bluuebunny/crossref_metadata_2025 huggingface dataset:
Integration of network pharmacology and molecular docking to explore the molecular mechanism of Cordycepin in the treatment of Alzheimer’s disease
Authors: Ma Xiaoying , Zhao Ying , Yang Tao , Gong Na , Chen Xun , Liu Guoli , Xiao Jun
Published: December 2022

Background

Cordycepin is a nucleoside adenosine analog and an active ingredient isolated from the liquid fermentation of Cordyceps. This study sought to explore the mechanism underlying the therapeutic effect of Cordycepin against Alzheimer’s disease using network pharmacology and molecular docking technology.

Methods

TCMSP, SYMMAP, CTD, Super-pred, SEA, GeneCards, DisGeNET database, and STRING platform were used to screen and construct the target and protein interaction network of Cordycepin for Alzheimer’s disease. The results of Gene Ontology annotation and KEGG pathway enrichment analysis were obtained based on the DAVID database. The Omicshare database was also applied in GO and KEGG pathway enrichment analysis of the key targets. The protein–protein interaction network was constructed using the STRING database, and the potential effective targets for AD were screened based on the degree values. The correlation between the potential targets of Cordycepin in the treatment of AD and APP, MAPT, and PSEN2 was analyzed using (GEPIA) databases. We obtained potential targets related to aging using the Aging Altas database. Molecular docking analysis was performed by AutoDock Vina and Pymol software. Finally, we validated the significant therapeutic targets in the Gene Expression Omnibus (GEO) database.

Results

A total of 74 potential targets of Cordycepin for treating Alzheimer’s disease were identified. The potential targets of Cordycepin for the treatment of AD mainly focused on Lipid and atherosclerosis (hsa05417), Platinum drug resistance (hsa01524), Apoptosis (hsa04210), and Pathways in cancer (hsa05200). Our findings suggest that the therapeutic effect of Cordycepin on AD is primarily associated with these biological processes. We obtained 12 potential therapeutic targets for AD using the degree value in Cytoscape. Interestingly, AKT1, MAPK8, BCL2L1, FOXO3, and CTNNB1 were not only significantly associated with pathogenic genes (APP, MAPT, and PSEN2) but also with longevity in Alzheimer’s Disease. Thus we speculated that the five target genes were potential core targets mediating the therapeutic effect of Cordycepin against AD. Moreover, molecular docking results analysis showed good binding affinity between Cordycepin and the five core targets. Overall, MAPK8, FOXO3 and CTNNB1 may have significant clinical and treatment implications.

Conclusion

Network pharmacology demonstrated that Cordycepin exerts a therapeutic effect against Alzheimer’s disease via multiple targets and signaling pathways and has huge prospects for application in treating neurodegenerative diseases.
Analysis of microglial BDNF function and expression in the motor cortex
Authors: Honey Diana , Wosnitzka Erin , Klann Eric , Weinhard Laetitia
Published: December 2022

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that regulates several aspects of brain function. Although numerous studies have demonstrated the expression and function of BDNF in neurons, its expression in microglia remains controversial. Using a combination of genetic tools and fluorescence imaging, we analyzed BDNF expression patterns and investigated the effect of microglial Bdnf deletion on neuronal activity, early-stage spine formation, and microglia-neuron attraction in the motor cortex. We did not detect BDNF expression in microglia at the transcriptional or translational level, in physiological or pathological conditions, and none of the assessed neuronal functions were found to be affected in conditional Bdnf knockout mice. Our results suggest that microglia do not express BDNF in sufficient amounts to modulate neuronal function.
Veteran-derived cerebral organoids display multifaceted pathological defects in studies on Gulf War Illness
Authors: Yates Philip L. , Case Kendra , Sun Xiaohuan , Sullivan Kimberly , Baas Peter W. , Qiang Liang
Published: December 2022

Approximately 30% of the veterans who fought in the 1991 Gulf War (GW) suffer from a disease called Gulf War Illness (GWI), which encompasses a constellation of symptoms including cognitive deficits. A coalescence of evidence indicates that GWI was caused by low-level exposure to organophosphate pesticides and nerve agents in combination with physical stressors of the battlefield. Until recently, progress on mechanisms and therapy had been limited to rodent-based models. Using peripheral blood mononuclear cells from veterans with or without GWI, we recently developed a bank of human induced pluripotent stem cells that can be differentiated into a variety of cellular fates. With these cells, we have now generated cerebral organoids, which are three-dimensional multicellular structures that resemble the human brain. We established organoid cultures from two GW veterans, one with GWI and one without. Immunohistochemical analyses indicate that these organoids, when treated with a GW toxicant regimen consisting of the organophosphate diisopropyl fluorophosphate (a sarin analog) and cortisol (to mimic battlefield stress), display multiple indicators consistent with cognitive deficits, including increased astrocytic reactivity, enhanced phosphorylation of tau proteins, decreased microtubule stability, and impaired neurogenesis. Interestingly, some of these phenotypes were more pronounced in the organoids derived from the veteran with GWI, potentially reflecting a stronger response to the toxicants in some individuals compared to others. These results suggest that veteran-derived human cerebral organoids not only can be used as an innovative human model to uncover the cellular responses to GW toxicants but can also serve as a platform for developing personalized medicine approaches for the veterans.
Preservation of EEG spectral power features during simultaneous EEG-fMRI
Authors: Gallego-Rudolf Jonathan , Corsi-Cabrera María , Concha Luis , Ricardo-Garcell Josefina , Pasaye-Alcaraz Erick
Published: December 2022

Introduction

Electroencephalographic (EEG) data quality is severely compromised when recorded inside the magnetic resonance (MR) environment. Here we characterized the impact of the ballistocardiographic (BCG) artifact on resting-state EEG spectral properties and compared the effectiveness of seven common BCG correction methods to preserve EEG spectral features. We also assessed if these methods retained posterior alpha power reactivity to an eyes closure-opening (EC-EO) task and compared the results from EEG-informed fMRI analysis using different BCG correction approaches.

