bluuebunny/crossref_metadata_2025 huggingface dataset:
A county-level spatial epidemiological study of hair selenium and Keshan disease
Authors: Jia Yuehui , Li Guijin , Wang Ruixiang , Feng Chen , Qi Lei , Wang Yuanyuan , Su Shengqi , Zou Yuanjie , Liu Xu , Wang Yanan , Zhang Yiyi , Du Linlin , Sun Huixin , Hao Shuxiu , Hou Jie , Feng Hongqi , Li Qi , Wang Tong
Published: November 2022

Background

No spatial analysis of hair selenium and Keshan disease (KD) on a nationwide county-level has been performed. Selenium deficiency is a recognized environmental risk factor for KD. Hair selenium is one of the recognized biomarkers of selenium nutrition. This study aimed to perform a geographically precise and visualized assessment of the achievement of KD prevention and control at the level of selenium nutrition in terms of etiology.

Methods

A spatial ecological study was conducted. The hair selenium content of the residents was assayed using an atomic fluorescence spectrometer. The spatial analysis was performed using ArcGIS.

Results

The median of the hair selenium levels of the 3,028 participants in the 1,174 counties was 0.38 mg/kg, and the content of inhabitants in KD endemic counties was significantly lower than that in KD non-endemic counties (0.34 vs. 0.39 mg/kg, z = −10.03, P < 0.0001). The proportion of Se-deficient and Se-marginal counties in KD endemic counties was significantly higher than that in KD non-endemic counties (59.4 vs. 29.0%, z = −7.45, P < 0.0001). The global autocorrelation analysis was not statistically significant (Moran's I = 0.0005, P = 0.68). Local autocorrelation analysis identified 174 low-low clusters of hair selenium levels, 83 (47.7%) of which are KD endemic counties located in KD endemic provinces of Henan, Gansu, Shaanxi, Inner Mongolia, Jilin, and Heilongjiang. The hair selenium featured a positive correlation with per capita GDP (rs = 0.20, P < 0.0001).

Conclusion

The median of the hair selenium levels of inhabitants living in KD endemic counties was significantly lower than that in KD non-endemic counties. All the 83 KD endemic counties with low-low clusters of hair selenium levels should be prioritized in KD precision prevention and control. These findings are geographically precise and visualized evidence of the assessment of the effectiveness of KD prevention and control at the level of selenium nutrition in terms of etiology.
A comparative study of characteristics in diploid and tetraploid Anoectochilus roxburghii
Authors: Huang Xiaoling , Ouyang Kunxi , Luo Yongzhi , Xie Guohong , Yang Yuesheng , Zhang Junjie
Published: November 2022

Artificial induction of polyploidy is an efficient technique for improving biological properties and developing new varieties of many plants. In this study, we analyzed and compared differences in characteristics (morphological and biological) of diploid and tetraploid Anoectochilus roxburghii plants. We found significant differences between tetraploid plants and their diploid counterparts. The tetraploid plants exhibited dwarfing and stockiness. They were also bigger and had more voluminous roots and larger stomata than the diploid plants. Moreover, the biochemical analyses showed that the contents of some amino acids and minerals elements were significantly higher in tetraploid plants. The chlorophyll content of the leaves exhibited no definitive changes, but the photosynthetic performance was higher in the tetraploid plants. In addition, contents of major bioactive compounds, such as kinsenoside and some flavonoids, were enhanced in tetraploids. This is the first detailed analysis of characteristics in diploid and tetraploid A. roxburghii plants. The results may facilitate breeding programs with the species.
Effect of β-cyclodextrin deodorization on the volatile chemicals and functional properties of three types of gelatins
Authors: Yang Lili , Zi Ye , Shi Cuiping , Chen Jiahui , Xu Jiamin , Wang Xichang , Zhong Jian
Published: November 2022

The exploration of deodorization is important for the application of gelatin in food industry. In this work, the effect of β-cyclodextrin (β-CD) deodorization on the volatile chemicals and functional properties of three types of gelatins (commercial porcine skin gelatin, cold water fish skin gelatin, and Chinese longsnout catfish skin gelatin) were studied. The results suggested the odors of commercial gelatins were significantly less than home-extracted gelatins. The β-CD deodorization efficiency was dependent on both β-CD concentration and volatile chemical. (E)-2-Octenal (C8H14O), 1-octen-3-ol (C8H16O), 2-pentyl-furan (C9H14O), and hentriacontane (C17H36) could be deodorized at low β-CD concentration (even at 2 mg/mL). The best β-CD deodorization concentration for 66.7 mg/mL of Chinese longsnout catfish skin gelatin was 30 mg/mL. β-CD addition could not change the gel forming ability and emulsion activity of gelatins, whereas it had different and concentration-dependent effects on the emulsion stability of gelatins. β-CD addition had no obvious effects on the droplet sizes, droplet coalescence and liquid-gel transition behaviors, but had different effects on the creaming of the emulsions stabilized by three types of gelatins. The encapsulation of β-carotene did not significantly change the droplet trimodal size distribution and liquid-gel transition of fish oil-loaded emulsions. However, β-carotene might delay the droplet coalescence. The creaming stability of β-carotene/fish oil-loaded gelatin/β-CD-stabilized emulsions was dependent on the gelatins, β-CD, and β-carotene. Finally, the β-carotene retention in the emulsions was dependent not on β-CD addition but on the nature of the gelatins. These results provided useful information to understand the molecular deodorization behaviors and explore the deodorization of emulsifiers for food emulsions.
Exploring the nucleotide molecular mechanism of compound kushen injection for lung adenocarcinoma based on network pharmacology and molecular docking
Authors: Ye Zhangpeng , Yao Xin , Chen Zhubei , Jin Qin , You Qingsheng
Published: November 2022

