bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinct respiratory microbiota associates with lung cancer clinicopathological characteristics
Authors: Zheng Xi , Lu Xingbing , Hu Yang
Published: February 2023

Introduction

Commensal microbiota dysbiosis is associated with the development of lung cancer. The current studies about composition of respiratory microbiota in lung cancer patients yielded inconsistent results. This study aimed to examine the association between airway microbiota and lung cancer clinicopathological characteristics.

Methods

Surgically removed lesion tissues from 75 non-small cell lung cancer patients and 7 patients with benign pulmonary diseases were analyzed by 16S rRNA sequencing. Taxonomy, relative abundance, and diversity of respiratory microbiota were compared among lung cancer of different pathology and TNM stages. The effects of antibiotic and cigarette exposure on respiratory microbiota in lung cancer patients were also evaluated.

Results

Bacterial relative abundance and alpha- and beta-diversity analysis of lung microbiota showed significant differences among lung cancer of different pathology and benign pulmonary diseases. At the genus level, the abundance differences of 13 taxa between lung squamous cell carcinoma and lung adenocarcinoma, 63 taxa between lung squamous cell carcinoma and benign pulmonary diseases, and 4 taxa between lung adenocarcinoma and benign pulmonary diseases reached statistical significance. In contrast, diversity differences were not as significant across lung cancer of different stages. No significant differences were observed in tissue taxonomic abundances and diversity at all taxonomic levels between lung cancer patients with and without antibiotic exposure 3 months prior to surgery. For lung adenocarcinoma, respiratory bacterial abundance and diversity at all taxonomic levels did not show significant differences between smokers and non-smokers.

Conclusions

Our results confirm significantly differential respiratory microbiome taxa, abundance, and diversity in lung cancer of different pathology and some stages. Short-term antibiotic application might play a minor role in molding airway microbiota in lung cancer patients. Composition and diversity of respiratory microbiota in lung adenocarcinoma are not affected by cigarette exposure.
Effects of plasma-derived exosomes from the normal and thin Bactrian camels on hepatocellular carcinoma and their differences at transcriptome and proteomics levels
Authors: Yao Hongqiang , Yu Siriguleng , Luo Yuchen , Wang Ming , Wang Xiuying , Xu Siriguleng , Chen Yufei , Xie Zhifeng
Published: February 2023

Background

Hepatocellular carcinoma (HCC) is a common malignant primary tumor. Bactrian camels have high economic and social values, but their potential medical value has not been studied. This study aimed to investigate the effects of Bactrian camel plasma-derived exosomes on HCC.

Methods

Plasma was obtained from thin and normal Bactrian camels, and used to isolate exosomes by ultracentrifugation. The exosomes were then characterized by transmission electron microscopy and Nano particle tracking analyzer. In vivo imaging of nude mice and hematoxylin eosin (HE) staining of liver tissues were used to explore the effects of the exosomes on tumor growth. Finally, the differences of the two exosomes were further analyzed using small RNA sequencing and proteomics.

Results

In vivo imaging and HE staining showed that no significant differences were found in fluorescence value and liver tissue morphology between the control mice and the mice treated with the exosomes from thin Bactrian camels; while the fluorescence value and the live histology changes were alleviated in the mice with the exosomes from normal Bactrian camels. After sequencing and proteomic analysis, 40 differentially expressed miRNAs (DE-miRNAs, 15 down-regulated and 25 up-regulated) and 172 differentially expressed proteins (DEPs, 77 up-regulated and 95 down-regulated) were identified in the plasma-derived exosomes from normal Bactrian camels. These identified DE-miRNAs and DEPs were significantly enriched in many signaling pathways.

Conclusions

Normal Bactrian camel plasma-derived exosomes may inhibit the growth of HCC cells through regulating pathways of Ras, Ras-Association Proximate 1 (Rap1), phosphoinositide 3-kinase-protein kinase B (PI3K-Akt), mitogen-activated protein kinase (MAPK), adenosine monophosphate-activated protein kinase (AMPK), and canonical Wnt signaling pathways.
Contribution of microvascular dysfunction to chronic pain
Authors: Coderre Terence J.
Published: February 2023

There is growing evidence that microvascular dysfunction is a pathology accompanying various injuries and conditions that produce chronic pain and may represent a significant contributing factor. Dysfunction that occurs within each component of the microvasculature, including arterioles, capillaries and venules impacts the health of surrounding tissue and produces pathology that can both initiate pain and influence pain sensitivity. This mini review will discuss evidence for a critical role of microvascular dysfunction or injury in pathologies that contribute to chronic pain conditions such as complex regional pain syndrome (CRPS) and fibromyalgia.
Neonatal pain assessment: Do we have the right tools?
Authors: Llerena Amelia , Tran Krystal , Choudhary Danyal , Hausmann Jacqueline , Goldgof Dmitry , Sun Yu , Prescott Stephanie M.
Published: February 2023

Background

The assessment and management of neonatal pain is crucial for the development and wellbeing of vulnerable infants. Specifically, neonatal pain is associated with adverse health outcomes but is often under-identified and therefore under-treated. Neonatal stress may be misinterpreted as pain and may therefore be treated inappropriately. The assessment of neonatal pain is complicated by the non-verbal status of patients, age-dependent variation in pain responses, limited education on identifying pain in premature infants, and the clinical utility of existing tools.

Objective

We review research surrounding neonatal pain assessment scales currently in use to assess neonatal pain in the neonatal intensive care unit.

Methods

We performed a systematic review of original research using PRISMA guidelines for literature published between 2016 and 2021 using the key words “neonatal pain assessment” in the databases Web of Science, PubMed, and CINAHL. Fifteen articles remained after review, duplicate, irrelevant, or low-quality articles were eliminated.

