bluuebunny/crossref_metadata_2025 huggingface dataset:
Bidirectional regulatory effects of Cordyceps on arrhythmia: Clinical evaluations and network pharmacology
Authors: Wang Lijuan , Sun Helin , Yang Meina , Xu Yulin , Hou Linlin , Yu Haomiao , Wang Xueyin , Zhang Zhongwen , Han Jinxiang
Published: August 2022

Background: Cordyceps is a precious Chinese herbal medicine with rich bio-active ingredients and is used for regulating arrhythmia alongside routine treatments. However, the efficacy and potential mechanisms of Cordyceps on patients with arrhythmia remain unclear.

Methods: Randomized controlled trials of bradycardia treatment with Cordyceps were retrieved from diverse databases and available data. Dichotomous variables were expressed as a risk ratio (RR) with a 95% confidence interval (CI). Continuous variables were expressed as a standardized mean difference (SMD) with a 95% CI. Network pharmacology was used to identify potential targets of Cordyceps for arrhythmia. Metascape was used for gene ontology (GO) and genome (KEGG) pathway enrichment analysis.

Results: Nineteen trials included 1,805 patients with arrhythmia, of whom 918 were treated with Ningxinbao capsule plus routine drugs, and, as a control, 887 were treated with only routine drugs. Six trials reported on bradycardia and the other 13 on tachycardia. Treatment with Cordyceps significantly improved the total efficacy rate in both bradycardia (RR = 1.24; 95% CI, 1.15 to 1.35; Pz <0.00001) and tachycardia (RR = 1.27; 95% CI, 1.17 to 1.39; Pz <0.00001). Cordyceps also had beneficial secondary outcomes. No serious adverse events occurred in patients treated with Cordyceps. The results of KEGG pathway enrichment analysis were mainly connected to adrenergic signaling in cardiomyocytes and the PI3K-Akt signaling pathway. IL6, TNF, TP53, CASP3, CTNNB1, EGF, and NOS3 might be key targets for Cordyceps in the treatment of arrhythmia.

Conclusion: This study confirmed that Cordyceps has a certain positive effect on the treatment of arrhythmia and that its main mechanism may be through the regulation of adrenergic signaling in cardiomyocytes and the PI3K-Akt signaling pathway.
Potential therapeutics against neurological disorders: Natural products-based drugs
Authors: Rauf Abdur , Rahman Md. Mominur
Published: August 2022

Neurodegenerative disorders, which are defined by the breakdown of neurons over time, are affecting an increasing number of people. Stroke, Alzheimer's, Parkinson's, Multiple Sclerosis, Migraine, and Amyotrophic Lateral Sclerosis are just a few examples of brain disorders that have no cure. Besides, there is a huge demand for drugs that can cure the diseases mentioned above because the majority of the medications we use to treat them only alleviate diseases. Different neurological disorders have responded satisfactorily to the pharmacological effects of medicinal plants. Despite the numerous multiple types of plants in the world, only a small number of them have been investigated for neurological disorders. As a result, there are many opportunities in this area for further research on plants and their bioactive chemicals. The search for natural therapeutic alternatives that promote faster healing and adverse effects avoidance has gained popularity in recent years. The aim of this mini-review is to explore some natural products that have strong therapeutic effects on neurodegenerative disorders such as Stroke, Alzheimer’s Disease, Parkinson’s Disease, Multiple Sclerosis, Migraine, Amyotrophic Lateral Sclerosis, and others. We have also shown the safety of natural products to improve their appropriate usage in neurological disorders from recent literature.
A comprehensive review on disposition kinetics and dosage of oral administration of Andrographis paniculata, an alternative herbal medicine, in co-treatment of coronavirus disease
Authors: Songvut Phanit , Suriyo Tawit , Panomvana Duangchit , Rangkadilok Nuchanart , Satayavivad Jutamaad
Published: August 2022

Coronavirus disease 2019 (COVID-19) is a present global health crisis that is driving the investigation of alternative phytomedicines for antiviral purposes. The evidence suggests that Andrographis paniculata crude or extract is a promising candidate for treating symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This review aims to consolidate the available reports on the disposition kinetics of andrographolide, a main active component of A. paniculata. The second objective of this review is to summarize the available reports on an appropriate oral dosage for the use of andrographolide in upper respiratory tract infections (URTIs) and other viral infectious diseases. The data were collected from the literature on absorption, distribution, biotransformation, and excretion of andrographolide, and information was also obtained from scientific databases about the use of A. paniculata. The finding of this review on pharmacokinetics indicates that andrographolide is slightly absorbed into the blood circulation and exhibits poor oral bioavailability, whereas its distribution process is unrestricted. In the termination phase, andrographolide preferentially undergoes biotransformation partly through phase I hydroxylation and phase II conjugation, and it is then eliminated via the renal excretion and hepatobiliary system. The key summary of the recommended dosage for andrographolide in uncomplicated URTI treatment is 30 mg/day for children and 60 mg/day for adults. The dose for adult patients with pharyngotonsillitis could be increased to 180 mg/day, but not exceed 360 mg/day. Co-treatment with A. paniculata in concert with the standard supportive care for influenza reduced the severity of symptoms, shortened treatment duration, and decreased the risk of developing post-influenza complications. The recommended starting dose for use in patients with mild COVID-19 is 180 mg/day of andrographolide, based on the dose used in patients experiencing a URTI with inflammation. This review is not only applicable for evaluating the appropriate doses of andrographolide for antiviral treatments but also encourages future research evaluating the effectiveness of these recommended dosages during the COVID-19 pandemic.
Genome-wide association analysis of anti-TNF-α treatment response in Chinese patients with psoriasis
Authors: Ren Yunqing , Wang Ling , Dai Huatuo , Qiu Guiying , Liu Jipeng , Yu Dianhe , Liu Jianjun , Lyu Cheng-Zhi , Liu Lunfei , Zheng Min
Published: August 2022

Background: TNF-α inhibitors are effective biological agents for treating psoriasis, but the treatment responses differ across patients. This study aimed to identify genetic biomarkers of anti-TNF-α response in Chinese psoriasis patients using a genome-wide association approach.

