bluuebunny/crossref_metadata_2025 huggingface dataset:
The RNA-Binding and RNA-Melting Activities of the Multifunctional Protein Nucleobindin 1
Authors: Mikhaylina Alisa , Svoeglazova Arina , Stolboushkina Elena , Tishchenko Svetlana , Kostareva Olga
Published: March 2023

Nucleobindin 1 (NUCB1) is a ubiquitous multidomain protein that belongs to the EF-hand Ca2+-binding superfamily. NUCB1 interacts with Galphai3 protein, cyclooxygenase, amyloid precursor protein, and lipids. It is involved in stress response and human diseases. In addition, this protein is a transcription factor that binds to the DNA E-box motif. Using surface plasmon resonance and molecular beacon approaches, we first showed the RNA binding and RNA melting activities of NUCB1. We suggest that NUCB1 could induce local changes in structured RNAs via binding to the GGAUAU loop sequence. Our results demonstrate the importance of the multidomain structure of NUCB1 for its RNA-chaperone activity in vitro.
Hypoxia-Inducible Factor 1-Alpha and Glucose Metabolism during Cardiac Remodeling Progression from Hypertrophy to Heart Failure
Authors: Sant’Ana Paula Grippa , Tomasi Loreta Casquel de , Murata Gilson Masahiro , Vileigas Danielle Fernandes , Mota Gustavo Augusto Ferreira , Souza Sérgio Luiz Borges de , Silva Vitor Loureiro , Campos Livia Paschoalino de , Okoshi Katashi , Padovani Carlos Roberto , Cicogna Antonio Carlos
Published: March 2023

In pathological cardiac hypertrophy, the heart is more dependent on glucose than fatty acids. This shift in energy metabolism occurs due to several factors, including the oxygen deficit, which activates hypoxia-inducible factor-1α (HIF-1α), a critical molecule related to glucose metabolism. However, there are gaps regarding the behavior of key proteins in the glycolytic pathway and HIF-1α during the transition from hypertrophy to heart failure (HF). This study assesses the hypothesis that there is an early change and enhancement of HIF-1α and the glycolytic pathway, as well as an association between them during cardiac remodeling. Sham and aortic stenosis Wistar rats were analyzed at 2, 6, and 18 weeks and in HF (n = 10–18). Cardiac structure and function were investigated by echocardiogram. Myocardial glycolysis, the aerobic and anaerobic pathways and glycogen were analyzed by enzymatic assay, Western blot, and enzyme-linked immunosorbent assay (ELISA). The following were observed: increased left ventricular hypertrophy; early diastolic function change and severe systolic and diastolic dysfunction in HF; increased HIF-1α in the 2nd week and in HF; precocious alteration and intensification of glycolysis with a shift to anaerobic metabolism from the 6th week onwards; association between HIF-1α, glycolysis, and the anaerobic pathway. Our hypothesis was confirmed as there was an early change and intensification in glucose metabolism, alteration in HIF-1α, and an association between data during the progression from hypertrophy to heart failure.
Integrated Physiological and Transcriptomic Analyses Revealed Improved Cold Tolerance in Cucumber (Cucumis sativus L.) by Exogenous Chitosan Oligosaccharide
Authors: Tan Chong , Li Na , Wang Yidan , Yu Xuejing , Yang Lu , Cao Ruifang , Ye Xueling
Published: March 2023

Cucumber (Cucumis sativus L.), sensitive to cold stress, is one of the most economically important vegetables. Here, we systematically investigated the roles of exogenous glycine betaine, chitosan, and chitosan oligosaccharide in alleviating cold stress in cucumber seedlings. The results showed that 50 mg·L−1 chitosan oligosaccharide had the best activity. It effectively increases plant growth, chlorophyll content, photosynthetic capacity, osmotic regulatory substance content, and antioxidant enzyme activities while reducing relative electrical conductivity and malondialdehyde levels in cucumber seedlings under cold stress. To reveal the protective effects of chitosan oligosaccharide in cold stress, cucumber seedlings pretreated with 50 mg·L−1 chitosan oligosaccharide were sampled after 0, 3, 12, and 24 h of cold stress for transcriptome analysis, with distilled water as a control. The numbers of differentially expressed genes in the four comparison groups were 656, 1274, 1122, and 957, respectively. GO functional annotation suggested that these genes were mainly involved in “voltage-gated calcium channel activity”, “carbohydrate metabolic process”, “jasmonic acid biosynthetic”, and “auxin response” biological processes. KEGG enrichment analysis indicated that these genes performed important functions in “phenylpropanoid biosynthesis”, “MAPK signaling pathway—plant”, “phenylalanine metabolism”, and “plant hormone signal transduction.” These findings provide a theoretical basis for the use of COS to alleviate the damage caused by cold stress in plant growth and development.
Peruvian Amaranth (kiwicha) Accumulates Higher Levels of the Unsaturated Linoleic Acid
Authors: Kanbar Adnan , Beisel Julia , Gutierrez Meylin Terrel , Graeff-Hönninger Simone , Nick Peter
Published: March 2023