Results

We found research evaluating 13 neonatal pain scales. Important measurement categories include behavioral parameters, physiological parameters, continuous pain, acute pain, chronic pain, and the ability to distinguish between pain and stress. Provider education, inter-rater reliability and ease of use are important factors that contribute to an assessment tool's success. Each scale studied had strengths and limitations that aided or hindered its use for measuring neonatal pain in the neonatal intensive care unit, but no scale excelled in all areas identified as important for reliably identifying and measuring pain in this vulnerable population.

Conclusion

A more comprehensive neonatal pain assessment tool and more provider education on differences in pain signals in premature neonates may be needed to increase the clinical utility of pain scales that address the different aspects of neonatal pain.
Exploratory examination of the association between physical-mental multimorbidity and physical activity in children
Authors: Bedard Chloe , Timmons Brian W. , Ferro Mark A.
Published: February 2023

Children with physical illnesses often experience co-occurring mental illness (known as multimorbidity; MM) and it is currently unknown if MM is associated with physical activity (PA) and if the association differs between internalizing and externalizing disorders. Therefore, the aim of this study was to examine the association between MM and PA. Baseline data from the Multimorbidity in Children and Youth Across the Life Course (MY LIFE) cohort was used. MY LIFE is an ongoing prospective study that follows children ages 2 to 16 years with a chronic physical illness and measures PA using accelerometry and mental illness using the Mini International Neuropsychiatric Interview for Children and Adolescents. 140 children (53.2%) provided valid accelerometer data. Children with internalizing disorders recorded less light (B = −5.87), moderate (B = −1.82), and vigorous PA (B = −1.93) and fewer days meeting PA guidelines [Exp(B) = 0.73] and those with externalizing disorders recorded more light (B = 4.85), moderate (B = 1.78), and vigorous PA (B = 2.41) and more days meeting PA guidelines [Exp(B) = 1.06]. However, only the association between internalizing disorder and days meeting PA guidelines was statistically significant. This study provides preliminary evidence that children with MM may accumulate less PA depending on the type of mental illness they experience.
Glutamine ameliorates hyperoxia-induced hippocampal damage by attenuating inflammation and apoptosis via the MKP-1/MAPK signaling pathway in neonatal rats
Authors: Xuan Chouhui , Cui Haixia , Jin Zhengyong , Yue Yuyang , Cao Shuxia , Cui Songbiao , Xu Dongyuan
Published: February 2023

Glutamine (Gln) is an immunomodulatory protein that mediates oxidative stress, inflammation, and apoptosis, but has not been reported in the treatment of hyperoxia (Hyp)-induced brain injury. The aim of this study was to determine whether Gln could improve hyp-induced brain injury in neonatal rats to and later learning and memory dysfunction, and to explore its possible mechanisms. We prepared a model of neonatal rat brain injury caused by normobaric hyperoxia while administered with Gln for 7 days for evaluation. Learning memory function was assessed with the Morris water maze test. Histological analysis, protein expression analysis, oxidative stress and inflammation level analysis were performed using hippocampal tissue. Gln treatment significantly reduced brain tissue water content, oxidative stress levels, microglia activation and inflammatory factor expression, and attenuated tissue damage and apoptosis in the hippocampal region. Gln ameliorates hyp-induced learning, memory impairment in neonatal rats in water maze test. It also increased MKP-1 protein expression and decreased p-p38, p-ERK and p-JNK. Therefore, it is hypothesized that Gln may exert neuroprotective effects by increasing MKP-1 expression to negatively regulate MAPK signaling, with potential cognitive improvement in hyp-induced brain injury.
Dendrophthoe falcata (L.f.) Ettingsh. and Dendrophthoe pentandra (L.) Miq.: A review of traditional medical uses, phytochemistry, pharmacology, toxicity, and applications
Authors: Kong Degang , Wang Lu , Niu Yingshuo , Cheng Lingmei , Sang Bo , Wang Dan , Tian Jinli , Zhao Wei , Liu Xue , Chen Yueru , Wang Fulin , Zhou Honglei , Jia Ruyi
Published: February 2023

Dendrophthoe falcata (L.f.) Ettingsh. (DF) and Dendrophthoe pentandra (L.) Miq. (DP) have been traditionally used for the treatment of various ailments, such as cancer, ulcers, asthma, paralysis, skin diseases, tuberculosis, and menstrual troubles, in the ethnomedicinal systems of India and Indonesia. Currently, the chemical structures of 46 compounds have been elucidated from DF and DP, including flavonoids, triterpenes, tannins, steroids, open-chain aliphatics, benzyl derivates, and cyclic chain derivatives. In vitro assays have revealed their anti-tumor and anti-microbial activities. In vivo studies have unraveled their pharmacological properties against tumors, depression, fertility disorders, inflammatory responses, and so on. Additionally, their weak toxicity to rats and brine shrimp, as well as their promising applications for pharmaceutical preparations and combined medication, were also revealed. Herein, we not only recapitulated traditional medical uses, phytochemistry, pharmacology, toxicity, and applications of DF and DP but also discussed current research limitations and future perspectives, which are instructive for those interested in them and are committed to advancing parasitic plants to the Frontier of phytomedicine. We highlighted that DF and DP will become promising medical plants rather than being discarded as notorious pests, provided that more and deeper research is undertaken.
Wound healing properties of a new formulated flavonoid-rich fraction from Dodonaea viscosa Jacq. leaves extract
Authors: Subramanian Shanthi , Duraipandian Chamundeeswari , Alsayari Abdulrhman , Ramachawolran Gobinath , Wong Ling Shing , Sekar Mahendran , Gan Siew Hua , Subramaniyan Vetriselvan , Seethalakshmi S , Jeyabalan Srikanth , Dhanasekaran Sivaraman , Chinni Suresh V. , Mat Rani Nur Najihah Izzati , Wahab Shadma
Published: February 2023

Background:Dodonaea viscosa Jacq. (D. viscosa) belongs to the family of Sapindaceae, commonly known as “Sinatha,” and is used as a traditional medicine for treating wounds due to its high flavonoids content. However, to date there is no experimental evidence on its flavonoid-rich fraction of D. viscosa formulation as an agent for healing wounds.

