bluuebunny/crossref_metadata_2025 huggingface dataset:
The Causal Effects of Primary Biliary Cholangitis on Thyroid Dysfunction: A Two-Sample Mendelian Randomization Study
Authors: Huang Peng , Hou Yuqing , Zou Yixin , Ye Xiangyu , Yu Rongbin , Yang Sheng
Published: December 2021

Background: Primary biliary cholangitis (PBC) is an autoimmune disease and is often accompanied by thyroid dysfunction. Understanding the potential causal relationship between PBC and thyroid dysfunction is helpful to explore the pathogenesis of PBC and to develop strategies for the prevention and treatment of PBC and its complications.

Methods: We used a two-sample Mendelian randomization (MR) method to estimate the potential causal effect of PBC on the risk of autoimmune thyroid disease (AITD), thyroid-stimulating hormone (TSH) and free thyroxine (FT4), hyperthyroidism, hypothyroidism, and thyroid cancer (TC) in the European population. We collected seven datasets of PBC and related traits to perform a series MR analysis and performed extensive sensitivity analyses to ensure the reliability of our results.

Results: Using a sensitivity analysis, we found that PBC was a risk factor for AITD, TSH, hypothyroidism, and TC with odds ratio (OR) of 1.002 (95% CI: 1.000–1.005, p = 0.042), 1.016 (95% CI: 1.006–1.027, p = 0.002), 1.068 (95% CI: 1.022–1.115, p = 0.003), and 1.106 (95% CI: 1.019–1.120, p = 0.042), respectively. Interestingly, using reverse-direction MR analysis, we also found that AITD had a significant potential causal association with PBC with an OR of 0.021 (p = 5.10E−4) and that the other two had no significant causal relation on PBC.

Conclusion: PBC causes thyroid dysfunction, specifically as AITD, mild hypothyroidism, and TC. The potential causal relationship between PBC and thyroid dysfunction provides a new direction for the etiology of PBC.
CCR5Δ32 in Brazil: Impacts of a European Genetic Variant on a Highly Admixed Population
Authors: Kulmann-Leal Bruna , Ellwanger Joel Henrique , Chies José Artur Bogo
Published: December 2021

The genetic background of Brazilians encompasses Amerindian, African, and European components as a result of the colonization of an already Amerindian inhabited region by Europeans, associated to a massive influx of Africans. Other migratory flows introduced into the Brazilian population genetic components from Asia and the Middle East. Currently, Brazil has a highly admixed population and, therefore, the study of genetic factors in the context of health or disease in Brazil is a challenging and remarkably interesting subject. This phenomenon is exemplified by the genetic variant CCR5Δ32, a 32 base-pair deletion in theCCR5gene. CCR5Δ32 originated in Europe, but the time of origin as well as the selective pressures that allowed the maintenance of this variant and the establishment of its current frequencies in the different human populations is still a field of debates. Due to its origin, the CCR5Δ32 allele frequency is high in European-derived populations (~10%) and low in Asian and African native human populations. In Brazil, the CCR5Δ32 allele frequency is intermediate (4-6%) and varies on the Brazilian States, depending on the migratory history of each region. CCR5 is a protein that regulates the activity of several immune cells, also acting as the main HIV-1 co-receptor. The CCR5 expression is influenced by CCR5Δ32 genotypes. No CCR5 expression is observed in CCR5Δ32 homozygous individuals. Thus, the CCR5Δ32 has particular effects on different diseases. At the population level, the effect that CCR5Δ32 has on European populations may be different than that observed in highly admixed populations. Besides less evident due to its low frequency in admixed groups, the effect of the CCR5Δ32 variant may be affected by other genetic traits. Understanding the effects of CCR5Δ32 on Brazilians is essential to predict the potential use of pharmacological CCR5 modulators in Brazil. Therefore, this study reviews the impacts of the CCR5Δ32 on the Brazilian population, considering infectious diseases, inflammatory conditions, and cancer. Finally, this article provides a general discussion concerning the impacts of a European-derived variant, the CCR5Δ32, on a highly admixed population.
The Gut-Liver Axis in Health and Disease: The Role of Gut Microbiota-Derived Signals in Liver Injury and Regeneration
Authors: Zheng Zhipeng , Wang Baohong
Published: December 2021

Diverse liver diseases undergo a similar pathophysiological process in which liver regeneration follows a liver injury. Given the important role of the gut-liver axis in health and diseases, the role of gut microbiota-derived signals in liver injury and regeneration has attracted much attention. It has been observed that the composition of gut microbiota dynamically changes in the process of liver regeneration after partial hepatectomy, and gut microbiota modulation by antibiotics or probiotics affects both liver injury and regeneration. Mechanically, through the portal vein, the liver is constantly exposed to gut microbial components and metabolites, which have immense effects on the immunity and metabolism of the host. Emerging data demonstrate that gut-derived lipopolysaccharide, gut microbiota-associated bile acids, and other bacterial metabolites, such as short-chain fatty acids and tryptophan metabolites, may play multifaceted roles in liver injury and regeneration. In this perspective, we provide an overview of the possible molecular mechanisms by which gut microbiota-derived signals modulate liver injury and regeneration, highlighting the potential roles of gut microbiota in the development of gut microbiota-based therapies to alleviate liver injury and promote liver regeneration.
Correlation Between Increased Homing Flight Duration and Altered Gene Expression in the Brain of Honey Bee Foragers After Acute Oral Exposure to Thiacloprid and Thiamethoxam
Authors: Christen Verena , Grossar Daniela , Charrière Jean-Daniel , Eyer Michael , Jeker Lukas
Published: December 2021