Grain amaranth (Amaranthus spp.) is an emerging crop rich in proteins and other valuable nutrients. It was domesticated twice, in Mexico and Peru. Although global trade is dominated by Mexican species of amaranth, Peruvian amaranth (A. caudatus, kiwicha) has remained neglected, although it harbours valuable traits. In the current study, we investigate the accumulation of polyunsaturated fatty acids, comparing four genotypes of A. caudatus with K432, a commercial variety deriving from the Mexican species A. hypochondriacus under the temperate environment of Southwest Germany. We show that the A. caudatus genotypes flowered later (only in late autumn), such that they were taller as compared to the Mexican hybrid but yielded fewer grains. The oil of kiwicha showed a significantly higher content of unsaturated fatty acids, especially of linoleic acid and α-linolenic acid compared to early flowering genotype K432. To gain insight into the molecular mechanisms behind these differences, we sequenced the genomes of the A. hypochondriacus × hybridus variety K432 and the Peruvian kiwicha genotype 8300 and identified the homologues for genes involved in the ω3 fatty-acid pathway and concurrent oxylipin metabolism, as well as of key factors for jasmonate signalling and cold acclimation. We followed the expression of these transcripts over three stages of seed development in all five genotypes. We find that transcripts for Δ6 desaturases are elevated in kiwicha, whereas in the Mexican hybrid, the concurrent lipoxygenase is more active, which is followed by the activation of jasmonate biosynthesis and signalling. The early accumulation of transcripts involved in cold-stress signalling reports that the Mexican hybrid experiences cold stress already early in autumn, whereas the kiwicha genotypes do not display indications for cold stress, except for the very final phase, when there were already freezing temperatures. We interpret the higher content of unsaturated fatty acids in the context of the different climatic conditions shaping domestication (tropical conditions in the case of Mexican amaranth, sharp cold snaps in the case of kiwicha) and suggest that kiwicha oil has high potential as functional food which can be developed further by tailoring genetic backgrounds, agricultural practice, and processing.
Iron Limitation Restores Autophagy and Increases Lifespan in the Yeast Model of Niemann–Pick Type C1
Authors: Martins Telma S. , Costa Rafaela S. , Vilaça Rita , Lemos Carolina , Teixeira Vitor , Pereira Clara , Costa Vítor
Published: March 2023

Niemann–Pick type C1 (NPC1) is an endolysosomal transmembrane protein involved in the export of cholesterol and sphingolipids to other cellular compartments such as the endoplasmic reticulum and plasma membrane. NPC1 loss of function is the major cause of NPC disease, a rare lysosomal storage disorder characterized by an abnormal accumulation of lipids in the late endosomal/lysosomal network, mitochondrial dysfunction, and impaired autophagy. NPC phenotypes are conserved in yeast lacking Ncr1, an orthologue of human NPC1, leading to premature aging. Herein, we performed a phosphoproteomic analysis to investigate the effect of Ncr1 loss on cellular functions mediated by the yeast lysosome-like vacuoles. Our results revealed changes in vacuolar membrane proteins that are associated mostly with vesicle biology (fusion, transport, organization), autophagy, and ion homeostasis, including iron, manganese, and calcium. Consistently, the cytoplasm to vacuole targeting (Cvt) pathway was increased in ncr1∆ cells and autophagy was compromised despite TORC1 inhibition. Moreover, ncr1∆ cells exhibited iron overload mediated by the low-iron sensing transcription factor Aft1. Iron deprivation restored the autophagic flux of ncr1∆ cells and increased its chronological lifespan and oxidative stress resistance. These results implicate iron overload on autophagy impairment, oxidative stress sensitivity, and cell death in the yeast model of NPC1.
Building Bricks of Integrated Care Pathway for Autism Spectrum Disorder: A Systematic Review
Authors: Fulceri Francesca , Gila Letizia , Caruso Angela , Micai Martina , Romano Giovanna , Scattoni Maria Luisa
Published: March 2023

An integrated plan within a defined care pathway for the diagnosis, continuative interventions, and periodic redefinition of care of autistic people is essential for better outcomes. Challenges include delivering services across all domains or life stages and effective coordination between health/social care providers and services. Further, in the ‘real world’, service provision varies greatly, and in many settings is significantly weighted towards diagnosis and children’s services rather than treatment and support or adult care. This study aims to identify existing care pathways for Autism Spectrum Disorder (ASD) from referral to care management after diagnosis. The study reviewed the international literature in PubMed and PsycInfo databases and collected information on care for autistic individuals from the Autism Spectrum Disorders in Europe (ASDEU) project partners. The study found that published data mainly focused on specific components of care pathways rather than an integrated and coordinated plan of care and legislative indications. They should be aimed at facilitating access to the services for support and the inclusiveness of autistic individuals. Given the need for care addressing the complex and heterogeneous nature of ASD, effective coordination between different health/social care providers and services is essential. It is also suggested that research priority should be given to the identification of an integrated care pathway ‘model’ centered around case management, individualization, facilitation, support, continuous training and updating, and quality management.
ABC Transporters in Bacterial Nanomachineries
Authors: Bilsing Florestan L. , Anlauf Manuel T. , Hachani Eymen , Khosa Sakshi , Schmitt Lutz
Published: March 2023

Members of the superfamily of ABC transporters are found in all domains of life. Most of these primary active transporters act as isolated entities and export or import their substrates in an ATP-dependent manner across biological membranes. However, some ABC transporters are also part of larger protein complexes, so-called nanomachineries that catalyze the vectorial transport of their substrates. Here, we will focus on four bacterial examples of such nanomachineries: the Mac system providing drug resistance, the Lpt system catalyzing vectorial LPS transport, the Mla system responsible for phospholipid transport, and the Lol system, which is required for lipoprotein transport to the outer membrane of Gram-negative bacteria. For all four systems, we tried to summarize the existing data and provide a structure-function analysis highlighting the mechanistical aspect of the coupling of ATP hydrolysis to substrate translocation.
HDAC Inhibition Restores Response to HER2-Targeted Therapy in Breast Cancer via PHLDA1 Induction
Authors: Clayton Natasha S. , Carter Edward P. , Fearon Abbie E. , Heward James A. , Rodríguez Fernández Lucía , Boughetane Lina , Wilkes Edmund H. , Cutillas Pedro R. , Grose Richard P.
Published: March 2023

