bluuebunny/crossref_metadata_2025 huggingface dataset:
Radiolabeled Monoclonal Antibody Against Colony-Stimulating Factor 1 Receptor Specifically Distributes to the Spleen and Liver in Immunocompetent Mice
Authors: Waaijer Stijn J. H. , Suurs Frans V. , Hau Cheei-Sing , Vrijland Kim , de Visser Karin E. , de Groot Derk Jan A. , de Vries Elisabeth G. E. , Lub-de Hooge Marjolijn N. , Schröder Carolina P.
Published: January 2022

Macrophages can promote tumor development. Preclinically, targeting macrophages by colony-stimulating factor 1 (CSF1)/CSF1 receptor (CSF1R) monoclonal antibodies (mAbs) enhances conventional therapeutics in combination treatments. The physiological distribution and tumor uptake of CSF1R mAbs are unknown. Therefore, we radiolabeled a murine CSF1R mAb and preclinically visualized its biodistribution by PET. CSF1R mAb was conjugated to N-succinyl-desferrioxamine (N-suc-DFO) and subsequently radiolabeled with zirconium-89 (89Zr). Optimal protein antibody dose was first determined in non-tumor-bearing mice to assess physiological distribution. Next, biodistribution of optimal protein dose and 89Zr-labeled isotype control was compared with PET and ex vivo biodistribution after 24 and 72 h in mammary tumor-bearing mice. Tissue autoradiography and immunohistochemistry determined radioactivity distribution and tissue macrophage presence, respectively. [89Zr]Zr-DFO-N-suc-CSF1R-mAb optimal protein dose was 10 mg/kg, with blood pool levels of 10 ± 2% injected dose per gram tissue (ID/g) and spleen and liver uptake of 17 ± 4 and 11 ± 4%ID/g at 72 h. In contrast, 0.4 mg/kg of [89Zr]Zr-DFO-N-suc-CSF1R mAb was eliminated from circulation within 24 h; spleen and liver uptake was 126 ± 44% and 34 ± 7%ID/g, respectively. Tumor-bearing mice showed higher uptake of [89Zr]Zr-DFO-N-suc-CSF1R-mAb in the liver, lymphoid tissues, duodenum, and ileum, but not in the tumor than did 89Zr-labeled control at 72 h. Immunohistochemistry and autoradiography showed that 89Zr was localized to macrophages within lymphoid tissues. Following [89Zr]Zr-DFO-N-suc-CSF1R-mAb administration, tumor macrophages were almost absent, whereas isotype-group tumors contained over 500 cells/mm2. We hypothesize that intratumoral macrophage depletion by [89Zr]Zr-DFO-N-suc-CSF1R-mAb precluded tumor uptake higher than 89Zr-labeled control. Translation of molecular imaging of macrophage-targeting therapeutics to humans may support macrophage-directed therapeutic development.
Hedgehog−Gli2 Signaling Promotes Chemoresistance in Ovarian Cancer Cells by Regulating MDR1
Authors: Wang Qian , Wei Xin , Hu Lanyan , Zhuang Lingling , Zhang Hong , Chen Qi
Published: January 2022

Background

Cisplatin (DDP) resistance remains a key challenge in improving the clinical outcome of patients with ovarian cancer (OC). Gli2 overexpression can lead to DDP resistance in OC cells, but the specific underlying regulatory mechanism remains unclear. The membrane transporter encoding gene MDR1 positively regulates chemotherapy resistance in various cancer types. We evaluated MDR1 as a potential Gli2 downstream target and the contribution of the Gli2/MDR1 axis in promoting DDP resistance in OC cells.

Methods

To generate drug-resistant SKOV3/DDP cells, SKOV3 cells were grown for six months under continuous induction wherein the DDP concentration was steadily increased. Gli2 expression in OC cells with varying DDP sensitivities was detected using western blot. Cell counting kit-8 assays were used to assess the DDP sensitivity of SKOV3, SKOV3/DDP, A2780, and A2780/DDP cells and reversal of DDP resistance in SKOV3/DDP and A2780/DDP cells. Cell proliferation was analyzed using 5-ethynyl-2′-deoxyuridine (EdU) incorporation assays. The transcriptional regulation of MDR1 by Gli2 was determined using luciferase reporter assays. Finally, xenograft OC tumors were generated in nude mice, which were then treated with intraperitoneal DDP or phosphate-buffered saline (PBS) injections to investigate if Gli2 affected DDP resistance in OC in vivo.

Results

DDP-resistant SKOV3/DDP and A2780/DDP cells showed higher expression of Gli2 and MDR1 as compared with that in DDP-sensitive OC cells. Gli2 knockdown in SKOV3/DDP cells significantly reduced MDR1 expression, whereas it increased DNA damage, thereby sensitizing OC cells to DDP. Similar results were obtained after targeting Gli2 expression with the Gli-antagonist 61 inhibitor (GANT61) in SKOV3/DDP and A2780/DDP cells. In cells stably overexpressing Gli2, treatment with gradient concentrations of verapamil, an MDR1 inhibitor, significantly inhibited MDR1 expression. Our findings indicate that downregulation of MDR1 expression may reverse OC cell resistance to DDP. Moreover, dual-luciferase reporter gene assays confirmed that MDR1 is a direct downstream target of Gli2, with Gli2 positively regulating MDR1 expression. Finally, subcutaneous xenotransplantation in nude mice demonstrated that Gli2 plays a key role in regulating OC drug resistance.