Objective: The present study aimed to evaluate the wound healing effect of ethyl acetate fraction of D. viscosa leaves on dermal wounds.

Methods: The ethyl acetate fraction was produced from a water-ethanol extract of D. viscosa leaves and was quantitatively evaluated using the HPLC technique. The in-vivo wound healing ability of the ethyl acetate fraction of D. viscosa ointment (DVFO, 2.5%w/w and 5%w/w) was investigated in Sprague-Dawley rats utilizing an incision and excision paradigm with povidone-iodine ointment (5% w/w) as a control. The percentage of wound closure, hydroxyproline and hexosamine concentrations, tensile strength and epithelialization duration were measured. Subsequently, histopathology analysis of skin samples as well as western blots were performed for collagen type 3 (COL3A1), basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF).

Results: The ethyl acetate fraction of D. viscosa revealed flavonoids with high concentrations of quercetin (6.46% w/w) and kaempferol (0.132% w/w). Compared to the control group, the DVFO (2.5% and 5.0% w/w) significantly accelerated wound healing in both models, as demonstrated by quicker wound contraction, epithelialization, elevated hydroxyproline levels and increased tensile strength. Histopathological investigations also revealed that DVFO treatment improved wound healing by re-epithelialization, collagen formation and vascularization of damaged skin samples. Western blot analysis further demonstrated an up-regulation of COL3A, vascular endothelial growth factor and bFGF protein in wound granulation tissue of the DVFO-treated group (p < 0.01).

Conclusion: It is concluded that flavonoid-rich D. viscosa ethyl acetate fraction promotes wound healing by up-regulating the expressions of COL3A, VEGF and bFGF protein in wound granulation tissue. However, extensive clinical and pre-clinical research on the flavonoid-rich fraction of D. viscosa is needed to determine its significant impact in the healing of human wounds.
Anticholinergic effect of resveratrol with vitamin E on scopolamine-induced Alzheimer’s disease in rats: Mechanistic approach to prevent inflammation
Authors: Foudah Ahmed I. , Devi Sushma , Alam Aftab , Salkini Mohammad Ayman , Ross Samir A.
Published: February 2023

The most common form of dementia, Alzheimer’s disease (AD), is characterized by gradual declines in cognitive abilities and behavior. It is caused by a combination of factors, including amyloid-β (Aβ) accumulation, acetylcholine (ACh) loss, oxidative stress, and inflammation. Phenolic compounds have a variety of health benefits, including antioxidant activities. Thus, the purpose of this study was to investigate how resveratrol (RES) alone and in combination with vitamin E affected rats with AD using scopolamine (SCO). Animals are categorized into groups; (i) control, (ii) SCO (1 mg/kg i.p.), (iii) SCO + donepezil, (iv) SCO + RES (50 mg/kg, p.o.), (v) SCO + RES (75 mg/kg, p.o.), (vi) SCO + RES (50 mg/kg + vitamin E 1 mg/kg, p.o.) for 17 days. In rats, studied behavioural (NOR and EPM) and biochemical characteristics. In addition, brain histopathology was examined to investigate any damage to the hippocampus and neuroprotection. SCO-induced changes in acetylcholinesterase, protein carbonyl, and TNF-α improved after resveratrol treatment. RES increased antioxidant levels, decreased SCO-induced lipid peroxidation, and reversed SCO-mediated changes compared with the drug donepezil. The results indicated that RES and vitamin E had nootropic action in the NOR and EPM tests, measured by the recognition index and the inflection ratio. This study supports the efficacy of RES as a preventive and treatment agent for AD. Vitamin E showed a synergistic effect on RES, which helps in managing cognitive impairment AD.
Role of ferroptosis in hypoxic preconditioning to reduce propofol neurotoxicity
Authors: Chen Jing , Xiao Fei , Chen Lifei , Zhou Zhan , Wei Yi , Zhong Yu , Li Li , Xie Yubo
Published: February 2023

Background: An increasing number of studies have reported that neurotoxicity of propofol may cause long-term learning and cognitive dysfunction. Hypoxic preconditioning has been shown to have neuroprotective effects, reducing the neurotoxicity of propofol. Ferroptosis is a new form of death that is different from apoptosis, necrosis, autophagy and pyroptosis. However, it is unclear whether hypoxic preconditioning reduces propofol neurotoxicity associated with ferroptosis. Thus, we aimed to evaluate the effect of propofol on primary hippocampal neurons in vitro to investigate the neuroprotective mechanism of hypoxic preconditioning and the role of ferroptosis in the reduction of propofol neurotoxicity by hypoxic preconditioning.

Methods: Primary hippocampal neurons were cultured for 8 days in vitro and pretreated with or without propofol, hypoxic preconditioning, agonists or inhibitors of ferroptosis. Cell counting kit-8, Calcein AM, Reactive oxygen species (ROS), Superoxide dismutase (SOD), Ferrous iron (Fe2+), Malondialdehyde (MDA) and Mitochondrial membrane potential assay kit with JC-1 (JC-1) assays were used to measure cell viability, Reactive oxygen species level, Superoxide dismutase content, Fe2+ level, MDA content, and mitochondrial membrane potential. Cell apoptosis was evaluated using flow cytometry analyses, and ferroptosis-related proteins were determined by Western blot analysis.

