bluuebunny/crossref_metadata_2025 huggingface dataset:
Phenotypes in Children With SYNGAP1 Encephalopathy in China
Authors: Zhang Huiting , Yang Liu , Duan Jing , Zeng Qi , Chen Li , Fang Yu , Hu Junjie , Cao Dezhi , Liao Jianxiang
Published: December 2021

Objective: We aimed to explore the associated clinical phenotype and the natural history of patients with SYNGAP1 gene variations during early childhood and to identify their genotype–phenotype correlations.

Methods: This study used a cohort of 13 patients with epilepsy and developmental disorder due to SYNGAP1 mutations, namely, 7 patients from Shenzhen Children’s Hospital between September 2014 and January 2020 and 6 patients from previously published studies. Their clinical data were studied.

Results: A total of 13 children with SYNGAP1 gene variants (eight boys and five girls) were identified. The age of disease onset was in infancy. Mutations were located between exons 8 and 15; most were frameshift or truncated mutations. Four mutation sites (c.924G > A, c.1532-2_1532del, c.1747_1755dup, and c.1735_1738del) had not been reported before. All patients had global developmental delay within the first year of life, and intellectual impairment became gradually apparent. Some of them developed behavioral problems. The developmental delay occurred before the onset of seizures. All seven patients in our cohort presented with epilepsy; myoclonic seizures, absence seizures, and epileptic spasms were the most common seizure types. Abnormal electroencephalograms were identified from five patients before the onset of their seizures. All patients suffered from drug-resistance seizures. However, comorbidities such as behavioral problems were less frequently observed.

Conclusion: The most common age of disease onset in SYNGAP1 gene mutations is in infancy, while neurodevelopmental delay and epilepsy are the major phenotypes. They have a higher percentage of drug-resistant epilepsy and epileptic spasms than those in previous reports. We should give attention to the patients with abnormal EEGs without seizures and think about the suitable time of the anti-seizure medications for them. We have not found the genotype–phenotype correlation.

Trial registration: Chinese Clinical Trial Registry, Registration number: ChiCTR2100049289 (https://www.chictr.org.cn/listbycreater.aspx).
Calcium Ions Aggravate Alzheimer’s Disease Through the Aberrant Activation of Neuronal Networks, Leading to Synaptic and Cognitive Deficits
Authors: Guan Pei-Pei , Cao Long-Long , Yang Yi , Wang Pu
Published: December 2021

Alzheimer’s disease (AD) is a neurodegenerative disease that is characterized by the production and deposition of β-amyloid protein (Aβ) and hyperphosphorylated tau, leading to the formation of β-amyloid plaques (APs) and neurofibrillary tangles (NFTs). Although calcium ions (Ca2+) promote the formation of APs and NFTs, no systematic review of the mechanisms by which Ca2+ affects the development and progression of AD has been published. Therefore, the current review aimed to fill the gaps between elevated Ca2+ levels and the pathogenesis of AD. Specifically, we mainly focus on the molecular mechanisms by which Ca2+ affects the neuronal networks of neuroinflammation, neuronal injury, neurogenesis, neurotoxicity, neuroprotection, and autophagy. Furthermore, the roles of Ca2+ transporters located in the cell membrane, endoplasmic reticulum (ER), mitochondria and lysosome in mediating the effects of Ca2+ on activating neuronal networks that ultimately contribute to the development and progression of AD are discussed. Finally, the drug candidates derived from herbs used as food or seasoning in Chinese daily life are summarized to provide a theoretical basis for improving the clinical treatment of AD.
The Role of Vitamin D in the Relationship Between Gender and Deep Vein Thrombosis Among Stroke Patients
Authors: Tao Jiejie , Lou Feiling , Liu Yuntao
Published: December 2021

Introduction: Accumulating evidence had demonstrated that females had a higher risk of deep vein thrombosis (DVT) than males, but the mechanism was still unknown. Vitamin D was found to play an essential role in DVT, and gender may influence the serum vitamin D levels. This study aimed to explore whether vitamin D played a role in the gender difference in DVT.

Materials and Methods: A total of 444 patients with acute stroke were recruited, which were divided into the DVT group (n = 222) and the non-DVT group (n = 222). Serum vitamin D levels were measured after admission and were split into three categories, including deficiency (<50 nmol/L), insufficiency (52.5–72.5 nmol/L), and sufficiency (more than 75 nmol/L). Hierarchical regression analysis was adopted to analyze the relationship between gender and DVT, controlling the confounding factors.

Results: Females showed a higher proportion of DVT than males (60.7 vs. 42.5%, p < 0.001), and lower serum vitamin D levels than males (53.44 ± 16.45 vs. 69.43 ± 23.14, p < 0.001). Moreover, serum vitamin D levels were lower in the DVT group than in the non-DVT group (59.44 ± 19.61 vs. 66.24 ± 23.86, p < 0.001). Besides, the DVT group showed a lower proportion of vitamin D sufficiency than the non-DVT group (21.2 vs. 32.9%, p < 0.05). Hierarchical regression analysis showed that females had 2.083-fold (p < 0.001, unadjusted model) and 1.413-fold (p = 0.155, adjusted model) risk to develop DVT. In addition, the sufficiency status of vitamin D showed an independent protective effect on DVT (unadjusted model OR, 0.504, p = 0.004; adjusted model OR, 0.686, p = 0.011).