Conclusions

We identified a mechanism by which Hedgehog-Gli signaling regulates OC chemoresistance by modulating MDR1 expression. Hence, Gli2 and MDR1 are potential biomarkers and therapeutic targets in patients with chemoresistant OC.
Uric Acid Is Elevated in Children With Obesity and Decreases After Weight Loss
Authors: Jørgensen Rasmus Møller , Bøttger Bjarke , Vestergaard Esben Thyssen , Kremke Britta , Bahnsen Rikke Frederiksen , Nielsen Bent Windelborg , Bruun Jens Meldgaard
Published: January 2022

Introduction: Childhood obesity is an increasing condition associated with continuous obesity into adulthood and development of comorbidities. Adult studies show an association between serum uric acid (SUA) levels and body mass index (BMI). The aim of this retro perspective exploratory study was to investigate SUA in obese children and adolescents and the effects of a subsequent weight reduction.

Materials and Methods: One hundred and seventy-one children (age 4–18), with obesity (i.e. BMI-SDS of +2 or higher) were included in a multifactorial lifestyle intervention. The children participating were annually measured for anthropometrics, blood samples and DEXA-scans for up to 3 years. Eighty-nine children were included for follow-up analysis.

Results: After a follow-up of 20.7 ± 9.4 months a reduction in BMI-SDS of −0.34 ± 0.53 (p < 0.01) was observed. SUA was found to be positively associated with changes in BMI-SDS. SUA levels decreased in the 65 children who lost weight during the trial, conversely, SUA increased in the 23 children who gained weight during the trial (p < 0.01 between groups).

Conclusion: SUA was found to correlate with measures of obesity and for the first time, this intervention demonstrates a positive relationship between SUA and weight reduction in children with obesity.
theLiTE™: A Screening Platform to Identify Compounds that Reinforce Tight Junctions
Authors: Gomes Teresa Lopes , Oliveira-Marques Virgínia de , Hampson Richard John , Jacinto António , de Moraes Luciana Vieira , Martinho Rui Gonçalo
Published: January 2022

Tight junctions (TJ) are formed by transmembrane and intracellular proteins that seal the intercellular space and control selective permeability of epithelia. Integrity of the epithelial barrier is central to tissue homeostasis and barrier dysfunction has been linked to many pathological conditions. TJ support the maintenance of cell polarity through interactions with the Par complex (Cdc42-Par-6-Par-3-aPKC) in which Par-6 is an adaptor and links the proteins of the complex together. Studies have shown that Par-6 overexpression delays the assembly of TJ proteins suggesting that Par-6 negatively regulates TJ assembly. Because restoring barrier integrity is of key therapeutic and prophylactic value, we focus on finding compounds that have epithelial barrier reinforcement properties; we developed a screening platform (theLiTE™) to identify compounds that modulate Par-6 expression in follicular epithelial cells from Par-6-GFP Drosophila melanogaster egg chambers. Hits identified were then tested whether they improve epithelial barrier function, using measurements of transepithelial electrical resistance (TEER) or dye efflux to evaluate paracellular permeability. We tested 2,400 compounds, found in total 10 hits. Here we present data on six of them: the first four hits allowed us to sequentially build confidence in theLiTE™ and two compounds that were shortlisted for further development (myricetin and quercetin). We selected quercetin due to its clinical and scientific validation as a compound that regulates TJ; food supplement formulated on the basis of this discovery is currently undergoing clinical evaluation in gastroesophageal reflux disease (GERD) sufferers.
Perilla Leaf Extract (PLE) Attenuates COPD Airway Inflammation via the TLR4/Syk/PKC/NF-κB Pathway In Vivo and In Vitro
Authors: Yuan Jiqiao , Li Xuyu , Fang Nan , Li Ping , Zhang Ziqian , Lin Mingbao , Hou Qi
Published: January 2022

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disease characterized by persistent airflow limitation but still lacking effective treatments. Perilla frutescens (L.) Britt., an important traditional medicinal plant with excellent antioxidant and anti-inflammatory properties, is widely used for the treatment of respiratory disease in China. However, its protective activity and mechanism against COPD airway inflammation have not been fully studied. Here, the anti-inflammatory effects of the PLE were investigated, and its underlying mechanisms were then elucidated. The presented results suggested a notable effect of the PLE on airway inflammation of COPD, by significantly ameliorating inflammatory cell infiltration in lung tissue, lessening leukocytes (lymphocytes, neutrophils, and macrophages) and inflammatory mediators (interleukin 4 (IL-4), IL-6, IL-17A, interferon γ (IFN-γ), and tumor necrosis factor α (TNF-α)) in the bronchoalveolar lavage fluid (BALF) of cigarette smoke (CS)/lipopolysaccharide (LPS)-induced COPD mice in vivo and inhibiting the production of inflammatory factors (nitric oxide (NO), IL-6, and TNF-α) and intracellular reactive oxygen species (ROS) in LPS-stimulated RAW264.7 cells in vitro. For further extent, PLE treatment significantly suppressed the expression and phosphorylation of TLR4, Syk, PKC, and NF-κB p65 in vivo and their mRNA in vitro. Subsequently, by co-treating with their inhibitors in vitro, its potential mechanism via TLR4/Syk/PKC/NF-κB p65 signals was disclosed. In summary, the obtained results indicated a noteworthy effective activity of the PLE on COPD inflammation, and partly, the TLR4/Syk/PKC/NF-κB p65 axis might be the potential mechanism.
Pharmacokinetic/Pharmacodynamic Based Breakpoints of Polymyxin B for Bloodstream Infections Caused by Multidrug-Resistant Gram-Negative Pathogens
Authors: Bian Xingchen , Liu Xiaofen , Hu Fupin , Feng Meiqing , Chen Yuancheng , Bergen Phillip J. , Li Jian , Li Xin , Guo Yan , Zhang Jing
Published: January 2022