Compound kushen injection is an effective traditional Chinese medicine for the treatment of lung cancer. However, its influence on the survival and prognosis of patients with lung adenocarcinoma patients was less studied; especially its pharmacological mechanism remains to be further elucidated. In the present study, we adopted a network pharmacology (NP)-based approach to screening effective compounds, screening and predicting target genes, analyzing biological functions and pathways, constructing a regulatory network and protein interaction network, and screening the key targets. Moreover, mass survival analysis and molecular docking were conducted. In the end, 35 key compounds and four possible central target genes were screened out, which could be used for the treatment of lung adenocarcinoma and affected the survival and prognosis of patients with lung adenocarcinoma. In addition, their key compounds had good docking affinity. Enrichment analysis showed that CKI might affect the treatment and prognosis of lung adenocarcinoma patients by regulating the PI3K–Akt signaling pathway, TNF signaling pathway, non-small cell lung cancer, Hepatitis C, etc. We discussed the pharmacological mechanisms and potential therapeutic targets of CKI in the treatment of lung adenocarcinoma, which verified the effect of CKI on the prognosis and survival of patients. The present study might promote the further clinical application of CKI and provide a theoretical basis for further experimental studies.
Efficacy and toxicity of Ipilimumab-Nivolumab combination therapy in elderly metastatic melanoma patients
Authors: Stoff Ronen , Grynberg Shirly , Asher Nethanel , Laks Shachar , Steinberg Yael , Schachter Jacob , Shapira-Frommer Ronnie , Ben-Betzalel Guy
Published: November 2022

Introduction

Immunotherapy has revolutionized metastatic Melanoma therapy. The most active regimen is combination therapy of Ipilimumab-Nivolumab (Ipi-Nivo) with response rates (RR) of ~60% and median overall survival (OS) of ~6 years. Immune-related adverse events (irAE) are common (~60% develop grade 3-4) and pose a challenge when treating frail patients. We sought to examine whether Ipi-Nivo therapy is feasible in elderly metastatic melanoma patients.

Methods

Electronic records of patients treated at the Ella Lemelbaum Institute with Ipi-Nivo between the years 2017-2021 were screened for age. Elderly patients were defined as age 75 and older (group A) and were matched with records of patients age <75 (group B). Records were analyzed for baseline parameters, immunotherapy regimen, RR, toxicity and progression-free survival (PFS).

Results

Twenty-six relevant patients age >75 (median 77) were identified and were matched to 34 younger patients (median age 57). No statistically significant differences were noted in terms of baseline parameters except for BRAF mutation status (group A 15%, group B 47%, p=0.008). Response rate in group A was 38% and is consistent with previously published data. Median PFS was the same for both groups (A = 5.5 months, B= 7.5 months, p=NS). Treatment was similarly tolerated: 35% of group A patients completed 4 cycles of therapy compared to 28% for group B (p=NS). Grade 2-4 irAE were the same (A=58%, B=66%, p=NS) and there was no difference in the need for hospitalization for G3-4 events between the groups. (A=63%, B=69%, p=NS). Further division into 4 age groups (>80 vs 75-79 in group A and 65-74 vs <65 in group B) found no difference in terms of response rate or G3-4 toxicity.

Conclusion

Ipilimumab-Nivolumab combination therapy in elderly metastatic Melanoma patients seems to be well tolerated and efficient in selected elderly patients based on performance status and comorbidities, just as in younger patients. This regimen seems to be a feasible treatment option for this age group.
Feasibility and efficacy of spinal microtubular technique for resection of lumbar dumbbell-shaped tumors
Authors: Wang Rui , Liang Zeyan , Chen Yan , Xu Xiongjie , Chen Chunmei
Published: November 2022

Objective

Minimally invasive surgical resection of lumbar dumbbell-shaped tumors is rarely reported. We retrospectively collected clinical data of lumbar dumbbell-shaped tumors treated with the spinal microtubular technique to evaluate the feasibility, complications and efficacy of the surgical methods.

Methods

From September 2013 to August 2021, clinical data of patients with lumbar dumbbell-shaped tumors that underwent paravertebral approach and micro-tubular tumorectomy (PAMT) were collected; neurological function was assessed using the pain visual analog scale (VAS) and the Japanese Orthopaedic Association (JOA) score.

Results

A total of 46 patients that underwent PAMT were included in this study. In all patients, total resection of the tumor was performed at one stage (100%). The median follow-up period was 27.5 months (P25, P75: 16.5- 57 months). Symptoms such as pain or lower extremity weakness were significantly relieved in 46 patients. The postoperative VAS score and JOA score were significantly higher compared with preoperative scores (p <0.001), and the patients had no tumor recurrence or spinal instability. According to the Eden classification, there were 7 cases of type I, 8 cases of type II, 15 cases of type III, and 16 cases of type IV. In the comparison of the improvement of VAS score at 12 months after PAMT, there were significant differences among different types of tumors (H =15.756, p =0.001); type I was better than type III (Z =2.768, p =0.029) and type IV (Z =2.763, p =0.029), and type II was also better than type III (Z =2.679, p =0.037) and type IV (Z =2.708, p =0.034). With respect to estimated blood loss (Z =-3.041, p =0.013) and postoperative hospital stays (Z =-3.003, p =0.014), type IV was less than type III; and type IV was also less than type II about operation time (Z =-2.653, p =0.040).