Conclusion: Females had a higher risk of DVT than males, and vitamin D may play an essential role in this relationship. Further studies are needed to explore whether vitamin D supplementation could reduce DVT risk in stroke patients, especially females.
Probiotics for the Treatment of Docetaxel-Related Weight Gain of Breast Cancer Patients—A Single-Center, Randomized, Double-Blind, and Placebo-Controlled Trial
Authors: Juan Zhang , Qing Zhang , Yongping Liang , Qian Liyuan , Wu Wei , Wen Yanguang , Tong Jianbin , Ding Boni
Published: December 2021

Background: Docetaxel is an important chemotherapy-agent for breast cancer treatment. One of its side-effects is weight gain, which increases the all-cause mortality rate. Considering gut microbiota is one important factor for weight regulation, we hypothesized that probiotics could be potentially used to reduce the docetaxel-related weight gain in breast cancer patients.

Methods: From 10/8/2018 to 10/17/2019, 100 breast cancer (Stage I-III) patients underwent four cycles of docetaxel-based chemotherapy were enrolled and randomly assigned to receive probiotics (Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis) or placebo (supplementary material of the probiotics capsule) treatment for 84 days with three capsules per time, twice/day. The primary outcome: the changes in body weight and body-fat percentage of the patients were measured by a designated physician using a fat analyzer, and the secondary outcomes: the fasting insulin, plasma glucose, and lipids were directly obtained from the Hospital Information System (HIS); The metabolites were measured using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS); The fecal microbiome was analyzed using bacterial 16S ribosomal RNA (rRNA) gene sequence. All indicators were measured 1 day before the first cycle of docetaxel-based chemotherapy and 21 days after the last cycle of docetaxel-based chemotherapy.

Results: Compared with the placebo group, the probiotic group showed significantly smaller changes in body weight (Mean [SD] 0.77 [2.58] vs. 2.70 [3.08], P = 0.03), body-fat percentage (Mean [SD] 0.04 [1.14] vs. 3.86 [11.09], P = 0.02), and low density lipoprotein (LDL) (Mean [SD]−0.05[0.68] vs. 0.39 [0.58], P = 0.002). Moreover, five of the 340 detected plasma metabolites showed significant differences between the two groups. The change of biliverdin dihydrochloride (B = −0.724, P = 0.02) was inverse correlated with weight gain. One strain of the phylum and three strains of the genus were detected to be significantly different between the two groups. Also, the changes of Bacteroides (B = −0.917, P < 0.001) and Anaerostipes (B = −0.894, P < 0.001) were inverse correlated with the change of LDL.

Conclusions: Probiotics supplement during docetaxel-based chemotherapy for breast cancer treatment may help to reduce the increase in body weight, body-fat percentage, plasma LDL, and minimize the metabolic changes and gut dysbacteriosis.

Clinical Trial Registration:http://www.chictr.org.cn/showproj.aspx?proj=24294, ChiCTR-INQ-17014181.
Germline Mutation Landscape and Associated Clinical Characteristics in Chinese Patients With Renal Cell Carcinoma
Authors: Kong Wen , Yang Tongtong , Wen Xiaodong , Mu Zhongyi , Zhao Cheng , Han Sujun , Tian Jing , Zhang Xinhao , Zhou Tao , Zhang Yanrui , Lou Feng , Cao Shanbo , Wang Huina , Zhang Jin
Published: December 2021

Background

Renal cell carcinoma (RCC) is a disease of genomic alterations, of which the complete panorama helps in facilitating molecular-guided therapy. Germline mutation profiles and associated somatic and clinical characteristics remains unexplored in Chinese RCC patients.

Methods

We retrospectively profiled the germline and somatic mutations of 322 unselected RCC patients using a panel consisting of 808 cancer-related genes. We categorized patients into three groups based on germline mutation status and compared the somatic mutation spectrum among different groups.

Results

Approximately one out of ten (9.9%) RCC patients were identified to carry pathogenic/likely pathogenic (P/LP) germline variants (PGVs), of which 3.7% were variants in syndromic RCC-associated genes and 6.2% were other cancer-predisposition genes. The most common PGV was found in VHL (2.2%), followed by FH, TSC2, ATM, BRCA1, NBN, and BLM (0.6% each). Young patients (≤46 years) were more likely to harbor PGVs. Variants in syndromic RCC-associated genes were predominant identified in young patients, while variants in other cancer-predisposition genes were found in patients >46 years more frequently. Furthermore, 39.3% (11/28) of patients carrying PGVs were detected to have somatic “second hit” events. Germline and somatic sequencing, including microsatellite instability (MSI) status analysis, provided potentially actionable therapeutic targets in 17.1% of patients in the whole cohort.

Conclusions

Our results revealed that approximately 10% of RCC patients carried clinically significant germline mutations. Current guidelines recommendation for genetic testing seemed not sensitive enough to identify patients with hereditary RCC susceptibility. It is rational to promote genetic testing in RCC population.
Tumor Stage-Based Gross Tumor Volume of Resectable Esophageal Squamous Cell Carcinoma Measured on CT: Association With Early Recurrence After Esophagectomy
Authors: Wu Yu-ping , Tang Sun , Tan Bang-guo , Yang Li-qin , Lu Fu-lin , Chen Tian-wu , Ou Jing , Zhang Xiao-ming , Gao Dan , Li Ke-ying , Yu Zi-yi , Tang Zhao
Published: December 2021

Objective

To investigate relationship of tumor stage-based gross tumor volume (GTV) of esophageal squamous cell carcinoma (ESCC) measured on computed tomography (CT) with early recurrence (ER) after esophagectomy.

Materials and Methods

Two hundred and four consecutive patients with resectable ESCC including 159 patients enrolled in the training cohort (TC) and 45 patients in validation cohort (VC) underwent contrast-enhanced CT less than 2 weeks before esophagectomy. GTV was retrospectively measured by multiplying sums of all tumor areas by section thickness. For the TC, univariate and multivariate analyses were performed to determine factors associated with ER. Mann-Whitney U test was conducted to compare GTV in patients with and without ER. Receiver operating characteristic (ROC) analysis was performed to determine if tumor stage-based GTV could predict ER. For the VC, unweighted Cohen’s Kappa tests were used to evaluate the performances of the previous ROC predictive models.

