bluuebunny/crossref_metadata_2025 huggingface dataset:
Gut microbiota of white-headed black langurs (Trachypithecus leucocephalus) in responses to habitat fragmentation
Authors: Lai Ying , Chen Yanqiong , Zheng Jingjin , Liu Zheng , Nong Dengpan , Liang Jipeng , Li Youbang , Huang Zhonghao
Published: February 2023

The white-headed black langur (Trachypithecus leucocephalus) is exclusively distributed in the karst forests and is critically endangered owing to habitat fragmentation. Gut microbiota can provide physiological data for a comprehensive study of the langur’s response to human disturbance in the limestone forest; to date, data on spatial variations in the langurs’ gut microbiota are limited. In this study, we examined intersite variations in the gut microbiota of white-headed black langurs in the Guangxi Chongzuo White-headed Langur National Nature Reserve, China. Our results showed that langurs in the Bapen area with a better habitat had higher gut microbiota diversity. In the Bapen group, the Bacteroidetes (13.65% ± 9.73% vs. 4.75% ± 4.70%) and its representative family, Prevotellaceae, were significantly enriched. In the Banli group, higher relative abundance of Firmicutes (86.30% ± 8.60% vs. 78.85% ± 10.35%) than the Bapen group was observed. Oscillospiraceae (16.93% ± 5.39% vs. 16.13% ± 3.16%), Christensenellaceae (15.80% ± 4.59% vs. 11.61% ± 3.60%), and norank_o__Clostridia_UCG-014 (17.43% ± 6.64% vs. 9.78% ± 3.83%) were increased in comparison with the Bapen group. These intersite variations in microbiota diversity and composition could be accounted for by differences in food resources caused by fragmentation. Furthermore, compared with the Banli group, the community assembly of gut microbiota in the Bapen group was influenced by more deterministic factors and had a higher migration rate, but the difference between the two groups was not significant. This might be attributed to the serious fragmentation of the habitats for both groups. Our findings highlight the importance of gut microbiota response for the integrity of wildlife habitats and the need in using physiological indicators to study the mechanisms by which wildlife responds to human disturbances or ecological variations.
Alkyl ferulic acid esters: Evaluating their structure and antibacterial properties
Authors: Song Wei , Xin Jiaying , Yu Chong , Xia Chungu , Pan Yu
Published: February 2023

Ferulic acid (FA) is a natural antibacterial agent rich in plants, FA has excellent antioxidant and antibacterial properties. However, because of its short alkane chain and large polarity, FA is difficult to penetrate the soluble lipid bilayer in the biofilm to enter the cell to play an inhibitory role, limiting its biological activity. To improve the antibacterial activity of FA, with the catalytic condition of Novozym 435, four alkyl ferulic acid esters (FCs) with different alkyl chain lengths were obtained by fatty alcohols (including 1-propanol (C3), 1-hexanol (C6), nonanol (C9), and lauryl alcohol (C12)) modification. The effect of FCs on P. aeruginosa was determined by Minimum inhibitory concentrations (MIC), minimum bactericidal concentrations (MBC), Growth curves, alkaline phosphatase (AKP) activity, crystal violet method, scanning electron microscopy (SEM), membrane potential, PI, cell contents leakage. Results showed that the antibacterial activity of FCs increased after esterification, and the antibacterial activity significantly increased and then decreased with the extension of the alkyl chain of the FCs. Hexyl ferulate (FC6) showed the best antibacterial activities against E. coli and P. aeruginosa (MIC for E. coli was 0.5 mg/ml, MIC for P. aeruginosa was 0.4 mg/ml). And Propyl ferulate (FC3) and FC6 showed the best antibacterial activities S. aureus and B. subtilis (MIC for S. aureus was 0.4 mg/ml, The MIC of B. subtilis was 1.1 mg/ml). In addition, the growth, AKP activity, bacterial biofilm, bacterial cell morphology, membrane potential and cell contents leakage of P. aeruginosa after different FCs were investigated, which found that FCs could damage the cell wall of P. aeruginosa and showed different effects on the P. aeruginosa cell biofilm. FC6 showed the best inhibition on the biofilm formation of P. aeruginosa cells, which caused the surface of P. aeruginosa cells to be rough and wrinkled. Some P. aeruginosa cells showed aggregation and adhesion, even rupture. The membrane hyperpolarization was obvious, which appeared as holes, leading to cell contents leakage (protein and nucleic acid). All these results concluded that the antibacterial activities FCs against foodborne pathogens depended on different fatty alcohol esterification of FA. FC6 showed the best inhibition on P. aeruginosa due to its effect on P. aeruginosa cell walls and biofilms and the leak of the cell contents. This study provides more practical methods and a theoretical basis for giving full play to the bacteriostatic effect of plant FA.
Machine learning within the Parkinson’s progression markers initiative: Review of the current state of affairs
Authors: Gerraty Raphael T. , Provost Allison , Li Lin , Wagner Erin , Haas Magali , Lancashire Lee
Published: February 2023