Method

Electroencephalographic data from 20 healthy young adults were recorded outside the MR environment and during simultaneous fMRI acquisition. The gradient artifact was effectively removed from EEG-fMRI acquisitions using Average Artifact Subtraction (AAS). The BCG artifact was corrected with seven methods: AAS, Optimal Basis Set (OBS), Independent Component Analysis (ICA), OBS followed by ICA, AAS followed by ICA, PROJIC-AAS and PROJIC-OBS. EEG signal preservation was assessed by comparing the spectral power of traditional frequency bands from the corrected rs-EEG-fMRI data with the data recorded outside the scanner. We then assessed the preservation of posterior alpha functional reactivity by computing the ratio between the EC and EO conditions during the EC-EO task. EEG-informed fMRI analysis of the EC-EO task was performed using alpha power-derived BOLD signal predictors obtained from the EEG signals corrected with different methods.

Results

The BCG artifact caused significant distortions (increased absolute power, altered relative power) across all frequency bands. Artifact residuals/signal losses were present after applying all correction methods. The EEG reactivity to the EC-EO task was better preserved with ICA-based correction approaches, particularly when using ICA feature extraction to isolate alpha power fluctuations, which allowed to accurately predict hemodynamic signal fluctuations during the EEG-informed fMRI analysis.

Discussion

Current software solutions for the BCG artifact problem offer limited efficiency to preserve the EEG spectral power properties using this particular EEG setup. The state-of-the-art approaches tested here can be further refined and should be combined with hardware implementations to better preserve EEG signal properties during simultaneous EEG-fMRI. Existing and novel BCG artifact correction methods should be validated by evaluating signal preservation of both ERPs and spontaneous EEG spectral power.
Association between probiotic, prebiotic, and yogurt consumption and chronic kidney disease: The NHANES 2010–2020
Authors: Liu Xiaoxian , Gao Wenyan , Yang Jie , Mao Genxiang , Lu Hong , Xing Wenmin
Published: December 2022

Background

Previous studies suggested that gut dysbacteriosis may promote the occurrence of chronic kidney disease (CKD), and probiotic, prebiotic, or yogurt supplements may alleviate CKD progression. This study aims to examine the association between probiotic, prebiotic, or yogurt supplements and the risk of CKD using the data from NHANES.

Methods

This study was designed to prospectively search data from the National Health and Nutrition Examination Survey (NHANES) (2011–2020). We examined dietary supplements and prescription medication labels to identify probiotic, or prebiotic product, and yogurt consumption during the dietary interview. The diagnosis of CKD was determined by the value of glomerular filtration rate (eGFR) and albumin creatinine ratio (ACR).

Results

The study enrolled a total of 6,522 individuals. The prevalence of CKD was lower in the probiotic, prebiotic, or yogurt consumption group [age-adjusted odds ratio (OR): 0.77, 95% CI: 0.62–0.95, P = 0.02; multivariable-adjusted OR: 0.86, 95% CI: 0.69–1.07, P = 0.05]. Furthermore, 32% reduced risk was observed in the older group aged 55 years or older, and 32% reduced risk was also observed in the female population. Probiotic, or prebiotic, or yogurt supplements was associated a 12% reduction in moderate risk of CKD and an 11% reduction in very high risk of CKD.

Conclusion

Our results suggest that probiotic, prebiotic, or yogurt supplements may contribute to the prevention of CKD and relieve its progression risk, especially in the female population and older population who were aged 55 years or older.
Detecting plasma hsa_circ_0061276 in patients with gastric cancer by reverse transcription-digital polymerase chain reaction
Authors: Ruan Yao , Li Zhe , Xie Yaoyao , Sun Weiliang , Guo Junming
Published: December 2022

Background

The role of circular RNAs (circRNAs) in the occurrence of gastric cancer is still unclear. Therefore, the diagnostic value and mechanisms underlying hsa_circ_0061276 in the occurrence of gastric cancer were explored.

Methods

Reverse transcription-droplet digital polymerase chain reaction was used to detect the copy number of hsa_circ_0061276 in plasma from healthy individuals, as well as from patients with gastric precancerous lesions or early-stage or advanced gastric cancer. Plasmids overexpressing or knocking down hsa_circ_0061276 expression were transfected into gastric cancer cells. The effects on the growth, migration, and cell cycle distribution of gastric cancer cells were then analyzed. Finally, miRanda and RNAhybrid were used to explore the binding sites between hsa_circ_0061276 and microRNAs (miRNAs). A double luciferase reporter gene assay was used to confirm the miRNA sponge effect.

Results

The results show that plasma hsa_circ_0061276 copy number showed a trend of a gradual decrease when comparing healthy controls to the early cancer group and advanced gastric cancer group. Overexpression of hsa_circ_0061276 inhibited the growth and migration of gastric cancer cells. Through bioinformatic analyses combined with cellular experiments, it was found that hsa_circ_0061276 inhibited the growth of gastric cancer by binding to hsa-miR-7705.