Results: Propofol had neurotoxic effects that led to decreased hippocampal neuronal viability, reduced mitochondrial membrane potential, decreased SOD content, increased ROS level, increased Fe2+ level, increased MDA content, increased neuronal apoptosis, altered expression of ferroptosis-related proteins and activation of ferroptosis. However, hypoxic preconditioning reversed these effects, inhibited ferroptosis caused by propofol and reduced the neurotoxicity of propofol.

Conclusion: The neurotoxicity of propofol in developing rats may be related to ferroptosis. Propofol may induce neurotoxicity by activating ferroptosis, while hypoxic preconditioning may reduce the neurotoxicity of propofol by inhibiting ferroptosis.
Long-term comparative effectiveness and safety of dabigatran, rivaroxaban, apixaban and edoxaban in patients with atrial fibrillation: A nationwide cohort study
Authors: Grymonprez Maxim , De Backer Tine L. , Bertels Xander , Steurbaut Stephane , Lahousse Lies
Published: February 2023

Background: Although non-vitamin K antagonist oral anticoagulants (NOACs) are recommended over vitamin K antagonists (VKAs) in atrial fibrillation (AF) management, direct long-term head-to-head comparisons are lacking. Therefore, their risk-benefit profiles were investigated compared to VKAs and between NOACs.

Methods: AF patients initiating anticoagulation between 2013–2019 were identified in Belgian nationwide data. Inverse probability of treatment weighted Cox regression was used to investigate effectiveness and safety outcomes and were additionally stratified by NOAC dose.

Results: Among 254,478 AF patients (328,796 person-years of follow-up), NOACs were associated with significantly lower risks of stroke or systemic embolism (stroke/SE) (hazard ratio (HR) 0.68, 95% confidence interval (CI) (0.64–0.72)), all-cause mortality (HR 0.76, 95%CI (0.74–0.79)), major or clinically relevant non-major bleeding (MB/CRNMB) (HR 0.94, 95%CI (0.91–0.98)) and intracranial hemorrhage (HR 0.73, 95%CI (0.66–0.79)), but non-significantly different risks of myocardial infarction, gastrointestinal and urogenital bleeding compared to VKAs. Despite similar stroke/SE risks, dabigatran and apixaban were associated with significantly lower MB/CRNMB risks compared to rivaroxaban (HR 0.86, 95%CI (0.83–0.90); HR 0.86, 95%CI (0.83–0.89), respectively) and edoxaban (HR 0.91, 95%CI (0.83–0.99); HR 0.86, 95%CI (0.81–0.91), respectively), and apixaban with significantly lower major bleeding risks compared to dabigatran (HR 0.86, 95%CI (0.80–0.92)) and edoxaban (HR 0.79, 95%CI (0.72–0.86)). However, higher mortality risks were observed in some risk groups including with apixaban in patients with diabetes or concomitantly using digoxin compared to dabigatran and edoxaban, respectively.

Conclusion: NOACs had better long-term risk-benefit profiles than VKAs. While effectiveness was comparable, apixaban was overall associated with a more favorable safety profile followed by dabigatran.
Combining non-negative matrix factorization with graph Laplacian regularization for predicting drug-miRNA associations based on multi-source information fusion
Authors: Wang Mei-Neng , Li Yu , Lei Li-Lan , Ding De-Wu , Xie Xue-Jun
Published: February 2023

Increasing evidences suggest that miRNAs play a key role in the occurrence and progression of many complex human diseases. Therefore, targeting dysregulated miRNAs with small molecule drugs in the clinical has become a new treatment. Nevertheless, it is high cost and time-consuming for identifying miRNAs-targeted with drugs by biological experiments. Thus, more reliable computational method for identification associations of drugs with miRNAs urgently need to be developed. In this study, we proposed an efficient method, called GNMFDMA, to predict potential associations of drug with miRNA by combining graph Laplacian regularization with non-negative matrix factorization. We first calculated the overall similarity matrices of drugs and miRNAs according to the collected different biological information. Subsequently, the new drug-miRNA association adjacency matrix was reformulated based on the K nearest neighbor profiles so as to put right the false negative associations. Finally, graph Laplacian regularization collaborative non-negative matrix factorization was used to calculate the association scores of drugs with miRNAs. In the cross validation, GNMFDMA obtains AUC of 0.9193, which outperformed the existing methods. In addition, case studies on three common drugs (i.e., 5-Aza-CdR, 5-FU and Gemcitabine), 30, 31 and 34 of the top-50 associations inferred by GNMFDMA were verified. These results reveal that GNMFDMA is a reliable and efficient computational approach for identifying the potential drug-miRNA associations.
Sildenafil affects the human Kir2.1 and Kir2.2 channels at clinically relevant concentrations: Inhibition potentiated by low Ba2+
Authors: Iijima Akimasa , Švecová Olga , Hošek Jan , Kula Roman , Bébarová Markéta
Published: February 2023