The Parkinson’s Progression Markers Initiative (PPMI) has collected more than a decade’s worth of longitudinal and multi-modal data from patients, healthy controls, and at-risk individuals, including imaging, clinical, cognitive, and ‘omics’ biospecimens. Such a rich dataset presents unprecedented opportunities for biomarker discovery, patient subtyping, and prognostic prediction, but it also poses challenges that may require the development of novel methodological approaches to solve. In this review, we provide an overview of the application of machine learning methods to analyzing data from the PPMI cohort. We find that there is significant variability in the types of data, models, and validation procedures used across studies, and that much of what makes the PPMI data set unique (multi-modal and longitudinal observations) remains underutilized in most machine learning studies. We review each of these dimensions in detail and provide recommendations for future machine learning work using data from the PPMI cohort.
Anti-ganglionic acetylcholine receptor antibodies in functional neurological symptom disorder/conversion disorder
Authors: Nagata Ryusei , Matsuura Eiji , Nozuma Satoshi , Dozono Mika , Noguchi Yutaka , Ando Masahiro , Hiramatsu Yu , Kodama Daisuke , Tanaka Masakazu , Kubota Ryuji , Yamakuchi Munekazu , Higuchi Yujiro , Sakiyama Yusuke , Arata Hitoshi , Higashi Keiko , Hashiguchi Teruto , Nakane Shunya , Takashima Hiroshi
Published: February 2023

Objective

Autoimmune autonomic ganglionopathy (AAG) is a rare disorder characterized by autonomic failure associated with the presence of anti-ganglionic acetylcholine receptor (gAChR) antibodies; however, several studies have reported that individuals with anti-gAChR antibodies present with central nervous system (CNS) symptoms such as impaired consciousness and seizures. In the present study, we investigated whether the presence of serum anti-gAChR antibodies correlated with autonomic symptoms in patients with functional neurological symptom disorder/conversion disorder (FNSD/CD).

Methods

Clinical data were collected for 59 patients presenting with neurologically unexplained motor and sensory symptoms at the Department of Neurology and Geriatrics between January 2013 and October 2017 and who were ultimately diagnosed with FNSD/CD according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition. Correlations between serum anti-gAChR antibodies and clinical symptoms and laboratory data were analyzed. Data analysis was conducted in 2021.

Results

Of the 59 patients with FNSD/CD, 52 (88.1%) exhibited autonomic disturbances and 16 (27.1%) were positive for serum anti-gAChR antibodies. Cardiovascular autonomic dysfunction, including orthostatic hypotension, was significantly more prevalent (75.0 vs. 34.9%, P = 0.008), whereas involuntary movements were significantly less prevalent (31.3 vs. 69.8%, P = 0.007), among anti-gAChR antibody-positive compared with -negative patients. Anti-gAChR antibody serostatus did not correlate significantly with the frequency of other autonomic, sensory, or motor symptoms analyzed.

Conclusions

An autoimmune mechanism mediated by anti-gAChR antibodies may be involved in disease etiology in a subgroup of FNSD/CD patients.
Early-onset, conjugal, twin-discordant, and clusters of sporadic ALS: Pathway to discovery of etiology via lifetime exposome research
Authors: Spencer Peter S. , Palmer Valerie S. , Kisby Glen E. , Lagrange Emmeline , Horowitz B. Zane , Valdes Angues Raquel , Reis Jacques , Vernoux Jean-Paul , Raoul Cédric , Camu William
Published: February 2023

The identity and role of environmental factors in the etiology of sporadic amyotrophic lateral sclerosis (sALS) is poorly understood outside of three former high-incidence foci of Western Pacific ALS and a hotspot of sALS in the French Alps. In both instances, there is a strong association with exposure to DNA-damaging (genotoxic) chemicals years or decades prior to clinical onset of motor neuron disease. In light of this recent understanding, we discuss published geographic clusters of ALS, conjugal cases, single-affected twins, and young-onset cases in relation to their demographic, geographic and environmental associations but also whether, in theory, there was the possibility of exposure to genotoxic chemicals of natural or synthetic origin. Special opportunities to test for such exposures in sALS exist in southeast France, northwest Italy, Finland, the U.S. East North Central States, and in the U.S. Air Force and Space Force. Given the degree and timing of exposure to an environmental trigger of ALS may be related to the age at which the disease is expressed, research should focus on the lifetime exposome (from conception to clinical onset) of young sALS cases. Multidisciplinary research of this type may lead to the identification of ALS causation, mechanism, and primary prevention, as well as to early detection of impending ALS and pre-clinical treatment to slow development of this fatal neurological disease.
Discrepancy between inter- and intra-subject variability in EEG-based motor imagery brain-computer interface: Evidence from multiple perspectives
Authors: Huang Gan , Zhao Zhiheng , Zhang Shaorong , Hu Zhenxing , Fan Jiaming , Fu Meisong , Chen Jiale , Xiao Yaqiong , Wang Jun , Dan Guo
Published: February 2023

Introduction

Inter- and intra-subject variability are caused by the variability of the psychological and neurophysiological factors over time and across subjects. In the application of in Brain-Computer Interfaces (BCI), the existence of inter- and intra-subject variability reduced the generalization ability of machine learning models seriously, which further limited the use of BCI in real life. Although many transfer learning methods can compensate for the inter- and intra-subject variability to some extent, there is still a lack of clear understanding about the change of feature distribution between the cross-subject and cross-session electroencephalography (EEG) signal.

Methods

To investigate this issue, an online platform for motor-imagery BCI decoding has been built in this work. The EEG signal from both the multi-subject (Exp1) and multi-session (Exp2) experiments has been analyzed from multiple perspectives.