The downregulation of Pleckstrin Homology-Like Domain family A member 1 (PHLDA1) expression mediates resistance to targeted therapies in receptor tyrosine kinase-driven cancers. The restoration and maintenance of PHLDA1 levels in cancer cells thus constitutes a potential strategy to circumvent resistance to inhibitors of receptor tyrosine kinases. Through a pharmacological approach, we identify the inhibition of MAPK signalling as a crucial step in PHLDA1 downregulation. Further ChIP-qPCR analysis revealed that MEK1/2 inhibition produces significant epigenetic changes at the PHLDA1 locus, specifically a decrease in the activatory marks H3Kme3 and H3K27ac. In line with this, we show that treatment with the clinically relevant class I histone deacetylase (HDAC) inhibitor 4SC-202 restores PHLDA1 expression in lapatinib-resistant human epidermal growth factor receptor-2 (HER2)+ breast cancer cells. Critically, we show that when given in combination, 4SC-202 and lapatinib exert synergistic effects on 2D cell proliferation and colony formation capacity. We therefore propose that co-treatment with 4SC-202 may prolong the clinical efficacy of lapatinib in HER2+ breast cancer patients.
Genome-Wide Association Study for Root Morphology and Phosphorus Acquisition Efficiency in Diverse Maize Panels
Authors: Ribeiro Carlos Alexandre Gomes , de Sousa Tinoco Sylvia Morais , de Souza Vander Fillipe , Negri Barbara França , Gault Christine Marie , Pastina Maria Marta , Magalhaes Jurandir Vieira , Guimarães Lauro José Moreira , de Barros Everaldo Gonçalves , Buckler Edward S. , Guimaraes Claudia Teixeira
Published: March 2023

Maximizing soil exploration through modifications of the root system is a strategy for plants to overcome phosphorus (P) deficiency. Genome-wide association with 561 tropical maize inbred lines from Embrapa and DTMA panels was undertaken for root morphology and P acquisition traits under low- and high-P concentrations, with 353,540 SNPs. P supply modified root morphology traits, biomass and P content in the global maize panel, but root length and root surface area changed differentially in Embrapa and DTMA panels. This suggests that different root plasticity mechanisms exist for maize adaptation to low-P conditions. A total of 87 SNPs were associated to phenotypic traits in both P conditions at −log10(p-value) ≥ 5, whereas only seven SNPs reached the Bonferroni significance. Among these SNPs, S9_137746077, which is located upstream of the gene GRMZM2G378852 that encodes a MAPKKK protein kinase, was significantly associated with total seedling dry weight, with the same allele increasing root length and root surface area under P deficiency. The C allele of S8_88600375, mapped within GRMZM2G044531 that encodes an AGC kinase, significantly enhanced root length under low P, positively affecting root surface area and seedling weight. The broad genetic diversity evaluated in this panel suggests that candidate genes and favorable alleles could be exploited to improve P efficiency in maize breeding programs of Africa and Latin America.
Discovery of SNP Molecular Markers and Candidate Genes Associated with Sacbrood Virus Resistance in Apis cerana cerana Larvae by Whole-Genome Resequencing
Authors: Hassanyar Aqai Kalan , Nie Hongyi , Li Zhiguo , Lin Yan , Huang Jingnan , Woldegiorgis Samuel Tareke , Hussain Mubasher , Feng Wangjiang , Zhang Zhaonan , Yu Kejun , Su Songkun
Published: March 2023

Sacbrood virus (SBV) is a significant problem that impedes brood development in both eastern and western honeybees. Whole-genome sequencing has become an important tool in researching population genetic variations. Numerous studies have been conducted using multiple techniques to suppress SBV infection in honeybees, but the genetic markers and molecular mechanisms underlying SBV resistance have not been identified. To explore single nucleotide polymorphisms (SNPs), insertions, deletions (Indels), and genes at the DNA level related to SBV resistance, we conducted whole-genome resequencing on 90 Apis cerana cerana larvae raised in vitro and challenged with SBV. After filtering, a total of 337.47 gigabytes of clean data and 31,000,613 high-quality SNP loci were detected in three populations. We used ten databases to annotate 9359 predicted genes. By combining population differentiation index (FST) and nucleotide polymorphisms (π), we examined genome variants between resistant (R) and susceptible (S) larvae, focusing on site integrity (INT < 0.5) and minor allele frequency (MAF < 0.05). A selective sweep analysis with the top 1% and top 5% was used to identify significant regions. Two SNPs on the 15th chromosome with GenBank KZ288474.1_322717 (Guanine > Cytosine) and KZ288479.1_95621 (Cytosine > Thiamine) were found to be significantly associated with SBV resistance based on their associated allele frequencies after SNP validation. Each SNP was authenticated in 926 and 1022 samples, respectively. The enrichment and functional annotation pathways from significantly predicted genes to SBV resistance revealed immune response processes, signal transduction mechanisms, endocytosis, peroxisomes, phagosomes, and regulation of autophagy, which may be significant in SBV resistance. This study presents novel and useful SNP molecular markers that can be utilized as assisted molecular markers to select honeybees resistant to SBV for breeding and that can be used as a biocontrol technique to protect honeybees from SBV.
Soybean GmSAUL1, a Bona Fide U-Box E3 Ligase, Negatively Regulates Immunity Likely through Repressing the Activation of GmMPK3
Authors: Li Jun-Mei , Ye Mei-Yan , Wang Chaofeng , Ma Xiao-Han , Wu Ni-Ni , Zhong Chen-Li , Zhang Yanjun , Cheng Ninghui , Nakata Paul A. , Zeng Lirong , Liu Jian-Zhong
Published: March 2023