Sildenafil (Viagra), the first approved and widely used oral drug for the treatment of erectile dysfunction, was occasionally associated with life-threatening ventricular arrhythmias in patients. Since inward rectifier potassium current (IK1) may considerably contribute to this arrhythmogenesis, we investigated the effect of sildenafil on the human Kir2.1 and Kir2.2, the prevailing subunits forming the ventricular IK1 channels. Experiments were performed by the whole-cell patch clamp technique at 37°C using Chinese hamster ovary cells transiently expressing the human Kir2.1 and Kir2.2 channels. Changes of both the inward and outward current components (at −110 and −50 mV, respectively) were tested to be able to consider the physiological relevance of the sildenafil effect (changes at −110 and −50 mV did not significantly differ, results at −50 mV are listed below). A significant Kir2.1 inhibition was observed at all applied sildenafil concentrations (16.1% ± 3.7%, 20.0% ± 2.6%, and 15.0% ± 3.0% at 0.1, 1, and 10 μM, respectively). The inhibitory effect of 0.1 μM sildenafil was potentiated by the presence of a low concentration of Ba2+ (0.1 μM) which induced only a slight Kir2.1 inhibition by 5.95% ± 0.75% alone (the combined effect was 35.5% ± 3.4%). The subtherapeutic and therapeutic sildenafil concentrations (0.1 and 1 μM) caused a dual effect on Kir2.2 channels whereas a significant Kir2.2 activation was observed at the supratherapeutic sildenafil concentration (10 μM: 34.1% ± 5.6%). All effects were fully reversible. This is the first study demonstrating that sildenafil at clinically relevant concentrations inhibits both the inward and outward current components of the main human ventricular IK1 subunit Kir2.1. This inhibitory effect was significantly potentiated by a low concentration of environmental contaminant Ba2+ in agreement with recently reported data on rat ventricular IK1 which additionally showed a significant repolarization delay. Considering the similar subunit composition of the human and rat ventricular IK1 channels, the observed effects might contribute to sildenafil-associated arrhythmogenesis in clinical practice.
Flexible CsPbCl3 inorganic perovskite thin-film detectors for real-time monitoring in protontherapy
Authors: Bruzzi M. , Calisi N. , Enea N. , Verroi E. , Vinattieri A.
Published: February 2023

Introduction: This paper deals with the class of versatile semiconducting materials called perovskites, which have been deposited for the first time on flexible substrates and then tested for radiation detection monitoring applications.

Methods: Lead halide inorganic perovskite, CsPbCl3, 0.4–1 μm-thick films have been grown on plastic flexible substrates equipped with interdigitated electrodes (IDEs) by magnetron sputtering at room temperature.

Results: First measurements in realtime configuration are reported for a 1–µm thick prototype under proton beams with energy in the range 100–228 MeV and 1–10 nA extraction currents, of interest for protontherapy applications.

Discussion: Experimental results evidence good performances of our sample as a real-time monitoring device. Current stability under UV and proton beam exposure has been tested in the range 0.1–120 s, as well as reproducibility under multiple exposures. The measured current signal proved to be linearly dependent on the extraction currents at a given proton energy. Linearity of the current signal of the device with proton fluxes was also proved within two order of magnitude range, about 107–109 p/s. These promising results, when coupled with easyness of fabrication, low processing costs and high versatility of electrode configurations, all features characterizing the manufacturing process, put into evidence lead halide perovskites as promising candidates for real-time radiation detection in protontherapy.
Identification of high-risk patients for development of type B aortic dissection based on novel morphological parameters
Authors: Li Da , Wang Jiarong , Zhao Jichun , Wang Tiehao , Zeng Xiangguo , Zheng Tinghui , Yuan Ding
Published: February 2023

Background: Predicting the development of sporadic type B aortic dissection (TBAD) always remains a difficult issue. This study aimed to identify high-risk patients for development of TBAD based on morphological parameters.

Methods: This propensity-score-matched case-control study collected and reconstructed the computed tomography angiography of acute TBAD patients and hospital-based control participants without aortic dissection from January 2013 to December 2016. Multivariate regression analysis was used to calculate the adjusted odds ratio (aOR) and 95% confidence interval (CI). Discriminant and reclassification abilities were compared between our model and a previously established model.

Results: Our study included 76 acute TBAD patients and 79 control patients (48 cases and 48 controls after propensity-score matching). The degree of question mark (aOR 1.07, 95% CI 1.04–1.11), brachiocephalic trunk diameter (aOR 1.49, 95% CI 1.20–1.85), brachiocephalic trunk angle (aOR 0.97, 95% CI 0.94–0.99), aortic root diameter (aOR 1.31, 95% CI 1.15–1.48), and aortic width (aOR 1.12, 95% CI 1.07–1.17) were associated with a significantly increased risk of TBAD formation. Similar findings were observed in the propensity-score matching and sensitivity analysis only including hyperacute TBAD patients. A novel prediction model was established based on the aforementioned parameters. The new model showed significantly improved discriminant ability compared with the previously established model (c-index 0.78 [95% CI 0.71–0.85] vs. 0.67 [95% CI 0.58–0.75], p = .03), driven by increased reclassification ability in identifying TBAD patients (NRI for events 0.16, 95% CI 0.02–0.30, p = .02).