Conclusion

Hsa_circ_0061276 may be a new biomarker for gastric cancer. The tumor suppressor role of hsa_circ_0061276 on gastric cancer likely occurs through a sponge effect on miRNAs such as hsa-miR-7705.
Preclinical profiles of SKB264, a novel anti-TROP2 antibody conjugated to topoisomerase inhibitor, demonstrated promising antitumor efficacy compared to IMMU-132
Authors: Cheng Yezhe , Yuan Xiaoxi , Tian Qiang , Huang Xiuying , Chen Yang , Pu Yuzhi , Long Hu , Xu Mingyu , Ji Yafei , Xie Jia , Tan Yuping , Zhao Xi , Song Hongmei
Published: December 2022

Purpose

The aim of this study was to improve the intratumoral accumulation of an antibody–drug conjugate (ADC) and minimize its off-target toxicity, SKB264, a novel anti-trophoblast antigen 2 (TROP2) ADC that was developed using 2-methylsulfonyl pyrimidine as the linker to conjugate its payload (KL610023), a belotecan-derivative topoisomerase I inhibitor. The preclinical pharmacologic profiles of SKB264 were assessed in this study.

Methods

The in vitro and in vivo pharmacologic profiles of SKB264, including efficacy, pharmacokinetics–pharmacodynamics (PK-PD), safety, and tissue distribution, were investigated using TROP2-positive cell lines, cell-derived xenograft (CDX), patient-derived xenograft (PDX) models, and cynomolgus monkeys. Moreover, some profiles were compared with IMMU-132.

Results

In vitro, SKB264 and SKB264 monoclonal antibody (mAb) had similar internalization abilities and binding affinities to TROP2. After cellular internalization, KL610023 was released and inhibited tumor cell survival. In vivo, SKB264 significantly inhibited tumor growth in a dose-dependent manner in both CDX and PDX models. After SKB264 administration, the serum or plasma concentration/exposure of SKB264 (conjugated ADC, number of payload units ≥1), total antibody (Tab, unconjugated and conjugated mAb regardless of the number of the payload units), and KL610023 in cynomolgus monkeys increased proportionally with increasing dosage from 1 to 10 mg/kg. The linker stability of SKB264 was significantly enhanced as shown by prolonged payload half-life in vivo (SKB264 vs. IMMU-132, 56.3 h vs. 15.5 h). At the same dose, SKB264’s exposure in tumor tissue was 4.6-fold higher than that of IMMU-132.

Conclusions

Compared with IMMU-132, the longer half-life of SKB264 had a stronger targeting effect and better antitumor activity, suggesting the better therapeutic potential of SKB264 for treating TROP2-positive tumors.
The significance of time interval between perioperative SOX/XELOX chemotherapy and clinical decision model in gastric cancer
Authors: Chen Jun-Bing , Liu Zi-Ning , Wang Yin-Kui , Shan Fei , Li Shuang-Xi , Jia Yong-Ning , Xue Kan , Miao Ru-Lin , Li Zhe-Min , Wu Zhou-Qiao , Ying Xiang-Ji , Zhang Yan , Li Zi-Yu , Ji Jia-Fu
Published: December 2022

Introduction

To investigate the influences of time interval between multimodality therapies on survival for locally advanced gastric cancer (LAGC) patients, 627 patients were included in a retrospective study, and 350 who received neoadjuvant chemotherapy (NACT) based on SOX (S-1 plus Oxaliplatin)/XELOX (Capecitabine plus Oxaliplatin) treatment, radical surgery, and adjuvant chemotherapy (AC) from 2005.01 to 2018.06 were eligible for analyses.

Methods

Three factors were used to assess influences, including time interval from NACT accomplishment to AC initiation (PECTI), time to surgery after NACT accomplishment (TTS), and time to adjuvant chemotherapy after surgery (TAC).

Results

Concerning PECTIs, 99 (28.29%) experienced it within 9 weeks, 188 (53.71%) within 9–13 weeks, 63 (18.00%) over 13 weeks. Patients’ 5-year overall survival (OS) significantly decreased as trichotomous PECTI increased (78.6% vs 66.7% vs 55.7%, P = .02). Analogously, there was a significant decrease for dichotomous TTS (within vs over 5 weeks) in OS (P = .03) and progression free survival (PFS) (P = .01) but not for dichotomous TAC (within vs over 6 weeks) in OS and PFS (P = .40). Through multivariate Cox analyses, patients with PECTI over 13 weeks had significantly worse OS (P = .03) and PFS (P = .02). Furthermore, extended TTS had significantly worse OS and PFS but insignificantly worse OS and PFS than extended TAC. Therefore, gastric patients receiving perioperative SOX/XELOX chemotherapy and surgery with extended PECTI over 9 weeks or TTS over 5 weeks would have a negative correlation with PFS and OS, and worse when PECTI over 13 weeks. Nomograms (including PECTI, ypT, ypN, Area Under Curve (AUC) = 0.81) could predict patient survival probability and guide intervention with net benefit.