Results

ER occurred in 63 of 159 patients (39.6%) in the TC. According to the univariate analysis, histologic differentiation, cT stage, cN stage, and GTV were associated with ER after esophagectomy (all P-values < 0.05). Multivariate analysis revealed that cT stage and GTV were independent risk factors with hazard ratios of 3.382 [95% confidence interval (CI): 1.533–7.459] and 1.222 (95% CI: 1.125–1.327), respectively (all P-values < 0.05). Mann-Whitney U tests showed that GTV could help differentiate between ESCC with and without ER in stages cT1-4a, cT2, and cT3 (all P-values < 0.001), and the ROC analysis demonstrated the corresponding cutoffs of 13.31, 17.22, and 17.83 cm3 with areas under the curve of more than 0.8, respectively. In the VC, the Kappa tests validated that the ROC predictive models had good performances for differentiating between ESCC with and without ER in stages cT1-4a, cT2, and cT3 with Cohen k of 0.696 (95% CI, 0.498–0.894), 0.733 (95% CI, 0.386–1.080), and 0.862 (95% CI, 0.603–1.121), respectively.

Conclusion

GTV and cT stage can be independent risk factors of ER in ESCC after esophagectomy, and tumor stage-based GTV measured on CT can help predict ER.
Transcriptional Networks Identify BRPF1 as a Potential Drug Target Based on Inflammatory Signature in Primary Lower-Grade Gliomas
Authors: Xia Mingyang , Chen Huiyao , Chen Tong , Xue Ping , Dong Xinran , Lin Yifeng , Ma Duan , Zhou Wenhao , Shi Wei , Li Hao
Published: December 2021

Gliomas are the most common tumors of the central nervous system and are classified into grades I-IV based on their histological characteristics. Lower-grade gliomas (LGG) can be divided into grade II diffuse low-grade gliomas and grade III moderate gliomas and have a relatively good prognosis. However, LGG often develops into high-grade glioma within a few years. This study aimed to construct and identify the prognostic value of an inflammatory signature and discover potential drug targets for primary LGG. We first screened differentially expressed genes in primary LGG (TCGA) compared with normal brain tissue (GTEx) that overlapped with inflammation-related genes from MSigDB. After survival analysis, nine genes were selected to construct an inflammatory signature. LGG patients with a high inflammatory signature score had a poor prognosis, and the inflammatory signature was a strong independent prognostic factor in both the training cohort (TCGA) and validation cohort (CGGA). Compared with the low-inflammatory signature group, differentially expressed genes in the high-inflammatory signature group were mainly enriched in immune-related signaling pathways, which is consistent with the distribution of immune cells in the high- and low-inflammatory signature groups. Integrating driver genes, upregulated genes and drug targets data, bromodomain and PHD finger-containing protein 1 (BRPF1) was selected as a potential drug target. Inhibition of BRPF1 function or knockdown of BRPF1 expression attenuated glioma cell proliferation and colony formation.
Study on Motion Management of Pancreatic Cancer Treated by CyberKnife
Authors: Jing Shenghua , Jiang Changchen , Ji Xiaoqin , Qiu Xiangnan , Li Jing , Sun Xiangdong , Zhu Xixu
Published: December 2021

Purpose

We investigated the movement characteristics of pancreas and the clinical accuracy of tracking pancreas with the Synchrony Respiratory Tracking System (SRTS) during the CyberKnife treatment. These data provide a clinical data basis for the expansion margins of pancreatic tumor target.

Methods and Materials

Forty-two patients with pancreatic cancer treated by CyberKnife were retrospectively studied. The pancreatic displacement calculated from the x-ray images collected during the time interval between two consecutive movements constituted a data set.

Results

The total mean motion amplitudes and standard deviations of pancreatic tumors in SI, LR, AP, and radial directions were 3.66 ± 1.71 mm, 0.97 ± 0.62 mm, 1.52 ± 1.02 mm, and 1.36 ± 0.49 mm, respectively. The overall mean correlation errors and standard deviations were 0.82 ± 0.46 mm, 0.47 ± 0.33 mm, 0.41 ± 0.24 mm, and 0.98 ± 0.37 mm, respectively. The overall mean prediction errors and standard deviations were 0.57 ± 0.14 mm, 0.62 ± 0.28 mm, 0.39 ± 0.17 mm, and 1.58 ± 0.36 mm, respectively. The correlation errors and prediction errors of pancreatic tumors at different anatomical positions in SI, LR, and AP directions were statistically significant (p < 0.05).

Conclusions

The tumor motion amplitude, the tumor location, and the treatment time are the main factors affecting the tracking accuracy. The pancreatic tumors at different anatomical locations should be treated differently to ensure sufficient dose coverage of the pancreatic target area.
Identification and Validation of Three Autophagy-Related Long Noncoding RNAs as Prognostic Signature in Cholangiocarcinoma
Authors: Liu Ya Jun , Hounye Alphonse Houssou , Wang Zheng , Liu Xiaowei , Yi Jun , Qi Min
Published: December 2021