The latest PK/PD findings have demonstrated negligible efficacy of intravenous polymyxins against pulmonary infections. We investigated pharmacokinetic/pharmacodynamic (PK/PD)-based breakpoints of polymyxin B for bloodstream infections and the rationality of the recent withdrawal of polymyxin susceptibility breakpoints by the CLSI. Polymyxin B pharmacokinetic data were obtained from a phase I clinical trial in healthy Chinese subjects and population pharmacokinetic parameters were employed to determine the exposure of polymyxin B at steady state. MICs of 1,431 recent clinical isolates of Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae collected from across China were determined. Monte-Carlo simulations were performed for various dosing regimens (0.42–1.5 mg/kg/12 h via 1 or 2-h infusion). The probability of target attainment, PK/PD breakpoints and cumulative fraction of response were determined for each bacterial species. MIC90 of polymyxin B was 1 mg/L for P. aeruginosa and 0.5 mg/L for A. baumannii and K. pneumoniae. With the recommended polymyxin B dose of 1.5–2.5 mg/kg/day, the PK/PD susceptible breakpoints for P. aeruginosa, A. baumannii and K. pneumoniae were 2, 1 and 1 mg/L respectively for bloodstream infection. For Chinese patients, polymyxin B dosing regimens of 0.75–1.5 mg/kg/12 h for P. aeruginosa and 1–1.5 mg/kg/12 h for A. baumannii and K. pneumoniae were appropriate. Breakpoint determination should consider the antimicrobial PK/PD at infection site and delivery route. The recent withdrawal of polymyxin susceptible breakpoint by CLSI primarily based on poor efficacy against lung infections needs to be reconsidered for bloodstream infections.
Magnesium Isoglycyrrhizinate Ameliorates Concanavalin A-Induced Liver Injury by Inhibiting Autophagy
Authors: Fan Zihao , Li Yuxian , Chen Sisi , Xu Ling , Tian Yuan , Cao Yaling , Pan Zhenzhen , Zhang Xiangying , Chen Yu , Ren Feng
Published: January 2022

Background and Aims: Acute liver failure (ALF) is a type of liver injury that is caused by multiple factors and leads to severe liver dysfunction; however, current treatments for ALF are insufficient. Magnesium isoglycyrrhizinate (MgIG), a novel glycyrrhizin extracted from the traditional Chinese medicine licorice, has a significant protective effect against concanavalin A (ConA)-induced liver injury, but its underlying therapeutic mechanism is unclear. Hence, this study aims to explore the potential therapeutic mechanism of MgIG against ConA-induced immune liver injury.

Methods: ConA (20 mg/kg, i. v.) was administered for 12 h to construct an immune liver injury model, and the treatment group was given MgIG (30 mg/kg, i. p.) injection 1 h in advance. Lethality, liver injury, cytokine levels, and hepatocyte death were evaluated. The level of autophagy was evaluated by electron microscopy, RT-PCR and western blotting, and hepatocyte death was assessed in vitro by flow cytometry.

Results: MgIG significantly increased the survival rate of mice and ameliorated severe liver injury mediated by ConA. The decrease in the number of autophagosomes, downregulation of LC3b expression and upregulation of p62 expression indicated that MgIG significantly inhibited ConA-induced autophagy in the liver. Reactivation of autophagy by rapamycin (RAPA) reversed the protective effect of MgIG against ConA-induced liver injury. Compared with MgIG treatment, activation of autophagy by RAPA also promoted the expression of liver inflammation markers (IL-1β, IL-6, TNF-α, CXCL-1, CXCL-2, CXCL-10, etc.) and hepatocyte death. In vitro experiments also showed that MgIG reduced ConA-induced hepatocyte death but did not decrease hepatocyte apoptosis by inhibiting autophagy.

Conclusion: MgIG significantly ameliorated ConA-induced immune liver injury in mice by inhibiting autophagy. This study provides theoretical support for the ability of MgIG to protect against liver injury in clinical practice.
Differential Mechanisms of Action and Efficacy of Vitamin E Components in Antioxidant Cytoprotection of Human Retinal Pigment Epithelium
Authors: Duncan R. Scott , Hurtado Daniel T. , Hall Conner W. , Koulen Peter
Published: January 2022