Discussion

In control of PECTI, TTS could be extended appropriately, and shortened TAC might make a remedy, and delayed TAC might be allowed when TTS was shortened.
Endoscopic endonasal resection of an epidermoid cyst in the cavernous sinus: A case report and literature review
Authors: Wu Yinzi , Li Zhimin , Gao Jun , Yao Yong , Wang Renzhi , Bao Xinjie
Published: December 2022

Background

Epidermoid cysts of cavernous sinus (CS) are rare congenital neoplasms of the central nervous system. In previous literature reports, the treatment for CS epidermoid cysts was mainly microsurgical resection, and the surgical methods included simple microsurgery and endoscope-assisted microsurgery. The present case report demonstrates the first case of complete resection of a CS epidermoid cyst by a simple endoscopic endonasal transcavernous (EET) approach.

Case presentation

A 54-year-old woman presented with chronic persistent headaches and occasional syncope. Brain MRI demonstrated a space-occupying lesion of the left CS, and digital substruction angiography (DSA) showed a small aneurysm at the beginning of the left ophthalmic artery. Thrombotic therapy of carotid–ophthalmic aneurysms was performed first, and the patient underwent resection of the CS lesion secondary. Considering the location of the lesion and the neuroendoscopy technology and experience of the doctor, we made bold innovations and used an EET approach to achieve complete resection of the lesion. The postoperative pathological results were consistent with the characteristics of epidermoid cyst. During the 1-year follow up, the patient showed no apparent signs of recurrence on head MRI.

Conclusion

Epidermoid cyst of cavernous sinus is a rare benign occupying lesion in cavernous sinus. Reviewing the previous literature, the main treatment is microneurosurgery, and neuroendoscopy is only used as an auxiliary equipment. We present the first case of complete endoscopic resection of CS epidermoid cyst by EET approach according to CARE guidelines, aiming to share the new surgical plan for CS epidermoid cyst and provide more surgical options for this disease for neurosurgery colleagues.
Knowledge, attitudes, and practices towards artificial intelligence among young pediatricians: A nationwide survey in France
Authors: Perrier Emma , Rifai Mahmoud , Terzic Arnaud , Dubois Constance , Cohen Jérémie F.
Published: December 2022

Objective

To assess the knowledge, attitudes, and practices (KAP) towards artificial intelligence (AI) among young pediatricians in France.

Methods

We invited young French pediatricians to participate in an online survey. Invitees were identified through various email listings and social media. We conducted a descriptive analysis and explored whether survey responses varied according to respondents’ previous training in AI and level of clinical experience (i.e., residents vs. experienced doctors).

Results

In total, 165 French pediatricians participated in the study (median age 27 years, women 78%, residents 64%). While 90% of participants declared they understood the term “artificial intelligence”, only 40% understood the term “deep learning”. Most participants expected AI would lead to improvements in healthcare (e.g., better access to healthcare, 80%; diagnostic assistance, 71%), and 86% declared they would favor implementing AI tools in pediatrics. Fifty-nine percent of respondents declared seeing AI as a threat to medical data security and 35% as a threat to the ethical and human dimensions of medicine. Thirty-nine percent of respondents feared losing clinical skills because of AI, and 6% feared losing their job because of AI. Only 5% of respondents had received specific training in AI, while 87% considered implementing such programs would be necessary. Respondents who received training in AI had significantly better knowledge and a higher probability of having encountered AI tools in their medical practice (p < 0.05 for both). There was no statistically significant difference between residents’ and experienced doctors’ responses.

Conclusion

In this survey, most young French pediatricians had favorable views toward AI, but a large proportion expressed concerns regarding the ethical, societal, and professional issues linked with the implementation of AI.
Effect of Pheretima aspergillum on reducing fibrosis: A systematic review and meta-analysis
Authors: Xu Tianren , Liu Xiaonan , Wang Shengguang , Kong Hongwei , Yu Xiaojun , Liu Congying , Song Huaying , Gao Peng , Zhang Xin
Published: December 2022

Background:Pheretima aspergillum (common name: Earthworm, Chinese name: dilong) has been used in traditional Chinese medicine for thousands of years. Recently, a few scientific studies have investigated the antifibrotic effects of Dilong extract (DE) and produced controversial results. We conducted a meta-analysis to make an informed decision on the antifibrotic effects of Dilong extract.

Methods: The studies on antifibrotic effects of Dilong extract published until July 2022 in the scientific databases [PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), VIP database for Chinese Technical Periodicals, SinoMed and WanFang database] were reviewed. The RevMan 5.4.1 software was used for standardized mean difference (SMD) analysis. Two researchers independently reviewed all the studies, and their quality was assessed using the Cochrane risk of bias tool.

Results: A total of 325 studies were found in the scientific databases; however, only 13 studies met the criteria for analysis. Dilong extract treatment was associated with antifibrotic effects via inhibiting the transforming growth factor beta 1 (TGF-β1, SMD = −3.16, 95% CI: −4.18, −2.14, p < .00001) and alpha-smooth muscle actin (α-SMA: SMD = −2.57, 95% CI: −3.47, −1.66, p < .00001).

Conclusion: Dilong extract effectively reduces tissue fibrosis; thus, further scientific studies should be conducted to investigate and develop it for clinical use.

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifier CRD42022357141.
Red ginseng extract improves skeletal muscle energy metabolism and mitochondrial function in chronic fatigue mice
Authors: Zhang Haijing , Zhao Chunhui , Hou Jinli , Su Ping , Yang Yifei , Xia Bing , Zhao Xiaoang , He Rong , Wang Lifang , Cao Chunyu , Liu Ting , Tian Jixiang
Published: December 2022

Background: Skeletal muscles are organs with high energy requirements, especially during vigorous exercise. Adequate mitochondrial function is essential to meet the high energy needs of skeletal muscle cells. Recent studies have reported that red ginseng can significantly improve chronic fatigue; however, the specific mechanism of action is still not clear.