Methods: We recruited two independent cohorts of Chinese psoriasis patients administered etanercept biosimilar (with or without methotrexate). We identified 61 and 87 good responders (PASI improvement ≥75%), 19 and 10 poor responders (PASI improvement <50%) after 24 weeks treatment in the two cohorts, respectively. Then we performed genome-wide association studies (GWAS) on anti-TNF-α response in each cohort independently, followed by a fixed-effects inverse-variance meta-analysis in the 148 good and 29 poor responders.

Results: We tested genetic associations with >3 million genetic variants in either cohort. Meta-analysis identified significant associations within seven loci at p < 10−5, which also showed consistent association evidence in the two cohorts. These seven loci include rs2431355 (OR = 6.65, p = 4.46 × 10−7, IQGAP2-F2RL2 on 5q13.3), rs11801616 (OR = 0.11, p = 1.75 × 10−6, SDC3 on 1p35.2), rs3754679 (OR = 0.17, p = 7.71 × 10−6, CNOT11 on 2q11.2), rs13166823 (OR = 0.09, p = 3.71 × 10−6, IRF1-AS1 on 5q31.1), rs10220768 (OR = 5.49, p = 1.48 × 10−6, NPAP1 on 15q11.2), rs4796752 (OR = 5.56, p = 1.49 × 10−6, KRT31 on 17q21.2), and rs13045590 (OR = 0.08, p = 9.67 × 10−7, CTSZ on 20q13.3). Of the seven SNPs, six SNPs showed significant eQTL effect (p < 1 × 10−6) for several genes in multiple tissues.

Conclusion: These results suggest novel biological mechanisms and potential biomarkers for the response to anti-TNF therapies. These findings warrant further validation.
Evaluation of in vivo antibacterial drug efficacy using Caenorhabditiselegans infected with carbapenem-resistant Klebsiella pneumoniae as a model host
Authors: Yao Huijuan , Xu Ajing , Liu Jingxian , Wang Fang , Yao Huimin , Chen Jihui
Published: August 2022

Objective: This study was developed to assess the in vivo antimicrobial activity of specific drugs using a model system consisting of Caenorhabditis elegans (C. elegans) infected with Carbapenem-resistant Klebsiella pneumoniae (CRKP) in an effort to identify promising drugs for CRKP-infected patient treatment.

Methods: A C. elegans-CRKP liquid assay platform was developed and used to conduct limited in vivo screening for antimicrobial agents with potential activity against CRKP. Time curves for 10 different concentrations of tested antimicrobial agents were tested in this model system at 0, 2, 6, 8, and 12 h after treatment. The protective effects of these different antimicrobial agents were compared at different time points. Furthermore, ten CRKP strains samples were isolated from clinical specimens to demonstrate the applicability of the nematode model method, and two typical clinical cases are presented.

Results: CRKP bacteria were sufficient to induce C. elegans death in a dose- and time-dependent fashion, while effective antimicrobial agents improved the survival of these nematodes in a dose-dependent manner. Notably, PB and TGC exhibited robust antibacterial protection within 12 h even at low tested concentrations, and clear efficacy remained evident for high doses of CAZ at this same time point as mediators of improved nematode survival. The results of C. elegans model method were well consistent with that using the Kirby-Bauer method in 10 CRKP strains samples, and two typical clinical cases showed applicability, reliability and efficacy of C. elegans model method.

Conclusion: Overall, nematode models in drug sensitivity testing have shown advantages in clinical settings. Our results highlight the value of C. elegans model systems as tools for the simultaneous screening of different agents for in vivo antibacterial efficacy and are deserved further study.
Kill two birds with one stone: Engineered exosome-mediated delivery of cholesterol modified YY1-siRNA enhances chemoradiotherapy sensitivity of glioblastoma
Authors: Liu Xiao , Cao Zhengcong , Liu Nannan , Gao Guangxun , Du Mingrui , Wang Yingwen , Cheng Boyang , Zhu Maorong , Jia Bo , Pan Luxiang , Zhang Wangqian , Jiang Yuran , He Wei , Xu Linlin , Zhang Wei , An Qunxing , Guo Qingdong , Gu Jintao
Published: August 2022