The purpose of this study was to determine if different vitamin E components exhibit similar efficacy and mechanism of action in protecting Retinal pigment epithelium (RPE) cells from oxidative damage. We hypothesized that α-tocopherol (αT) is unique among vitamin E components in its cytoprotective mechanism of action against oxidative stress in RPE cells and that it requires protein synthesis for optimal antioxidant effect. We used cell viability assays, fluorescent chemical labeling of DNA and actin and immuno-labeling of the antioxidant proteins Nrf2 and Sod2 and of the tight junction protein, ZO-1, and confocal microscopy to determine the effects of αT and γT against oxidative stress in immortalized human RPE cells (hTERT-RPE). Using the four main vitamin E components, αT, γT, δ-tocopherol (δT) and α-tocotrienol (αTr), we ascertained that they exhibit similar, but not identical, antioxidant activity as αT when used at equimolar concentrations. In addition, we determined that the exposure time of RPE cells to α-tocopherol is critical for its ability to protect against oxidative damage. Lastly, we determined that αT, but not γT, partially requires the synthesis of new proteins within a 24-h period and prior to exposure to tBHP for optimal cytoprotection. We conclude that, unlike γT and δT, αT appears to be unique in its requirement for transport and/or signaling for it to be an effective antioxidant. As a result, more focus should be paid to which vitamin E components are used for antioxidant interventions.
Natural Products in Modulating Methamphetamine-Induced Neuronal Apoptosis
Authors: Zeng Yiwei , Chen Yunhui , Zhang Su , Ren Huan , Xia Jialin , Liu Mengnan , Shan Baozhi , Ren Yulan
Published: January 2022

Methamphetamine (METH), an amphetamine-type psychostimulant, is highly abused worldwide. Chronic abuse of METH causes neurodegenerative changes in central dopaminergic neurons with numerous neuropsychiatric consequences. Neuronal apoptosis plays a critical role in METH-induced neurotoxicity and may provide promising pharmacological targets for preventing and treating METH addiction. In recent years, accumulating evidence has revealed that natural products may possess significant potentials to inhibit METH-evoked neuronal apoptosis. In this review, we summarized and analyzed the improvement effect of natural products on METH-induced neuronal apoptosis and their potential molecular mechanisms on modulating dopamine release, oxidative stress, mitochondrial-dependent apoptotic pathway, endoplasmic reticulum stress-mediated apoptotic pathway, and neuroinflammation. Hopefully, this review may highlight the potential value of natural products in modulating METH-caused neuronal apoptosis and provide useful information for future research and developments of novel and efficacious pharmacotherapies in this field.
San-Huang-Yi-Shen Capsule Ameliorates Diabetic Nephropathy in Rats Through Modulating the Gut Microbiota and Overall Metabolism
Authors: Su Xiuhai , Yu Wenxia , Liu Airu , Wang Congxiang , Li Xiuzhen , Gao Juanjuan , Liu Xiaofei , Jiang Wenhui , Yang Yue , Lv Shuquan
Published: January 2022

San-Huang-Yi-Shen capsule (SHYS) has been used in the treatment of diabetic nephropathy (DN) in clinic. However, the mechanisms of SHYS on DN remain unknown. In this study, we used a high-fat diet (HFD) combined with streptozotocin (STZ) injection to establish a DN rat model. Next, we used 16S rRNA sequencing and untargeted metabolomics to study the potential mechanisms of SHYS on DN. Our results showed that SHYS treatment alleviated the body weight loss, hyperglycemia, proteinuria, pathological changes in kidney in DN rats. SHYS could also inhibite the oxidative stress and inflammatory response in kidney. 16S rRNA sequencing analysis showed that SHYS affected the beta diversity of gut microbiota community in DN model rats. SHYX could also decrease the Firmicutes to Bacteroidetes (F to B) ratio in phylum level. In genus level, SHYX treatment affected the relative abundances of Lactobacillus, Ruminococcaceae UCG-005, Allobaculum, Anaerovibrio, Bacteroides and Candidatus_Saccharimonas. Untargeted metabolomics analysis showed that SHYX treatment altered the serum metabolic profile in DN model rats through affecting the levels of guanidineacetic acid, L-kynurenine, prostaglandin F1α, threonine, creatine, acetylcholine and other 21 kind of metabolites. These metabolites are mainly involved in glycerophospholipid metabolism, tryptophan metabolism, alanine, aspartate and glutamate metabolism, arginine biosynthesis, tricarboxylic acid (TCA) cycle, tyrosine metabolism, arginine and proline metabolism, arginine and proline metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, and D-glutamine and D-glutamate metabolism pathways. Spearman correlation analysis showed that Lactobacillus, Candidatus_Saccharimonas, Ruminococcaceae UCG-005, Anaerovibrio, Bacteroides, and Christensenellaceae_R-7_group were closely correlated with most of physiological data and the differential metabolites following SHYS treatment. In conclusion, our study revealed multiple ameliorative effects of SHYS on DN including the alleviation of hyperglycemia and the improvement of renal function, pathological changes in kidney, oxidative stress, and the inflammatory response. The mechanism of SHYS on DN may be related to the improvement of gut microbiota which regulates arginine biosynthesis, TCA cycle, tyrosine metabolism, and arginine and proline metabolism.
Gram-Negative Bacteria Salmonella typhimurium Boost Leukotriene Synthesis Induced by Chemoattractant fMLP to Stimulate Neutrophil Swarming
Authors: Golenkina Ekaterina A. , Galkina Svetlana I. , Pletjushkina Olga , Chernyak Boris , Gaponova Tatjana V. , Romanova Yulia M. , Sud’ina Galina F.
Published: January 2022