Conclusion

In small lumbar dumbbell-shaped tumors, PAMT is indicated for Eden types I-IV and different pathological types of tumors, and can achieve complete resection of the tumor (GTR) in one stage with a good prognosis.
TAM-targeted reeducation for enhanced cancer immunotherapy: Mechanism and recent progress
Authors: Shen Xinyuan , Zhou Shengcheng , Yang Yidong , Hong Tu , Xiang Ze , Zhao Jing , Zhu Chaojie , Zeng Linghui , Zhang Lingxiao
Published: November 2022

Tumor-associated macrophage (TAM) as an important component of tumor microenvironment (TME) are closely related with the occurrence, development, and metastasis of malignant tumors. TAMs are generally identified as two distinct functional populations in TME,i.e., inflammatory/anti-tumorigenic (M1) and regenerative/pro-tumorigenic (M2) phenotype. Evidence suggests that occupation of the TME by M2-TAMs is closely related to the inactivation of anti-tumor immune cells such as T cells in TME. Recently, efforts have been made to reeducate TAMs from M2- to M1- phenotype to enhance cancer immunotherapy, and great progress has been made in realizing efficient modulation of TAMs using nanomedicines. To help readers better understand this emerging field, the potential TAM reeducation targets for potentiating cancer immunotherapy and the underlying mechanisms are summarized in this review. Moreover, the most recent advances in utilizing nanomedicine for the TAM immunomodulation for augmented cancer immunotherapy are introduced. Finally, we conclude with our perspectives on the future development in this field.
Multilevel analysis of individual and community level factors associated with the application of cow dung and oil on the umbilical cord stump in Ethiopia
Authors: Dessie Anteneh Mengist , Geremew Habtamu , Feleke Sefineh Fenta , Anley Denekew Tenaw , Mruts Kalayu Brhane , Yenew Chalachew , Bantie Berihun , Misganaw Natnael Moges , Kerebeh Gashaw , Gebeyehu Asaye Alamneh , Asnakew Desalegn Tesfa , Anteneh Rahel Mulatie
Published: November 2022

Background

Hygienic umbilical cord care is one of the essential interventions advocated to reduce neonatal mortality. However, traditional cord care measures-applying cow dung and oil-that have harmful health consequences are commonly practiced in Ethiopia. Hence, in this study, it was planned to analyze individual and community-level factors associated with the application of cow dung and oil on the umbilical cord stump in Ethiopia.

Methods

Data from the 2016 Ethiopian demographic and health survey were used to identify individual and community level factors associated with women's practice of applying cow dung and oil on the umbilical cord stump of their neonate. Taking into account for the hierarchical structure of the data; multilevel binary logistic regression analysis has been employed to a nationally representative weighted sample of 7,168 women.

Results

In Ethiopia, 780 (10.88%) with 95% CI (10.18–11.62) women apply oil and/or cow dung on the neonate's umbilical cord stump. Age increase by one year [AOR = 0.97; 95% CI (0.94–0.99)] and giving birth in a health facility [AOR = 0.61; 95% CI (0.42–0.89)] were individual-level factors that reduced women's practice of applying cow dung and oil on the umbilical cord stump of their neonate. Whereas, rural residence [AOR = 2.54; 95% CI (1.28–5.06)] was the predictor at the community level that raised the practice of applying cow dung and oil on the neonate's umbilical cord stump.

Conclusion

This nationwide study revealed that a significant number of mothers in Ethiopia still apply cow dung and/or oil on the umbilical cord stump of their neonates. Both the individual and community level characteristics: maternal age, place of delivery, and residence were found to have significant inﬂuence on the practice of applying cow dung and/or oil on the umbilical cord stump in Ethiopia. Thus, to reduce neonatal mortality due to avoidable umbilical cord infections, clean cord care practice strategies should be designed by considering these factors.
Genetic analysis and prenatal diagnosis of recessive dystrophic epidermolysis bullosa caused by compound heterozygous variants of the COL7A1 gene in a Chinese family
Authors: Wang Yu , Song Zhen , Zhang Lihua , Li Na , Zhao Jie , Yang Ruifang , Ji Shuhua , Sun Ping
Published: November 2022

Background

Dystrophic epidermolysis bullosa (DEB) is an incurable and inherited skin disorder mainly caused by mutations in the gene encoding type VII collagen (COL7A1). The purpose of this study was to identify the causative genetic variants and further perform genetic diagnosis in a Chinese family affected by DEB.

Methods

High-throughput sequencing was performed to analyze the genetic skin disorder-related genes of parents of the proband, and the variants were further confirmed in the other members by Sanger sequencing. Sanger sequencing, karyotype analysis, and chromosomal microarray analysis (CMA) were used together for prenatal diagnosis after the second pregnancy. The phenotype of the fetus was tracked after the diagnosis and induction of labor. Moreover, skin and muscle pathological examination and whole-exome sequencing (WES) of the skin and muscle tissue of the induced fetus were performed.

Results

Here, we determined two heterozygous variants of the COL7A1 gene that contributed to the autosomal recessive DEB (RDEB) in the family, i.e., a novel pathogenic variant (c.8335G > T, p.E2779*) and a likely pathogenic variant (c.7957G > A, p.G2653R). Sanger sequencing of amniotic fluid cells showed that the fetus carried the above two compound heterozygous variants, and the karyotype analysis and CMA results showed no abnormality. The clinical phenotype and pathological results of the induced fetus were consistent with the characteristics of DEB. Further, WES analysis also confirmed a novel compound heterozygous variation in COL7A1, consisting of two variants, namely, c.8335G > T and c.7957G > A in the fetus.