Results

Firstly we found that with the similar variability of classification results, the time-frequency response of the EEG signal within-subject in Exp2 is more consistent than cross-subject results in Exp1. Secondly, the standard deviation of the common spatial pattern (CSP) feature has a significant difference between Exp1 and Exp2. Thirdly, for model training, different strategies for the training sample selection should be applied for the cross-subject and cross-session tasks.

Discussion

All these findings have deepened the understanding of inter- and intra-subject variability. They can also guide practice for the new transfer learning methods development in EEG-based BCI. In addition, these results also proved that BCI inefficiency was not caused by the subject’s unable to generate the event-related desynchronization/synchronization (ERD/ERS) signal during the motor imagery.
Glycine receptor autoantibody binding to the extracellular domain is independent from receptor glycosylation
Authors: Rauschenberger Vera , Piro Inken , Kasaragod Vikram Babu , Hörlin Verena , Eckes Anna-Lena , Kluck Christoph J. , Schindelin Hermann , Meinck Hans-Michael , Wickel Jonathan , Geis Christian , Tüzün Erdem , Doppler Kathrin , Sommer Claudia , Villmann Carmen
Published: February 2023

Glycine receptor (GlyR) autoantibodies are associated with stiff-person syndrome and the life-threatening progressive encephalomyelitis with rigidity and myoclonus in children and adults. Patient histories show variability in symptoms and responses to therapeutic treatments. A better understanding of the autoantibody pathology is required to develop improved therapeutic strategies. So far, the underlying molecular pathomechanisms include enhanced receptor internalization and direct receptor blocking altering GlyR function. A common epitope of autoantibodies against the GlyRα1 has been previously defined to residues 1A-33G at the N-terminus of the mature GlyR extracellular domain. However, if other autoantibody binding sites exist or additional GlyR residues are involved in autoantibody binding is yet unknown. The present study investigates the importance of receptor glycosylation for binding of anti-GlyR autoantibodies. The glycine receptor α1 harbors only one glycosylation site at the amino acid residue asparagine 38 localized in close vicinity to the identified common autoantibody epitope. First, non-glycosylated GlyRs were characterized using protein biochemical approaches as well as electrophysiological recordings and molecular modeling. Molecular modeling of non-glycosylated GlyRα1 did not show major structural alterations. Moreover, non-glycosylation of the GlyRα1N38Q did not prevent the receptor from surface expression. At the functional level, the non-glycosylated GlyR demonstrated reduced glycine potency, but patient GlyR autoantibodies still bound to the surface-expressed non-glycosylated receptor protein in living cells. Efficient adsorption of GlyR autoantibodies from patient samples was possible by binding to native glycosylated and non-glycosylated GlyRα1 expressed in living not fixed transfected HEK293 cells. Binding of patient-derived GlyR autoantibodies to the non-glycosylated GlyRα1 offered the possibility to use purified non-glycosylated GlyR extracellular domain constructs coated on ELISA plates and use them as a fast screening readout for the presence of GlyR autoantibodies in patient serum samples. Following successful adsorption of patient autoantibodies by GlyR ECDs, binding to primary motoneurons and transfected cells was absent. Our results indicate that the glycine receptor autoantibody binding is independent of the receptor’s glycosylation state. Purified non-glycosylated receptor domains harbouring the autoantibody epitope thus provide, an additional reliable experimental tool besides binding to native receptors in cell-based assays for detection of autoantibody presence in patient sera.
Paclitaxel effects on axonal localization and vesicular trafficking of NaV1.8
Authors: Baker Christopher A. , Tyagi Sidharth , Higerd-Rusli Grant P. , Liu Shujun , Zhao Peng , Dib-Hajj Fadia B. , Waxman Stephen G. , Dib-Hajj Sulayman D.
Published: February 2023

Patients treated with paclitaxel (PTX) or other antineoplastic agents can experience chemotherapy-induced peripheral neuropathy (CIPN), a debilitating side effect characterized by numbness and pain. PTX interferes with microtubule-based transport, which inhibits tumor growth via cell cycle arrest but can also affect other cellular functions including trafficking of ion channels critical to transduction of stimuli by sensory neurons of the dorsal root ganglia (DRG). We examined the effects of PTX on voltage-gated sodium channel NaV1.8, which is preferentially expressed in DRG neurons, using a microfluidic chamber culture system and chemigenetic labeling to observe anterograde channel transport to the endings of DRG axons in real time. PTX treatment increased the numbers of NaV1.8-containing vesicles traversing the axons. Vesicles in PTX-treated cells exhibited greater average velocity, along with shorter and less frequent pauses along their trajectories. These events were paralleled by greater surface accumulation of NaV1.8 channels at the distal ends of DRG axons. These results were consistent with observations that NaV1.8 is trafficked in the same vesicles containing NaV1.7 channels, which are also involved in pain syndromes in humans and are similarly affected by PTX treatment. However, unlike Nav1.7, we did not detect increased NaV1.8 current density measured at the neuronal soma, suggesting a differential effect of PTX on trafficking of NaV1.8 in soma versus axonal compartments. Therapeutic targeting of axonal vesicular traffic would affect both Nav1.7 and Nav1.8 channels and increase the possibilities of alleviating pain associated with CIPN.
Body composition parameters, immunonutritional indexes, and surgical outcome of pancreatic cancer patients resected after neoadjuvant therapy: A retrospective, multicenter analysis
Authors: Paiella Salvatore , Azzolina Danila , Trestini Ilaria , Malleo Giuseppe , Nappo Gennaro , Ricci Claudio , Ingaldi Carlo , Vacca Pier Giuseppe , De Pastena Matteo , Secchettin Erica , Zamboni Giulia , Maggino Laura , Corciulo Maria Assunta , Sandini Marta , Cereda Marco , Capretti Giovanni , Casadei Riccardo , Bassi Claudio , Mansueto Giancarlo , Gregori Dario , Milella Michele , Zerbi Alessandro , Gianotti Luca , Salvia Roberto
Published: February 2023

Background and aims

Body composition parameters and immunonutritional indexes provide useful information on the nutritional and inflammatory status of patients. We sought to investigate whether they predict the postoperative outcome in patients with pancreatic cancer (PC) who received neoadjuvant therapy (NAT) and then pancreaticoduodenectomy.