Leukotriene synthesis in neutrophils is critical for host survival during infection. In particular, leukotriene B4(LTB4) is a powerful neutrophil chemoattractant that plays a crucial role in neutrophil swarming. In this work, we demonstrated that preincubation of human neutrophils withSalmonella typhimuriumstrongly stimulated LTB4production induced by the bacterial chemoattractant, peptide N-formyl-L-methionyl-L-leucyl-l-phenylalanine (fMLP), while the reverse sequence of additions was ineffective. Preincubation with bacterial lipopolysaccharide or yeast polysaccharide zymosan particles gives weaker effect on fMLP-induced LTB4production. Activation of 5-lipoxygenase (5-LOX), a key enzyme in leukotrienes biosynthesis, depends on rise of cytosolic concentration of Ca2+and on translocation of the enzyme to the nuclear membrane. Both processes were stimulated byS. typhimurium. With an increase in the bacteria:neutrophil ratio, the transformation of LTB4to ω-OH-LTB4was suppressed, which further supported increased concentration of LTB4. These data indicate that in neutrophils gathered around bacterial clusters, LTB4production is stimulated and at the same time its transformation is suppressed, which promotes neutrophil swarming and elimination of pathogens simultaneously.
The Human Dive Reflex During Consecutive Apnoeas in Dry and Immersive Environments: Magnitude and Synchronicity
Authors: Nordine Michael , Schwarz Anton , Bruckstein Renana , Gunga Hanns-Christian , Opatz Oliver
Published: January 2022

Introduction: The human dive reflex (HDR), an O2 conserving reflex, is characterised by an interplay of central parasympathetic and peripheral sympathetic reactions, which are presumed to operate independently of each other. The HDR is fully activated during apnoea with facial immersion in water and complete immersion in water is thought to increase the magnitude of HDR during consecutive apnoeas. A comparison of HDR activity between consecutive apnoeas in full-body immersion with consecutive apnoeas in dry conditions has not been fully explored. Also, the interplay between parasympathetic and sympathetic reactions involved in the HDR has not been thoroughly analysed.

Methods: 11 human volunteers performed 3 consecutive 60 s apnoeas with facial immersion in dry conditions (FIDC) and 3 consecutive apnoeas with facial immersion in full immersion (FIFI). Heart rate (HR), R-R interval (RRI), finger pulse amplitude (FPA), splenic width (SW) and SpO2 were all measured before, during and after apnoeas. A one-way ANOVA using Dunn’s post hoc test was performed to assess HDR activity, and a Pearson’s correlation test was performed to assess HDR synchronisation between physiological parameters during both conditions.

Results: Although HDR activity was not significantly different between both conditions, HR and RRI showed progressively greater changes during FIFI compared with FIDC, while SW and FPA changes were relatively equivalent. During FIDC, significant correlations were found between SW & SpO2 and FPA & SpO2. During FIFI, significant correlations were found between RRI & FPA, SW & FPA, HR & SpO2 and FPA & SpO2.

Discussion: While there was no significant difference found between HDR activity during FIDC and FIFI, consecutive apnoeas during FIFI triggered a greater magnitude of cardiac activity. Furthermore, significant correlations between RRI and SW with FPA indicate a crosstalk between parasympathetic tone with splenic contraction and increased peripheral sympathetic outflow during FIFI compared to FIDC. In conclusion, HDR activity during consecutive apnoeas does not differ between FIDC and FIFI. There appears to be however a greater level of synchronicity during apnoeas in FIFI compared to FIDC and that this is most likely due to the physiological effects of immersion, which could induce neural recruitment and increased cross talk of HDR pathways.
Effect of the Knee and Hip Angles on Knee Extensor Torque: Neural, Architectural, and Mechanical Considerations
Authors: Garnier Yoann M. , Lepers Romuald , Canepa Patrizio , Martin Alain , Paizis Christos
Published: January 2022

This study examined the influence of knee extensors’ hip and knee angle on force production capacity and their neuromuscular and architectural consequences. Sixteen healthy men performed sub-maximal and maximal voluntary isometric contractions (MVIC) of knee extensors with four different combinations of the knee and hip angles. Muscle architecture, excitation-contraction coupling process, muscular activity, and corticospinal excitability were evaluated on the vastus lateralis (VL) and rectus femoris (RF) muscles. MVIC and evoked peak twitch (Pt) torques of knee extensors increased significantly (p < 0.05) by 42 ± 12% and 47 ± 16% on average, respectively, under knee flexed positions (110° flexion, 0° = full extension) compared to knee extended positions (20° flexion) but were not different between hip positions (i.e., 0° or 60° flexion). Knee flexion also affected VL and RF muscle and fascicle lengths toward greater length than under knee extended position, while pennation angle decreased for both muscles with knee flexion. Pennation angles of the VL muscle were also lower under extended hip positions. Alternatively, no change in maximal muscle activation or corticospinal activity occurred for the VL and RF muscles across the different positions. Altogether these findings evidenced that MVIC torque of knee extensors depended particularly upon peripheral contractile elements, such as VL and RF muscle and fascicle lengths, but was unaffected by central factors (i.e., muscle activation). Furthermore, the hip position can affect the pennation angle of the VL, while VL muscle length can affect the pennation angle of the RF muscle. These elements suggest that the VL and RF muscles exert a mutual influence on their architecture, probably related to the rectus-vastus aponeurosis.
Association Between Basal Metabolic Rate and All-Cause Mortality in a Prospective Cohort of Southern Chinese Adults
Authors: Han Fengyu , Hu Feng , Wang Tao , Zhou Wei , Zhu Linjuan , Huang Xiao , Bao Huihui , Cheng Xiaoshu
Published: January 2022

Objective: The aim of this study was to assess the relationship between basal metabolic rate (BMR) and all-cause mortality in southern Chinese adults.