Neonicotinoids as thiamethoxam and thiacloprid are suspected to be implicated in the decline of honey bee populations. As nicotinic acetylcholine receptor agonists, they disturb acetylcholine receptor signaling in insects, leading to neurotoxicity and are therefore globally used as insecticides. Several behavioral studies have shown links between neonicotinoid exposure of bees and adverse effects on foraging activity, homing flight performance and reproduction, but the molecular aspects underlying these effects are not well-understood. In the last years, several studies through us and others showed the effects of exposure to neonicotinoids on gene expression in the brain of honey bees. Transcripts of acetylcholine receptors, hormonal regulation, stress markers, detoxification enzymes, immune system related genes and transcripts of the energy metabolism were altered after neonicotinoid exposure. To elucidate the link between homing flight performance and shifts in gene expression in the brain of honey bees after neonicotinoid exposure, we combined homing flight activity experiments applying RFID technology and gene expression analysis. We analyzed the expression of endocrine factors, stress genes, detoxification enzymes and genes linked to energy metabolism in forager bees after homing flight experiments. Three different experiments (experiment I: pilot study; experiment II: “worst-case” study and experiment III: laboratory study) were performed. In a pilot study, we wanted to investigate if we could see differences in gene expression between controls and exposed bees (experiment I). This first study was followed by a so-called “worst-case” study (experiment II), where we investigated mainly differences in the expression of transcripts linked to energy metabolism between fast and slow returning foragers. We found a correlation between homing flight duration and the expression of cytochrome c oxidase subunit 5A, one transcript linked to oxidative phosphorylation. In the third experiment (experiment III), foragers were exposed in the laboratory to 1 ng/bee thiamethoxam and 8 ng/bee thiacloprid followed by gene expression analysis without a subsequent flight experiment. We could partially confirm the induction of cytochrome c oxidase subunit 5A, which we detected in experiment II. In addition, we analyzed the effect of the feeding mode (group feeding vs. single bee feeding) on data scattering and demonstrated that single bee feeding is superior to group feeding as it significantly reduces variability in gene expression. Based on the data, we thus hypothesize that the disruption of energy metabolism may be one reason for a prolongation of homing flight duration in neonicotinoid treated bees.
Case Report: Homozygous Pathogenic Variant P209L in the TTC21B Gene: A Rare Cause of End Stage Renal Disease and Biliary Cirrhosis Requiring Combined Liver-Kidney Transplantation. A Case Report and Literature Review
Authors: Gambino Giuseppe , Catalano Concetta , Marangoni Martina , Geers Caroline , Moine Alain Le , Boon Nathalie , Smits Guillaume , Ghisdal Lidia
Published: December 2021

Background: Ciliopathies are rare diseases causing renal and extrarenal manifestations. Here, we report the case of a ciliopathy induced by a homozygous pathogenic variant in the TTC21B gene.

Case Description: A 47-year-old patient started hemodialysis for chronic kidney disease (CKD) of unknown origin. She presented with early onset of hypertension, pre-eclampsia, myopia and cirrhosis. Renal biopsy showed mild interstitial fibrosis, tubular atrophy, and moderate arteriosclerosis while liver pathology demonstrates grade B biliary cirrhosis. Family history revealed several cases of early-onset severe hypertension and one case of end-stage renal disease (ESRD) needing kidney transplantation at twenty years of age. Clinical exome sequencing showed homozygosis for the pathogenic variant c.626C>T (p.Pro209Leu) in the TTC21B gene. The patient underwent combined liver-renal transplantation with an excellent renal and hepatic graft outcome.

Conclusions:TTC21B gene mutations can lead heterogeneous to clinical manifestations and represent an underappreciated cause of ESRD. The paradigm in diagnosis of CKD of early onset and/or of unknown origin is changing and genetic counseling should be performed in all patients and families that meet those criteria. Renal or combined liver-renal transplantation represents the best option for patients suffering from those diseases in terms of prognosis and quality of life.
Plasmid Mediated mcr-1.1 Colistin-Resistance in Clinical Extraintestinal Escherichia coli Strains Isolated in Poland
Authors: Majewski Piotr , Gutowska Anna , Smith David G. E. , Hauschild Tomasz , Majewska Paulina , Hryszko Tomasz , Gizycka Dominika , Kedra Boguslaw , Kochanowicz Jan , Glowiński Jerzy , Drewnowska Justyna , Swiecicka Izabela , Sacha Pawel T. , Wieczorek Piotr , Iwaniuk Dominika , Sulewska Anetta , Charkiewicz Radoslaw , Makarewicz Katarzyna , Zebrowska Agnieszka , Czaban Slawomir , Radziwon Piotr , Niklinski Jacek , Tryniszewska Elzbieta A.
Published: December 2021

Objectives: The growing incidence of multidrug-resistant (MDR) bacteria is an inexorable and fatal challenge in modern medicine. Colistin is a cationic polypeptide considered a “last-resort” antimicrobial for treating infections caused by MDR Gram-negative bacterial pathogens. Plasmid-borne mcr colistin resistance emerged recently, and could potentially lead to essentially untreatable infections, particularly in hospital and veterinary (livestock farming) settings. In this study, we sought to establish the molecular basis of colistin-resistance in six extraintestinal Escherichia coli strains.