Methods: A chronic fatigue syndrome mouse model was developed using C57BL/6J mice through long-term compound stimulation of stress factors. Following this, the animals were orally administered 200, 400, or 600 mg/kg red ginseng extracts for 28 days. Skeletal muscle lactate acid, serum lactate dehydrogenase, urea concentrations, ATP level, mitochondrial membrane potential, activities of Na+-K+-ATPase and cytochrome c oxidase were determined using assay kits or an automatic biochemical analyser detection system. Skeletal muscle mitochondria morphology was observed using electron microscopy and the expression of p-AMPK, PGC-1α, ACO2 and complex I in skeletal muscle protein was determined by western blotting.

Results: Oral administration of 400 or 600 mg/kg red ginseng extract in mice with chronic fatigue reduced lactic acid, lactate dehydrogenase and urea, rescued the density and morphology of skeletal muscle mitochondria, increased the activities of Na+-K+-ATPase and cytochrome c oxidase, and activated the AMPK/PGC-1α cascade pathway, resulting in improved skeletal muscle mitochondrial function by restoring ATP level, mitochondrial membrane potential, complex I and mitochondrial biogenesis.

Conclusion: The anti-fatigue effects of red ginseng are partly related to its potent mitochondrial improving activity, including decreasing mitochondrial swelling and mitochondrial membrane permeability, increasing mitochondrial biogenesis, thus ameliorating mitochondrial dysfunction.
Multiple airy beams light-sheet fluorescence microscopy
Authors: Gu Shuangyu , Yu Xianghua , Bai Chen , Min Junwei , Li Runze , Yang Yanlong , Yao Baoli
Published: December 2022

Light-sheet fluorescence microscopy (LSFM) is a kind of volumetric imaging methodology suited for long term living specimens at high temporal-spatial resolution. A single Airy beam (SAB) light-sheet can extend the field of view of Light-sheet fluorescence microscopy benefiting from its non-diffracting nature, but at the cost of out-of-focus background and low imaging contrast caused by side lobes illumination. Here, we propose a method to generate a sort of multiple Airy beams (MAB), which are linearly superimposed of multiple single Airy beams with different scale factors. Compared to the SAB light-sheet, the energy of the multiple Airy beams light-sheet is more concentrated on the focal plane of the detection objective, which can improve the imaging contrast and decrease the photodamage effect. Furthermore, we combined the complementary beam subtraction (CBS) strategy to increase the axial resolution, termed as multiple Airy beams-complementary beam subtraction method, which enables the axial resolution of 1.2 μm while keeping the field of view of 450 μm × 450 μm. The effectiveness of the method is demonstrated by imaging of fluorescent beads and aspergillus conidiophores.
TRPC1 channels underlie stretch-modulated sarcoplasmic reticulum calcium leak in cardiomyocytes
Authors: Streiff Molly E. , Corbin Andrea C. , Ahmad Azmi A. , Hunter Chris , Sachse Frank B.
Published: December 2022

Transient receptor potential canonical 1 (TRPC1) channels are Ca2+-permeable ion channels expressed in cardiomyocytes. An involvement of TRPC1 channels in cardiac diseases is widely established. However, the physiological role of TRPC1 channels and the mechanisms through which they contribute to disease development are still under investigation. Our prior work suggested that TRPC1 forms Ca2+ leak channels located in the sarcoplasmic reticulum (SR) membrane. Prior studies suggested that TRPC1 channels in the cell membrane are mechanosensitive, but this was not yet investigated in cardiomyocytes or for SR localized TRPC1 channels. We applied adenoviral transfection to overexpress or suppress TRPC1 expression in neonatal rat ventricular myocytes (NRVMs). Transfections were evaluated with RT-qPCR, western blot, and fluorescent imaging. Single-molecule localization microscopy revealed high colocalization of exogenously expressed TRPC1 and the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA2). To test our hypothesis that TRPC1 channels contribute to mechanosensitive Ca2+ SR leak, we directly measured SR Ca2+ concentration ([Ca2+]SR) using adenoviral transfection with a novel ratiometric genetically encoded SR-targeting Ca2+ sensor. We performed fluorescence imaging to quantitatively assess [Ca2+]SR and leak through TRPC1 channels of NRVMs cultured on stretchable silicone membranes. [Ca2+]SR was increased in cells with suppressed TRPC1 expression vs. control and Transient receptor potential canonical 1-overexpressing cells. We also detected a significant reduction in [Ca2+]SR in cells with Transient receptor potential canonical 1 overexpression when 10% uniaxial stretch was applied. These findings indicate that TRPC1 channels underlie the mechanosensitive modulation of [Ca2+]SR. Our findings are critical for understanding the physiological role of TRPC1 channels and support the development of pharmacological therapies for cardiac diseases.
Gut microbiota contributes to lignocellulose deconstruction and nitrogen fixation of the larva of Apriona swainsoni
Authors: Zhang Lei , Zhuang Tian , Hu Mengxue , Liu Shuwen , Wu Daqiang , Ji Baozhong
Published: December 2022