Methods: We prospectively examined the relationship between BMR and all-cause mortality in 12,608 Southern Chinese adults with age ≥ 35 years who participated in the National Key R&D Program from 2013–2014 to 2019–2020. Cox proportional hazard models were used to examine the association between BMR and all-cause mortality.

Results: A total of 809 deaths (including 478 men and 331 women) occurred during a median follow-up period of 5.60 years. All-cause mortality was higher in elderly individuals than in non-elderly individuals (11.48 vs. 2.04%, P < 0.001) and was higher in male subjects than in female subjects (9.84 vs. 4.56%, P < 0.001). There was a significantly inverse relationship between BMR levels and all-cause mortality in elderly male individuals (adjusted-HR per SD increase: 0.80, 95% CI: 0.70–0.91, P < 0.001). Compared with BMR levels ≤ 1,115 kJ/day, there was lower all-cause mortality in third and highest BMR quartiles in the elderly male subjects (adjusted-HR: 0.71, 95% CI: 0.53–0.95, P = 0.022; adjusted-HR: 0.60, 95% CI: 0.43–0.84, P = 0.003, respectively).

Conclusion: An elevated BMR was independently inversely associated with all-cause mortality in elderly male subjects in a southern Chinese population.
Multiplexed Genome Editing via an RNA Polymerase II Promoter-Driven sgRNA Array in the Diatom Phaeodactylum tricornutum: Insights Into the Role of StLDP
Authors: Taparia Yogesh , Dolui Achintya Kumar , Boussiba Sammy , Khozin-Goldberg Inna
Published: January 2022

CRISPR/Cas9-mediated genome editing has been demonstrated in the model diatom P. tricornutum, yet the currently available genetic tools do not combine the various advantageous features into a single, easy-to-assemble, modular construct that would allow the multiplexed targeting and creation of marker-free genome-edited lines. In this report, we describe the construction of the first modular two-component transcriptional unit system expressing SpCas9 from a diatom episome, assembled using the Universal Loop plasmid kit for Golden Gate assembly. We compared the editing efficiency of two constructs with orthogonal promoter-terminator combinations targeting the StLDP gene, encoding the major lipid droplet protein of P. tricornutum. Multiplexed targeting of the StLDP gene was confirmed via PCR screening, and lines with homozygous deletions were isolated from primary exconjugants. An editing efficiency ranging from 6.7 to 13.8% was observed in the better performing construct. Selected gene-edited lines displayed growth impairment, altered morphology, and the formation of lipid droplets during nutrient-replete growth. Under nitrogen deprivation, oversized lipid droplets were observed; the recovery of cell proliferation and degradation of lipid droplets were impaired after nitrogen replenishment. The results are consistent with the key role played by StLDP in the regulation of lipid droplet size and lipid homeostasis.
Leaf Physiological Responses of Three Psammophytes to Combined Effects of Warming and Precipitation Reduction in Horqin Sandy Land, Northeast China
Authors: Huang Wen-Da , He Yuan-Zheng , Wang Huai-Hai , Zhu Yuan-Zhong
Published: January 2022

The decreasing precipitation with global climate warming is the main climatic condition in some sandy grassland ecosystems. The understanding of physiological responses of psammophytes in relation to warming and precipitation is a possible way to estimate the response of plant community stability to climate change. We selected Lespedeza davurica, Artemisia scoparia, and Cleistogenes squarrosa in sandy grassland to examine the effect of a combination of climate warming and decreasing precipitation on relative water content (RWC), chlorophyll, proline, and antioxidant enzyme activities. We found that all experimental treatments have influenced RWC, chlorophyll, proline, and antioxidant enzyme activities of three psammophytes. L. davurica has the highest leaf RWC among the three psammophytes. With the intensification of precipitation reduction, the decreasing amplitude of chlorophyll from three psammophytes was L. davurica > C. squarrosa > A. scoparia. At the natural temperature, the malondialdehyde (MDA) content of the three psammophytes under severe drought treatment was much higher than other treatments, and their increasing degree was as follows: A. scoparia > C. squarrosa > L. davurica. At the same precipitation gradient, the proline of three psammophytes under warming was higher than the natural temperature. The differences in superoxide dismutase (SOD) among the three psammophytes were A. scoparia > L. davurica > C. squarrosa. Moreover, at natural temperature, more than 40% of precipitation reduction was most significant. Regardless of warming or not, the catalase (CAT) activity of A. scoparia under reduced precipitation treatments was higher than natural temperature, while the response of L. davurica was opposite. Correlation analyses evidenced that warming (T) was significant in L. davurica and precipitation (W) was significant in A. scoparia and C. squarrosa according to the Monte-Carlo permutation test (p = 0.002, 0.004, and 0.004). The study is important in predicting how local plants will respond to future climate change and assessing the possible effects of climate change on sandy grassland ecosystems.
Genome-Wide Investigation of the Cysteine Synthase Gene Family Shows That Overexpression of CSase Confers Alkali Tolerance to Alfalfa (Medicago sativa L.)
Authors: Yuan Yuying , Song Tingting , Yu Jinqiu , Zhang Wenkai , Hou Xiangyin , Kong Ling Zelai , Cui Guowen
Published: January 2022