Conclusion: Morphological predictors, including the degree of question mark, aortic width, aortic root diameter, brachiocephalic trunk angle, and brachiocephalic trunk diameter, may be used to identify patients at high risk of TBAD.
Age-associated declining of the regeneration potential of skeletal stem/progenitor cells
Authors: Mancinelli Luigi , Intini Giuseppe
Published: February 2023

Bone fractures represent a significant health burden worldwide, mainly because of the rising number of elderly people. As people become older, the risk and the frequency of bone fractures increase drastically. Such increase arises from loss of skeletal integrity and is also associated to a reduction of the bone regeneration potential. Central to loss of skeletal integrity and reduction of regeneration potential are the skeletal stem/progenitor cells (SSPCs), as they are responsible for the growth, regeneration, and repair of the bone tissue. However, the exact identity of the SSPCs has not yet been determined. Consequently, their functions, and especially dysfunctions, during aging have never been fully characterized. In this review, with the final goal of describing SSPCs dysfunctions associated to aging, we first discuss some of the most recent findings about their identification. Then, we focus on how SSPCs participate in the normal bone regeneration process and how aging can modify their regeneration potential, ultimately leading to age-associated bone fractures and lack of repair. Novel perspectives based on our experience are also provided.
Mechanism of Zn alleviates Cd toxicity in mangrove plants (Kandelia obovata)
Authors: Chen Shan
Published: February 2023

Cadmium (Cd) pollution is very common and serious in mangrove ecosystems in China. Zinc (Zn) has been used to reduce Cd accumulation in plants, and phenolic acid metabolism plays an important role in plant response to stress. In present study, in order to clarify whether Zn alleviates Cd toxicity in mangrove plants through phenolic acid metabolism, the Cd-contaminated Kandelia obovata plants were treated with different concentrations of (0, 80,300, and 400 mg·kg–1) ZnSO4 in a set of pot experiments and the biomass, the contents of Cd, Zn, soluble sugar, chlorophyll and the activities of 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferric-reducing antioxidant power (FRAP), l-phenylalanine ammonia-lyase (PAL), shikimic acid dehydrogenase (SKDH), cinnamyl alcohol dehydrogenase (CAD) and polyphenol oxidase (PPO) in the leaves were analyzed. The results showed that Cd contents in the leaves of Kandelia obovata ranged from 0.077 to 0.197 mg·kg–1 under different treatments, and Zn contents ranged from 90.260 to 114.447 mg·kg–1. Low-dose ZnSO4 treatment (80 mg·kg–1) performed significant positive effects on the biomass, phenolic acid metabolism-related enzyme activities, antioxidant capacity, and chlorophyll and soluble sugar contents in the leaves of Cd-contaminated mangrove plants. At the meantime, the addition of low-dose ZnSO4 promoted the biosynthesis of hydroxycinnamic acid, hydroxybenzoic acid, and enhanced the plant antioxidant capacity, thus alleviated Cd toxicity in mangrove plants.
β-D-XYLOSIDASE 4 modulates systemic immune signaling in Arabidopsis thaliana
Authors: Bauer Kornelia , Nayem Shahran , Lehmann Martin , Wenig Marion , Shu Lin-Jie , Ranf Stefanie , Geigenberger Peter , Vlot A. Corina
Published: February 2023

Pectin- and hemicellulose-associated structures of plant cell walls participate in defense responses against pathogens of different parasitic lifestyles. The resulting immune responses incorporate phytohormone signaling components associated with salicylic acid (SA) and jasmonic acid (JA). SA plays a pivotal role in systemic acquired resistance (SAR), a form of induced resistance that - after a local immune stimulus - confers long-lasting, systemic protection against a broad range of biotrophic invaders. β-D-XYLOSIDASE 4 (BXL4) protein accumulation is enhanced in the apoplast of plants undergoing SAR. Here, two independent Arabidopsis thaliana mutants of BXL4 displayed compromised systemic defenses, while local resistance responses to Pseudomonas syringae remained largely intact. Because both phloem-mediated and airborne systemic signaling were abrogated in the mutants, the data suggest that BXL4 is a central component in SAR signaling mechanisms. Exogenous xylose, a possible product of BXL4 enzymatic activity in plant cell walls, enhanced systemic defenses. However, GC-MS analysis of SAR-activated plants revealed BXL4-associated changes in the accumulation of certain amino acids and soluble sugars, but not xylose. In contrast, the data suggest a possible role of pectin-associated fucose as well as of the polyamine putrescine as regulatory components of SAR. This is the first evidence of a central role of cell wall metabolic changes in systemic immunity. Additionally, the data reveal a so far unrecognized complexity in the regulation of SAR, which might allow the design of (crop) plant protection measures including SAR-associated cell wall components.
Two genes, ANS and UFGT2, from Vaccinium spp. are key steps for modulating anthocyanin production
Authors: Nguyen Han M. , Putterill Joanna , Dare Andrew P. , Plunkett Blue J. , Cooney Janine , Peng Yongyan , Souleyre Edwige J. F. , Albert Nick W. , Espley Richard V. , Günther Catrin S.
Published: February 2023

Anthocyanins are a major group of red to blue spectrum plant pigments with many consumer health benefits. Anthocyanins are derived from the flavonoid pathway and diversified by glycosylation and methylation, involving the concerted action of specific enzymes. Blueberry and bilberry (Vaccinium spp.) are regarded as ‘superfruits’ owing to their high content of flavonoids, especially anthocyanins. While ripening-related anthocyanin production in bilberry (V. myrtillus) and blueberry (V. corymbosum) is regulated by the transcriptional activator MYBA1, the role of specific structural genes in determining the concentration and composition of anthocyanins has not been functionally elucidated. We isolated three candidate genes, CHALCONE SYNTHASE (VmCHS1), ANTHOCYANIDIN SYNTHASE (VmANS) and UDP-GLUCOSE : FLAVONOID-3-O-GLYCOSYLTRANSFERASE (VcUFGT2), from Vaccinium, which were predominantly expressed in pigmented fruit skin tissue and showed high homology between bilberry and blueberry. Agrobacterium-mediated transient expression of Nicotiana benthamiana showed that overexpression of VcMYBA1 in combination with VmANS significantly increased anthocyanin concentration (3-fold). Overexpression of VmCHS1 showed no effect above that induced by VcMYBA1, while VcUFGT2 modulated anthocyanin composition to produce delphinidin-3-galactosylrhamnoside, not naturally produced in tobacco. In strawberry (Fragaria × ananassa), combined transient overexpression of VcUFGT2 with a FLAVONOID 3´,5´-HYDROXYLASE from kiwifruit (Actinidia melanandra) modulated the anthocyanin profile to include galactosides and arabinosides of delphinidin and cyanidin, major anthocyanins in blueberry and bilberry. These findings provide insight into the role of the final steps of biosynthesis in modulating anthocyanin production in Vaccinium and may contribute to the targeted breeding of new cultivars with improved nutritional properties.
Predicting the growth suitability of Larix principis-rupprechtii Mayr based on site index under different climatic scenarios
Authors: Cheng Ruiming , Zhang Jing , Wang Xinyue , Ge Zhaoxuan , Zhang Zhidong
Published: February 2023