Apriona swainsoni is a vital forest pest prevalent in China. The larvae of A. swainsoni live solely in the branches of trees and rely entirely on the xylem for nutrition. However, there is still a lack of in-depth research on the gut microbiota’s use of almost nitrogen-free wood components to provide bio-organic macromolecular components needed for their growth. Thus, in this study, the metagenome, metaproteome, and metabolome of the A. swainsoni larvae in four gut segments (foregut; midgut; anterior hindgut; posterior hindgut) were analyzed by the multi-omics combined technology, to explore the metabolic utilization mechanism of the corresponding gut microbiota of A. swainsoni. Firstly, we found that the metagenome of different gut segments was not significantly different in general, but there were different combinations of dominant bacteria and genes in different gut segments, and the metaproteome and metabolome of four gut segments were significantly different in general. Secondly, the multi-omics results showed that there were significant gradient differences in the contents of cellulose and hemicellulose in different segments of A. swainsoni, and the expression of corresponding metabolic proteins was the highest in the midgut, suggesting the metabolic characteristics of these lignocellulose components in A. swainsoni gut segments. Finally, we found that the C/N ratio of woody food was significantly lower than that of frass, and metagenomic results showed that nitrogen fixation genes mainly existed in the foregut and two hindgut segments. The expression of the key nitrogen fixing gene nifH occurred in two hindgut parts, indicating the feature of nitrogen fixation of A. swainsoni. In conclusion, our results provide direct evidence that the larvae of A. swainsoni can adapt to the relatively harsh niche conditions through the highly organized gut microbiome in four gut segments, and may play a major role in their growth.
Comparative transcriptomics and genomic analyses reveal differential gene expression related to Colletotrichum brevisporum resistance in papaya (Carica papaya L.)
Authors: Yang Min , Zhou Chenping , Yang Hu , Kuang Ruibin , Liu Kaidong , Huang Bingxiong , Wei Yuerong
Published: December 2022

Colletotrichum brevisporum is an important causal pathogen of anthracnose that seriously affects the fruit quality and yield of papaya (Carica papaya L.). Although many genes and biological processes involved in anthracnose resistance have been reported in other species, the molecular mechanisms involved in the response or resistance to anthracnose in post-harvest papaya fruits remain unclear. In this study, we compared transcriptome changes in the post-harvest fruits of the anthracnose-susceptible papaya cultivar Y61 and the anthracnose-resistant cultivar G20 following C. brevisporum inoculation. More differentially expressed genes (DEGs) and differentially expressed long non-coding RNAs (DElnRNAs) were identified in G20 than in Y61, especially at 24 h post-inoculation (hpi), suggesting a prompt activation of defense responses in G20 in the first 24 h after C. brevisporum inoculation. These DEGs were mainly enriched in plant-pathogen interaction, phenylpropanoid biosynthesis/metabolism, and peroxisome and flavonoid biosynthesis pathways in both cultivars. However, in the first 24 hpi, the number of DEGs related to anthracnose resistance was greater in G20 than in Y61, and changes in their expression levels were faster in G20 than in Y61. We also identified a candidate anthracnose-resistant gene cluster, which consisted of 12 genes, 11 in G20 and Y61, in response to C. brevisporum inoculation. Moreover, 529 resistance gene analogs were identified in papaya genome, most of which responded to C. brevisporum inoculation and were genetically different between papaya cultivars and wild-type populations. The total expression dose of the resistance gene analogs may help papaya resist C. brevisporum infection. This study revealed the mechanisms underlying different anthracnose resistance between the anthracnose-resistant and anthracnose-susceptible cultivars based on gene expression, and identified some potential anthracnose resistance-related candidate genes/major regulatory factors. Our findings provided potential targets for developing novel genetic strategies to overcome anthracnose in papaya.
Highly efficient Agrobacterium rhizogenes-mediated hairy root transformation for gene editing analysis in cotton
Authors: Zhou Lili , Wang Yali , Wang Peilin , Wang Chunling , Wang Jiamin , Wang Xingfen , Cheng Hongmei
Published: December 2022

CRIPSR/Cas9 gene editing system is an effective tool for genome modification in plants. Multiple target sites are usually designed and the effective target sites are selected for editing. Upland cotton (Gossypium hirsutum L., hereafter cotton) is allotetraploid and is commonly considered as difficult and inefficient to transform, it is important to select the effective target sites that could result in the ideal transgenic plants with the CRISPR-induced mutations. In this study, Agrobacterium rhizogenes-mediated hairy root method was optimized to detect the feasibility of the target sites designed in cotton phytoene desaturase (GhPDS) gene. A. rhizogenes showed the highest hairy root induction (30%) when the bacteria were cultured until OD600 reached to 0.8. This procedure was successfully applied to induce hairy roots in the other three cultivars (TM–1, Lumian–21, Zhongmian–49) and the mutations were detected in GhPDS induced by CRISPR/Cas9 system. Different degrees of base deletions at two sgRNAs (sgRNA5 and sgRNA10) designed in GhPDS were detected in R15 hairy roots. Furthermore, we obtained an albino transgenic cotton seeding containing CRISPR/Cas9-induced gene editing mutations in sgRNA10. The hairy root transformation system established in this study is sufficient for selecting sgRNAs in cotton, providing a technical basis for functional genomics research of cotton.
Wheat potassium transporter TaHAK13 mediates K+ absorption and maintains potassium homeostasis under low potassium stress
Authors: Run Yonghang , Cheng Xiyong , Dou Wei , Dong Yue , Zhang Yanan , Li Bingbing , Liu Tengfei , Xu Haixia
Published: December 2022