Alfalfa is widely grown worldwide as a perennial high-quality legume forage and as a good ecological landcover. The cysteine synthase (CSase) gene family is actively involved in plant growth and development and abiotic stress resistance but has not been systematically investigated in alfalfa. We identified 39 MsCSase genes on 4 chromosomes of the alfalfa genome. Phylogenetic analysis demonstrated that these genes were clustered into six subfamilies, and members of the same subfamily had similar physicochemical properties and sequence structures. Overexpression of the CSase gene in alfalfa increased alkali tolerance. Compared with control plants, the overexpression lines presented higher proline, soluble sugars, and cysteine and reduced glutathione contents and superoxide dismutase and peroxidase activities as well as lower hydrogen peroxide and superoxide anion contents after alkali stress. The relative expression of γ-glutamyl cysteine synthetase gene (a downstream gene of CSase) in the overexpression lines was much higher than that in the control line. The CSase gene enhanced alkalinity tolerance by regulating osmoregulatory substances and improving antioxidant capacity. These results provide a reference for studying the CSase gene family in alfalfa and expanding the alkali tolerance gene resources of forage plants.
A Mathematical Model for Characterizing the Biomass and the Physiological/Biochemical Indicators of Salvia miltiorrhiza Based on Growth-Defense Tradeoff
Authors: Wang Ke , Yan Zhu-Yun , Ma Yuntong , Li Bo , Wang Wei , Qi Luming , Jia Hongmei , Li Na , Wang Zhun
Published: January 2022

Carbon(C) and nitrogen(N) metabolisms are important for plant growth and defense, and enzymes play a major role in these two metabolisms. Current studies show that the enzymes of N Metabolism, C Metabolism, and defense are correlated with biomass. Then, we conducted this research under the assumption that enzymes could characterize the relationship based on growth-defense tradeoff, and some of the enzymes could be used to represent the plant growth. From the mechanism model, we picked out 18 physiological/biochemical indicators and obtained the data from 24 tissue culture seedlings of Salvia miltiorrhiza (S.miltiorrhiza) which were grafted with 11 endophytic fungi. Then, the relationship between the biomass and the physiological/biochemical indicators was investigated by using statistical analysis, such as correlation analysis, variable screening, and regression analysis. The results showed that many physiological/biochemical indicators, especially enzyme activities, were related to biomass accumulation. Through a rigorous logical reasoning process, we established a mathematical model of the biomass and 6 key physiological/biochemical indicators, including glutamine synthetase (GS), glutamate synthase (GLS), glutamate dehydrogenase (GDH), peroxidase (POD), catalase (CAT), and soluble protein from Cobb-Douglas production function. This model had high prediction accuracy, and it could simplify the measurement of biomass. During the artificial cultivation of S.miltiorrhiza, we can monitor the biomass accumulation by scaling the key physiological/biochemical indicators in the leaves. Interestingly, the coefficients of Lasso regression during our analysis were consistent with the mechanism of growth-defense tradeoff. Perhaps, the key physiological/biochemical indicators obtained in the statistical analysis are related to the indicators affecting biomass accumulation in practice.
Peripheralization, Political Discontent, and Social and Solidarity Economy—Case Studies From Rural Hungary and Germany
Authors: Mihály Melinda
Published: January 2022

The reintegration of Central and Eastern European (CEE) economies into globalized capitalism resulted in increasing regional polarization and the emergence of internal peripheries. The crisis of the globalized capitalist economy in 2008 resulted in the further peripheralization of rural areas, and the related crisis of representative democracies triggered rural resentment against the existing order. Inhabitants of peripheralized areas have a feeling of abandonment and political discontent. The rise of right-wing populism may be understood as a revolt of people living in precarious conditions in peripheralized areas both in Hungary and Germany. Left-wing populism, which builds on equality and social justice and is based on radical democracy, has not been able so far to reach the precaritized inhabitants of peripheralized rural areas. Solidarity economy, which is a contemporary social movement, refers to a comprehensive program aimed at transforming the entire economy, and may have the potential to address the political discontent of people living in peripheralized rural areas. In spite of the rising support for right-wing populism, social and solidarity economy (SSE) initiatives are being carried out in rural peripheries. These initiatives are based on the principles of participatory and economic democracy. Spaces provided by SSE initiatives can become forums for deliberation and co-management to develop economic democracy and become seeds of a solidarity economy movement in CEE. Therefore, based on a critical realist ethnographic approach, this paper aims to answer the question of how SSE initiatives may address the everyday material challenges and political discontent of people living in peripheralized villages by studying two SSE initiatives being carried out in two contrasting cases of peripheralization. Studying SSE initiatives in relation to 1) the locality they are embedded in, 2) “subaltern” groups within the locality, and 3) participatory, economic and 4) representative democracy helps to better understand in what ways SSE initiatives can mobilize political discontent to strengthen the solidarity economy movement in CEE.
Self-Concept as a Mediator of the Relation Between University Students’ Resilience and Academic Achievement
Authors: García-Martínez Inmaculada , Augusto-Landa José María , Quijano-López Rocío , León Samuel P.
Published: January 2022