Methods: Molecular investigation of colistin-resistance was performed in six extraintestinal E. coli strains isolated from patients hospitalized in Medical University Hospital, Bialystok, Poland. Complete structures of bacterial chromosomes and plasmids were recovered with use of both short- and long-read sequencing technologies and Unicycler hybrid assembly. Moreover, an electrotransformation assay was performed in order to confirm IncX4 plasmid influence on colistin-resistance phenotype in clinical E. coli strains.

Results: Here we report on the emergence of six mcr-1.1-producing extraintestinal E. coli isolates with a number of virulence factors. Mobile pEtN transferase-encoding gene, mcr-1.1, has been proved to be encoded within a type IV secretion system (T4SS)-containing 33.3 kbp IncX4 plasmid pMUB-MCR, next to the PAP2-like membrane-associated lipid phosphatase gene.

Conclusion: IncX4 mcr-containing plasmids are reported as increasingly disseminated among E. coli isolates, making it an “epidemic” plasmid, responsible for (i) dissemination of colistin-resistance determinants between different E. coli clones, and (ii) circulation between environmental, industrial, and clinical settings. Great effort needs to be taken to avoid further dissemination of plasmid-mediated colistin resistance among clinically relevant Gram-negative bacterial pathogens.
Peroxin FgPEX22-Like Is Involved in FgPEX4 Tethering and Fusarium graminearum Pathogenicity
Authors: Zhang Li , Liu Chunjie , Wang Mingyu , Tao Yilin , Liang Yuancun , Yu Jinfeng
Published: December 2021

Peroxisomes are essential organelles that play important roles in a variety of biological processes in eukaryotic cells. To understand the synthesis of peroxisomes comprehensively, we identified the gene FgPEX22-like, encoding FgPEX22-like, a peroxin, in Fusarium graminearum. Our results showed that although FgPEX22-like was notably different from other peroxins (PEX) in Saccharomyces cerevisiae, it contained a predicted PEX4-binding site and interacted with FgPEX4 as a rivet protein of FgPEX4. To functionally characterize the roles of FgPEX22-like in F. graminearum, we performed homologous recombination to construct a deletion mutant (ΔPEX22-like). Analysis of the mutant showed that FgPEX22-like was essential for sexual and asexual reproduction, fatty acid utilization, pathogenicity, and production of the mycotoxin deoxynivalenol. Deletion of FgPEX22-like also led to increased production of lipid droplets and decreased elimination of reactive oxygen species. In addition, FgPEX22-like was required for the biogenesis of Woronin bodies. Taken together, our data demonstrate that FgPEX22-like is a peroxin in F. graminearum that interacts with PEX4 by anchoring PEX4 at the peroxisomal membrane and contributes to the peroxisome function in F. graminearum.
Flow Cytometric Analysis of Bacterial Protein Synthesis: Monitoring Vitality After Water Treatment
Authors: Lindivat Mathilde , Bratbak Gunnar , Larsen Aud , Hess-Erga Ole-Kristian , Hoell Ingunn Alne
Published: December 2021

Bacterial vitality after water disinfection treatment was investigated using bio-orthogonal non-canonical amino acid tagging (BONCAT) and flow cytometry (FCM). Protein synthesis activity and DNA integrity (BONCAT–SYBR Green) was monitored in Escherichia coli monocultures and in natural marine samples after UV irradiation (from 25 to 200 mJ/cm2) and heat treatment (from 15 to 45 min at 55°C). UV irradiation of E. coli caused DNA degradation followed by the decrease in protein synthesis within a period of 24 h. Heat treatment affected both DNA integrity and protein synthesis immediately, with an increased effect over time. Results from the BONCAT method were compared with results from well-known methods such as plate counts (focusing on growth) and LIVE/DEAD™ BacLight™ (focusing on membrane permeability). The methods differed somewhat with respect to vitality levels detected in bacteria after the treatments, but the results were complementary and revealed that cells maintained metabolic activity and membrane integrity despite loss of cell division. Similarly, analysis of protein synthesis in marine bacteria with BONCAT displayed residual activity despite inability to grow or reproduce. Background controls (time zero blanks) prepared using different fixatives (formaldehyde, isopropanol, and acetic acid) and several different bacterial strains revealed that the BONCAT protocol still resulted in labeled, i.e., apparently active, cells. The reason for this is unclear and needs further investigation to be understood. Our results show that BONCAT and FCM can detect, enumerate, and differentiate bacterial cells after physical water treatments such as UV irradiation and heating. The method is reliable to enumerate and explore vitality of single cells, and a great advantage with BONCAT is that all proteins synthesized within cells are analyzed, compared to assays targeting specific elements such as enzyme activity.
Mitochondrial Deficits With Neural and Social Damage in Early-Stage Alzheimer’s Disease Model Mice
Authors: Misrani Afzal , Tabassum Sidra , Huo Qingwei , Tabassum Sumaiya , Jiang Jinxiang , Ahmed Adeel , Chen Xiangmao , Zhou Jianwen , Zhang Jiajia , Liu Sha , Feng Xiaoyi , Long Cheng , Yang Li
Published: December 2021