E3 ubiquitin ligases play important roles in plant immunity, but their role in soybean has not been investigated previously. Here, we used Bean pod mottle virus (BPMV)-mediated virus-induced gene silencing (VIGS) to investigate the function of GmSAUL1 (Senescence-Associated E3 Ubiquitin Ligase 1) homologs in soybean. When two closely related SAUL1 homologs were silenced simultaneously, the soybean plants displayed autoimmune phenotypes, which were significantly alleviated by high temperature, suggesting that GmSAUL1a/1b might be guarded by an R protein. Interestingly, silencing GmSAUL1a/1b resulted in the decreased activation of GmMPK6, but increased activation of GmMPK3 in response to flg22, suggesting that the activation of GmMPK3 is most likely responsible for the activated immunity observed in the GmSAUL1a/1b-silenced plants. Furthermore, we provided evidence that GmSAUL1a is a bona fide E3 ligase. Collectively, our results indicated that GmSAUL1 plays a negative role in regulating cell death and immunity in soybean.
Androgen Receptor Upregulates Mucosa-Associated Lymphoid Tissue 1 to Induce NF-κB Activity via Androgen-Dependent and -Independent Pathways in Prostate Carcinoma Cells
Authors: Chang Kang-Shuo , Chen Syue-Ting , Sung Hsin-Ching , Hsu Shu-Yuan , Lin Wei-Yin , Hou Chen-Pang , Lin Yu-Hsiang , Feng Tsui-Hsia , Tsui Ke-Hung , Juang Horng-Heng
Published: March 2023

The androgen-dependent or -independent pathways are regarded as primary therapeutic targets for the neoplasm of the prostate. Mucosa-associated lymphoid tissue 1 (MALT1) acting as a paracaspase in the regulation of nuclear factor κB (NF-κB) signal transduction plays a central role in inflammation and oncogenesis in cancers. This study confirmed the potential linkages between androgen and NF-κB activation by inducing MALT1 in the androgen receptor-full length (ARFL)-positive LNCaP and 22Rv1 prostate cancer cells. Although androgen did not stimulate MALT1 expression in AR-null or ectopic ARFL-overexpressed PC-3 cells, the ectopic overexpression of the AR splicing variant 7 (ARv7) upregulated MALT1 to activate NF-κB activities in 22Rv1 and PC-3 cells. Since the nuclear translocation of p50 and p65 was facilitated by ARv7 to motivate NF-κB activity, the expressions of MALT1, prostate-specific antigen (PSA), and N-myc downstream regulated 1 (NDRG1) were therefore induced in ectopic ARv7-overexpressed prostate cancer cells. Ectopic ARv7 overexpression not only enhanced 22Rv1 or PC-3 cell growth and invasion in vitro but also the tumor growth of PC-3 cells in vivo. These results indicate that an androgen receptor induces MALT1 expression androgen-dependently and -independently in ARFL- or ARv7-overexpressed prostate cancer cells, suggesting a novel ARv7/MALT1/NF-κB-signaling pathway may exist in the cells of prostate cancer.
Zinc/Cerium-Substituted Magnetite Nanoparticles for Biomedical Applications
Authors: Chircov Cristina , Mincă Maria-Andreea , Serban Andreea Bianca , Bîrcă Alexandra Cătălina , Dolete Georgiana , Ene Vladimir-Lucian , Andronescu Ecaterina , Holban Alina-Maria
Published: March 2023

Numerous studies have reported the possibility of enhancing the properties of materials by incorporating foreign elements within their crystal lattice. In this context, while magnetite has widely known properties that have been used for various biomedical applications, the introduction of other metals within its structure could prospectively enhance its effectiveness. Specifically, zinc and cerium have demonstrated their biomedical potential through significant antioxidant, anticancer, and antimicrobial features. Therefore, the aim of the present study was to develop a series of zinc and/or cerium-substituted magnetite nanoparticles that could further be used in the medical sector. The nanostructures were synthesized through the co-precipitation method and their morpho-structural characteristics were evaluated through X-ray diffraction (XRD), inductively coupled plasma mass spectrometry (ICP-MS), X-ray photoelectron spectroscopy (XPS), dynamic light scattering (DLS), zeta potential, scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDX) analyses. Furthermore, the nanostructures were subjected to a ROS-Glo H2O2 assay for assessing their antioxidant potential, MTT assay for determining their anticancer effects, and antimicrobial testing against S. aureus, P. aeruginosa, and C. albicans strains. Results have proven promising for future biomedical applications, as the nanostructures inhibit oxidative stress in normal cells, with between two- and three-fold reduction and cell proliferation in tumor cells; a two-fold decrease in cell viability and microbial growth; an inhibition zone diameter of 4–6 mm and minimum inhibitory concentration (MIC) of 1–2 mg/mL.
Ab Initio Modelling of the Structure of ToxA-like and MAX Fungal Effector Proteins
Authors: Rozano Lina , Mukuka Yvonne M. , Hane James K. , Mancera Ricardo L.
Published: March 2023