Glioblastoma (GBM) is the most malignant tumor of the central nervous system in adults. Irradiation (IR) and temozolomide (TMZ) play an extremely important role in the treatment of GBM. However, major impediments to effective treatment are postoperative tumor recurrence and acquired resistance to chemoradiotherapy. Our previous studies confirm that Yin Yang 1 (YY1) is highly expressed in GBM, whereby it is associated with cell dedifferentiation, survival, and therapeutic resistance. Targeted delivery of small interfering RNA (siRNA) without blood-brain barrier (BBB) restriction for eradication of GBM represents a promising approach for therapeutic interventions. In this study, we utilize the engineering technology to generate T7 peptide-decorated exosome (T7-exo). T7 is a peptide specifically binding to the transferrin receptor. T7-exo shows excellent packaging and protection of cholesterol-modified Cy3-siYY1 while quickly releasing payloads in a cytoplasmic reductive environment. The engineered exosomes T7-siYY1-exo could deliver more effciently to GBM cells both in vitro and in vivo. Notably, in vitro experiments demonstrate that T7-siYY1-exo can enhance chemoradiotherapy sensitivity and reverse therapeutic resistance. Moreover, T7-siYY1-exo and TMZ/IR exert synergistic anti-GBM effect and significantly improves the survival time of GBM bearing mice. Our findings indicate that T7-siYY1-exo may be a potential approach to reverse the chemoradiotherapy resistance in GBM.
The combination of Lonicerae Japonicae Flos and Forsythiae Fructus herb-pair alleviated inflammation in liver fibrosis
Authors: Zhang Jing-Bei , Jin Hong-Liu , Feng Xiao-Ying , Feng Sen-ling , Zhu Wen-Ting , Nan Hong-Mei , Yuan Zhong-Wen
Published: August 2022

Objective: To explore the active components and epigenetic regulation mechanism underlying the anti-inflammatory effects of Lonicerae Japonicae Flos and Forsythiae Fructus herb-pair (LFP) in carbon tetrachloride (CCl4)-induced rat liver fibrosis.

Methods: The main active ingredients and disease-related gene targets of LFP were determined using TCMSP and UniProt, and liver fibrosis disease targets were screened in the GeneCards database. A network was constructed with Cytoscape 3.8.0 and the STRING database, and potential protein functions were analyzed using bioinformatics analysis. Based on these analyses, we determined the main active ingredients of LFP and evaluated their effects in a CCl4-induced rat liver fibrosis model. Serum biochemical indices were measured using commercial kits, hepatocyte tissue damage and collagen deposition were evaluated by histopathological studies, and myofibroblast activation and inflammation were detected by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. High-performance liquid chromatography-mass spectrometry was performed to determine the levels of homocysteine, reduced glutathione, and oxidized glutathione, which are involved in inflammation and oxidative stress.

Results: The main active components of LFP were quercetin, kaempferol, and luteolin, and its main targets were α-smooth muscle actin, cyclooxygenase-2, formyl-peptide receptor-2, prostaglandin-endoperoxide synthase 1, nuclear receptor coactivator-2, interleukinβ, tumor necrosis factor α, CXC motif chemokine ligand 14, and transforming growth factor β1. A combination of quercetin, kaempferol, and luteolin alleviated the symptoms of liver fibrosis.

Conclusion: The results of this study support the role of LFP in the treatment of liver fibrosis, and reveal that LFP reduces collagen formation, inflammation, and oxidative stress. This study suggests a potential mechanism of action of LFP in the treatment of liver fibrosis.
Optical measurement of an impact reaction in a modeled wing
Authors: Saldaña-Heredia Alonso , Martínez-Calzada Víctor , Del Villar-Ramírez Víctor Uriel , Rodríguez-Torres Adriana
Published: August 2022

In this research, an impact reaction which was provoked far from its origins was studied. A metal box filled with sand was used to emulate a rigid body in which a steel bar was embedded; these conditions simulated the fuselage and wing, respectively, and the impact was applied to the rigid body and the measurement to the bar. For this, an optical technique was used to measure the relative displacement of the steel bar, and the measurements are obtained by applying digital image correlation; 2D images were obtained from the speckles generated as a reflection of the beam on the material. The results were studied through the modified Gauss–Newton analytical approach obtaining a maximum standard error deviation of 0.144 from the experimental results.
Multiple pathway quantum beat spectroscopy
Authors: Yi Zhenhuan , Begzjav Tuguldur Kh. , Ariunbold Gombojav O. , Zheltikov Aleksei M. , Sokolov Alexei V. , Scully Marlan O.
Published: August 2022

We investigate quantum beats by monitoring cooperative emission from rubidium vapor and demonstrate correlated beats via coupled emission channels. We develop a theoretical model, and our simulations are in good agreement with experimental results. The results pave the way for advanced techniques measuring interactions between atoms that are excited to high energy levels.
Effects of cGMP/Akt/GSK-3β signaling pathway on atrial natriuretic peptide secretion in rabbits with rapid atrial pacing
Authors: Cao Shuxia , Han Chengyong , Xuan Chunhua , Li Xiangdan , Wen Jing , Xu Dongyuan
Published: August 2022

Atrial natriuretic peptide (ANP) plays a pivotal role in the regulation of the cardiovascular system. The ANP level increases during atrial fibrillation (AF), suggesting that AF may provoke ANP secretion, but its potential mechanism is still unclear. In the present study, the potential mechanisms of rapid atrial pacing (RAP) regulating ANP secretion was explored. Rabbits were subjected to burst RAP, ANP secretion increased whereas cyclic guanosine monophosphate (cGMP) concentrations decreased during RAP. The p-Akt and p-GSK-3β levels decreased in atrial tissues. Natriuretic peptide receptor A (NPR-A) protein and particulate guanylate cyclase (PGC) activity were detected. The sensitivity of NPR-A to ANP decreased, leading to the decrease of PGC activity. Also, the isolated atrial perfusion system were made in the rabbit model, cGMP was shown to inhibit ANP secretion, and the Akt inhibitor LY294002 (LY) and GSK-3β inhibitor SB216763 (SB) attenuated the inhibitory effects of cGMP on ANP secretion and enhanced the inhibitory effects of cGMP on atrial dynamics. In conclusion, NPR-A interacts with ANP to regulate PGC expression, and influence the expression of cGMP during RAP, which involves in the Akt/GSK-3β signaling pathway. From the aforementioned points we conclude that cGMP regulates ANP secretion by the Akt/GSK-3β signaling pathway during atrial pacing.
Mitochondrial translocator protein deficiency exacerbates pathology in acute experimental ulcerative colitis
Authors: Jimenez Isabel A. , Stilin Allison P. , Morohaku Kanako , Hussein Mahmoud H. , Koganti Prasanthi P. , Selvaraj Vimal
Published: August 2022