Alzheimer’s disease (AD) is the most common neurodegenerative disorder worldwide. Mitochondrial dysfunction is thought to be an early event in the onset and progression of AD; however, the precise underlying mechanisms remain unclear. In this study, we investigated mitochondrial proteins involved in organelle dynamics, morphology and energy production in the medial prefrontal cortex (mPFC) and hippocampus (HIPP) of young (1∼2 months), adult (4∼5 months) and aged (9∼10, 12∼18 months) APP/PS1 mice. We observed increased levels of mitochondrial fission protein, Drp1, and decreased levels of ATP synthase subunit, ATP5A, leading to abnormal mitochondrial morphology, increased oxidative stress, glial activation, apoptosis, and altered neuronal morphology as early as 4∼5 months of age in APP/PS1 mice. Electrophysiological recordings revealed abnormal miniature excitatory postsynaptic current in the mPFC together with a minor connectivity change between the mPFC and HIPP, correlating with social deficits. These results suggest that abnormal mitochondrial dynamics, which worsen with disease progression, could be a biomarker of early-stage AD. Therapeutic interventions that improve mitochondrial function thus represent a promising approach for slowing the progression or delaying the onset of AD.
Molecular Segmentation of the Spinal Trigeminal Nucleus in the Adult Mouse Brain
Authors: García-Guillén Isabel M. , Martínez-de-la-Torre Margaret , Puelles Luis , Aroca Pilar , Marín Faustino
Published: December 2021

The trigeminal column is a hindbrain structure formed by second order sensory neurons that receive afferences from trigeminal primary (ganglionic) nerve fibers. Classical studies subdivide it into the principal sensory trigeminal nucleus located next to the pontine nerve root, and the spinal trigeminal nucleus which in turn consists of oral, interpolar and caudal subnuclei. On the other hand, according to the prosomeric model, this column would be subdivided into segmental units derived from respective rhombomeres. Experimental studies have mapped the principal sensory trigeminal nucleus to pontine rhombomeres (r) r2-r3 in the mouse. The spinal trigeminal nucleus emerges as a plurisegmental formation covering several rhombomeres (r4 to r11 in mice) across pontine, retropontine and medullary hindbrain regions. In the present work we reexamined the issue of rhombomeric vs. classical subdivisions of this column. To this end, we analyzed its subdivisions in an AZIN2-lacZ transgenic mouse, known as a reference model for hindbrain topography, together with transgenic reporter lines for trigeminal fibers. We screened as well for genes differentially expressed along the axial dimension of this structure in the adult and juvenile mouse brain. This analysis yielded genes from multiple functional families that display transverse domains fitting the mentioned rhombomeric map. The spinal trigeminal nucleus thus represents a plurisegmental structure with a series of distinct neuromeric units having unique combinatorial molecular profiles.
The Effect of Socioeconomic Disparities on Prefrontal Activation in Initiating Joint Attention: A Functional Near-Infrared Spectroscopy Evidence From Two Socioeconomic Status Groups
Authors: Ding Keya , Li Chuanjiang , Li Yanwei , Wang Hongan , Yu Dongchuan
Published: December 2021

Low socioeconomic status (SES) may generally have a long-lasting negative effect on cognitive development, and show deficits in the development of executive functions. However, it is unclear whether there is an SES-dependent disparity in the functional brain development of the prefrontal cortex. By collecting task-related functional near-infrared spectroscopy (fNIRS) data and behavioral data (e.g., intelligence, language, home reading environment (HRE), family income, and parental education level), the current study aimed to detect whether the SES of preschool children (N = 86) is associated with prefrontal activation during the joint attention task. Results verified that low-SES children show lower right prefrontal activation during joint attention than Relatively High-SES children. In addition, our findings confirmed the mediating effect of HRE on the association between SES and brain activation during joint attention, as well as that between SES and language ability. These results suggest that SES contributes to functional development of the prefrontal regions, and the improvement of HRE could be a potential strategy to intervene SES-related disparities on child development.
Analyzing Complex Problem Solving by Dynamic Brain Networks
Authors: Alchihabi Abdullah , Ekmekci Omer , Kivilcim Baran B. , Newman Sharlene D. , Yarman Vural Fatos T.
Published: December 2021