Cholangiocarcinoma (CCA) is featured by common occurrence and poor prognosis. Autophagy is a biological process that has been extensively involved in the progression of tumors. Long noncoding RNAs (lncRNAs) have been discovered to be critical in diagnosing and predicting various tumors. It may be valuable to elaborate autophagy-related lncRNAs (ARlncRNAs) in CCA, and indeed, there are still few studies concerning the role of ARlncRNAs in CCA. Here, a prognostic ARlncRNA signature was constructed to predict the survival outcome of CCA patients. Through identification, three differentially expressed ARlncRNAs (DEARlncRNAs), including CHRM3.AS2, MIR205HG, and LINC00661, were screened and were considered predictive signatures. Furthermore, the overall survival (OS) of patients with high-risk scores was significantly lower than that of patients with low scores. Interestingly, the risk score was an independent factor for the OS of patients with CCA. Moreover, receiver operating characteristic (ROC) curve analysis showed that the screened and constructed prognosis signature for 1 year (AUC = 0.884), 3 years (AUC =0.759), and 5 years (AUC = 0.788) presented a high score of accuracy in predicting OS of CCA patients. Gene set enrichment analysis (GSEA) revealed that the three DEARlncRNAs were significantly enriched in CCA-related signaling pathways, including “pathways of basal cell carcinoma”, “glycerolipid metabolism”, etc. Quantitative real-time PCR (qRT-PCR) showed that expressions of CHRM3.AS2, MIR205HG, and LINC00661 were higher in CCA tissues than those in normal tissues, similar to the trends detected in the CCA dataset. Furthermore, Pearson’s analysis reported an intimate correlation of the risk score with immune cell infiltration, indicating a predictive value of the signature for the efficacy of immunotherapy. In addition, the screened lncRNAs were found to have the ability to modulate the expression of mRNAs by interacting with miRNAs based on the established lncRNA-miRNA-mRNA network. In conclusion, our study develops a novel nomogram with good reliability and accuracy to predict the OS of CCA patients, providing a significant guiding value for developing tailored therapy for CCA patients.
Two Novel Mutations in the SI Gene Associated With Congenital Sucrase-Isomaltase Deficiency: A Case Report in China
Authors: Zhou Jianli , Zhao Yuzhen , Qian Xia , Cheng Yongwei , Cai Huabo , Chen Moxian , Zhou Shaoming
Published: December 2021

Background: Congenital sucrase-isomaltase deficiency (CSID) is an autosomal recessive inherited disease that leads to the maldigestion of disaccharides and is associated with mutation of the sucrase-isomaltase (SI) gene. Cases of CSID are not very prevalent in China or worldwide but are gradually being identified and reported.

Case Presentation: We report a case involving a 14-month-old male who presented with failure to thrive that had begun after food diversification and was admitted for chronic diarrhea. We used a whole-exome sequencing (WES) approach to identify mutations in this patient's genome. WES revealed two novel heterozygous mutations in the SI gene, c.2626C > T (p.Q876*) and c.2872C > T (p.R958C), which were confirmed by Sanger DNA sequencing. With a strict sucrose- and starch-restricted diet, the patient's diarrhea was resolved, and he began to gain weight.

Conclusions: We report a case of novel variants in the SI gene that caused CSID. This report provides valuable information for the clinical field, especially in China.
Developing a Reference Database for Typical Body and Organ Growth of the Artificially Reared Pig as a Biomedical Research Model
Authors: Vu Vinh H. , Donovan Sharon M. , Brink Lauren R. , Li Qian , Gross Gabriele , Dilger Ryan N. , Fleming Stephen A.
Published: December 2021

Objectives: The pig is a common model utilized to support substantiation of novel bioactive components in infant formula. However, reference ranges for outcomes to determine safety are unclear. Our objective was to use historical data to objectively define typical body and organ growth metrics of the domesticated pig in research.

Methods: Twenty-two studies were compiled to assess typical growth of body and organ weights in young pigs. Metadata were organized to include milk replacer sources, bioactive components, sex, breed, source of herd, feeding regimen, and rearing environment. A combination of statistical models including simple linear regression and linear mixed effect models were used to assess typical growth patterns.

Results: Over 18,000 data points from 786 animals were available. In general, minimal differences in the growth of pigs who were male and female, artificially- or sow-reared, or fed ad libitum- or by scheduled-feeding, were observed in the first 30 days of life (P > 0.05). A weight-for-age chart from reference pigs was developed to compare body weights of pigs demonstrating growth characterized as accelerated, typical, reduced, and failure to thrive to illustrate effects of dietary interventions. Distributions of relative brain, liver, and intestine weights (as % of total body weight) were similar between rearing environments and sexes. An alternative bivariate level approach was utilized for the analysis of organ weights. This approach revealed significant biologically-relevant insights into how deficient diets can affect organ weight that a univariate level assessment of weight distribution was unable to detect.

Conclusions: Ultimately, these data can be used to better interpret whether bioactive ingredients tested in the pig model affect growth and development within typical reference values for pigs in the first 30 days of life.
Heparin-Binding Protein in Critically Ill Children With Severe Community-Acquired Pneumonia
Authors: Huang Caizhi , Zhang Cong , Zhang Jie , Zhang Lin , Mo Yi , Mo Liya
Published: December 2021

Objective: The aim of this study was to investigate possible associations between Heparin-binding protein (HBP) and the development of respiratory failure (RF) and sepsis in critically ill children with severe community-acquired pneumonia (CAP).

Methods: This study enrolled 157 children with severe CAP admitted to Intensive Care Unit (ICU). At ICU admission, the levels of HBP and other biomarkers, including C-reactive protein, interleukin-6 (IL-6), procalcitonin, white blood cells, neutrophil percentage, and D-dimer, were determined.