In human patients and animal models of ulcerative colitis (UC), upregulation of the mitochondrial translocator protein (TSPO) in the colon is consistent with inflammation. Although the molecular function for TSPO remains unclear, it has been investigated as a therapeutic target for ameliorating UC pathology. In this study, we examined the susceptibility ofTspogene-deleted (Tspo−/−) mice to insults as provided by the dextran sodium sulfate (DSS)-induced acute UC model. Our results show that UC clinical signs and pathology were severely exacerbated inTspo−/−mice compared to controlTspofl/flcohorts. Histopathology showed extensive inflammation and epithelial loss inTspo−/−mice that caused an aggravated disease. Colonic gene expression in UC uncovered an etiology linked to precipitous loss of epithelial integrity and disproportionate mast cell activation assessed by tryptase levels inTspo−/−colons. Evaluation of baseline homeostatic shifts inTspo−/−colons revealed gene expression changes noted in elevated epithelialCdx2, mast cellCd36andMcp6, with general indicators of lower proliferation capacity and elevated mitochondrial fatty acid oxidation. These findings demonstrate that intact physiological TSPO function serves to limit inflammation in acute UC, and provide a systemic basis for investigating TSPO-targeting mechanistic therapeutics.
The role of mechanosensitive ion channels in the gastrointestinal tract
Authors: Yang Haoyu , Hou Chaofeng , Xiao Weidong , Qiu Yuan
Published: August 2022

Mechanosensation is essential for normal gastrointestinal (GI) function, and abnormalities in mechanosensation are associated with GI disorders. There are several mechanosensitive ion channels in the GI tract, namely transient receptor potential (TRP) channels, Piezo channels, two-pore domain potassium (K2p) channels, voltage-gated ion channels, large-conductance Ca2+-activated K+ (BKCa) channels, and the cystic fibrosis transmembrane conductance regulator (CFTR). These channels are located in many mechanosensitive intestinal cell types, namely enterochromaffin (EC) cells, interstitial cells of Cajal (ICCs), smooth muscle cells (SMCs), and intrinsic and extrinsic enteric neurons. In these cells, mechanosensitive ion channels can alter transmembrane ion currents in response to mechanical forces, through a process known as mechanoelectrical coupling. Furthermore, mechanosensitive ion channels are often associated with a variety of GI tract disorders, including irritable bowel syndrome (IBS) and GI tumors. Mechanosensitive ion channels could therefore provide a new perspective for the treatment of GI diseases. This review aims to highlight recent research advances regarding the function of mechanosensitive ion channels in the GI tract. Moreover, it outlines the potential role of mechanosensitive ion channels in related diseases, while describing the current understanding of interactions between the GI tract and mechanosensitive ion channels.
Hemodynamic and cardiorespiratory responses to submaximal and maximal exercise in adults with Down syndrome
Authors: Oviedo Guillermo R. , Carbó-Carreté María , Guerra-Balic Myriam , Tamulevicius Nauris , Esquius Laura , Guàrdia-Olmos Joan , Javierre Casimiro
Published: August 2022

Introduction: The genetic disorder causing Down syndrome (DS) affects the cardiorespiratory and hemodynamic parameters. When exercising, sufficient blood flow is necessary for active muscles. Cardiac output (Q) must be proportional to the peripheral requirements. In case the stroke volume (SV) is lower, the heart rate (HR) will increase further in order to maintain an adequate blood flow in the active territories (HR compensatory response). People with DS have a lower HR response to maximal exercise. Nevertheless, the response of the hemodynamic and cardiorespiratory parameters during the submaximal phases of maximal exercise was not well studied.

Objective: to evaluate cardiorespiratory and hemodynamic parameters 1) during submaximal and 2) maximal metabolic treadmill test in individuals with and without DS.

Methods: fifteen adults with DS (age = 27.33 ± 4.98 years old; n = 12 males/3 females) and 15 adults without disabilities, matched by age and sex, participated in this cross-sectional study. Peak and submaximal cardiorespiratory and hemodynamic parameters were measured during a treadmill test. Linear mixed-effects models were used to analyse interactions between the variables. Post-hoc analyses were employed to assess within and between-group differences.

Results: The DS group showed lower peak values for ventilation (VE), respiratory exchange ratio (RER), tidal volume (VT), ventilatory equivalent for O2 (VEqO2), end-tidal partial pressure for O2 (PETO2), O2 uptake (VO2) and CO2 production (all p < 0 .050), Q, SV, systolic and diastolic blood pressure (SBP, DBP), and HR (all p < 0 .050). There were group-by-time interactions (all p < 0 .050) for all ventilatory submaximal values. Significant group and time differences were observed for VE; RER; respiratory rate (RR); VEqO2; PETO2; VO2, and VT (all p < 0 .050). There were also group-by-time interactions (all p < 0 .050) and group and time differences for SBP, mean arterial blood pressure (MAP) and HR (all p < 0.010).