Conclusion

This study expands the spectrum of disease-causing variants of COL7A1 and provides a theoretical basis for diagnosis, genetic counseling, and prognosis of families affected by RDEB
Clustering patterns of metabolic syndrome: A cross-sectional study in children and adolescents in Kyiv
Authors: Aliusef Maiia H. , Gnyloskurenko Ganna V. , Churylina Alina V. , Mityuryayeva Inga O.
Published: November 2022

Objective

The aim: to identify subgroups by cluster analysis according parameters: original homeostatic model of insulin resistance (HOMA-1 IR), updated computer model of insulin resistance (HOMA-2 IR), β-cell function (%B) and insulin sensitivity (%S) for the prognosis of different variants of metabolic syndrome in children for more individualized treatment selection.

Patients and methods

The observational cross-sectional study on 75 children aged from 10 to 17 with metabolic syndrome according to the International Diabetes Federation criteria was conducted at the Cardiology Department of Children's Clinical Hospital No.6 in Kyiv. HOMA-1 IR was calculated as follows: fasting insulin (µIU/ml) × fasting glucose (mmol/L)/22.5. HOMA-2 IR with %B and %S were calculated according to the computer model in [http://www.dtu.ox.ac.uk]. All biochemical analysis were carried out using Cobas 6000 analyzer and Roche Diagnostics (Switzerland). The statistical analysis was performed using STATISTICA 7.0 and Easy R. The hierarchical method Ward was used for cluster analysis according the parameters: HOMA-1 IR, HOMA-2 IR, %B and %S.

Results

Four clusters were identified from the dendrogram, which could predict four variants in the course of metabolic syndrome such that children in cluster 1 would have the worst values of the studied parameters and those in cluster 4 – the best. It was found that HOMA-1 IR was much higher in cluster 1 (6.32 ± 0.66) than in cluster 4 (2.19 ± 0.13). HOMA-2 IR was also much higher in cluster 1 (3.80 ± 0.34) than in cluster 4 (1.31 ± 0.06). By the analysis of variance using Scheffe's multiple comparison method, a statistically significant difference was obtained between the laboratory parameters among the subgroups: HOMA-1 IR (p < 0,001), glucose (p < 0.001), insulin (p < 0,001), HOMA-2 IR (p < 0.001), %B (p < 0.001), %S (p < 0.001), TG (p = 0.005) and VLDL-C (p = 0.002).

Conclusions

A cluster analysis revealed that the first two subgroups of children had the worst insulin resistance and lipid profile parameters. It was found positive correlation between HOMA-1 IR, HOMA-2 IR, %B and %S with lipid metabolism parameters TG and VLDL-C and negative correlation between %B and HDL-C in children with metabolic syndrome (MetS).The risk of getting a high TG result in the blood analysis in children with MetS was significantly dependent with the HOMA-2 IR >2.26.
Seroprevalence of SARS CoV-2 among children after the second surge (June 2021) in a rural district of South India: Findings and lessons from a population-based survey
Authors: George Carolin Elizabeth , Inbaraj Leeberk Raja , Rajukutty Shon , Joan Roshni Florina , Muthuraj Sangeetha , Chandrasingh Sindhulina
Published: November 2022

Objective

To determine the seroprevalence of SARS COV 2 among children in the Bangalore Rural district.

Methods

We conducted a cross-sectional study after the second surge of COVID-19 from 14 June to 13 July 2021 and recruited 412 children through house to house visits from four villages in a rural district. We administered a questionnaire to collect demographics and details of COVID-19 infection and used the ABCHEK Antibody Card test (NuLifecare,India) which is an ICMR approved test for detecting antibodies (IgG & IgM) by immunochromatography using the finger prick method. We used Statistical Package for the Social Sciences version 20.0 for analysis.

Results

Our participants had an age group ranging from 11 months to 18 years. There was an almost equal distribution of boys (48.3%) and girls (51.7%). We estimated seroprevalence of 45.9% (95% CI: 41–50.8) among children. Seroprevalence was significantly associated with a history of symptoms suggestive of COVID-19 in the past, the seropositive status of the parents, and any other family members being tested positive. Age and gender of the child, education and occupation of the parents were not associated with the seropositivity status of the child.

Conclusion

Seroprevalence of COVID-19 among children corresponds to adult seroprevalence during the same time interval. This knowledge can be of practical application where adult prevalence is documented. Unvaccinated children in low-resource settings need special attention with respect to monitoring for new mutations as well as managing endemic needs.
Natural product-based pharmacological studies for neurological disorders
Authors: Puri Vivek , Kanojia Neha , Sharma Ameya , Huanbutta Kampanart , Dheer Divya , Sangnim Tanikan
Published: November 2022