Pathogenic fungal diseases in crops are mediated by the release of effector proteins that facilitate infection. Characterising the structure of these fungal effectors is vital to understanding their virulence mechanisms and interactions with their hosts, which is crucial in the breeding of plant cultivars for disease resistance. Several effectors have been identified and validated experimentally; however, their lack of sequence conservation often impedes the identification and prediction of their structure using sequence similarity approaches. Structural similarity has, nonetheless, been observed within fungal effector protein families, creating interest in validating the use of computational methods to predict their tertiary structure from their sequence. We used Rosetta ab initio modelling to predict the structures of members of the ToxA-like and MAX effector families for which experimental structures are known to validate this method. An optimised approach was then used to predict the structures of phenotypically validated effectors lacking known structures. Rosetta was found to successfully predict the structure of fungal effectors in the ToxA-like and MAX families, as well as phenotypically validated but structurally unconfirmed effector sequences. Interestingly, potential new effector structural families were identified on the basis of comparisons with structural homologues and the identification of associated protein domains.
Anti-Inflammatory Activity of Synaptamide in the Peripheral Nervous System in a Model of Sciatic Nerve Injury
Authors: Starinets Anna , Tyrtyshnaia Anna , Manzhulo Igor
Published: March 2023

N-docosahexaenoylethanolamine (DHEA), or synaptamide, is an endogenous metabolite of docosahexaenoic acid (DHA) that exhibits synaptogenic and neurogenic effects. In our previous studies, synaptamide administration inhibited the neuropathic pain-like behavior and reduced inflammation in the central nervous system following sciatic nerve injury. In the present study, we examine the effect of synaptamide on the peripheral nervous system in a neuropathic pain condition. The dynamics of ionized calcium-binding adapter molecule 1 (iba-1), CD68, CD163, myelin basic protein, and the production of interleukin 1β and 6 within the sciatic nerve, as well as the neuro-glial index and the activity of iba-1, CD163, glial fibrillary acidic protein (GFAP), neuronal NO synthase (nNOS), substance P (SP), activating transcription factor 3 (ATF3) in the dorsal root ganglia (DRG), are studied. According to our results, synaptamide treatment (4 mg/kg/day) (1) decreases the weight-bearing deficit after nerve trauma; (2) enhances the remyelination process in the sciatic nerve; (3) shows anti-inflammatory properties in the peripheral nervous system; (4) decreases the neuro-glial index and GFAP immunoreactivity in the DRG; (5) inhibits nNOS- and SP-ergic activity in the DRG, which might contribute to neuropathic pain attenuation. In general, the current study demonstrates the complex effect of synaptamide on nerve injury, which indicates its high potential for neuropathic pain management.
6-Gingerol Ameliorates Hepatic Steatosis, Inflammation and Oxidative Stress in High-Fat Diet-Fed Mice through Activating LKB1/AMPK Signaling
Authors: Liu Yuzhe , Li Dong , Wang Shang , Peng Ze , Tan Qi , He Qifeng , Wang Jianwei
Published: March 2023

6-Gingerol, one of the major pharmacologically active ingredients extracted from ginger, has been reported experimentally to exert hepatic protection in non-alcoholic fatty liver disease (NAFLD). However, the molecular mechanism remains largely elusive. RNA sequencing indicated the significant involvement of the AMPK signaling pathway in 6-gingerol-induced alleviation of NAFLD in vivo. Given the significance of the LKB1/AMPK pathway in metabolic homeostasis, this study aims to investigate its role in 6-gingerol-induced mitigation on NAFLD. Our study showed that 6-gingerol ameliorated hepatic steatosis, inflammation and oxidative stress in vivo and in vitro. Further experiment validation suggested that 6-gingerol activated an LKB1/AMPK pathway cascade in vivo and in vitro. Co-immunoprecipitation analysis demonstrated that the 6-gingerol-elicited activation of an LKB1/AMPK pathway cascade was related to the enhanced stability of the LKB1/STRAD/MO25 complex. Furthermore, radicicol, an LKB1 destabilizer, inhibited the activating effect of 6-gingerol on an LKB1/AMPK pathway cascade via destabilizing LKB1/STRAD/MO25 complex stability in vitro, thus reversing the 6-gingerol-elicited ameliorative effect. In addition, molecular docking analysis further predicated the binding pockets of LKB1 necessary for binding with 6-gingerol. In conclusion, our results indicate that 6-gingerol plays an important role in regulating the stability of the LKB1/STRAD/MO25 complex and the activation of LKB1, which might weigh heavily in the 6-gingerol alleviation of NAFLD.
Adaptive Reproductive Strategies of an Ectoparasitoid Sclerodermus guani under the Stress of Its Entomopathogenic Fungus Beauveria bassiana
Authors: Wei Yun , Li Li , Pan Shumei , Liu Zhudong , Fan Jianting , Tang Ming
Published: March 2023

Complex interspecific relationships between parasites and their insect hosts involve multiple factors and are affected by their ecological and evolutionary context. A parasitoid Sclerodermus guani (Hymenoptera: Bethylidae) and an entomopathogenic fungus Beauveria bassiana (Hypocreales: Cordycipitaceae) shared the same host in nature, Monochamus alternatus (Coleoptera: Cerambycidae). They often encountered the semi-enclosed microhabitat of the host larvae or pupae. We tested the survival and reproduction of the parasitoid’s parent and its offspring fitness under different concentrations of B. bassiana suspension. The results show that S. guani parent females carrying higher concentrations of the pathogen shorten the pre-reproductive time and regulate their own fertility and their offspring’s survival and development. This minimal model of the interspecific interactions contains three dimensionless parameters, vulnerability (θ), dilution ratio (δ), and PR, which were used to evaluate the mortality effect of the parasitoid S. guani on its host M. alternatus under the stress of the entomopathogenic fungus B. bassiana. We compared the infection and lethal effect of the fungus B. bassiana with different concentrations to the parasitoid S. guani and the host larvae M. alternatus. At higher concentrations of the pathogen, the parasitoid parent females shorten the pre-reproductive time and regulate their own fertility and their offspring’s survival and development. At moderate concentrations of the pathogen, however, the ability of the parasitoid to exploit the host is more flexible and efficient, possibly reflecting the potential interspecific interactions between the two parasites which were able to coexist and communicate with their hosts in ecological contexts (with a high overlap in time and space) and cause interspecific competition and intraguild predation.
Safety and Efficacy of Ab Interno XEN 45 Gel Stent in Patients with Glaucoma and High Myopia
Authors: Sacchi Matteo , Fea Antonio M. , Monsellato Gianluca , Tagliabue Elena , Villani Edoardo , Ranno Stefano , Nucci Paolo
Published: March 2023