Methods

Data from locally advanced PC patients who underwent NAT followed by pancreaticoduodenectomy between January 2012 and December 2019 in four high-volume institutions were collected retrospectively. Only patients with two available CT scans (before and after NAT) and immunonutritional indexes (before surgery) available were included. Body composition was assessed and immunonutritional indexes collected were: VAT, SAT, SMI, SMA, PLR, NLR, LMR, and PNI. The postoperative outcomes evaluated were overall morbidity (any complication occurring), major complications (Clavien-Dindo ≥ 3), and length of stay.

Results

One hundred twenty-one patients met the inclusion criteria and constituted the study population. The median age at the diagnosis was 64 years (IQR16), and the median BMI was 24 kg/m2 (IQR 4.1). The median time between the two CT-scan examined was 188 days (IQR 48). Skeletal muscle index (SMI) decreased after NAT, with a median delta of −7.8 cm2/m2 (p < 0.05). Major complications occurred more frequently in patients with a lower pre-NAT SMI (p = 0.035) and in those who gained in subcutaneous adipose tissue (SAT) compartment during NAT (p = 0.043). Patients with a gain in SMI experienced fewer major postoperative complications (p = 0.002). The presence of Low muscle mass after NAT was associated with a longer hospital stay [Beta 5.1, 95%CI (1.5, 8.7), p = 0.006]. An increase in SMI from 35 to 40 cm2/m2 was a protective factor with respect to overall postoperative complications [OR 0.43, 95% (CI 0.21, 0.86), p < 0.001]. None of the immunonutritional indexes investigated predicted the postoperative outcome.

Conclusion

Body composition changes during NAT are associated with surgical outcome in PC patients who receive pancreaticoduodenectomy after NAT. An increase in SMI during NAT should be favored to ameliorate the postoperative outcome. Immunonutritional indexes did not show to be capable of predicting the surgical outcome.
Association between daidzein intake and metabolic associated fatty liver disease: A cross-sectional study from NHANES 2017–2018
Authors: Yang Zheng , Gong Daoqing , He Xinxiang , Huang Fei , Sun Yi , Hu Qinming
Published: February 2023

Background

Metabolic associated fatty liver disease (MAFLD) has become the most common liver disease globally, yet no new drugs have been approved for clinical treatment. Therefore, we investigated the relationship between dietary intake of soy-derived daidzein and MAFLD, to find potentially effective treatments.

Methods

We conducted a cross-sectional study using data from 1,476 participants in National Health and Nutrition Examination Survey (NHANES) from 2017 to 2018 and their associated daidzein intake from the flavonoid database in the USDA Food and Nutrient Database for Dietary Studies (FNDDS). We investigated the relationship between MAFLD status, controlled attenuation parameter (CAP), AST/Platelet Ratio Index (APRI), Fibrosis-4 Index (FIB-4), liver stiffness measurement (LSM), nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS), hepatic steatosis index (HSI), fatty liver index (FLI), and daidzein intake by adjusting for confounding variables using binary logistic regression models and linear regression models.

Results

In the multivariable-adjusted model II, there was a negative association between daidzein intake and the incidence of MAFLD (OR for Q4 versus Q1 was 0.65, 95% confidence interval [CI] = 0.46–0.91, p = 0.0114, p for trend was 0.0190). CAP was also negatively associated with daidzein intake, β = −0.37, 95% CI: −0.63 to −0.12, p = 0.0046 in model II after adjusting for age, sex, race, marital status, education level, family income-to-poverty ratio (PIR), smoking, and alcohol consumption. Stratified by quartiles of daidzein intake, trend analysis of the relationship between daidzein intake and CAP remained significant (p for trend = 0.0054). In addition, we also found that HSI, FLI, and NFS were negatively correlated with daidzein intake. LSM was negatively related to daidzein intake but had no statistical significance. The correlation between APRI, FIB-4, and daidzein intake was not strong (although p < 0.05, β values were all 0).

Conclusion

We found that MAFLD prevalence, CAP, HSI, and FLI, all decreased with increased daidzein intake, suggesting that daidzein intake may improve hepatic steatosis. Therefore, dietary patterns of soy food or supplement consumption may be a valuable strategy to reduce the disease burden and the prevalence of MAFLD.
Two simple-to-use web-based nomograms to predict overall survival and cancer-specific survival in patients with extremity fibrosarcoma
Authors: Li Yubo , Yang Jianing , Zhao Long , Chen Bin , An Yongsheng
Published: February 2023

Background

Fibrosarcoma is a rare sarcoma of the soft tissue in adults, occurring most commonly in the extremities. This study aimed to construct two web-based nomograms to predict overall survival (OS) and cancer-specific survival (CSS) in patients with extremity fibrosarcoma (EF) and validate it with multicenter data from the Asian/Chinese population.