Central nervous system (CNS) disorders and diseases are expected to rise sharply in the coming years, partly because of the world’s aging population. Medicines for the treatment of the CNS have not been successfully made. Inadequate knowledge about the brain, pharmacokinetic and dynamic errors in preclinical studies, challenges with clinical trial design, complexity and variety of human brain illnesses, and variations in species are some potential scenarios. Neurodegenerative diseases (NDDs) are multifaceted and lack identifiable etiological components, and the drugs developed to treat them did not meet the requirements of those who anticipated treatments. Therefore, there is a great demand for safe and effective natural therapeutic adjuvants. For the treatment of NDDs and other memory-related problems, many herbal and natural items have been used in the Ayurvedic medical system. Anxiety, depression, Parkinson’s, and Alzheimer’s diseases (AD), as well as a plethora of other neuropsychiatric disorders, may benefit from the use of plant and food-derived chemicals that have antidepressant or antiepileptic properties. We have summarized the present level of knowledge about natural products based on topological evidence, bioinformatics analysis, and translational research in this review. We have also highlighted some clinical research or investigation that will help us select natural products for the treatment of neurological conditions. In the present review, we have explored the potential efficacy of phytoconstituents against neurological diseases. Various evidence-based studies and extensive recent investigations have been included, which will help pharmacologists reduce the progression of neuronal disease.
(+)-Borneol inhibits the generation of reactive oxygen species and neutrophil extracellular traps induced by phorbol-12-myristate-13-acetate
Authors: Chen Hanze , Xu Xinxin , Tang Qiwen , Ni Linhui , Cao Shuxia , Hao Yonggang , Wang Li , Hu Xingyue
Published: November 2022

Background and purpose: Neutrophil extracellular traps (NETs) are special web-like structures that can be generated in both infectious and noninfectious diseases. Previous studies showed that reactive oxygen species (ROS) were crucial in the formation of NETs (NETosis). The purpose of this study is to evaluate the effect of (+)-borneol, an antioxidant, on NETosis.

Methods: Human neutrophils were stimulated with phorbol-12-myristate-13-acetate (PMA) to induce NETosis in vitro. Neutrophils treated with (+)-borneol at three different time points (−30 min, 0, and 30 min) associated with PMA stimulation were used to examine the effect of (+)-borneol on the formation of NETs. The ROS generation of neutrophils was also measured to explore the potential mechanism of the inhibitory effect of (+)-borneol on NETosis.

Results: (+)-Borneol pretreatment inhibited NETosis induced by PMA. Immunofluorescence staining visualized and confirmed the inhibitory effect. (+)-Borneol inhibited the burst of ROS in neutrophils caused by PMA. Suppressing NADPH oxidase or protein kinase C (PKC) eliminated the effect of (+)-borneol on NETosis. Moreover, inhibiting Toll-like receptor 2 (TLR2) led to increased NETosis which can be inhibited by (+)-borneol.

Conclusion: (+)-Borneol decreases the ROS level in activated neutrophils and inhibits NETosis triggered by PMA stimulation in vitro. (+)-Borneol therapy may be effective in some NET-dependent conditions.
Mechanistic insights into the role of plant polyphenols and their nano-formulations in the management of depression
Authors: Kabra Atul , Garg Ruchika , Brimson James , Živković Jelena , Almawash Saud , Ayaz Muhammad , Nawaz Asif , Hassan Syed Shams Ul , Bungau Simona
Published: November 2022

Depression is a condition characterized by low mood and an aversion to activity, that causes behavioral problems, poor quality of life and limits daily life activities. It is considered as the fourth leading cause of disability worldwide. Selective Serotonin Reuptake Inhibitors (SSRIs) Monoamine Oxidase (MAO) inhibitors, Tricyclic Antidepressants (TCAs), and atypical antidepressants are some of the conventional medications used to treat depression. However, only about half of patients with major depressive disorder (MDD) respond effectively to first-line antidepressant therapy. Additionally, there are a number of drawbacks to standard antidepressants, such as anti-cholinergic side effects, drug-drug interactions, and food-drug interactions, which prompts researchers to look at alternative approaches to the treatment of depression. Medicinal plants and their metabolites are extensively tested for their efficacy against depression. Electronic databases such as Google scholar, Science Direct, SciFinder and PubMed were used to search relevant literature on the role of polyphenols in depression. Plants-derived Polyphenols represent a major class of compounds extensively distributed in plants. Number of polyphenols have demonstrated antidepressant activity, among which berberine, piperine, curcumin, naringenin, ascorbic acid and ginsenosides are extensively evaluated. The medicinal plants and their derived compounds mediated synthesized green nanoparticles have also exhibited considerable efficacy in the management of depression. The therapeutic effects of these phytochemicals is mediated via differentiation and inhibition of neuronal cell apoptosis, promotion of neuronal cell survival and modulation of key neurotransmitters. The aim of this study is to review compressively the chemical, pharmacological and neurological evidence showing the potential of polyphenols in depression.
Drug delivery systems for treatment of temporomandibular joint osteoarthritis
Authors: Huang Xinqi , Pan Xuefeng , Xiong Xiner , Zhao Zhihe , Cen Xiao
Published: November 2022

The number of people suffering from temporomandibular joint osteoarthritis (TMJOA) has been increasing. TMJOA cause joint noise, pain on TMJ and/or masticatory muscles, and restricted mandibular movement, which disturb eating, laughing and conversation, and impose serious lifestyle impediments. Chondrocyte apoptosis, extracellular matrix degradation, synovitis, and subchondral bone remodeling are the main pathological features of TMJOA. Various drug delivery systems are developed to controlled release at specific activation sites with high bioactivity and inhibit rapid dilution to enable long-term therapeutic response, which present great potential for the treatment of TMJOA. This review focuses on recently developed drug delivery systems by different administration in the TMJOA treatment, and summarizes their effects, duration, safety, and limitations, which would pave the way for development of TMJOA therapy.
Comparison of seven cyclosporine A formulations for dry eye disease: A systematic review and network meta-analysis
Authors: Gao Dongyang , Da Zhuoli , Yang Kan , Shi Yuanyuan
Published: November 2022

Background: Dry eye disease is a common ocular surface disease affecting tens of millions of people worldwide. It is characterized by an unstable tear film and increasing prevalence. Different commercial formulations of cyclosporine A for dry eye have been approved, however, it is still unclear whether the differences in formulations of these products will make a difference in clinical efficacy and safety.