Results: Of the enrolled patients, 106 developed RF (35 with RF at enrollment and 71 with RF after enrollment), while 51 did not developed RF. The number of patients progressing to sepsis in those with or without RF were 34 (21 with severe sepsis) and 14, respectively. The plasma level of HBP at admission was more than eightfold higher than the upper normal value. HBP, IL-6, and D-dimer could significantly predict the development of RF, and a high level of HBP (odds ratio = 1.008, 95% confidence interval: 1.003–1.013) was independently associated with the development of RF in this population. Compared with other biomarkers, HBP was the best indicator of progression to severe sepsis, with an area under the receiver operating characteristic curve of 0.85, the best specificity at 96.30%, and a positive predictive value of 92.86% at the optimal cut-off value of 340.29 ng/mL. The HBP level was also positively correlated with other conventional biomarkers.

Conclusion: HBP might represent a better predictor of disease progression in children with severe CAP than currently used biomarkers.
Impact of SARS-CoV-2 Infection During Pregnancy on Infant Neurobehavioral Development: A Case-Control Study
Authors: Cheng Yao , Teng Haoyue , Xiao Yue , Yao Mengxin , Yin Jieyun , Sun Guoqiang
Published: December 2021

Background: Previous studies on the pneumonia outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have focused on the general population and pregnant women, while little is known about the effects of SARS-CoV-2 on retardation during and after pregnancy. The purpose of this study was to evaluate the potential influence of SARS-CoV-2 on infant neurobehavioral development.

Methods: A case-control study was conducted in Maternal and Child Health Hospital of Hubei Province. Nine pregnant women with SARS-CoV-2 infection and 9 controls matched by maternal age, parity, and status of chronic disease were included. Infantile neurobehavioral development was assessed through the Ages and Stages Questionnaires Edition 3 (ASQ-3).

Results: The majority of pregnant women with SARS-CoV-2 experienced cesarean section (7 of 9), which was higher than the control group (5 of 9). The throat swabs of all newborn were negative. We found that compared with the control group, neonates of mothers with SARS-CoV-2 infection during pregnancy had lower scores in communication, gross movement, fine movement, problem solving, and personal-social domains; but only fine movement domain yielded statistical significance (P = 0.031).

Conclusion: Infection with SARS-CoV-2 during pregnancy may have a certain impact on infant neurobehavioral development. Further studies with larger sample size are warranted for validation.
The Anti-Inflammatory and Anti-Pruritus Mechanisms of Huanglian Jiedu Decoction in the Treatment of Atopic Dermatitis
Authors: Xu Yubin , Chen Saizhen , Zhang Lingling , Chen Guirong , Chen Jinguang
Published: December 2021

Atopic dermatitis (AD) is a common chronic skin disease driven by a T-cell-mediated immune response, with inflammation and pruritus being its main clinical manifestations. Huanglian Jiedu decoction (HLJDT), which is an ancient Chinese medicine herbal formula derived from Wai-Tai-Mi-Yao, is a potentially effective treatment for AD. We aimed to clarify the anti-inflammatory and anti-pruritus mechanisms of HLJDT in AD treatment. We performed immunohistochemistry, Western blotting, reverse transcriptase-polymerase chain reaction, Luminex-based direct multiplex immunoassay, enzyme-linked immunosorbent assays, and flow cytometry to address the abovementioned aims. HLJDT significantly reduced clinical symptoms and ear swelling in AD-like mice by inhibiting the production of cytokines [histamine, interleukin (IL)-3, IL-4, IL-5, IL-13, IL-17A, IL-31, and IL-33], substance P (SP), transient receptor potential cation channel subfamily V member 1 (TRPV-1), and gastrin-releasing peptide (GRP). Additionally, HLJDT significantly suppressed the protein expression levels and positive cell percentage of CD28, CD80, CD86, CD207, CD326, MHCII, and OX40 in the lymphoid nodes. Moreover, HLJDT significantly suppressed mRNA and protein expression of tyrosine–protein kinase (JAK1), histamine H4 receptor, and IL-4Rα, as well as the protein expression of GRP, SP, and TRPV-1 in the root ganglion. Our findings indicate that HLJDT can treat AD by regulating the antigen presentation function of dendritic cells, weakening T-lymphocyte activation, and subsequently exerting anti-inflammatory and anti-pruritus effects.
An Integration of Network Pharmacology and Experimental Verification to Investigate the Mechanism of Guizhi to Treat Nephrotic Syndrome
Authors: He Dan , Li Qiang , Du Guangli , Meng Guofeng , Sun Jijia , Chen Shaoli
Published: December 2021

Background: Guizhi has the pharmacological activity of anti-inflammatory. However, the effect mechanism of Guizhi against nephrotic syndrome (NS) remains unclear. A network pharmacological approach with experimental verification in vitro and in vivo was performed to investigate the potential mechanisms of Guizhi to treat NS.

Methods: Active compounds and potential targets of Guizhi, as well as the related targets of NS were obtained from the public databases. The intersecting targets of Guizhi and NS were obtained through Venny 2.1.0. The key targets and signaling pathways were determined by protein-protein interaction (PPI), genes ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis. And the overall network was constructed with Cytoscape. Molecular docking verification was carried out by AutoDock Vina. Finally, in vitro and in vivo experiments were performed to verify the mechanism of Guizhi to treat NS.

Results: 63 intersecting targets were obtained, and the top five key targets mainly involed in NF- Kappa B and MAPK signaling pathway. In the overall network, cinnamaldehyde (CA) was the top one active compound with the highest degree value. The molecular docking showed that the top five key targets were of good binding activity with the active components of Guizhi. To in vitro experiment, CA, the main active component of Guizhi, inhibited the secretion of IL-1β, IL-6, TNF-α in LPS challenged RAW264.7 cells, and down regulated the protein expression of p-NF-κB p65 and p-p38 MAPK in LPS challenged RAW264.7 cells. In vitro experiment showed that, 24 urinary protein and renal function were increased in ADR group. To western blot, CA down regulated the protein expression of p-p38 MAPK in rats of adriamycin-induced nephropathy.