Complex problem solving is a high level cognitive task of the human brain, which has been studied over the last decade. Tower of London (TOL) is a game that has been widely used to study complex problem solving. In this paper, we aim to explore the underlying cognitive network structure among anatomical regions of complex problem solving and its subtasks, namely planning and execution. A new computational model for estimating a brain network at each time instant of fMRI recordings is proposed. The suggested method models the brain network as an Artificial Neural Network, where the weights correspond to the relationships among the brain anatomic regions. The first step of the model is preprocessing that manages to decrease the spatial redundancy while increasing the temporal resolution of the fMRI recordings. Then, dynamic brain networks are estimated using the preprocessed fMRI signal to train the Artificial Neural Network. The properties of the estimated brain networks are studied in order to identify regions of interest, such as hubs and subgroups of densely connected brain regions. The representation power of the suggested brain network is shown by decoding the planning and execution subtasks of complex problem solving. Our findings are consistent with the previous results of experimental psychology. Furthermore, it is observed that there are more hubs during the planning phase compared to the execution phase, and the clusters are more strongly connected during planning compared to execution.
The Inhibitory Effects of 6-Thioguanine and 6-Mercaptopurine on the USP2a Target Fatty Acid Synthase in Human Submaxillary Carcinoma Cells
Authors: Cheng Chiao-Pei , Liu Shu-Ting , Chiu Yi-Lin , Huang Shih-Ming , Ho Ching-Liang
Published: December 2021

Overexpression of the deubiquitinase USP2a leads to stabilization of fatty acid synthase (FAS), the levels of which are often elevated in aggressive human cancers. Consequently, there is an urgent need for inhibitors to suppress the deubiquitination activity of USP2a so as to upregulate FAS protein degradation. We first analyzed the relationship between the expression level of USP2a and survival using The Cancer Genome Atlas Head-Neck Squamous Cell Carcinoma (HNSC) data collection. Our results suggested survival rates were lower among HNSC patients expressing higher levels of USP2a. We then investigated two thiopurine drugs, 6-thioguanine (6-TG) and 6-mercaptopurine (6-MP), to determine whether they could potentially serve as inhibitors of USP2a. Western blot analysis showed that levels of two USP2a target proteins, FAS and Mdm2, were dose-dependently decreased in A253 submaxillary carcinoma cells treated with 6-TG or 6‐MP. Responding to the degradation of Mdm2, levels of p53 were increased. We found that 6-TG and 6-MP also suppressed levels of both USP2a mRNA and protein, suggesting these two thiopurines do not act solely through direct inhibition of USP2a. The effects of 6-TG and 6-MP were not cell type-specific, as they elicited similar decreases in FAS protein in leukemia, prostate and cervical cancer cell lines. 6-TG and 6-MP had effects on several cell cycle proteins, including another USP2a target protein, cyclin D1. The populations of cells in subG1 and S phase were increased by 6-TG and 6-MP, which was accompanied by reductions in G1 phase cells. In untreated cells, USP2a transfection increased FAS and cyclin D1 levels compared to an enzyme-dead USP2a C276A mutant, which lacked deubiquitinating activity. However, USP2a transfection failed to reverse the suppressive effects of 6‐TG and 6-MP on FAS levels. In summary, these findings suggest 6-TG and 6-MP reduce the stability of some USP2a targets, including FAS and Mdm2, by inhibiting USP2a-catalyzed deubiquitination in some cancer cells. Our work also provides repurposing evidence supporting 6‐TG and 6-MP as target therapeutic drugs, such as USP2a/FAS in this study.
Osteosarcoma and Metastasis
Authors: Sheng Gaohong , Gao Yuan , Yang Yong , Wu Hua
Published: December 2021

Osteosarcoma is the most common primary bone malignancy in adolescents. Its high propensity to metastasize is the leading cause for treatment failure and poor prognosis. Although the research of osteosarcoma has greatly expanded in the past decades, the knowledge and new therapy strategies targeting metastatic progression remain sparse. The prognosis of patients with metastasis is still unsatisfactory. There is resonating urgency for a thorough and deeper understanding of molecular mechanisms underlying osteosarcoma to develop innovative therapies targeting metastasis. Toward the goal of elaborating the characteristics and biological behavior of metastatic osteosarcoma, it is essential to combine the diverse investigations that are performed at molecular, cellular, and animal levels from basic research to clinical translation spanning chemical, physical sciences, and biology. This review focuses on the metastatic process, regulatory networks involving key molecules and signaling pathways, the role of microenvironment, osteoclast, angiogenesis, metabolism, immunity, and noncoding RNAs in osteosarcoma metastasis. The aim of this review is to provide an overview of current research advances, with the hope to discovery druggable targets and promising therapy strategies for osteosarcoma metastasis and thus to overcome this clinical impasse.
Prostate Microbiota and Prostate Cancer: A New Trend in Treatment
Authors: Che Bangwei , Zhang Wenjun , Xu Shenghan , Yin Jingju , He Jun , Huang Tao , Li Wei , Yu Ying , Tang Kaifa
Published: December 2021