Potassium (K) is an essential nutrient for plant physiological processes. Members of the HAK/KUP/KT gene family act as potassium transporters, and the family plays an important role in potassium uptake and utilization in plants. In this study, the TaHAK13 gene was cloned from wheat and its function characterized. Real-time quantitative PCR (RT-qPCR) revealed that TaHAK13 expression was induced by environmental stress and up-regulated under drought (PEG6000), low potassium (LK), and salt (NaCl) stress. GUS staining indicated that TaHAK13 was mainly expressed in the leaf veins, stems, and root tips in Arabidopsis thaliana, and expression varied with developmental stage. TaHAK13 mediated K+ absorption when heterologously expressed in yeast CY162 strains, and its activity was slightly stronger than that of a TaHAK1 positive control. Subcellular localization analysis illustrated that TaHAK13 was located to the plasma membrane. When c(K+) ≤0.01 mM, the root length and fresh weight of TaHAK13 transgenic lines (athak5/TaHAK13, Col/TaHAK13) were significantly higher than those of non-transgenic lines (athak5, Col). Non-invasive micro-test technology (NMT) indicated that the net K influx of the transgenic lines was also higher than that of the non-transgenic lines. This suggests that TaHAK13 promotes K+ absorption, especially in low potassium media. Membrane-based yeast two-hybrid (MbY2H) and luciferase complementation assays (LCA) showed that TaHAK13 interacted with TaNPF5.10 and TaNPF6.3. Our findings have helped to clarify the biological functions of TaHAK13 and established a theoretical framework to dissect its function in wheat.
Fucoidan treatment alleviates chilling injury in cucumber by regulating ROS homeostasis and energy metabolism
Authors: Lin Duo , Yan Ruyu , Xing Mengying , Liao Shuyuan , Chen Jinyin , Gan Zengyu
Published: December 2022

Introduction

Chilling injury is a major hindrance to cucumber fruit quality during cold storage.

Methods and Results

In this study, we evaluated the effects of fucoidan on fruit quality, reactive oxygen species homeostasis, and energy metabolism in cucumbers during cold storage. The results showed that, compared with the control cucumber fruit, fucoidan-treated cucumber fruit exhibited a lower chilling injury index and less weight loss, as well as reduced electrolyte leakage and malondialdehyde content. The most pronounced effects were observed following treatment with fucoidan at 15 g/L, which resulted in increased 1,1-diphenyl-2-picrylhydrazyl and hydroxyl radical scavenging rates and reduced superoxide anion production rate and hydrogen peroxide content. The expression and activity levels of peroxidase, catalase, and superoxide dismutase were enhanced by fucoidan treatment. Further, fucoidan treatment maintained high levels of ascorbic acid and glutathione, and high ratios of ascorbic acid/dehydroascorbate and glutathione/oxidized glutathione. Moreover, fucoidan treatment increased the activities of ascorbate peroxidase, monodehydroascorbate reductase, dehydroascorbate reductase, and glutathione reductase and their gene expression. Fucoidan treatment significantly delayed the decrease in ATP and ADP, while preventing an increase in AMP content. Finally, fucoidan treatment delayed the decrease of energy charge and the activities and gene expression of H+-ATPase, Ca2+-ATPase, cytochrome c oxidase, and succinate dehydrogenase in cucumber fruits.

Conclusion

Altogether, our findings indicate that fucoidan can effectively enhance antioxidant capacity and maintain energy metabolism, thereby improving cucumber cold resistance during cold storage.
Unexpected resilience in relict Abies pinsapo Boiss forests to dieback and mortality induced by climate change
Authors: Cortés-Molino Álvaro , Linares Juan Carlos , Viñegla Benjamín , Lechuga Víctor , Salvo-Tierra A. Enrique , Flores-Moya Antonio , Fernández-Luque Ismael , Carreira Jose A.
Published: December 2022

Acute and early symptoms of forest dieback linked to climate warming and drought episodes have been reported for relict Abies pinsapo Boiss. fir forests from Southern Spain, particularly at their lower ecotone. Satellite, orthoimages, and field data were used to assess forest decline, tree mortality, and gap formation and recolonization in the lower half of the altitudinal range of A. pinsapo forests (850-1550 m) for the last 36 years (1985-2020). Field surveys were carried out in 2003 and in 2020 to characterize changes in stand canopy structure and mortality rates across the altitudinal range. Time series of the Normalized Difference Vegetation Index (NDVI) at the end of the dry season (derived from Landsat 5 and 7 imagery) were used for a Dynamic Factor Analysis to detect common trends across altitudinal bands and topographic solar incidence gradients (SI). Historical canopy cover changes were analyzed through aerial orthoimages classification. Here we show that extensive decline and mortality contrast to the almost steady alive basal area for 17 years, as well as the rising photosynthetic activity derived from NDVI since the mid-2000s and an increase in the forest canopy cover in the late years at mid and high altitudes. We hypothesized that these results suggest an unexpected resilience in A. pinsapo forests to climate change-induced dieback, that might be promoted by compensation mechanisms such as (i) recruitment of new A. pinsapo individuals; (ii) facilitative effects on such recruitment mediated by revegetation with other species; and (iii) a ‘release effect’ in which surviving trees can thrive with fewer resource competition. Future research is needed to understand these compensation mechanisms and their scope in future climate change scenarios.
The impact of price transparency of bundled vacation packages on travel decision making: An experimental study
Authors: Bai Shizhen , Chu Lingyun , Fam Kim-Shyan , Wei Sheng
Published: December 2022