Conclusion: CA might be the main active component of Guizhi to treat NS, and the underlying mechanism might mainly be achieved by inhibiting MAPK signaling pathway.
Fourier-Domain Optical Coherence Tomographic Assessment of Changes in the Schlemm’s Canal of Nonglaucomatous Subjects After Keratoplasty
Authors: Zhao Yujin , Li Yue , Hong Jiaxu , Le Qihua , Xu Jianjiang
Published: December 2021

Purpose: This study aimed to evaluate the impact of keratoplasty on the in vivo anatomical structures in the Schlemm’s canal (SC) of nonglaucomatous subjects using Fourier-domain optical coherence tomography (FD-OCT).

Methods: Sixty-six nonglaucomatous eyes that underwent penetrating keratoplasty (PK), deep anterior lamellar keratoplasty (DALK), or triple surgery were enrolled in this prospective, comparative, observational study. The SC imaging was performed using FD-OCT before and after surgery in both the nasal and temporal quadrants. Patient demographics, SC parameters [e.g., cross-sectional area (CSA), meridional diameter of SC (MSC), sagittal diameter of SC (SSC), and circumference (CCF)], and the correlations between the variation of SC parameters and intraocular pressure (IOP) were analyzed.

Results: The mean age of all subjects was 40.27 ± 18.97 years. Among all cases, the nasal, temporal, and mean MSC significantly decreased on the first day after surgery and then increased at 1 week (p = 0.04, 0.017, and 0.01, respectively). Temporal CSA (tCSA), temporal MSC (tMSC), and temporal circumference (tCCF) after PK (p = 0.017, 0.020, and 0.018, respectively) and nasal MSC (nMSC) after DALK (p = 0.025) decreased significantly on the first day after surgery. The shift in mean IOP was significantly correlated with the changes in tMSC (r = 0.341, p = 0.003) and CCF (r = 0.207, p = 0.048).

Conclusion: SC had significant in vivo morphological changes in the early period after keratoplasty in nonglaucomatous eyes, accompanied with elevation of IOP. Early intervention might be necessary to prevent secondary glaucoma early after keratoplasty.
Human Bone Marrow Mesenchymal Stromal Cell-Derived Extracellular Vesicles Promote Proliferation of Degenerated Nucleus Pulposus Cells and the Synthesis of Extracellular Matrix Through the SOX4/Wnt/β-Catenin Axis
Authors: Wang Haoyu , Li Fei , Ban Wenrui , Zhang Jing , Zhang Guiqi
Published: December 2021

Objective: Intervertebral disk degeneration (IDD) is a major cause of pain in the back, neck, and radiculus. Mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) are therapeutic in musculoskeletal degenerative diseases such as IDD. This study explored the effect and functional mechanism of human bone MSCs (hBMSCs)-derived EVs in proliferation and apoptosis of degenerated nucleus pulposus cells (DNPCs) and extracellular matrix (ECM) synthesis.

Methods: Extracellular vesicles were isolated from hBMSCs and identified. DNPCs were induced by TNF-α. EVs were incubated with DNPCs for 24h. Internalization of EVs by DNPCs, DNPCs proliferation, apoptosis, and expressions of ECM synthetic genes, degrading genes and miR-129-5p were assessed. Downstream target genes of miR-129-5p were predicted. Target relation between miR-129-5p and SRY-box transcription factor 4 (SOX4) was verified. DNPCs proliferation, apoptosis, and ECM synthesis were measured after treatment with EVs and miR-129-5p inhibitor or SOX4 overexpression. Expressions of SOX4 and Wnt/β-catenin pathway-related proteins were determined.

Results: hBMSC-EVs promoted DNPCs proliferation, inhibited apoptosis, increased expressions of ECM synthetic genes, and reduced expressions of ECM degrading genes. hBMSC-EVs carried miR-129-5p into DNPCs. Silencing miR-129-5p in EVs partially inverted the effect of EVs on DNPCs proliferation and ECM synthesis. miR-129-5p targeted SOX4. SOX4 overexpression annulled the effect of EVs on DNPCs proliferation and ECM synthesis. Expressions of Wnt1 and β-catenin were decreased in EVs-treated DNPCs, while silencing miR-129-5p in EVs promoted expressions of Wnt1 and β-catenin.

Conclusion: hBMSC-EVs promoted DNPCs proliferation and ECM synthesis by carrying miR-129-5p into DNPCs to target SOX4 and deactivating the Wnt/β-catenin axis.
The Sorghum (Sorghum bicolor) Brown Midrib 30 Gene Encodes a Chalcone Isomerase Required for Cell Wall Lignification
Authors: Tetreault Hannah M. , Gries Tammy , Liu Sarah , Toy John , Xin Zhanguo , Vermerris Wilfred , Ralph John , Funnell-Harris Deanna L. , Sattler Scott E.
Published: December 2021

In sorghum (Sorghum bicolor) and other C4 grasses, brown midrib (bmr) mutants have long been associated with plants impaired in their ability to synthesize lignin. The brown midrib 30 (Bmr30) gene, identified using a bulk segregant analysis and next-generation sequencing, was determined to encode a chalcone isomerase (CHI). Two independent mutations within this gene confirmed that loss of its function was responsible for the brown leaf midrib phenotype and reduced lignin concentration. Loss of the Bmr30 gene function, as shown by histochemical staining of leaf midrib and stalk sections, resulted in altered cell wall composition. In the bmr30 mutants, CHI activity was drastically reduced, and the accumulation of total flavonoids and total anthocyanins was impaired, which is consistent with its function in flavonoid biosynthesis. The level of the flavone lignin monomer tricin was reduced 20-fold in the stem relative to wild type, and to undetectable levels in the leaf tissue of the mutants. The bmr30 mutant, therefore, harbors a mutation in a phenylpropanoid biosynthetic gene that is key to the interconnection between flavonoids and monolignols, both of which are utilized for lignin synthesis in the grasses.
Genome-Wide Identification and Gene Expression Analysis of Acyl-Activating Enzymes Superfamily in Tomato (Solanum lycopersicum) Under Aluminum Stress
Authors: Jin Jian Feng , He Qi Yu , Li Peng Fei , Lou He Qiang , Chen Wei Wei , Yang Jian Li
Published: December 2021