Although the incidence and mortality of prostate cancer have gradually begun to decline in the past few years, it is still one of the leading causes of death from malignant tumors in the world. The occurrence and development of prostate cancer are affected by race, family history, microenvironment, and other factors. In recent decades, more and more studies have confirmed that prostate microflora in the tumor microenvironment may play an important role in the occurrence, development, and prognosis of prostate cancer. Microorganisms or their metabolites may affect the occurrence and metastasis of cancer cells or regulate anti-cancer immune surveillance. In addition, the use of tumor microenvironment bacteria in interventional targeting therapy of tumors also shows a unique advantage. In this review, we introduce the pathway of microbiota into prostate cancer, focusing on the mechanism of microorganisms in tumorigenesis and development, as well as the prospect and significance of microorganisms as tumor biomarkers and tumor prevention and treatment.
Design and Analysis of Commercially Viable Free-Space Optical Communication Link for Diverse Beam Divergence Profiles
Authors: Singh Harjeevan , Miglani Rajan , Mittal Nitin , Gaba Gurjot Singh , Masud Mehedi , Aljahdali Sultan
Published: December 2021

With an exponential increase in the use of smart devices and with increasing demand for high-speed data applications, the Radio Frequency and Microwave links will find themselves almost incapable of meeting this deficit. Free-space optical (FSO) links are poised to take the leading role as communication systems for futuristic needs in providing cost-effective and high-speed connectivity to end-users. However, on the flip side, the reliability of FSO links has an intrinsic relationship with the characteristics of the atmospheric channel. During the propagation, the atmospheric adversities result in the geometrical spreading of the FSO beam which in turn has consequential degrading effects on the link performance. In this work, an FSO communication system based on practical, commercial, and realistic parameters has been proposed with the intent of accurately determining the co-relation between different beam divergence profiles and overall link performance. For different beam divergence profiles, the proposed link has been evaluated for reference bit error rate (BER) of 10–9 which is an ideal condition for delivering high-speed data access to the end-users. During the analysis, the practical constraints related to the trade-off between the maximum possible link range and beam divergence have also been optimized. The findings of this work will be crucial for engineers and designers in configuring FSO links for improved link range and reliability.
Exploring the Diversity and Regulation of Apocarotenoid Metabolic Pathways in Plants
Authors: Zheng Xiongjie , Yang Yu , Al-Babili Salim
Published: December 2021

In plants, carotenoids are subjected to enzyme-catalyzed oxidative cleavage reactions as well as to non-enzymatic degradation processes, which produce various carbonyl products called apocarotenoids. These conversions control carotenoid content in different tissues and give rise to apocarotenoid hormones and signaling molecules, which play important roles in plant growth and development, response to environmental stimuli, and in interactions with surrounding organisms. In addition, carotenoid cleavage gives rise to apocarotenoid pigments and volatiles that contribute to the color and flavor of many flowers and several fruits. Some apocarotenoid pigments, such as crocins and bixin, are widely utilized as colorants and additives in food and cosmetic industry and also have health-promoting properties. Considering the importance of this class of metabolites, investigation of apocarotenoid diversity and regulation has increasingly attracted the attention of plant biologists. Here, we provide an update on the plant apocarotenoid biosynthetic pathway, especially highlighting the diversity of the enzyme carotenoid cleavage dioxygenase 4 (CCD4) from different plant species with respect to substrate specificity and regioselectivity, which contribute to the formation of diverse apocarotenoid volatiles and pigments. In addition, we summarize the regulation of apocarotenoid metabolic pathway at transcriptional, post-translational, and epigenetic levels. Finally, we describe inter- and intraspecies variation in apocarotenoid production observed in many important horticulture crops and depict recent progress in elucidating the genetic basis of the natural variation in the composition and amount of apocarotenoids. We propose that the illustration of biochemical, genetic, and evolutionary background of apocarotenoid diversity would not only accelerate the discovery of unknown biosynthetic and regulatory genes of bioactive apocarotenoids but also enable the identification of genetic variation of causal genes for marker-assisted improvement of aroma and color of fruits and vegetables and CRISPR-based next-generation metabolic engineering of high-value apocarotenoids.
A Pathogen-Inducible Rice NAC Transcription Factor ONAC096 Contributes to Immunity Against Magnaprothe oryzae and Xanthomonas oryzae pv. oryzae by Direct Binding to the Promoters of OsRap2.6, OsWRKY62, and OsPAL1
Authors: Wang Hui , Bi Yan , Gao Yizhou , Yan Yuqing , Yuan Xi , Xiong Xiaohui , Wang Jiajing , Liang Jiayu , Li Dayong , Song Fengming
Published: December 2021

The rice NAC transcriptional factor family harbors 151 members, and some of them play important roles in rice immunity. Here, we report the function and molecular mechanism of a pathogen-inducible NAC transcription factor, ONAC096, in rice immunity against Magnaprothe oryzae and Xanthomonas oryzae pv. oryzae. Expression of ONAC096 was induced by M. oryzae and by abscisic acid and methyl jasmonate. ONAC096 had the DNA binding ability to NAC recognition sequence and was found to be a nucleus-localized transcriptional activator whose activity depended on its C-terminal. CRISPR/Cas9-mediated knockout of ONAC096 attenuated rice immunity against M. oryzae and X. oryzae pv. oryzae as well as suppressed chitin- and flg22-induced reactive oxygen species burst and expression of PTI marker genes OsWRKY45 and OsPAL4; by contrast, overexpression of ONAC096 enhanced rice immunity against these two pathogens and strengthened chitin- or flg22-induced PTI. RNA-seq transcriptomic profiling and qRT-PCR analysis identified a small set of defense and signaling genes that are putatively regulated by ONAC096, and further biochemical analysis validated that ONAC096 could directly bind to the promoters of OsRap2.6, OsWRKY62, and OsPAL1, three known defense and signaling genes that regulate rice immunity. ONAC096 interacts with ONAC066, which is a positive regulator of rice immunity. These results demonstrate that ONAC096 positively contributes to rice immunity against M. oryzae and X. oryzae pv. oryzae through direct binding to the promoters of downstream target genes including OsRap2.6, OsWRKY62, and OsPAL1.
Becoming More Rugged and Better Resourced: The R2 Resilience Program’s© Psychosocial Approach to Thriving
Authors: Ungar Michael , Jefferies Philip
Published: December 2021