This study reports on the safety and efficacy of Xen 45 in patients with glaucoma and high myopia. It was a retrospective study including patients with high myopia (>6D) who underwent Xen implant with 2 years of follow-up. The primary outcome was to report the incidence of hypotony (IOP ≤ 5 mmHg) and hypotony-related complications. Patients with high myopia treated with mitomycin-C-augmented trabeculectomy were included as a control group. We included 14 consecutive patients who underwent Xen implant (seven eyes) and trabeculectomy (seven eyes). The mean myopia was −14.71 ± 5.36 and −15.07 ± 6.11 in the trabeculectomy and Xen groups, respectively (p > 0.05). The success rate and the mean IOP at 1 and 2 years from the intervention were statistically comparable between the two groups. The group undergoing trabeculectomy showed a higher incidence of hypotony (six eyes (85.71%) vs. two eyes (28.57%)) and hypotony maculopathy (three eyes (42.86%) vs. zero eyes (0%)) and required more postoperative procedures. Patients with high myopia were at higher risk of hypotony-related complications after trabeculectomy. The Xen implant can achieve an IOP control comparable to trabeculectomy with a significantly better safety profile and can be considered as an option for the management of patients with high myopia and glaucoma.
The Dark Side of Ultrasound Imaging in Parathyroid Disease
Authors: Centello Roberta , Sesti Franz , Feola Tiziana , Sada Valentina , Pandozzi Carla , Di Serafino Marco , Pacini Patrizia , Cantisani Vito , Giannetta Elisa , Tarsitano Maria Grazia
Published: March 2023

The diagnosis of parathyroid diseases by imaging still has some intrinsic technical limitations due to the differential diagnosis of different structures of the neck that mimic the parathyroid glands. In this view, ultrasound (US) is an established, low-cost, and non-invasive imaging technique that still represents the first-line approach for evaluating patients with parathyroid disease. The objective of this article is to provide a comprehensive review of the applications of USs in clinical practice, discussing the histopathological and US characteristics of the parathyroid glands in normal and pathological conditions, the advantages of preoperative imaging, and novel updates on the most useful and currently available multiparameter US techniques.
First Application of the Orbeye™ 4K 3D Exoscope in Recurrent Papillary Thyroid Cancer Surgery
Authors: D’Ambra Michele , Tedesco Anna , Iacone Biancamaria , Bracale Umberto , Corcione Francesco , Peltrini Roberto
Published: March 2023

Reoperation for recurrent papillary thyroid cancer (RPTC) is much more complex than primary surgery is, with a higher rate of complications. We describe, for the first time, the use of the Orbeye™ surgical microscope/exoscope for the treatment of RPTC with lymphadenectomy. This system offers 4K, three-dimensional magnified and illuminated imaging without the need for eyepieces. Magnification of the field of view facilitates a more precise dissection, preserving the anatomical structure. Currently, the Orbeye™ is regularly used in neurosurgery; however, its potential in conventional open surgery has not yet been fully exploited. Owing to its magnification capacity, the Orbeye™ exoscope is a valuable tool to help surgeons identify and preserve the integrity of the recurrent laryngeal nerves and parathyroids during thyroid surgery.
Alliance for Sleep Clinical Practice Guideline on Switching or Deprescribing Hypnotic Medications for Insomnia
Authors: Watson Nathaniel F. , Benca Ruth M. , Krystal Andrew D. , McCall William V. , Neubauer David N.
Published: March 2023

Determining the most effective insomnia medication for patients may require therapeutic trials of different medications. In addition, medication side effects, interactions with co-administered medications, and declining therapeutic efficacy can necessitate switching between different insomnia medications or deprescribing altogether. Currently, little guidance exists regarding the safest and most effective way to transition from one medication to another. Thus, we developed evidence-based guidelines to inform clinicians regarding best practices when deprescribing or transitioning between insomnia medications. Five U.S.-based sleep experts reviewed the literature involving insomnia medication deprescribing, tapering, and switching and rated the quality of evidence. They used this evidence to generate recommendations through discussion and consensus. When switching or discontinuing insomnia medications, we recommend benzodiazepine hypnotic drugs be tapered while additional CBT-I is provided. For Z-drugs zolpidem and eszopiclone (and not zaleplon), especially when prescribed at supratherapeutic doses, tapering is recommended with a 1–2-day delay in administration of the next insomnia therapy when applicable. There is no need to taper DORAs, doxepin, and ramelteon. Lastly, off-label antidepressants and antipsychotics used to treat insomnia should be gradually reduced when discontinuing. In general, offering individuals a rationale for deprescribing or switching and involving them in the decision-making process can facilitate the change and enhance treatment success.
Fetal Growth Restriction Is Associated with Pregnancy Associated Plasma Protein A and Uterine Artery Doppler in First Trimester
Authors: Springer Stephanie , Worda Katharina , Franz Marie , Karner Eva , Krampl-Bettelheim Elisabeth , Worda Christof
Published: March 2023

