targets. Treatment of CD fibrosis mice with PD reduced the degree of fibrosis, with downregulation of the p-AKT, AKT, p-mTOR, mTOR, p-ERK1/2, ERK1/2, and PKC targets.

Conclusion: Network pharmacology analysis was able to predict bioactive compounds in PD and their potential targets in CD. Several of these targets were validated experimentally, providing insight into the pharmacological mechanisms underlying the biological activities of PD in patients with CD.
Quantitative Comparison of Avian and Mammalian Physiologies for Parameterization of Physiologically Based Kinetic Models
Authors: Scanes Colin G. , Witt Johannes , Ebeling Markus , Schaller Stephan , Baier Vanessa , Bone Audrey J. , Preuss Thomas G. , Heckmann David
Published: April 2022

Physiologically based kinetic (PBK) models facilitate chemical risk assessment by predicting in vivo exposure while reducing the need for animal testing. PBK models for mammals have seen significant progress, which has yet to be achieved for avian systems. Here, we quantitatively compare physiological, metabolic and anatomical characteristics between birds and mammals, with the aim of facilitating bird PBK model development. For some characteristics, there is considerable complementarity between avian and mammalian species with identical values for the following: blood hemoglobin and hemoglobin concentrations per unit erythrocyte volume together with relative weights of the liver, heart, and lungs. There are also systematic differences for some major characteristics between avian and mammalian species including erythrocyte volume, plasma concentrations of albumin, total protein and triglyceride together with liver cell size and relative weights of the kidney, spleen, and ovary. There are also major differences between characteristics between sexually mature and sexually immature female birds. For example, the relative weights of the ovary and oviduct are greater in sexually mature females compared to immature birds as are the plasma concentrations of triglyceride and vitellogenin. Both these sets of differences reflect the genetic “blue print” inherited from ancestral archosaurs such as the production of large eggs with yolk filled oocytes surrounded by egg white proteins, membranes and a calciferous shell together with adaptions for flight in birds or ancestrally in flightless birds.