Conclusion: During submaximal exercise, we verified a compensatory response of HR, and greater VE and VO2 in the individuals with DS. In addition, we were able to observe that the DS group had a reduced SBP and MAP response to submaximal exercise. On the other hand, we found that adults with DS have lower peak hemodynamic and cardiorespiratory values, and a lower cardiac reserve. Further research is warranted to investigate the effects of these results on the general health of adults with DS and the impact of long-term exercise programs on these parameters.
Diversification of aminoacyl-tRNA synthetase activities via genomic duplication
Authors: Krahn Natalie , Söll Dieter , Vargas-Rodriguez Oscar
Published: August 2022

Intricate evolutionary events enabled the emergence of the full set of aminoacyl-tRNA synthetase (aaRS) families that define the genetic code. The diversification of aaRSs has continued in organisms from all domains of life, yielding aaRSs with unique characteristics as well as aaRS-like proteins with innovative functions outside translation. Recent bioinformatic analyses have revealed the extensive occurrence and phylogenetic diversity of aaRS gene duplication involving every synthetase family. However, only a fraction of these duplicated genes has been characterized, leaving many with biological functions yet to be discovered. Here we discuss how genomic duplication is associated with the occurrence of novel aaRSs and aaRS-like proteins that provide adaptive advantages to their hosts. We illustrate the variety of activities that have evolved from the primordial aaRS catalytic sites. This precedent underscores the need to investigate currently unexplored aaRS genomic duplications as they may hold a key to the discovery of exciting biological processes, new drug targets, important bioactive molecules, and tools for synthetic biology applications.
Aberrant activation of KRAS in mouse theca-interstitial cells results in female infertility
Authors: Sun Penghao , Wang Hongliang , Liu Lingyun , Guo Kaimin , Li Xian , Cao Yin , Ko Chemyong , Lan Zi-Jian , Lei Zhenmin
Published: August 2022

KRAS plays critical roles in regulating a range of normal cellular events as well as pathological processes in many tissues mediated through a variety of signaling pathways, including ERK1/2 and AKT signaling, in a cell-, context- and development-dependent manner. The in vivo function of KRAS and its downstream targets in gonadal steroidogenic cells for the development and homeostasis of reproductive functions remain to be determined. To understand the functions of KRAS signaling in gonadal theca and interstitial cells, we generated a Kras mutant (tKrasMT) mouse line that selectively expressed a constitutively active KrasG12D in these cells. KrasG12D expression in ovarian theca cells did not block follicle development to the preovulatory stage. However, tKrasMT females failed to ovulate and thus were infertile. The phosphorylated ERK1/2 and forkhead box O1 (FOXO1) and total FOXO1 protein levels were markedly reduced in tKrasMT theca cells. KrasG12D expression in theca cells also curtailed the phosphorylation of ERK1/2 and altered the expression of several ovulation-related genes in gonadotropin-primed granulosa cells. To uncover downstream targets of KRAS/FOXO1 signaling in theca cells, we found that the expression of bone morphogenic protein 7 (Bmp7), a theca-specific factor involved in ovulation, was significantly elevated in tKrasMT theca cells. Chromosome immunoprecipitation assays demonstrated that FOXO1 interacted with the Bmp7 promoter containing forkhead response elements and that the binding activity was attenuated in tKrasMT theca cells. Moreover, Foxo1 knockdown caused an elevation, whereas Foxo1 overexpression resulted in an inhibition of Bmp7 expression, suggesting that KRAS signaling regulates FOXO1 protein levels to control Bmp7 expression in theca cells. Thus, the anovulation phenotype observed in tKrasMT mice may be attributed to aberrant KRAS/FOXO1/BMP7 signaling in theca cells. Our work provides the first in vivo evidence that maintaining normal KRAS activity in ovarian theca cells is crucial for ovulation and female fertility.
The CO2 fertilization effect on leaf photosynthesis of maize (Zea mays L.) depends on growth temperatures with changes in leaf anatomy and soluble sugars
Authors: Liu Liang , Hao Lihua , Zhang Yunxin , Zhou Haoran , Ma Baoguo , Cheng Yao , Tian Yinshuai , Chang Zhijie , Zheng Yunpu
Published: August 2022

Understanding the potential mechanisms and processes of leaf photosynthesis in response to elevated CO2 concentration ([CO2]) and temperature is critical for estimating the impacts of climatic change on the growth and yield in crops such as maize (Zea mays L.), which is a widely cultivated C4 crop all over the world. We examined the combined effect of elevated [CO2] and temperature on plant growth, leaf photosynthesis, stomatal traits, and biochemical compositions of maize with six environmental growth chambers controlling two CO2 levels (400 and 800 μmol mol−1) and three temperature regimes (25/19°C, 31/25°C, and 37/31°C). We found that leaf photosynthesis was significantly enhanced by increasing growth temperature from 25/19°C to 31/25°C independent of [CO2]. However, leaf photosynthesis drastically declined when the growth temperature was continually increased to 37/31°C at both ambient CO2 concentration (400 μmol mol−1, a[CO2]) and elevated CO2 concentration (800 μmol mol−1, e[CO2]). Meanwhile, we also found strong CO2 fertilization effect on maize plants grown at the highest temperature (37/31°C), as evidenced by the higher leaf photosynthesis at e[CO2] than that at a[CO2], although leaf photosynthesis was similar between a[CO2] and e[CO2] under the other two temperature regimes of 25/19°C and 31/25°C. Furthermore, we also found that e[CO2] resulted in an increase in leaf soluble sugar, which was positively related with leaf photosynthesis under the high temperature regime of 37/31°C (R2 = 0.77). In addition, our results showed that e[CO2] substantially decreased leaf transpiration rates of maize plants, which might be partially attributed to the reduced stomatal openness as demonstrated by the declined stomatal width and stomatal area. These results suggest that the CO2 fertilization effect on plant growth and leaf photosynthesis of maize depends on growth temperatures through changing stomatal traits, leaf anatomy, and soluble sugar contents.
Alfalfa modified the effects of degraded black soil cultivated land on the soil microbial community
Authors: Mei Linlin , Zhang Na , Wei Qianhao , Cao Yuqi , Li Dandan , Cui Guowen
Published: August 2022