Fetal growth restriction (FGR) is a major cause of stillbirth and poor neurodevelopmental outcomes. The early prediction may be important to establish treatment options and improve neonatal outcomes. The aim of this study was to assess the association of parameters used in first-trimester screening, uterine artery Doppler pulsatility index and the development of FGR. In this retrospective cohort study, 1930 singleton pregnancies prenatally diagnosed with an estimated fetal weight under the third percentile were included. All women underwent first-trimester screening assessing maternal serum pregnancy-associated plasma protein A (PAPP-A), free beta-human chorionic gonadotrophin levels, fetal nuchal translucency and uterine artery Doppler pulsatility index (PI). We constructed a Receiver Operating Characteristics curve to calculate the sensitivity and specificity of early diagnosis of FGR. In pregnancies with FGR, PAPP-A was significantly lower, and uterine artery Doppler pulsatility index was significantly higher compared with the normal birth weight group (0.79 ± 0.38 vs. 1.15 ± 0.59, p < 0.001 and 1.82 ± 0.7 vs. 1.55 ± 0.47, p = 0.01). Multivariate logistic regression analyses demonstrated that PAPP-A levels and uterine artery Doppler pulsatility index were significantly associated with FGR (p = 0.009 and p = 0.01, respectively). To conclude, these two parameters can predict FGR < 3rd percentile.
Chondrosarcoma: A Clinical Review
Authors: Gazendam Aaron , Popovic Snezana , Parasu Naveen , Ghert Michelle
Published: March 2023

Chondrosarcomas are a diverse group of malignant cartilaginous matrix-producing neoplasms. Conventional chondrosarcomas are a continuum of disease based on the biologic activity of the tumor. The tumors range from the relatively biologically benign low-grade tumors or intermediate atypical cartilaginous tumors (ACTs), to malignant, aggressive high-grade tumors. The clinical presentation, radiographic and pathologic findings, treatments and outcomes vary significantly based on the histologic grade of the tumor. Chondrosarcomas present a diagnostic dilemma, particularly in the differentiation between high- and intermediate-grade tumors and that of low-grade tumors from benign enchondromas. A multidisciplinary team at a tertiary sarcoma centre allows for optimal care of these patients.
Use of Long-Acting Injectable Antipsychotics in a Clinical Sample of Community-Dwelling Patients with Schizophrenia-Spectrum Disorders in Rural Greece
Authors: Peritogiannis Vaios , Tsoli Fotini , Gioti Panagiota , Bakola Maria , Jelastopulu Eleni
Published: March 2023

Data on the use of long-acting injectable antipsychotics (LAIs) in rural community mental healthcare settings are scarce. This study aimed to investigate the prescription patterns of LAIs in a clinical sample of patients with schizophrenia-spectrum disorders in rural Greece. All patients with schizophrenia-spectrum disorders who regularly attend the Mobile Mental Health Unit of the prefectures of Ioannina and Thesprotia (MMHU I-T) in northwestern Greece were included in the study. The sample consists of 87 patients (59 males and 28 females) with a mean age of 54.4 years and a mean illness duration of 28 years. Most patients (72.4%) received antipsychotic monotherapy, and nearly 30% received an LAI formulation, mostly a second-generation LAI (20 of 26 patients, 76.9%). The treatment regimen comprised benzodiazepines in one-third of the patients and antidepressants in one-quarter. There was no statistically significant association between treatment regimen and the clinical and demographic variables studied, except for biological sex (female). The percentage of patients treated with LAIs in this study was almost three times higher than the rate previously reported in Greece and is higher than the rates reported in other countries. Patients with schizophrenia-spectrum disorders in rural Greece may have adequate access to innovative treatment with second-generation LAIs. Further research is needed to demonstrate the cost-effectiveness of LAI treatment in rural communities and to elucidate the factors associated with such treatment.
Coordination and Cognition in Pure Nutritional Wernicke’s Encephalopathy with Cerebellar Degeneration after COVID-19 Infection: A Unique Case Report
Authors: Arts Nicolaas J. M. , van Dorst Maud E. G. , Vos Sandra H. , Kessels Roy P. C.
Published: March 2023

Background: Alcoholic cerebellar degeneration is a restricted form of cerebellar degeneration, clinically leading to an ataxia of stance and gait and occurring in the context of alcohol misuse in combination with malnutrition and thiamine depletion. However, a similar degeneration may also develop after non-alcoholic malnutrition, but evidence for a lasting ataxia of stance and gait and lasting abnormalities in the cerebellum is lacking in the few patients described with purely nutritional cerebellar degeneration (NCD). Methods: We present a case of a 46-year-old woman who developed NCD and Wernicke’s encephalopathy (WE) due to COVID-19 and protracted vomiting, resulting in thiamine depletion. We present her clinical course over the first 6 months after the diagnosis of NCD and WE, with thorough neuropsychological and neurological examinations, standardized clinical observations, laboratory investigations, and repeated MRIs. Results: We found a persistent ataxia of stance and gait and evidence for an irreversible restricted cerebellar degeneration. However, the initial cognitive impairments resolved. Conclusions: Our study shows that NCD without involvement of alcohol neurotoxicity and with a characteristic ataxia of stance and gait exists and may be irreversible. We did not find any evidence for lasting cognitive abnormalities or a cerebellar cognitive-affective syndrome (CCAS) in this patient.
Efficacy and Safety of Leadless Pacemakers for Atrioventricular Synchronous Pacing: A Systematic Review and Meta-Analysis
Authors: Wu Sijin , Jin Yuanhao , Lu Wenzhao , Chen Zhongli , Dai Yan , Chen Keping
Published: March 2023