Price transparency is a vital factor in consumers’ judgements and decisions. When selecting a bundled vacation package, travelers are often influenced by transparency in the prices of individual elements of the package. However, because of the diversity of elements bundled in a vacation package, it is a challenge to research the impact of price transparency. To try to overcome this challenge, our study used five experiments to examine the primary impact of element price transparency on travelers’ purchases, along with the moderating effects of consumer involvement and the vertical position of element prices in product descriptions. For the primary effect, we found that tourists preferred vacation packages with low transparency in element prices. We also found that the primary effect of price transparency remained consistent and robust across both revised and actual vacation packages. For moderating effects, we found that tourists with low involvement attached greater importance to price transparency than those with high involvement when the element price was presented higher in the product description of the travel package. The findings of the five experiments have theoretical implications for price transparency and Heuristic-systematic Model and practical implications for tourism professionals designing and marketing vacation packages.
The effects of bilingualism on cognition and behaviour in individuals with attention deficits: A scoping review
Authors: Köder Franziska , Sharma Curtis , Cameron Sarah , Garraffa Maria
Published: December 2022

Background

Weaknesses in executive function have persistently been found to be associated with Attention Deficit Hyperactivity Disorder (ADHD), while bilinguals have been argued to show advantages in executive functions. While there has been some research into how bilingualism affects cognitive skills and behaviour in individuals with attention deficits, the question is still very much open. The aim of this systematic review is to gather, synthesise and evaluate existing evidence on how bilingual language experience and attention deficits affect executive function performance and ADHD-related symptoms in children and adults.

Methods

Following PRISMA guidelines, a comprehensive literature search in relevant databases (PsycInfo, PubMed, Scopus, ERIC, Web of Science, EMBASE, MEDLINE, LLBA) was performed using search strings related to attention difficulties/ADHD and bilingualism. All quantitative studies were included that presented original empirical data on the combined effects of bilingualism and attention levels, regardless of age group and methodology. The screening procedure revealed nine relevant studies.

Results

Across the nine identified studies, a total of 2071 participants were tested. Of these, seven studies involved children and two adults. The studies varied considerably with respect to their design and methodology, the targeted executive function skills or behavioural symptoms, as well as their measure of bilingualism and attention levels. Most studies assessed aspects of executive function performance such as interference control, response inhibition, working memory or cognitive flexibility. Three studies looked at the effects of bilingualism on ADHD-related symptoms or ADHD diagnosis. Across the studies, no systematic advantage or disadvantage of bilingualism on cognitive performance or behaviour in people with attention deficits was observed.

Conclusion

The limited number of identified studies provide no consistent evidence that bilingualism alleviates or intensifies attention difficulties in adults or children with ADHD. Based on the current state of research, individuals with ADHD and their families should not be concerned that learning additional languages has a negative impact on functioning or cognitive performance.

Systematic review registration

https://doi.org/10.17605/OSF.IO/PK768.
The mediating effect of cognitive and emotional processing on PTSD and depression symptoms reduction in women victims of IPV
Authors: Procaccia Rossella , Castiglioni Marco
Published: December 2022

Intimate partner violence (IPV) is a serious social, physical and mental health issue. Women victims of IPV can develop short- and long-term consequences such as depression and post-traumatic stress disorder (PTSD). Where trauma has been incurred, standard psychotherapies may usefully be complemented by interventions based on expressive writing (EW). Numerous studies have explored the mechanisms underpinning improvement after writing, focusing on the cognitive and emotional processing of traumatic experiences. The aims of this study were to evaluate changes in PTSD and depression symptoms following EW and to examine the mediating effect of emotional and cognitive processing on symptom reduction in subjects who engaged in EW. Seventy-seven abused women (mean age = 41.43, SD = 10.75) were randomly assigned to a three-session expressive writing condition (n = 43) or a neutral writing condition (n = 34). Psychological distress (PTSD and depression) was assessed both before and after the writing sessions. Linguistic inquiry word count software was used to analyze the women’s narratives in relation to emotional processing (positive and negative emotions) and cognitive processing (insight and causal attributions). The mediation model indicated that the reduction in depression was fully mediated by negative emotion processing and partially mediated by cognitive processing, while the reduction in PTSD was partially mediated by negative emotion processing and fully mediated by cognitive processing. No effect of positive emotion processing was found. The clinical implications are discussed.
Functional relevance as a principle of translation problem-solving
Authors: Sang Zhonggang
Published: December 2022

Translation is both an interpretive use of language and problem-solving activity. In his work, Ernst-August Gutt adopts a Relevance-Theoretic approach to unveil the inferential nature of translation as interpretive language use. He holds that in translating a translator aims to seek the interpretive resemblance between the ST (source text) and the TT (target text). However, Gutt does not explain how interpretive resemblance can be achieved when translation problems arise. Textual function refers to the intended cognitive effects that a text yields on the part of the readers. Considering that it is only when the textual outcome of a translation activity is both relevant and functional that it is a successful interpretive use of language, we propose Functional Relevance as a principle of translation problem-solving. Namely, a translator needs to strategize their solutions to translation problems by making the explicatures and implicatures of the TT resemblant enough both to justify its reader’s processing effort and to fulfill the contextualized textual functions of translation. This can be exemplified by two English translations of Chinese medicine pun poems in a pien wen, an archaic literary genre popular in China during the tenth century.