The past decade has seen growing interest in interventions that build resilience as a complementary practice to trauma-informed care. From school-based programs focused on self-regulation and academic success to programs that support the well-being of disadvantaged populations or healthcare workers at risk of burnout, the concept of resilience is being used most commonly for programming that builds the capacity of individuals to adapt under conditions of adversity. Critiques have raised concerns that resilience-promoting programs demonstrate bias toward changing individual-level factors such as cognitions (e.g., mindfulness and grit), behavior (e.g., expressing gratitude and changing personal routines), or attachments (e.g., feeling secure in relationships) which help people adapt to socially toxic situations without changing access to the resources they require to overcome exposure to adverse psychosocial factors. This trend belies advances to the theory of resilience which support a more contextualized, multisystemic understanding of how external protective factors (resources) enhance individual qualities (ruggedness) and vice versa. Building on a multisystemic description of resilience, the R2 Resilience Program© was developed and piloted with six different populations ranging from clients of urban social services to workers in a long-term care facility, managers in the health care sector, staff of a Fortune 500 corporation, students in a primary to grade 12 school, and adult volunteers affiliated with an international NGO. Focused on building both individual ruggedness and enhancing people’s resources (the two Rs), the program provides contextualized content for each population by selecting from 52 resilience promoting factors with a strong evidence base to create training curricula that enhance the personal qualities and social, physical, and institutional resources most likely to support resilience. This paper reviews the justification for a multisystemic approach to designing resilience interventions and then explains the process of implementation of the R2 program. Preliminary findings are reported, which suggest the program is experienced as effective, with evaluations ongoing.
Analysis of Factors That Influenced the Mental Health Status of Public Health Workers During the COVID-19 Epidemic Based on Bayesian Networks: A Cross-Sectional Study
Authors: Peng Xin , Pu Yangyang , Jiang Xiaoyong , Zheng Qingmei , Gu Jing , Zhou Huan , Deng Dan
Published: December 2021

Background: Public health workers are essential to responding to the coronavirus disease 2019 (COVID-19) epidemic, but research on anxiety and stress among public health workers during the epidemic is limited. This study aimed to evaluate related factors affecting mental health among public health workers during the epidemic.

Methods: Between February 19 and 25, 2020, an online, cross-sectional study was conducted among public health workers in a city in China. Mental health status was assessed using the Chinese versions of the Generalized Anxiety Disorder-7 (GAD-7) scale and Patient Health Questionnaire-9 (PHQ-9), both with a cutoff score of 5. Work-related variables, workloads and sacrifices, and personal perceptions were also assessed.

Results: The prevalence of anxiety and depression were 49.2% and 45.7%, respectively, among public health workers. Three risk factors and one protective factor, namely, overcommitment (OR = 1.10∼1.20, p < 0.001), perceived troubles at work (OR = 1.14∼1.18, p < 0.001), perceived tension (OR = 1.11, p < 0.001) and the capability to persist for more than 1 month at the current work intensity (OR = 0.41∼0.42, p < 0.001) were found to be independently associated with anxiety and depression in the multivariable logistic regression analyses after propensity score matching. But the Bayesian networks analysis found that the last three factors directly affect anxiety and depression.

Conclusion: Psychological responses to COVID-19 were dramatic among public health workers during the severe phase of the outbreak. To minimize the impact of the epidemic, working conditions should be improved, and easily accessible psychological support services should be implemented.
Therapist Attachment and the Working Alliance: The Moderating Effect of Emotional Regulation
Authors: Ruiz-Aranda Desireé , Cardoso-Álvarez Sara , Fenollar-Cortés Javier
Published: December 2021

Objective: To explore whether the therapist’s emotional regulation strategies moderate the relationship between therapist attachment and the working alliance from the therapist’s perspective.

Method: A non-experimental, descriptive correlational design was used. Sixty-three psychotherapists (6 men, 57 women) participated in this study, ranging in age from 27 to 69 years, with a mean age of 39.3 years. The therapists completed the Attachment evaluation questionnaire for adults, the Spanish Adaptation of the Working Alliance Inventory, and the Difficulties in Emotion Regulation Scale. Associations between attachment and emotional regulation traits and working alliance were examined using multilevel modeling, controlling for therapist demographics, and clinical experience.

Results: Moderation analyses revealed significant interaction effects between therapist attachment and emotional regulation strategies.