Legume alfalfa (Medicago sativa L.) is extensively planted to reduce chemical fertilizer input to the soil and remedy damaged fields. The soil mechanism of these effects is potentially related to the variations in alfalfa-mediated interactions of the soil microbial community. To understand the impact of planting alfalfa on the soil microbial community in degraded black soil cultivated land, a 4-year experiment was conducted in degraded black soil cultivated land. We assessed soil parameters and characterized the functional and compositional diversity of the microbial community by amplicon sequencing that targeted the 16S rDNA gene of bacteria and ITS of fungi in four systems under corn cultivation at the Harbin corn demonstration base (Heilongjiang, China): multiyear corn planting (more than 30 years, MC1); 2 years of alfalfa-corn rotation (OC); 3 years of alfalfa planting (TA); and 4 years of alfalfa planting (FA). It was found out that alfalfa led to changes in the alpha diversity of soil bacteria rather than in fungi in the degraded arable land. The abundance of the bacterial groups Gemmatimonadetes, Actinobacteria, Planctomycetes, and Chloroflexi was increased in OC, while Proteobacteria and Acidobacteria and the fungal group Glomeromycota were increased in TA and FA. OC, TA, and FA significantly increased the pH level but reduced soil electrical conductivity, but they had no impact on soil available nitrogen and soil available potassium at the 0–15 cm soil depth. However, with the years of alfalfa planting, soil available nitrogen and soil available potassium were reduced at the 15–30 cm soil depth. OC, TA, and FA significantly reduced the soil available phosphorus and soil total phosphorus at the 15–30 cm soil depth. There was no significant impact made on soil total nitrogen. FA significantly reduced the soil organic matter at the 15–30 cm soil depth. Planting alfalfa in degraded black soil cultivated land can reduce the salt content of the soil, and the nutrient content of soil planted with alfalfa without fertilization was equivalent to that of degraded corn cultivated land with annual fertilization. Besides, alfalfa recruited and increased contained taxa with the capacity to improve soil nutrient utilization and inhibit the harmful influences of pathogens for subsequent crops. Meanwhile, the planting of alfalfa can modify soil conditions by promoting the proliferation of specific beneficial microbiota groups.
Genome-wide characterization of chalcone synthase genes in sweet cherry and functional characterization of CpCHS1 under drought stress
Authors: Hou Qiandong , Li Shuang , Shang Chunqiong , Wen Zhuang , Cai Xiaowei , Hong Yi , Qiao Guang
Published: August 2022

Cherries are one of the important fruit trees. The growth of cherry is greatly affected by abiotic stresses such as drought, which hinders its development. Chalcone synthase (CHS, EC 2.3.1.74) is a crucial rate-limiting enzyme in the flavonoid biosynthetic pathway that plays an important role in regulating plant growth, development, and abiotic stress tolerance. In the current study, three genes encoding chalcone synthase were identified in the genome of sweet cherry (Prunus avium L.). The three genes contained fewer introns and showed high homology with CHS genes of other Rosaceae members. All members are predicted to localize in the cytoplasm. The conserved catalytic sites may be located at the Cys163, Phe214, His302, and Asn335 residues. These genes were differentially expressed during flower bud dormancy and fruit development. The total flavonoid content of Chinese cherry (Cerasus pseudocerasus Lindl.) was highest in the leaves and slightly higher in the pulp than in the peel. No significant difference in total flavonoid content was detected between aborted kernels and normally developing kernels. Overexpression of Chinese cherry CpCHS1 in tobacco improved the germination frequency of tobacco seeds under drought stress, and the fresh weight of transgenic seedlings under drought stress was higher than that of the wild type, and the contents of SOD, POD, CAT, and Pro in OE lines were significantly increased and higher than WT under drought stress. These results indicate cherry CHS genes are conserved and functionally diverse and will assist in elucidating the functions of flavonoid synthesis pathways in cherry and other Rosaceae species under drought stress.
Diversifying academic medicine: One search committee at a time
Authors: Jacobs N. Nicole , Esquierdo-Leal Jovonnie , Smith Gregory S. , Piasecki Melissa , Houmanfar Ramona A.
Published: August 2022