Methods: Randomized controlled trials of commercial cyclosporine A formulation for dry eye disease were searched in Pubmed, EMBASE, Scopus, and Cochrane controlled trials registries and Web of Science from inception till 1 December 2021. Independent literature screening, data extraction, quality evaluation, and the study in line with quality standards were analyzed by using Stata16.0 software. The study is registered with PROSPERO under the number CRD42022301423. Code and data for this study is publicly available (https://github.com/DongYangGao/Dongyang.github.io.git).

Results: 21 randomized clinical trials with a total of 4,107 participants were included in this study. Restasis® (OR-4.82, 95% CI-6.18 to 3.45, SUCRA 77.2%) was the most effective commercial formulation for reducing OSDI, Zirun® (SUCRA 73.9%) performed better in improving Schirmer’s test. TJ Cyporin® (SUCRA 65.3%) ranked first in terms of improving tear film break-up time. For treatment-emergent adverse events incidence, Clacier® was close to placebo. The risk of reporting bias is considered low.

Conclusion: In the comparison of outcomes included in this study, the optimal order of various commercial cyclosporine A formulations is different, so it is difficult to select the optimal formula. Appropriate commercial formulations should be selected according to patients’ conditions in clinical practice.
Cell survival prediction in hadrontherapy with the NanOx biophysical model
Authors: Alcocer-Ávila Mario , Monini Caterina , Cunha Micaela , Testa Étienne , Beuve Michaël
Published: November 2022

Biophysical models are useful tools for predicting the biological effects of ionizing radiation. From a practical point of view, these models can help clinicians to optimize the radiation absorbed dose delivered to patients in particle therapy. The biophysical model NanOx was recently developed to predict cell survival fractions in the context of radiotherapy. The model takes into account the stochastic nature of radiation at different levels and considers as well the accumulation of radio-induced oxidative stress in cells caused by reactive chemical species. We show in this work how the general formalism of NanOx is adapted to hadrontherapy applications. We then use NanOx to compute the cell survival fractions for three cell lines (V79, CHO-K1 and HSG) in response to carbon ions of different energies, and benchmark the predictions against experimental data. The results attest that NanOx provides a good description of both the overkill effect and the evolution of the shoulders of cell survival curves with linear energy transfer.
Meta-analysis assessing the effectiveness of SGLT2i+GLP1RA combination therapy versus monotherapy on cardiovascular and cerebrovascular outcomes in diabetic patients
Authors: Du Lixin , Qin Jiao , Wang Dengchuan , Zhao Yunhui , Xu Ning , Wu Chaowen , Yuan Jianpeng
Published: November 2022

Relevant meta-analyses have confirmed the cardiovascular and renal benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) among patients with type 2 diabetes (T2D) and/or cardiorenal disease. However, it is not established whether the combination therapy of SGLT2i and GLP1RA will yield an additive benefit on cardiorenal endpoints. Lopez and colleagues recently did a cohort study (Lopez et al., Am. J. Cardiol., 2022, 181, 87–93) and aimed to address this issue. However, their findings are not consistent with those of previous studies. To confirm Lopez et al.’s findings (Lopez et al., Am. J. Cardiol., 2022, 181, 87–93) and address the aforementioned inconsistencies, we conducted a meta-analysis based on relevant studies. Our meta-analysis identified that SGLT2i + GLP1RA combination therapy was significantly associated with the reduced risks of cardiovascular/cerebrovascular atherosclerotic, heart failure-associated, and death outcomes compared with SGLT2i/GLP1RA monotherapy. These might support this combination therapy used for better reducing cardiovascular and death events in T2D patients, especially in those with high or very high cardiovascular risk. This is a commentary on a previous article (Lopez et al.’s study (Lopez et al., Am. J. Cardiol., 2022, 181, 87–93)) published outside of Frontiers. Therefore, we submitted this manuscript as an Opinion article, as suggested in the Author Guidelines.
Explore the interaction between root metabolism and rhizosphere microbiota during the growth of Angelica sinensis
Authors: Chen Jing-Mei , Feng Wei-Meng  , Yan Hui , Liu Pei , Zhou Gui-Sheng , Guo Sheng , Yu Guang  , Duan Jin-Ao
Published: November 2022

Angelica sinensis is a medicinal plant widely used to treat multiple diseases in Asia and Europe, which contains numerous active components with therapeutic value. The interaction between root and rhizosphere microorganisms is crucial for the growth and quality formation of medicinal plants. But the micro-plant-metabolite regulation patterns for A. sinensis remain largely undetermined. Here, we collected roots and rhizosphere soils from A. sinensis in seedling stage (M) and picking stage (G), respectively cultivated for one year and two years, generated metabolite for roots, microbiota data for rhizospheres, and conducted a comprehensive analysis. Changes in metabolic and microbial communities of A.sinensis over growth were distinct. The composition of rhizosphere microbes in G was dominated by proteobacteria, which had a strong correlation with the synthesis of organic acids, while in M was dominated by Actinobacteria, which had a strong correlation with the synthesis of phthalide and other organoheterocyclic compounds, flavonoids, amines, and fatty acid. Additionally, co-occurrence network analysis identified that Arthrobacter was found to be strongly correlated with the accumulation of senkyunolide A and n-butylidenephthalide. JGI 0001001.H03 was found to be strongly correlated with the accumulation of chlorogenic acid. Based on rhizosphere microorganisms, this study investigated the correlation between root metabolism and rhizosphere microbiota of A. sinensis at different growth stages in traditional geoherb region, which could provide references for exploring the quality formation mechanism of A. sinensis in the future.
Genome-wide characterization of the chitinase gene family in wild apple (Malus sieversii) and domesticated apple (Malus domestica) reveals its role in resistance to Valsa mali
Authors: Haxim Yakupjan , Kahar Gulnaz , Zhang Xuechun , Si Yu , Waheed Abdul , Liu Xiaojie , Wen Xuejing , Li Xiaoshuang , Zhang Daoyuan
Published: November 2022