Larix principis-rupprechtii Mayr (larch) is one of the main afforestation and timber production species used in North China. Climate change has led to a change in its suitable distribution and growth. However, the impact of climate change on its growth suitability is not clear. In this study, using forest resource inventory data and spatially continuous environmental factor data (temperature, precipitation, topography, and soil) in Hebei and Shanxi Provinces, China, the random forest model (RF) was used to simulate the larch site index (SI) and growth suitability under three shared socioeconomic pathways (SSPs: SSP1-2.6, SSP2-4.5, and SSP5-8.5) for the current and future (2021–2040, 2041–2060 and 2080–2100). The results revealed that (1) RF had excellent performance in predicting the regional SI (R2 = 0.73, MAE = 0.93 m, RMSE = 1.35 m); (2) the main factors affecting the productivity of larch were the mean temperature of the warmest quarter (BIO10), elevation (ELEV), mean diurnal range (BIO2), and annual precipitation (BIO12); and (3) larch currently had a higher SI in the Bashang areas and in the high-altitude mountains. The areas characterized as unsuitable, poorly suitable, moderately suitable, and highly suitable accounted for 15.45%, 42.12%, 31.94%, and 10.49% of the total area, respectively. (4) Future climate warming had an obvious inhibitory effect on the SI, and the effect strengthened with increasing radiation intensity and year. (5) The moderately suitable and highly suitable areas of larch growth showed a downward trend under future climate scenarios. By the end of this century, the suitable growth areas would decrease by 14.14% under SSP1-2.6, 15.17% under SSP2-4.5, and 19.35% under SSP5-8.5. The results revealed the impact of climate change on larch growth suitability, which can provide a scientific basis for larch forest management.
Identification of QTNs, QTN-by-environment interactions, and their candidate genes for grain size traits in main crop and ratoon rice
Authors: Zhao Qiong , Shi Xiao-Shi , Wang Tian , Chen Ying , Yang Rui , Mi Jiaming , Zhang Ya-Wen , Zhang Yuan-Ming
Published: February 2023

Although grain size is an important quantitative trait affecting rice yield and quality, there are few studies on gene-by-environment interactions (GEIs) in genome-wide association studies, especially, in main crop (MC) and ratoon rice (RR). To address these issues, the phenotypes for grain width (GW), grain length (GL), and thousand grain weight (TGW) of 159 accessions of MC and RR in two environments were used to associate with 2,017,495 SNPs for detecting quantitative trait nucleotides (QTNs) and QTN-by-environment interactions (QEIs) using 3VmrMLM. As a result, 64, 71, 67, 72, 63, and 56 QTNs, and 0, 1, 2, 2, 2, and 1 QEIs were found to be significantly associated with GW in MC (GW-MC), GL-MC, TGW-MC, GW-RR, GL-RR, and TGW-RR, respectively. 3, 4, 7, 2, 2, and 4 genes were found to be truly associated with the above traits, respectively, while 2 genes around the above QEIs were found to be truly associated with GL-RR, and one of the two known genes was differentially expressed under two soil moisture conditions. 10, 7, 1, 8, 4, and 3 candidate genes were found by differential expression and GO annotation analysis to be around the QTNs for the above traits, respectively, in which 6, 3, 1, 2, 0, and 2 candidate genes were found to be significant in haplotype analysis. The gene Os03g0737000 around one QEI for GL-MC was annotated as salt stress related gene and found to be differentially expressed in two cultivars with different grain sizes. Among all the candidate genes around the QTNs in this study, four were key, in which two were reported to be truly associated with seed development, and two (Os02g0626100 for GL-MC and Os02g0538000 for GW-MC) were new. Moreover, 1, 2, and 1 known genes, along with 8 additional candidate genes and 2 candidate GEIs, were found to be around QTNs and QEIs for GW, GL, and TGW, respectively in MC and RR joint analysis, in which 3 additional candidate genes were key and new. Our results provided a solid foundation for genetic improvement and molecular breeding in MC and RR.
The grapevine LysM receptor-like kinase VvLYK5-1 recognizes chitin oligomers through its association with VvLYK1-1
Authors: Roudaire Thibault , Marzari Tania , Landry David , Löffelhardt Birgit , Gust Andrea A. , Jermakow Angelica , Dry Ian , Winckler Pascale , Héloir Marie-Claire , Poinssot Benoit
Published: February 2023