Despite increasing attention to lack of diversity among medical education faculty, those traditionally underrepresented in medicine remain so. In 2017, the University of Nevada, Reno School of Medicine approved a new policy to increase diversity in the faculty search process, which includes a mandatory 2-h workshop on best practices in search processes and implicit bias training. Workshop participants were 179 search committee members making up 55 committees from February 2017 to March 2020. Participants completed two separate social validity surveys, one immediately following the workshop and another following the close of their search, and rated various aspects of the workshop. Each search committee completed a Diversity Checklist (DCL) of various mandatory and best practices to be implemented during each search. Historical data on diversity of job applicants, interviewees, and hires over the 5-year period immediately preceding workshop implementation were compared with corresponding diversity data from the participant search committees for a 3-year period following implementation of the workshop. Social validity surveys indicated high ratings pertaining to the benefits of the workshop (means 3.82–4.39 out of 5). Implementation of practices outlined in the DCL were high (94% of mandatory and 87% of best practices). Chi-square analyses of diversity data before and after implementation revealed significant increases in overall diversity (both race and gender) of applicants (p < 0.001), interviewees (p = 0.002), and those offered a position (p = 0.002), in the time period following implementation. Follow-up comparisons found greater increases for gender relative to race/ethnicity.
Assessing the efficacy and safety of Juan Bi Tang for dialysis-related myofascial pain in the fistula arm: Study protocol for a randomized cross-over trial
Authors: Hsu Yung-Tang , Ng Hwee-Yeong , Chen Yung-Hsiang , Huang Yu-Chuen , Lee Yan-Yuh , Tsai Ming-Yen
Published: August 2022

Background

Dialysis-related myofascial pain in hemodialysis (HD) patients is an important issue that is associated with many other psychosomatic problems. Effective interventions are required to alleviate pain in this group. Chinese herbal medicine (CHM) may be a potential therapeutic treatment for reducing pain. The aim of this study is to evaluate the effects of a classic CHM formula intervention on pain intensity, daily function, quality of life (QOL), and safety in patients receiving HD in a dialysis center within the context of southern Taiwan.

Methods

This will be a randomized, open label, cross-over trial with two parallel groups in a pre- and post-test study. Forty patients reporting myofascial pain related to the arteriovenous (AV) fistula in the arm during regular HD sessions will be recruited. Participants will receive 4 weeks of treatment with Juan Bi Tang (JBT) and 4 weeks of no treatment in a random order, separated by a washout period of 2 weeks. Treatment doses (3 g JBT) will be consumed thrice daily. The primary outcome measure will be the Kidney Disease Quality of Life 36-Item Short-Form Survey. Secondary outcomes will include the Fugl-Meyer Assessment-arm, Visual Analogue Scale (VAS) of pain, and grip strength. Outcomes will be collected before and after each intervention, for a total of four times per participant. The safety evaluation will focus on adverse events (AEs).

Discussion

This study will be the first to use CHM to treat patients receiving HD with dialysis-related myofascial pain in their fistula arm and to perform a complete assessment of the treatment, including records of QOL, arm function and muscle power, severity of pain, and safety. The results of the study will provide convincing evidence on the use of JBT as an adjuvant treatment for dialysis-related myofascial pain.

Trial registration

Clinicaltrials.govregistry (NCT04417101) registered 30 May 2020.
“How PrEPared are you?”: Knowledge of and attitudes toward PrEP among overseas-born and newly arrived gay, bisexual, and other men who have sex with men in Australia
Authors: Sudarto Budiadi , Chow Eric P. F. , Medland Nicholas , Fairley Christopher K. , Wright Edwina J. , Armishaw Jude , Price Brian , Phillips Tiffany R. , Ong Jason J.
Published: August 2022

Introduction

Overseas-born and newly arrived gay and bisexual men and men who have sex with men (GBMSM) are at higher risk of acquiring HIV in comparison to Australian-born GBMSM. Pre-exposure prophylaxis (PrEP) is subsidized by the Australian government under Medicare, Australia's universal health insurance scheme, however many members of this population are Medicare-ineligible, which could prevent them from accessing PrEP. We wanted to explore participants' knowledge of and attitudes toward PrEP and their opinions of new PrEP modalities, namely injectable PrEP and PrEP implants.

Methods

We conducted in-depth qualitative interviews between February 2021 to September 2021 with 22 overseas-born, newly arrived (<5 years in Australia) GBMSM of varying PrEP use. We asked their opinions of PrEP and their preferences of new PrEP modalities. Interviews were audio recorded and transcribed verbatim. We conducted a reflexive thematic analysis to interpret the data.

Results

Participants' views reflect the intersections between systemic factors, such as Medicare ineligibility and the high cost of PrEP, with socio-cultural factors, such as lack of knowledge about PrEP, internalized stigma stemming from homo- and sex-negativity, and stigmatizing attitudes toward PrEP and PrEP users. For participants who were on PrEP, being community connected, having a positive relationship with doctors and nurses, and being informed of the option to purchase PrEP from overseas pharmacies at a low cost helped them to overcome some of these barriers. Additionally, there was a strong preference for injectable PrEP but not PrEP implants. Participants stressed the importance of providing a comprehensive information about PrEP specific to this population and to make PrEP free for all.

Conclusions

We concluded that resources about PrEP specific to this population that address both systemic and socio-cultural factors are needed, and for these resources to be available in languages other than English. This is to coincide with on-going advocacy to increase the capacity of publicly funded sexual health clinics to provide multilingual PrEP services for people without Medicare, and to make PrEP free for all. These combined strategies have the potential to increase PrEP knowledge and uptake among this population.
Influence of perceived importance of the internet on life satisfaction and health of the older people: An analysis based on intermediary and moderating effects
Authors: Gao Kai , Jiang Mao-min , Wu Zheng-yu , Guo Pei-pei
Published: August 2022