Chitinases are responsible for catalyzing the hydrolysis of chitin and contribute to plant defense against fungal pathogens by degrading fungal chitin. In this study, genome-wide identification of the chitinase gene family of wild apple (Malus sieversii) and domesticated apple (Malus domestica) was conducted, and the expression profile was analyzed in response to Valsa mali infection. A total of 36 and 47 chitinase genes belonging to the glycosyl hydrolase 18 (GH18) and 19 (GH19) families were identified in the genomes of M. sieversii and M. domestica, respectively. These genes were classified into five classes based on their phylogenetic relationships and conserved catalytic domains. The genes were randomly distributed on the chromosomes and exhibited expansion by tandem and segmental duplication. Eight of the 36 MsChi genes and 17 of the 47 MdChi genes were differentially expressed in response to V. mali inoculation. In particular, MsChi35 and its ortholog MdChi41, a class IV chitinase, were constitutively expressed at high levels in M. sieversii and domesticated apple, respectively, and may play a crucial role in the defense response against V. mali. These results improve knowledge of the chitinase gene family in apple species and provide a foundation for further studies of fungal disease prevention in apple.
Transcriptome analysis identifies key gene LiMYB305 involved in monoterpene biosynthesis in Lilium ‘Siberia’
Authors: Yang Yun-Yao , Ma Bo , Li Ying-Ying , Han Ming-Zheng , Wu Jing , Zhou Xiao-Feng , Tian Ji , Wang Wen-He , Leng Ping-Sheng , Hu Zeng-Hui
Published: November 2022

Lilium is a popular cut flower that is highly favored by consumers due to its snowy white color and strong fragrance, which originates from the release of monoterpenes. However, the underlying molecular mechanism of monoterpene synthesis remains poorly understood. In this study, the content of three main monoterpenes (linalool, ocimene, and myrcene) was examined in Lilium ‘Siberia’, and RNA sequencing of the 11 stages of flower development was conducted. The biosynthesis of the three monoterpenes increased with flower development, reaching their peak levels at the full flowering stage. Transcriptome data revealed 257,140 unigenes, with an average size of 794 bp, from which 43,934 differentially expressed genes were identified and enriched in the KEGG pathways partly involved in plant hormone signal transduction and monoterpenoid biosynthesis. Furthermore, the essential factor LiMYB305 was identified by WGCNA after the release of the flower fragrance. The transient silencing of LiMYB305 in petals using VIGS technology showed that the mRNA expression levels of LiLiS, LiOcS, and LiMyS were significantly downregulated and that the release of linalool, ocimene, and myrcene had decreased significantly. Y1H, LUC, and EMSA experiments revealed that LiMYB305 directly bound and activated the LiOcS promoter to increase the synthesis of monoterpenes. Taken together, these results provide insight into the molecular mechanism of monoterpene synthesis and provide valuable information to investigate the formation of the flower fragrance in Lilium.
Mechanistic insights derived from re-establishment of desiccation tolerance in germinating xerophytic seeds: Caragana korshinskii as an example
Authors: Peng Long , Huang Xu , Qi Manyao , Pritchard Hugh W. , Xue Hua
Published: November 2022

Germplasm conservation strongly depends on the desiccation tolerance (DT) of seeds. Xerophytic seeds have strong desiccation resistance, which makes them excellent models to study DT. Although some experimental strategies have been applied previously, most methods are difficult to apply to xerophytic seeds. In this review, we attempted to synthesize current strategies for the study of seed DT and provide an in-depth look at Caragana korshinskii as an example. First, we analyze congenital advantages of xerophytes in the study of seed DT. Second, we summarize several strategies used to study DT and illustrate a suitable strategy for xerophytic species. Then, based on our previous studies work with C. korshinskii, a feasible technical strategy for DT re-establishment is provided and we provide illustrate some special molecular mechanisms seen in xerophytic seeds. Finally, several steps to unveil the DT mechanism of xerophytic seeds are suggested, and three scientific questions that the field should consider are listed. We hope to optimize and utilize this strategy for more xerophytic species to more systematically decipher the physiological and molecular processes of seed DT and provide more candidate genes for molecular breeding.
Maximizing genetic gain through unlocking genetic variation in different ecotypes of kalmegh (Andrographis paniculata (Burm. f.) Nee)
Authors: Chaturvedi Trishna , Gupta Anil Kumar , Shanker Karuna , Dubey Basant Kumar , Tiwari Gunjan
Published: November 2022