The establishment of defense reactions to protect plants against pathogens requires the recognition of invasion patterns (IPs), mainly detected by plasma membrane-bound pattern recognition receptors (PRRs). Some IPs, also termed elicitors, are used in several biocontrol products that are gradually being developed to reduce the use of chemicals in agriculture. Chitin, the major component of fungal cell walls, as well as its deacetylated derivative, chitosan, are two elicitors known to activate plant defense responses. However, recognition of chitooligosaccharides (COS) in Vitis vinifera is still poorly understood, hampering the improvement and generalization of protection tools for this important crop. In contrast, COS perception in the model plant Arabidopsis thaliana is well described and mainly relies on a tripartite complex formed by the cell surface lysin motif receptor-like kinases (LysM-RLKs) AtLYK1/CERK1, AtLYK4 and AtLYK5, the latter having the strongest affinity for COS. In grapevine, COS perception has for the moment only been demonstrated to rely on two PRRs VvLYK1-1 and VvLYK1-2. Here, we investigated additional players by overexpressing in Arabidopsis the two putative AtLYK5 orthologs from grapevine, VvLYK5-1 and VvLYK5-2. Expression of VvLYK5-1 in the atlyk4/5 double mutant background restored COS sensitivity, such as chitin-induced MAPK activation, defense gene expression, callose deposition and conferred non-host resistance to grapevine downy mildew (Erysiphe necator). Protein-protein interaction studies conducted in planta revealed a chitin oligomer-triggered interaction between VvLYK5-1 and VvLYK1-1. Interestingly, our results also indicate that VvLYK5-1 mediates the perception of chitin but not chitosan oligomers showing a part of its specificity.
Sense of agency predicts severity of moral judgments
Authors: Spaccasassi Chiara , Cenka Kamela , Petkovic Stella , Avenanti Alessio
Published: February 2023

Sense of Agency (SoA) refers to the awareness of being the agent of our own actions. A key feature of SoA relies on the perceived temporal compression between our own actions and their sensory consequences, a phenomenon known as “Intentional Binding.” Prior studies have linked SoA to the sense of responsibility for our own actions. However, it is unclear whether SoA predicts the way we judge the actions of others – including judgments of morally wrong actions like harming others. To address this issue, we ran an on-line pilot experiment where participants underwent two different tasks designed to tap into SoA and moral cognition. SoA was measured using the Intentional Binding task which allowed us to obtain both implicit (Intentional Binding) and explicit (Agency Rating) measures of SoA. Moral cognition was assessed by asking the same participants to evaluate videoclips where an agent could deliberately or inadvertently cause suffering to a victim (Intentional vs. Accidental Harm) compared with Neutral scenarios. Results showed a significant relation between both implicit and explicit measures of SoA and moral evaluation of the Accidental Harm scenarios, with stronger SoA predicting stricter moral judgments. These findings suggest that our capacity to feel in control of our actions predicts the way we judge others’ actions, with stronger feelings of responsibility over our own actions predicting the severity of our moral evaluations of other actions. This was particularly true in ambiguous scenarios characterized by an incongruency between an apparently innocent intention and a negative action outcome.
Can proactively confessing obtain your embrace? Exploring for leader’s pro-social rule-breaking consequences based on a self-verification perspective
Authors: Wang Fan , Weng Haolin , Yang Peilin , Li Yi , Zhang Man , Das Anupam Kumar
Published: February 2023

Introduction

The effect of leader pro-social rule breaking on employees is a critical albeit underexplored topic within the domain of study on the consequences of pro-social rule breaking in organizations. This study attempts to make up for the gap by exploring the relationship between leader pro-social rule breaking and employee voice. Drawing on the theory of self-verification, we theorize that leaders who perform pro-social rule breaking will seek feedback from their subordinates, while employees being sought will be triggered to voice upwardly, the extent to which intensity of voice is moderated by the moral courage of employees.

Methods

A total of 283 dyads data of supervisor–subordinate from Shanghai, China, in a three-wave time-lagged survey provided support for our hypotheses.

Results

The results show that leader pro-social rule breaking is positively related to leader feedback-seeking, which is positively related to employee upward voice and mediates the relationship between the two. Moreover, the positive relationship between leader pro-social rule breaking and leader feedback-seeking as well as the indirect effect of leader pro-social rule breaking on employee upward voice via leader feedback-seeking was weakened when moral courage is high.

Discussion

The present study promotes the theoretical research on the positive results of leader pro-social rule breaking and also suggests that feedback-seeking would be an effective way for leaders to motivate employees’ upward voice.
Technology moral sense: Development, reliability, and validity of the TMS scale in Chinese version
Authors: Wu Wen , Huang Xiuqing , Li Xinyu
Published: February 2023

Introduction

The aggregation of intelligent technologies such as big data, algorithms, and biometrics poses new moral risks to humanity and has raised awareness of technology ethics. Based on the research on moral issues in the fields of ethics and psychology, we built the concept of technology moral sense (TMS) by investigating three dimensions—technology moral consensus, cognition, and emotion.

Methods

We focused on the field of intelligent surveillance technology, adopted a scale, and conducted a questionnaire survey with more than 1,000 respondents. We used exploratory and confirmatory factor analysis to test two different samples.

Results

First, by combining item analysis and Cronbach’s alpha coefficient, we established that all three dimensions are reliable. Our results indicated a Cronbach’s alpha coefficient of 0.944, 0.891 and 0.938 for technology moral consensus, emotion, and cognition. Second, exploratory factor analysis verified that there were three factors, the eigenvalues were all greater than one, and the cumulative variance explanation rate was 74.953%, and the factor loading coefficient of the 18 items are greater than 0.5. Finally, we used confirmatory factor analysis to test the fit of the model. The test shows that RMSEA = 0.078, CFI and TLI are greater than 0.9, which indicating the fit was suitable and the construct validity was good.

Discussion

Our findings demonstrated that the new scale is a reliable tool for assessing the technology moral sense in China. The results support the reliability and validity of the Technology Moral Sense (TMS) scale, and explain the existence of the concept of technology moral sense through three dimensions.