Leadless pacemakers with an atrioventricular synchrony algorithm represent a novel technology for patients qualified for VDD pacing. The current evidence of their performance is limited to several small-scale observational studies. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of this new technology. We systematically searched the PubMed, Embase, and Cochrane library databases from their inception to 12 September 2022. The primary efficacy outcome was atrioventricular synchrony after implantation, whereas the secondary efficacy outcome was the change in cardiac output represented by the left ventricular outflow tract velocity time integral (LVOT-VTI). The primary safety outcome was major complications related to the procedures and the algorithm. Means or mean differences with 95% confidence interval (95% CI) were combined using a random-effects model or a fixed-effects model. Finally, 8 published studies with 464 participants were included in the qualitative analysis. The pooled atrioventricular synchrony proportion was 78.9% (95% CI 71.9–86.0%), and a further meta-regression did not screen factors that contributed significantly to the heterogeneity. Additionally, a significant increase in atrioventricular synchrony of 11.3% (95% CI 7.0–15.7%, p < 0.01) was achieved in patients experiencing programming optimization. LVOT-VTI was significantly increased by 1.9 cm (95% CI 1.2–2.6, p < 0.01), compared with the VVI pacing mode. The overall incidence of complications was approximately 6.3%, with major complications related to the algorithm being extremely low. Overall, leadless pacemakers with atrioventricular synchronous pacing demonstrated favorable safety and efficacy. Future data on their long-term performance are required to facilitate their widespread adoption in clinical practice.
The Impact of Body Mass Composition on Outcome in Multiple Traumatized Patients—Results from the Fourth Thoracic and Third Lumbar Vertebrae: A Single-Center Retrospective Observational Study
Authors: Belger Esref , Truhn Daniel , Weber Christian David , Neumann Ulf Peter , Hildebrand Frank , Horst Klemens
Published: March 2023

Background: Body mass composition (BC) was shown to correlate with outcome in patients after surgery and minor trauma. As BC is assessed using computed tomography (CT) and routinely applied in multiple trauma (MT), this study will help to analyze whether BC variables also correlate with outcome in trauma patients. Materials and Methods: Inclusion criteria were MT (Injury Severity Score (ISS) > 15) and whole-body CT (WBCT) scan on admission. Muscle and fat tissue were assessed at the level of the fourth thoracic vertebra (T4) and the third lumbar vertebra (L3) using Slice-O-matic software, version 5.0 (Tomovision, Montreal, QC, Canada). Univariate and multivariate regression models were used with regard to outcome parameters such as duration of ventilation, hospital stay, local (i.e., pneumonia, wound infection) and systemic (i.e., MODS, SIRS) complications, and mortality. Results: 297 patients were included. BC correlated with both the development and severity of complications. Skeletal muscle index (SMI) and subcutaneous adipose tissue index (SATI) at both T4 and L3 correlated positively with the occurrence of systemic infections. Local infections positively correlated with SMI at T4. Low muscle mass and high visceral adipose tissue (VAT) predicted the severity of systemic and local complications. Muscle tissue markers at both T4 and L3 predicted the severity of complications in roughly the same way. Moreover, higher muscle mass at the L3 level was significantly associated with higher overall survival, while SATI at the T4 level correlated positively with hospital stay, length of stay in the ICU, and duration of ventilation. Conclusions: A lower muscle mass and a high adipose tissue index are associated with a poor outcome in MT. For the first time, it was shown that BC at the fourth thoracic vertebra is associated with comparable results to those found at the third lumbar level.
Effectiveness of Repetitive Transcranial Magnetic Stimulation (rTMS) Add-On Therapy to a Standard Treatment in Individuals with Multiple Sclerosis and Concomitant Symptoms of Depression—Results from a Randomized Clinical Trial and Pilot Study
Authors: Ahmadpanah Mohammad , Amini Shiva , Mazdeh Mehrdokht , Haghighi Mohammad , Soltanian Alireza , Jahangard Leila , Keshavarzi Amir , Brand Serge
Published: March 2023

Background: Compared to the general population, persons with multiple sclerosis (MS) are at increased risk of suffering from major depressive disorder (MDD). Repetitive Transcranial Magnetic Stimulation (rTMS) was used successfully to treat individuals with MDD. Here, we conducted a randomized clinical trial and pilot study, and tested the effectiveness of rTMS adjuvant to a standard pharmacological treatment among persons with MS, compared to a sham condition. Materials and Methods: A total of 40 persons with MS (mean age: 32 years; 42.5% females; median EDSS score: 4) and with moderate to severe symptoms of depression were randomly assigned to the rTMS or to the rTMS sham condition, always as adjuvant intervention to the standard treatment with sertraline, a selective serotonin reuptake inhibitor (SSRI). rTMS consisted of 10 sessions each of 37.5 min; the sham condition was identical to the active condition except for the absence of rTMS stimuli. At the beginning and two weeks after the end of the study, participants reported on their fatigue, while experts rated the severity of participants’ depressive symptoms (Montgomery–Asberg Depression Rating Scale; MADRS), cognitive performance (Montreal Cognitive Assessment; MoCA), and degree of disability (Expanded Disability Status Scale; EDSS). Results: Data were analyzed per intent-to-treat. Scores for depression, fatigue, and EDSS declined significantly over time (large effect sizes), but more so in the rTMS condition than in the sham condition (large effect sizes for the time by group-interactions). Compared to the sham condition, scores for depression were significantly lower in the rTMS condition. Scores for cognition improved over time in both study conditions (large effect size). Conclusion: Compared to a sham condition, adjuvant rTMS to a standard pharmacological treatment ameliorated typical MS-related symptoms (depression; fatigue; EDSS scores). Results from this pilot study suggested that rTMS might be routinely applied in persons with MS displaying symptoms of depression and fatigue.