Method

Patients with EF in the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015 were included in this study and were randomly divided into a training cohort and a verification cohort. The nomogram was developed based on the independent prognostic factors determined by univariate and multivariate Cox proportional hazard regression analyses. The predictive accuracy of the nomogram was validated with the Harrell’s concordance index (C-index), receiver operating curve, and calibration curve. Decision curve analysis (DCA) was utilized to compare the clinical usefulness between the novel model and the existing staging system.

Result

A total of 931 patients finally were obtained in our study. Multivariate Cox analysis determined five independent prognostic factors for OS and CSS, namely, age, M stage, tumor size, grade, and surgery. The nomogram and the corresponding web-based calculator were developed to predict OS (https://orthosurgery.shinyapps.io/osnomogram/) and CSS (https://orthosurgery.shinyapps.io/cssnomogram/) probability at 24, 36, and 48 months. The C-index of the nomogram was 0.784 in the training cohort and 0.825 in the verification cohort for OS and 0.798 in the training cohort and 0.813 in the verification cohort for CSS, respectively, indicating excellent predictive performance. The calibration curves showed excellent agreement between the prediction by the nomogram and actual outcomes. Additionally, the results of DCA showed that the newly proposed nomogram was significantly better than the conventional staging system with more clinical net benefits. The Kaplan–Meier survival curves showed that patients assigned into the low-risk group had a more satisfactory survival outcome than the high-risk group.

Conclusion

In this study, we constructed two nomograms and web-based survival calculators including five independent prognostic factors for the survival prediction of patients with EF, which could help clinicians make personalized clinical decisions.
A molecular study of pediatric pilomyxoid and pilocytic astrocytomas: Genome-wide copy number screening, retrospective analysis of clinicopathological features and long-term clinical outcome
Authors: AlShail Essam , Alahmari Ahmed Nasser , Dababo Anas A. M. , Alsagob Maysoon , Al-Hindi Hindi , Khalil Hala , Al Masseri Zainab , AlSalamah Razan , Almohseny Ethar , Alduhaish Amjad , Colak Dilek , Kaya Namik
Published: February 2023

Background

Pilocytic Astrocytoma (PA) is the most common pediatric brain tumors. PAs are slow-growing tumors with high survival rates. However, a distinct subgroup of tumors defined as pilomyxoid astrocytoma (PMA) presents unique histological characteristics and have more aggressive clinical course. The studies on genetics of PMA are scarce.

Methods

In this study, we report one of the largest cohort of pediatric patients with pilomyxoid (PMA) and pilocytic astrocytomas (PA) in Saudi population providing a comprehensive clinical picture, retrospective analysis with long-term follow-up, genome-wide copy number changes, and clinical outcome of these pediatric tumors. We examined and compared genome-wide copy number aberrations (CNAs) and the clinical outcome of the patients with PA and PMA.

Results

The median progression free survival for the whole cohort was 156 months and it was 111 months for the PMA, however, not statistically significantly different between the groups (log-rank test, P = 0.726). We have identified 41 CNAs (34 gains and 7 losses) in all tested patients. Our study yielded the previously reported KIAA1549-BRAF Fusion gene in over 88% of the tested patients (89% and 80% in PMA and PA, respectively). Besides the fusion gene, twelve patients had additional genomic CNAs. Furthermore, pathway and gene network analyses of genes in the fusion region revealed alterations in retinoic acid mediated apoptosis and MAPK signaling pathways and key hub genes that may potentially be involved in tumor growth and progression, including BRAF, LUC7L2, MKRN1, RICTOR, TP53, HIPK2, HNF4A, POU5F, and SOX4.

Conclusion

Our study is the first report of a large cohort of patients with PMA and PA in the Saudi population that provides detailed clinical features, genomic copy number changes, and outcome of these pediatric tumors and may help better diagnosis and characterization of PMA.
The emerging role of microtubules in invasion plasticity
Authors: Legátová Anna , Pelantová Markéta , Rösel Daniel , Brábek Jan , Škarková Aneta
Published: February 2023

The ability of cells to switch between different invasive modes during metastasis, also known as invasion plasticity, is an important characteristic of tumor cells that makes them able to resist treatment targeted to a particular invasion mode. Due to the rapid changes in cell morphology during the transition between mesenchymal and amoeboid invasion, it is evident that this process requires remodeling of the cytoskeleton. Although the role of the actin cytoskeleton in cell invasion and plasticity is already quite well described, the contribution of microtubules is not yet fully clarified. It is not easy to infer whether destabilization of microtubules leads to higher invasiveness or the opposite since the complex microtubular network acts differently in diverse invasive modes. While mesenchymal migration typically requires microtubules at the leading edge of migrating cells to stabilize protrusions and form adhesive structures, amoeboid invasion is possible even in the absence of long, stable microtubules, albeit there are also cases of amoeboid cells where microtubules contribute to effective migration. Moreover, complex crosstalk of microtubules with other cytoskeletal networks participates in invasion regulation. Altogether, microtubules play an important role in tumor cell plasticity and can be therefore targeted to affect not only cell proliferation but also invasive properties of migrating cells.
Diagnosis potential of subarachnoid hemorrhage using miRNA signatures isolated from plasma-derived extracellular vesicles
Authors: Sheng Bin , Lai Niansheng , Tao Tao , Chen Xiangxin , Gao Sen , Zhu Qi , Li Wei , Zhang Qingrong , Hang Chunhua
Published: February 2023