Andrographis paniculata, commonly known as kalmegh is among the most popular medicinal herbs in Southeast Asia. It is widely cultivated for medicinal purposes. The bioactive molecule, Andrographolide accumulated in herb leaves has immense therapeutic and economic potential. However, comprehensive information regarding genetic diversity is very limited in this species. The present study assessed genetic diversity between and within the six populations (ecotypes) of twenty-four kalmegh accessions using multiple datasets (agro-morphological traits, phytochemical traits, and genic markers). This is the established report where EST-SSR (Expressed sequence tags-Simple Sequence Repeat) markers have been used to unlock genetic variation in kalmegh. Here, we identified and developed ninety-one metabolic pathway-specific EST-SSR markers. Finally, 32 random EST-SSR primer pairs were selected for genetic diversity assessment. Multivariate analysis to unveil the agro-morphological, phytochemical and genotypic variability was helpful in discriminating various germplasms studied in the present study. Among all the morphological discriptors used in present study, days to fifty percent flowering and dry herb yield were found as potential selection index for AP genetic improvement. Hierarchical cluster analysis built with agro-morphological data identified three major groups. However, corresponding analysis with phytochemical and molecular data generated two clear-cut groups among the studied individuals. Moreover, the grouping of individuals into different clusters using multiple datasets was geographically independent, and also showed inconsistency in grouping among agromorphological, phytochemical and molecular dataset based clusters. However, joint analysis using agro-morphological, phytochemical and genotypic information generated two genetic groups, which could be a valuable resource for identifying complementary crossing panels in the kalmegh breeding program. The accessions AP7, AP13, AP5, AP3 belong to cluster I and accessions AP17, AP18 belong to cluster II could be utilized as potential donors for high dry herb yield and andrographolide content, respectively in different selective breeding programs of AP. Thus, our results provided useful information about the overall genetic diversity and variation in economic traits useful for initiating selective breeding programs for contrasting traits of interest and maximizing genetic gain in kalmegh.
A novel heuristic target-dependent neural architecture search method with small samples
Authors: Fu Leiyang , Li Shaowen , Rao Yuan , Liang Jinxin , Teng Jie , He Quanling
Published: November 2022

It is well known that crop classification is essential for genetic resources and phenotype development. Compared with traditional methods, convolutional neural networks can be utilized to identify features automatically. Nevertheless, crops and scenarios are quite complex, which makes it challenging to develop a universal classification method. Furthermore, manual design demands professional knowledge and is time-consuming and labor-intensive. In contrast, auto-search can create network architectures when faced with new species. Using rapeseed images for experiments, we collected eight types to build datasets (rapeseed dataset (RSDS)). In addition, we proposed a novel target-dependent search method based on VGGNet (target-dependent neural architecture search (TD-NAS)). The result shows that test accuracy does not differ significantly between small and large samples. Therefore, the influence of the dataset size on generalization is limited. Moreover, we used two additional open datasets (Pl@ntNet and ICL-Leaf) to test and prove the effectiveness of our method due to three notable features: (a) small sample sizes, (b) stable generalization, and (c) free of unpromising detections.
Plastid and cytoplasmic origins of 1O2-mediated transcriptomic responses
Authors: Koh Eugene , Brandis Alexander , Fluhr Robert
Published: November 2022

The reactive oxygen species singlet oxygen, 1O2, has an extremely short half-life, yet is intimately involved with stress signalling in the cell. We previously showed that the effects of 1O2 on the transcriptome are highly correlated with 80S ribosomal arrest due to oxidation of guanosine residues in mRNA. Here, we show that dysregulation of chlorophyll biosynthesis in the flu mutant or through feeding by δ-aminolevulinic acid can lead to accumulation of photoactive chlorophyll intermediates in the cytoplasm, which generates 1O2 upon exposure to light and causes the oxidation of RNA, eliciting 1O2-responsive genes. In contrast, transcriptomes derived from DCMU treatment, or the Ch1 mutant under moderate light conditions display commonalties with each other but do not induce 1O2 gene signatures. Comparing 1O2 related transcriptomes to an index transcriptome induced by cycloheximide inhibition enables distinction between 1O2 of cytosolic or of plastid origin. These comparisons provide biological insight to cases of mutants or environmental conditions that produce 1O2.
Near-infrared hyperspectral imaging for online measurement of the viability detection of naturally aged watermelon seeds
Authors: Yasmin Jannat , Ahmed Mohammed Raju , Wakholi Collins , Lohumi Santosh , Mukasa Perez , Kim Geonwoo , Kim Juntae , Lee Hoonsoo , Cho Byoung-Kwan
Published: November 2022

The viability status of seeds before sowing is important to farmers as it allows them to make yield predictions. Monitoring the seed quality in a rapid and nondestructive manner may create a perfect solution, especially for industrial sorting applications. However, current offline laboratory-based strategies employed for the monitoring of seed viability are time-consuming and thus cannot satisfy industrial needs where there is a substantial number of seeds to be analyzed. In this study, we describe a prototype online near-infrared (NIR) hyperspectral imaging system that can be used for the rapid detection of seed viability. A wavelength range of 900–1700 nm was employed to obtain spectral images of three different varieties of naturally aged watermelon seed samples. The partial least square discriminant analysis (PLS-DA) model was employed for real-time viability prediction for seed samples moving through a conveyor unit at a speed of 49 mm/sec. A suction unit was further incorporated to develop the online system and it was programmatically controlled to separate the detected viable seeds from nonviable ones. For an external validation sample set showed classification accuracy levels of 91.8%, 80.7%, and 77.8% in relation to viability for the three varieties of watermelon seed with healthy seedling growth. The regression coefficients of the classification model distinguished some chemical differences in viable and nonviable seed which was verified by the chromatographic analysis after the detection of the proposed online system. The results demonstrated that the developed online system with the viability prediction model has the potential to be used in the seed industry for the quality monitoring of seeds.