Academic achievement is a factor of interest in both psychology and education. Determining which factors have a negative or positive influence on academic performance has produced different investigations. The present study focuses on analyzing the relationship between resilience, emotional intelligence, self-concept and the academic achievement of university students. For this purpose, different self-report tools were administered to a sample of 1,020 university students from Southern Spain. The Structural Equation-based mediational analysis suggests that there is no direct relationship between resilience and academic achievement, nor between emotional intelligence and academic achievement. Likewise, self-concept is positioned as a mediating factor in the relationship between resilience and academic achievement. The findings indicate that university students who exhibit high levels of resilience tend to cope better with difficult moments and understand and value the effort required and invested in study time. This study supports positive beliefs and behaviors for better academic achievement.
Enhancing Meaning in Life and Psychological Well-Being Among a European Cohort of Young Adults via a Gratitude Intervention
Authors: Czyżowska Natalia , Gurba Ewa
Published: January 2022

Background: Strengthening the sense of meaning in life and psychological well-being brings benefits for mental health. The group particularly vulnerable to mental problems are young adults, therefore the aim of our research was to explore how a gratitude intervention will affect the sense of meaning in life, psychological well-being, general health and perceived stress among them. The research also took into account the issue of expressing gratitude.

Method: The study involved 80 young adults (58 women and 22 men) who were randomly assigned to the experimental group that filled out the specially prepared diaries for a week (participants were asked to list three things for which they feel grateful, to whom they are grateful and if and how they expressed their gratitude) or the control group. Participants completed the Meaning in Life Questionnaire (MLQ), the General Health Questionnaire – 28 (GHQ-28), the Perceived Stress Scale (PSS), and the Ryff Scales of Psychological Well-Being (PWBS) twice (before and after intervention).

Results: In the experimental group significant increases were observed in three areas of psychological well-being: environmental mastery, relationships with others and purpose in life. The significant decrease was also noted in anxiety/insomnia and depression symptoms as well as in perceived stress. There were no differences in the level of meaning in life. There was a positive relationship between expressing gratitude and meaning in life and psychological well-being.

Conclusion: Proposed gratitude intervention has the potential to enhance psychological well-being among young adults, however, it may not be effective in enhancing meaning in life.
Character Customization With Cosmetic Microtransactions in Games: Subjective Experience and Objective Performance
Authors: Böffel Christian , Würger Sophie , Müsseler Jochen , Schlittmeier Sabine J.
Published: January 2022

Free games that are monetized by selling virtual items, such as cosmetic microtransactions for one’s avatar, seem to offer a better gaming experience to paying players. To experimentally explore this phenomenon, the effects of character customization with cosmetic microtransactions on objective and self-estimated player performance, subjective identification with the avatar, fun and the players’ perceived competence were examined in the game League of Legends. This study introduces a new laboratory-based, experimental task to objectively measure within-game player performance. Each participant performed this game-based task in two different conditions: With a character that was customized using a provided set of cosmetic microtransactions and with a default character. Results showed that customization increased subjective identification with the player character. However, objective performance measures were unaffected by this manipulation although the novel experimental approach provided reliable performance results. Additionally, identification was positively related to perceived competence, fun, and self-estimated performance. Implications for the design of cosmetic microtransactions and their influence on competitive gaming are discussed.
School Burnout Inventory: Factorial Validity, Reliability, and Measurement Invariance in a Chilean Sample of High School Students
Authors: Carmona-Halty Marcos , Mena-Chamorro Patricio , Sepúlveda-Páez Geraldy , Ferrer-Urbina Rodrigo
Published: January 2022

This brief report assessed the psychometric validity and gender invariance of the School Burnout Inventory (SBI) –a measure of students’ exhaustion, cynicism, and inadequacy– in a convenience sample of 972 high school Chilean students ranging between 12 and 18 years old. The results showed that: (1) the SBI produces adequate scores in terms of reliability; (2) two models (one solution of three related factors and one of second-order and three first-order factors) fitted adequately fit to our sample and was invariant across gender; and (3) the SBI scores were significantly related to other related constructs (i.e., study-related emotions, academic psychological capital, and academic engagement). Overall, the SBI was found to be a reliable and valid inventory to assess school burnout in Chilean high school students.
Spontaneous Facial Expressions and Micro-expressions Coding: From Brain to Face
Authors: Dong Zizhao , Wang Gang , Lu Shaoyuan , Li Jingting , Yan Wenjing , Wang Su-Jing
Published: January 2022

Facial expressions are a vital way for humans to show their perceived emotions. It is convenient for detecting and recognizing expressions or micro-expressions by annotating a lot of data in deep learning. However, the study of video-based expressions or micro-expressions requires that coders have professional knowledge and be familiar with action unit (AU) coding, leading to considerable difficulties. This paper aims to alleviate this situation. We deconstruct facial muscle movements from the motor cortex and systematically sort out the relationship among facial muscles, AU, and emotion to make more people understand coding from the basic principles:

We derived the relationship between AU and emotion based on a data-driven analysis of 5,000 images from the RAF-AU database, along with the experience of professional coders.

We discussed the complex facial motor cortical network system that generates facial movement properties, detailing the facial nucleus and the motor system associated with facial expressions.

The supporting physiological theory for AU labeling of emotions is obtained by adding facial muscle movements patterns.

We present the detailed process of emotion labeling and the detection and recognition of AU.

Based on the above research, the video's coding of spontaneous expressions and micro-expressions is concluded and prospected.