The diagnosis and clinical management of aneurysmal subarachnoid hemorrhage (aSAH) is currently limited by the lack of accessible molecular biomarkers that reflect the pathophysiology of disease. We used microRNAs (miRNAs) as diagnostics to characterize plasma extracellular vesicles in aSAH. It is unclear whether they can diagnose and manage aSAH. Next-generation sequencing (NGS) was used to detect the miRNA profile of plasma extracellular vesicles (exosomes) in three patients with SAH and three healthy controls (HCs). We identified four differentially expressed miRNAs and validated the results using quantitative real-time polymerase chain reaction (RT-qPCR) with 113 aSAH patients, 40 HCs, 20 SAH model mice, and 20 sham mice. Exosomal miRNA NGS revealed that six circulating exosomal miRNAs were differentially expressed in patients with aSAH versus HCs and that the levels of four miRNAs (miR-369-3p, miR-410-3p, miR-193b-3p, and miR-486-3p) were differentially significant. After multivariate logistic regression analysis, only miR-369-3p, miR-486-3p, and miR-193b-3p enabled prediction of neurological outcomes. In a mouse model of SAH, greater expression of miR-193b-3p and miR-486-3p remained statistically significant relative to controls, whereas expression levels of miR-369-3p and miR-410-3p were lower. miRNA gene target prediction showed six genes associated with all four of these differentially expressed miRNAs. The circulating exosomes miR-369-3p, miR-410-3p, miR-193b-3p, and miR-486-3p may influence intercellular communication and have potential clinical utility as prognostic biomarkers for aSAH patients.
The multifaceted roles of natural products in mitochondrial dysfunction
Authors: Chen Qianrun , Ruan Danhua , Shi Jiayan , Du Dongru , Bian Ce
Published: February 2023

Mitochondria are the primary source of energy production in cells, supporting the metabolic demand of tissue. The dysfunctional mitochondria are implicated in various diseases ranging from neurodegeneration to cancer. Therefore, regulating dysfunctional mitochondria offers a new therapeutic opportunity for diseases with mitochondrial dysfunction. Natural products are pleiotropic and readily obtainable sources of therapeutic agents, which have broad prospects in new drug discovery. Recently, many mitochondria-targeting natural products have been extensively studied and have shown promising pharmacological activity in regulating mitochondrial dysfunction. Hence, we summarize recent advances in natural products in targeting mitochondria and regulating mitochondrial dysfunction in this review. We discuss natural products in terms of their mechanisms on mitochondrial dysfunction, including modulating mitochondrial quality control system and regulating mitochondrial functions. In addition, we describe the future perspective and challenges in the development of mitochondria-targeting natural products, emphasizing the potential value of natural products in mitochondrial dysfunction.
Drug resistance mechanism of kinase inhibitors in the treatment of hepatocellular carcinoma
Authors: Jiang Lei , Li Luan , Liu Yongzhuang , Zhan Meixiao , Lu Ligong , Yuan Shengtao , Liu Yanyan
Published: February 2023

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, and it usually occurs following chronic liver disease. Although some progress has been made in the treatment of HCC, the prognosis of patients with advanced HCC is not optimistic, mainly because of the inevitable development of drug resistance. Therefore, multi-target kinase inhibitors for the treatment of HCC, such as sorafenib, lenvatinib, cabozantinib, and regorafenib, produce small clinical benefits for patients with HCC. It is necessary to study the mechanism of kinase inhibitor resistance and explore possible solutions to overcome this resistance to improve clinical benefits. In this study, we reviewed the mechanisms of resistance to multi-target kinase inhibitors in HCC and discussed strategies that can be used to improve treatment outcomes.
The dual role of heme oxygenase in regulating apoptosis in the nervous system of Drosophila melanogaster
Authors: Abaquita Terence Al L. , Damulewicz Milena , Tylko Grzegorz , Pyza Elżbieta
Published: February 2023

Accumulating evidence from mammalian studies suggests the dual-faced character of heme oxygenase (HO) in oxidative stress-dependent neurodegeneration. The present study aimed to investigate both neuroprotective and neurotoxic effects of heme oxygenase after the ho gene chronic overexpression or silencing in neurons of Drosophila melanogaster. Our results showed early deaths and behavioral defects after pan-neuronal ho overexpression, while survival and climbing in a strain with pan-neuronal ho silencing were similar over time with its parental controls. We also found that HO can be pro-apoptotic or anti-apoptotic under different conditions. In young (7-day-old) flies, both the cell death activator gene (hid) expression and the initiator caspase Dronc activity increased in heads of flies when ho expression was changed. In addition, various expression levels of ho produced cell-specific degeneration. Dopaminergic (DA) neurons and retina photoreceptors are particularly vulnerable to changes in ho expression. In older (30-day-old) flies, we did not detect any further increase in hid expression or enhanced degeneration, however, we still observed high activity of the initiator caspase. In addition, we used curcumin to further show the involvement of neuronal HO in the regulation of apoptosis. Under normal conditions, curcumin induced both the expression of ho and hid, which was reversed after exposure to high-temperature stress and when supplemented in flies with ho silencing. These results indicate that neuronal HO regulates apoptosis and this process depends on ho expression level, age of flies, and cell type.
Exposure of chlorothalonil and acetamiprid reduce the survival and cause multiple internal disturbances in Apis mellifera larvae reared in vitro
Authors: Lu Ying , Gao Jing , Wu Tong , Han Bo , Qian Bingnan , Shi Min , Yang Sa , Diao Qingyun , Bu Chunya , Dai Pingli
Published: February 2023

Background: Chlorothalonil and acetamiprid are chemical pesticides commonly used in agricultural production and have been shown to have negative effects on bee’s fitness. Despite many studies have revealed that honey bee (Apis mellifera L.) larvae are posting a high risk on exposure to pesticides, but the toxicology information of chlorothalonil and acetamiprid on bee larvae remain limited.