With the global growth of the aging population, healthy aging and active aging has become an important goal for the future social development of all countries. The purpose of this study is to explore the potential relationships between the older people's perceived importance of the Internet, family atmosphere, behavioral independence, life satisfaction, and health. The data come from the China Family Panel Studies' fourth wave (2015–2016) and fifth wave (2017–2018) investigations. According to an analysis of data of 5,948 people over 60 years old performed using LISREL 8.8 software, the selected cases answered the same questions about the perceived importance of the Internet, life satisfaction, and health status in two waves of surveys. The results show that life satisfaction and self-rated health have cross influences, while at the same time both are persistent in the time baseline, and family atmosphere and behavioral independence play an important intermediary role. Therefore, strengthening parent–child interaction, promoting parent–child relationships, and improving behavioral independence can effectively improve the life satisfaction and health status of the older people.
Determinants of observing health protocols related to preventing COVID-19 in adult women: A qualitative study in Iran
Authors: Yoosefi Lebni Javad , Pavee Saeede , Saki Mandana , Ziapour Arash , Ahmadi Ahmad , Khezeli Mehdi
Published: August 2022

Background

The best way to prevent COVID-19 is to observe health protocols. Therefore, identifying the reasons of following these protocols in order to plan and make intervention seems necessary. Therefore, the purpose of this study was to identify the determinants of observing health protocols related to prevention of COVID-19 among the Iranian adult women with a qualitative approach.

Method

In this qualitative study, the conventional content analysis approach was used. saturation was obtained after face-to-face semi-structured interviews with 38 women from Kermanshah who were selected through purposeful sampling and snowball sampling. Guba and Lincoln criteria were used for the strength of the research and Graneheim and Lundman method was used for its analysis.

Results

After analyzing the interviews, 5 categories, 12 subcategories and 110 initial codes were obtained. Categories and sub-categories were: 1- Individual factors (personality traits, health literacy about COVID-19); 2- Perceived risk having underlying disease in oneself and family, history of getting COVID-19 and death in close relatives; 3- Fear of the destructive consequences of the disease (concern about the economic consequences of getting the disease, concern about the treatment process); 4- Social and cultural factors (social monitoring, religious insight, ability to properly manage social interactions, impressionability from important others); 5- Environmental factors (supportive living environment, access to health and anti-infective materials).

Conclusion

Increasing the adherence of adult women to health instructions related to COVID-19 requires interventions at different levels of individual, environmental and social, and without accurate knowledge of the customs and culture of a society effective interventions cannot be established.
Research trends and hotspots of COVID-19 impact on sexual function: A bibliometric analysis based on Web of Science
Authors: Xie Xiaodu , Lei Pan , Liu Lumiao , Hu Jian , Liang Peihe
Published: August 2022

Background

The outbreak of coronavirus disease 2019 (COVID-19) has brought indelible harms to the world and aroused great concern worldwide. This paper aims to analyze the impact of COVID-19 on sexual function using bibliometrics, and summarize research hotspots in this field.

Methods

Relevant publications concerning the impact of COVID-19 on sexual function in the Web of Science collection database (WoSCC) between January 1, 2020 and March 12, 2022 were screened and analyzed by bibliometric analysis using the visualization software CiteSpace and VOSviewer.

Results

Of the 1,054 publications screened, the United States (US) contributed the most (398/37.8%), followed by the United Kingdom (UK) (119/11.3%). Among all institutions, the University of Toronto in Canada enjoyed the largest number of publications (30), and Johns Hopkins University in the US enjoyed the highest frequency of citation (235). The journal INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH published the largest number of studies in this field (31), and the most-cited journal was LANCET. “Chow, Eric,” “Ong, Jason J,” and “Stephenson, Rob” tied for first place in publications (8), and “Fish, Jessica N.” enjoyed the highest number of citations (99). Burstness analysis of references and keywords showed that the developing research trends in this field mainly focused on “sexual transmission” and “angiotensin converting-enzyme 2 (ACE2)” during the COVID-19 pandemic.

Conclusion

The impact of COVID-19 on sexual function remains an urgent concern at present, and the management of sexual health during the pandemic needs to be further improved. More frequent and deeper cooperation between countries and institutions is required in future. Meanwhile, searching for more evidence on whether COVID-19 can achieve sexual transmission and the pathophysiological mechanisms underlying the impact of COVID-19 on sexual function remains a focus of research in the coming years.
Age-dependent accumulation of tau aggregation in Caenorhabditis elegans
Authors: Aquino Nunez Wendy , Combs Benjamin , Gamblin T. Chris , Ackley Brian D.
Published: August 2022

Aging is the primary risk factor for Alzheimer’s disease (AD) and related disorders (ADRDs). Tau aggregation is a hallmark of AD and other tauopathies. Even in normal aging, tau aggregation is found in brains, but in disease states, significantly more aggregated tau is present in brain regions demonstrating synaptic degeneration and neuronal loss. It is unclear how tau aggregation and aging interact to give rise to the phenotypes observed in disease states. Most AD/ADRD animal models have focused on late stages, after significant tau aggregation has occurred. There are fewer where we can observe the early aggregation events and progression during aging. In an attempt to address this gap, we created C. elegans models expressing a GFP-tagged version of the human tau protein. Here we examined how tau-gfp behaved during aging, comparing wild-type tau (hTau40), a disease-associated mutation (P301S), and an aggregation-prone variant (3PO). We measured age-dependent changes in GFP intensity and correlated those changes to normal aging in the nematode. We found differences in tau stability and accumulation depending on the tau variant expressed. hTau40GFP and P301SGFP were localized to axons and cell bodies, while 3POGFP was more concentrated within cell bodies. Expression of 3POGFP resulted in decreased lifespan and variations in locomotor rate, consistent with a pathological effect. Finally, we found that the human tau interacted genetically with the C. elegans ortholog of human tau, ptl-1, where the loss of ptl-1 significantly accelerated the time to death in animals expressing 3PO.