In response to changing environments, plants regulate gene expression and subsequent metabolism to acclimate and survive. A superfamily of acyl-activating enzymes (AAEs) has been observed in every class of creatures on planet. Some of plant AAE genes have been identified and functionally characterized to be involved in growth, development, biotic, and abiotic stresses via mediating diverse metabolic pathways. However, less information is available about AAEs superfamily in tomato (Solanum lycopersicum), the highest value fruit and vegetable crop globally. In this study, we aimed to identify tomato AAEs superfamily and investigate potential functions with respect to aluminum (Al) stress that represents one of the major factors limiting crop productivity on acid soils worldwide. Fifty-three AAE genes of tomato were identified and named on the basis of phylogenetic relationships between Arabidopsis and tomato. The phylogenetic analysis showed that AAEs could be classified into six clades; however, clade III contains no AAE genes of tomato. Synteny analyses revealed tomato vegetable paralogs and Arabidopsis orthologs. The RNA-seq and quantitative reverse-transcriptase PCR (qRT-PCR) analysis indicated that 9 out of 53 AAEs genes were significantly up- or downregulated by Al stress. Numerous cis-acting elements implicated in biotic and abiotic stresses were detected in the promoter regions of SlAAEs. As the most abundantly expressed gene in root apex and highly induced by Al, there are many potential STOP1 cis-acting elements present in the promoter of SlAAE3-1, and its expression in root apex was specific to Al. Finally, transgenic tobacco lines overexpressing SlAAE3-1 displayed increased tolerance to Al. Altogether, our results pave the way for further studies on the functional characterization of SlAAE genes in tomato with a wish of improvement in tomato crop in the future.
Mechanism Underlying the Shading-Induced Chlorophyll Accumulation in Tea Leaves
Authors: Chen Jiaming , Wu Shuhua , Dong Fang , Li Jianlong , Zeng Lanting , Tang Jinchi , Gu Dachuan
Published: December 2021

Besides aroma and taste, the color of dry tea leaves, tea infusion, and infused tea leaves is also an important index for tea quality. Shading can significantly increase the chlorophyll content of tea leaves, leading to enhanced tea leaf coloration. However, the underlying regulatory mechanism remains unclear. In this study, we revealed that the expressions of chlorophyll synthesis genes were significantly induced by shading, specially, the gene encoding protochlorophyllide oxidoreductase (CsPOR). Indoor control experiment showed that decreased light intensity could significantly induce the expression of CsPOR, and thus cause the increase of chlorophyll content. Subsequently, we explored the light signaling pathway transcription factors regulating chlorophyll synthesis, including CsPIFs and CsHY5. Through expression level and subcellular localization analysis, we found that CsPIF3-2, CsPIF7-1, and CsHY5 may be candidate transcriptional regulators. Transcriptional activation experiments proved that CsHY5 inhibits CsPORL-2 transcription. In summary, we concluded that shading might promote the expression of CsPORL-2 by inhibiting the expression of CsHY5, leading to high accumulation of chlorophyll in tea leaves. The results of this study provide insights into the mechanism regulating the improvements to tea plant quality caused by shading.
Distinguishing Stoichiometric Homeostasis of Soil Microbial Biomass in Alpine Grassland Ecosystems: Evidence From 5,000 km Belt Transect Across Qinghai–Tibet Plateau
Authors: Fan Jihui , Liu Tianyuan , Liao Ying , Li Yiying , Yan Yan , Lu Xuyang
Published: December 2021

The biogeographic characteristics of soil microbial biomass stoichiometry homeostasis and also its mechanisms are commonly thought to be key factors for the survival strategies and resource utilization of soil microbes under extreme habitat. In this work, we conducted a 5,000-km transect filed survey in alpine grassland across Qinghai–Tibet Plateau in 2015 to measure soil microbial biomass carbon (MBC) and nitrogen (MBN) across alpine steppe and meadow. Based on the differences of climate and soil conditions between alpine steppe and meadow, the variation coefficient was calculated to investigate the homeostatic degree of MBC to MBN. Furthermore, the “trade-off” model was utilized to deeply distinguish the homeostasis degree of MBC/MBN between alpine steppe and meadow, and the regression analysis was used to explore the variability of trade-off in response to environmental factors in the alpine grassland. The results showed that the coefficient of variation (CV) of MBC/MBN in alpine meadow (CV = 0.4) was lower than alpine steppe (CV = 0.7). According to the trade-off model, microbial turnover activity of soil N relative to soil C increased rapidly and then decreased slightly with soil organic carbon (SOC), soil total nitrogen (STN), and soil water content across alpine meadow. Nevertheless, in alpine steppe, SOC/STN had a positive effect on microbial turnover of soil N. These results suggested that water, heat, and soil nutrients availability were the key factors affecting the C:N stoichiometry homeostasis of soil microbial biomass in Qinghai–Tibet Plateau (QTP)’s alpine grassland. Since the difference of survival strategy of the trade-off demands between soil C and N resulting in different patterns and mechanism, the stoichiometry homeostasis of soil microbial biomass was more stable in alpine meadow than in alpine steppe.
Re-examination of the APETALA2/Ethylene-Responsive Factor Gene Family in Barley (Hordeum vulgare L.) Indicates a Role in the Regulation of Starch Synthesis
Authors: Ding Jinjin , Karim Hassan , Li Yulong , Harwood Wendy , Guzmán Carlos , Lin Na , Xu Qiang , Zhang Yazhou , Tang Huaping , Jiang Yunfeng , Qi Pengfei , Deng Mei , Ma Jian , Wang Jirui , Chen Guoyue , Lan Xiujin , Wei Yuming , Zheng Youliang , Jiang Qiantao
Published: December 2021