Results: The no observed adverse effect concentration (NOAEC) of chlorothalonil and acetamiprid for honey bee larvae were 4 μg/mL and 2 μg/mL, respectively. Except for CarE, the enzymic activities of GST and P450 were not influenced by chlorothalonil at NOAEC, while chronic exposure to acetamiprid slightly increased the activities of the three tested enzymes at NOAEC. Further, the exposed larvae showed significantly higher expression of genes involved in a series of different toxicologically relevant process following, including caste development (Tor (GB44905), InR-2 (GB55425), Hr4 (GB47037), Ac3 (GB11637) and ILP-2 (GB10174)), immune system response (abaecin (GB18323), defensin-1 (GB19392), toll-X4 (GB50418)), and oxidative stress response (P450, GSH, GST, CarE).

Conclusion: Our results suggest that the exposure to chlorothalonil and acetamiprid, even at concentrations below the NOAEC, showed potentially effects on bee larvae’s fitness, and more important synergistic and behavioral effects that can affect larvae fitness should be explored in the further.
Beyond conventional microscopy: Observing kidney tissues by means of fourier ptychography
Authors: Valentino Marika , Bianco Vittorio , Miccio Lisa , Memmolo Pasquale , Brancato Valentina , Libretti Paolo , Gambacorta Marcello , Salvatore Marco , Ferraro Pietro
Published: February 2023

Kidney microscopy is a mainstay in studying the morphological structure, physiology and pathology of kidney tissues, as histology provides important results for a reliable diagnosis. A microscopy modality providing at same time high-resolution images and a wide field of view could be very useful for analyzing the whole architecture and the functioning of the renal tissue. Recently, Fourier Ptychography (FP) has been proofed to yield images of biology samples such as tissues and in vitro cells while providing high resolution and large field of view, thus making it a unique and attractive opportunity for histopathology. Moreover, FP offers tissue imaging with high contrast assuring visualization of small desirable features, although with a stain-free mode that avoids any chemical process in histopathology. Here we report an experimental measuring campaign for creating the first comprehensive and extensive collection of images of kidney tissues captured by this FP microscope. We show that FP microscopy unlocks a new opportunity for the physicians to observe and judge renal tissue slides through the novel FP quantitative phase-contrast microscopy. Phase-contrast images of kidney tissue are analyzed by comparing them with the corresponding renal images taken under a conventional bright-field microscope both for stained and unstained tissue samples of different thicknesses. In depth discussion on the advantages and limitations of this new stain-free microscopy modality is reported, showing its usefulness over the classical light microscopy and opening a potential route for using FP in clinical practice for histopathology of kidney.
A physiological comparison of the new—over 70 years of age—marathon record holder and his predecessor: A case report
Authors: Van Hooren Bas , Lepers Romuald
Published: February 2023

Purpose: This study assessed the body composition, cardiorespiratory fitness, fiber type and mitochondrial function, and training characteristics of a 71-year-old runner who broke the world record marathon of the men’s 70–74 age category and held several other world records. The values were compared to those of the previous world-record holder.

Methods: Body fat percentage was assessed using air-displacement plethysmography. V˙O2max, running economy, and maximum heart rate were measured during treadmill running. Muscle fiber typology and mitochondrial function were evaluated using a muscle biopsy.

Results: Body fat percentage was 13.5%, V˙O2max was 46.6 ml kg−1 min−1, and maximum heartrate was 160 beats∙min-1. At the marathon pace (14.5 km h−1), his running economy was 170.5 ml kg−1 km−1. The gas exchange threshold and respiratory compensation point occurred at 75.7% and 93.9% of the V˙O2max, i.e., 13 km h−1 and 15 km h−1, respectively. The oxygen uptake at the marathon pace corresponded to 88.5% of V˙O2max. Vastus lateralis fiber content was 90.3% type I and 9.7% type II. Average distance was 139 km∙w−1 in the year prior to the record.

Conclusion: The 71-year-old world-record holder marathon showed a relatively similar V˙O2max, lower percentage of V˙O2max at marathon pace, but a substantially better running economy than his predecessor. The better running economy may result from an almost double weekly training volume compared to the predecessor and a high type I fiber content. He trained every day in the last ∼1.5 years and achieved international performance in his age group category with a small (<5% per decade) age-related decline in marathon performance.
The transcription factor MebHLH18 in cassava functions in decreasing low temperature-induced leaf abscission to promote low-temperature tolerance
Authors: Liao Wenbin , Cai Jie , Xu Haixia , Wang Yilin , Cao Yingjie , Ruan Mengbin , Chen Songbi , Peng Ming
Published: February 2023