The APETALA2/Ethylene-Responsive factor (AP2/ERF) gene family is a large plant-specific transcription factor family, which plays important roles in regulating plant growth and development. A role in starch synthesis is among the multiple functions of this family of transcription factors. Barley (Hordeum vulgare L.) is one of the most important cereals for starch production. However, there are limited data on the contribution of AP2 transcription factors in barley. In this study, we used the recently published barley genome database (Morex) to identify 185 genes of the HvAP2/ERF family. Compared with previous work, we identified 64 new genes in the HvAP2/ERF gene family and corrected some previously misannotated and duplicated genes. After phylogenetic analysis, HvAP2/ERF genes were classified into four subfamilies and 18 subgroups. Expression profiling showed different patterns of spatial and temporal expression for HvAP2/ERF genes. Most of the 12 HvAP2/ERF genes analyzed using quantitative reverse transcription–polymerase chain reaction had similar expression patterns when compared with those of starch synthase genes in barley, except for HvAP2-18 and HvERF-73. HvAP2-18 is homologous to OsRSR1, which negatively regulates the synthesis of rice starch. Luciferase reporter gene, and yeast one-hybrid assays showed that HvAP2-18 bound the promoter of AGP-S and SBE1 in vitro. Thus, HvAP2-18 might be an interesting candidate gene to further explore the mechanisms involved in the regulation of starch synthesis in barley.
Work-Family Enrichment: Influence of Job Autonomy on Job Satisfaction of Knowledge Employees
Authors: Jing Song , Li Zhuoyu , Stanley Daniel M. J. J. , Guo Xia , Wenjing Wang
Published: December 2021

In order to explore the specific path of the influence of job autonomy on the satisfaction of knowledge employees, the current study deduced and established a Chain Mediation Model, which was based on the Resource-Gain-Development Model and the Conservation of Resources Theory. Primary data were gathered through questionnaire surveys at several cities in China by using a professional platform named “Wenjuanxing.” The target populations were employees with a bachelor’s degree or above, who were engaged in higher knowledge content and have mastered certain professional knowledge and skills, including technical R & D personnel, management personnel, professionals (such as accountants, lawyers, and medics) and other personnel generally recognized by the academic community. In order to improve the reliability of the sample and reduce the error caused by regional differences, the questionnaires were disseminated to involve as many cities in China as possible, such as Tianjin, Beijing, Chengdu, Wuhan, and Guangzhou. SPSS24.0 and Aoms24.0 were used as multivariate data analysis tools for statistical analysis. The results showed that job autonomy can significantly improve the satisfaction of knowledge employees; however, it cannot affect the satisfaction of knowledge employees through self-efficacy. The findings of the study also revealed that job autonomy has a positive impact on both resource source domain satisfaction and resource acceptance domain satisfaction through work-family enrichment, especially the positive emotions in the resource source domain. Job autonomy improves the self-efficacy of knowledge employees, which, in turn, improves their overall satisfaction through the work-family enrichment path.
Technology for Healthy Aging and Wellbeing: Co-producing Solutions
Authors: Astell Arlene J. , Andrews Jacob A. , Bennion Matthew R. , Clayton David
Published: December 2021

Methods to facilitate co-production in mental health are important for engaging end users. As part of the Technology for Healthy Aging and Wellbeing (THAW) initiative we organized two interactive co-production workshops, to bring together older adults, health and social care professionals, non-governmental organizations, and researchers. In the first workshop, we used two activities: Technology Interaction and Scavenger Hunt, to explore the potential for different stakeholders to discuss late life mental health and existing technology. In the second workshop, we used Vignettes, Scavenger Hunt, and Invention Test to examine how older adults and other stakeholders might co-produce solutions to support mental wellbeing in later life using new and emerging technologies. In this paper, we share the interactive materials and activities and consider their value for co-production. Overall, the interactive methods were successful in engaging stakeholders with a broad range of technologies to support mental health and wellbeing and in co-producing ideas for how they could be leveraged and incorporated into older people’s lives and support services. We offer this example of using interactive methods to facilitate co-production to encourage greater involvement of older adults and other under-represented groups in co-producing mental health technologies and services.
How to Implement Game-Based Learning in a Smart Classroom? A Model Based on a Systematic Literature Review and Delphi Method
Authors: Pan Liuxia , Tlili Ahmed , Li Jiaping , Jiang Feng , Shi Gaojun , Yu Huiju , Yang Junfeng
Published: December 2021

Game-based learning (GBL) can allow learners to acquire and construct knowledge in a fun and focused learning atmosphere. A systematic literature review of 42 papers from 2010 to 2020 in this study showed that the current difficulties in implementing GBL in classrooms could be classified into the following categories: infrastructure, resources, theoretical guidance, teacher’s capabilities and acceptance of GBL. In order to solve the above problems, the study constructs a technology enhanced GBL model, from the four parts of learning objective, learning process, learning evaluation, and smart classroom. In addition, this study adopted the Delphi method, inviting a total of 29 scholars, experts, teachers and school managers to explore how to implement GBL in smart classrooms. Finally, the technology enhanced GBL model was validated and the utilization approaches were provided at the conclusion part.