The reactive oxygen species (ROS) signal regulates stress-induced leaf abscission in cassava. The relationship between the function of the cassava transcription factor bHLH gene and low temperature-induced leaf abscission is still unclear. Here, we report that MebHLH18, a transcription factor, involved in regulating low temperature-induced leaf abscission in cassava. The expression of the MebHLH18 gene was significantly related to low temperature-induced leaf abscission and POD level. Under low temperatures, the levels of ROS scavengers in different cassava genotypes were significantly different in the low temperature-induced leaf abscission process. Cassava gene transformation showed that MebHLH18 overexpression significantly decreased the low temperature-induced leaf abscission rate. Simultaneously, interference expression increased the rate of leaf abscission under the same conditions. ROS analysis showed a connection between the decrease in the low temperature-induced leaf abscission rate caused by MebHLH18 expression and the increase in antioxidant activity. A Genome-wide association studies analysis showed a relationship between the natural variation of the promoter region of MebHLH18 and low temperature-induced leaf abscission. Furthermore, studies showed that the change in MebHLH18 expression was caused by a single nucleotide polymorphism variation in the promoter region upstream of the gene. The high expression of MebHLH18 led to a significant increase in POD activity. The increased POD activity decreased the accumulation of ROS at low temperatures and the rate of leaf abscission. It indicates that the natural variation in the promoter region of MebHLH18 increases antioxidant levels under low temperatures and slows down low temperature-induced leaf abscission.
Insights into taxonomy and phylogenetic relationships of eleven Aristolochia species based on chloroplast genome
Authors: Bai Xuanjiao , Wang Gang , Ren Ying , Su Yuying , Han Jinping
Published: February 2023

Introduction

The Aristolochia, as an important genus comprised of over 400 species, has attracted much interest because of its unique chemical and pharmacological properties. However, the intrageneric taxonomy and species identification within Aristolochia have long been difficult because of the complexity of their morphological variations and lack of high-resolution molecular markers.

Methods

In this study, we sampled 11 species of Aristolochia collected from distinct habitats in China, and sequenced their complete chloroplast (cp) genomes.

Results

The 11 cp genomes of Aristolochia ranged in size from 159,375bp (A. tagala) to 160,626 bp (A. tubiflora), each containing a large single-copy (LSC) region (88,914-90,251 bp), a small single-copy (SSC) region (19,311-19,917 bp), and a pair of inverted repeats (IR) (25,175-25,698 bp). These cp genomes contained 130-131 genes each, including 85 protein-coding genes (CDS), 8 ribosomal RNA genes, and 37-38 transfer RNA genes. In addition, the four types of repeats (forward, palindromic, reverse, and complement repeats) were examined in Aristolochia species. A. littoralis had the highest number of repeats (168), while A. tagala had the lowest number (42). The total number of simple sequence repeats (SSRs) is at least 99 in A. kwangsiensis, and, at most, 161 in A. gigantea. Interestingly, we detected eleven highly mutational hotspot regions, including six gene regions (clpP, matK, ndhF, psbT, rps16, trnK-UUU) and five intergenic spacer regions (ccsA-ndhD, psbZ-trnG-GCC, rpl33-rps18, rps16-trnQ-UUG, trnS-GCU-trnG-UCC). The phylogenetic analysis based on the 72 protein-coding genes showed that 11 Aristolochia species were divided into two clades which strongly supported the generic segregates of the subgenus Aristolochia and Siphisia.

Discussion

This research will provide the basis for the classification, identification, and phylogeny of medicinal plants of Aristolochiaceae.
Remixing war: An analysis of the reimagination of the Russian–Ukraine war on TikTok
Authors: Primig Florian , Szabó Hanna Dorottya , Lacasa Pilar
Published: February 2023

Interpretative struggles of global crises are increasingly being reflected on social media networks. TikTok is a relatively new social media platform that has achieved substantial popularity among young people in many parts of the world and is now being used to disseminate and make sense of information about the Russian invasion of Ukraine. Through a user-centered sampling approach, we collected 62 TikTok videos and conducted an in-depth qualitative analysis of them and their uploading profiles to explore how the war was being represented on the platform. Our analysis revealed a strong prevalence of remixing practices among content creators; that is, they recontextualise images, sounds and embodied self-performance within the platform-specific affordances of trends. We found that distant suffering is mediated through the emotive online self-performance of content creators, cuing their audiences toward appropriate emotional responses. Trending sounds situate videos within a singular-motif and context-diverse environment, facilitating what we theorize asaffective audio networks.
Cognitive-pragmatic functions of mitigation in therapeutic conversations emphasizing rapport management
Authors: Cheng Lulu , Mao Haoran , Zhang Ting
Published: February 2023

Based on conversations between 15 clients and 5 therapists in the context of daily treatment, this study investigated therapist-client linguistic mitigation in a natural setting. The study found that (1) the therapists and clients mainly used three major types of mitigation, among which illocutionary mitigation and propositional mitigation were employed more frequently. Furthermore, direct dissuasion and disclaimers, as subtypes of mitigators, were the most regularly employed by therapists and clients, respectively. (2) Through cognitive-pragmatic interpretation under rapport management theory, it was found that mitigation in the therapist-client conversations mainly performed cognitive-pragmatic functions in giving the means to preserve positive face, maintaining social rights and concentrating on interactive goals, which were interpenetrated with each other in therapeutic conversations. (3) This study proposed that three cognitive-pragmatic functions jointly devoted to a rapport in therapeutic relationship to reduce therapeutic risk of conflicts.