Conclusion: Attachment styles would not significantly affect the therapist’s ability to establish an adequate therapeutic alliance bond. The results show that the attachment style of the therapists interacted with their emotional regulation abilities.
How Facial Attractiveness Affects Time Perception: Increased Arousal Results in Temporal Dilation of Attractive Faces
Authors: Zhou Sihong , Li Lingjing , Wang Fuyun , Tian Yu
Published: December 2021

Time perception plays a fundamental role in people’s daily life activities, and it is modulated by changes in environmental contexts. Recent studies have observed that attractive faces generally result in temporal dilation and have proposed increased arousal to account for such dilation. However, there is no direct empirical result to evidence such an account. The aim of the current study, therefore, was to clarify the relationship between arousal and the temporal dilation effect of facial attractiveness by introducing a rating of arousal to test the effect of arousal on temporal dilation (Experiment 1) and by regulating arousal via automatic expression suppression to explore the association between arousal and temporal dilation (Experiment 2). As a result, Experiment 1 found that increased arousal mediated the temporal dilation effect of attractive faces; Experiment 2 showed that the downregulation of arousal attenuated the temporal dilation of attractive faces. These results highlighted the role of increased arousal, which is a dominating mechanism of the temporal dilation effect of attractive faces.
Interpersonal Musical Synchronization and Prosocial Behavior in Children: No Effects in a Controlled Field Experiment
Authors: Baier Janina , Wöllner Clemens , Wolf Anna
Published: December 2021

Prosocial effects of music have recently attracted increased attention in research and media. An often-cited experiment, carried out by Kirschner and Tomasello in 2010 under laboratory conditions, found that children at the age of four years were more willing to help each other after they had engaged in synchronous musical activities. The aim of the current study was to replicate this research under controlled field conditions in the children's social environment, and to disentangle the musical synchronization effect by introducing a verbal interaction (singing together) and a motor interaction (tapping together) task, contrasted by an asynchronous control condition. In a between-participants design, no effects of musical synchronization nor the children's gender were found. Furthermore, age was not related to prosocial behavior. Explanations are systematically discussed, yet it remains possible that the original effect found in 2010 might be overestimated and less consistently reproducible as previously assumed.
Cultural Management of Terror and Worry During the COVID-19 Pandemic: How Religiosity and a Dream of Human Solidarity Help the Polish People Cope
Authors: Gut Arkadiusz , Miciuk Łukasz , Gorbaniuk Oleg , Gut Przemysław , Karczmarczyk Anna
Published: December 2021

The COVID-19 pandemic, which involves the threat of contracting a potentially fatal disease, can be understood as a source of terror. According to terror management theory, people shield themselves from terror by adopting culturally specific worldviews and protecting self-esteem. The study investigates the protective role of worldviews that are culturally specific to Poles: religiosity and social solidarity. The hypothesis was that Poles who tend to worry, entertain these worldviews and are more likely to maintain high self-esteem and concentrate on the current moment (carpe diem), which theoretically allows them to reduce future-related anxiety. Path analysis confirmed that self-esteem, the centrality of religiosity, and expectation of solidarity due to the COVID-19 pandemic mediate the relationship between the worry trait and carpe diem.
Post-secondary Student Mental Health During COVID-19: A Meta-Analysis
Authors: Zhu Jenney , Racine Nicole , Xie Elisabeth Bailin , Park Julianna , Watt Julianna , Eirich Rachel , Dobson Keith , Madigan Sheri
Published: December 2021

The COVID-19 pandemic has posed notable challenges to post-secondary students, causing concern for their psychological well-being. In the face of school closures, academic disruptions, and constraints on social gatherings, it is crucial to understand the extent to which mental health among post-secondary students has been impacted in order to inform support implementation for this population. The present meta-analysis examines the global prevalence of clinically significant depression and anxiety among post-secondary students during the COVID-19 pandemic. Several moderator analyses were also performed to examine sources of variability in depression and anxiety prevalence rates. A systematic search was conducted across six databases on May 3, 2021, yielding a total of 176 studies (1,732,456 participants) which met inclusion criteria. Random-effects meta-analyses of 126 studies assessing depression symptoms and 144 studies assessing anxiety symptoms were conducted. The pooled prevalence estimates of clinically elevated depressive and anxiety symptoms for post-secondary students during the COVID-19 pandemic was 30.6% (95% CI: 0.274, 0.340) and 28.2% (CI: 0.246, 0.321), respectively. The month of data collection and geographical region were determined to be significant moderators. However, student age, sex, type (i.e., healthcare student vs. non-healthcare student), and level of training (i.e., undergraduate, university or college generally; graduate, medical, post-doctorate, fellow, trainee), were not sources of variability in pooled rates of depression and anxiety symptoms during the pandemic. The current study indicates a call for continued access to mental health services to ensure post-secondary students receive adequate support during and after the COVID-19 pandemic.

Systematic Review Registration: PROSPERO website: https://www.crd.york.ac.uk/prospero/, identifier: CRD42021253547.
Correlates of Objectively Measured Physical Activity Among People With Multiple Sclerosis: A Cross-Sectional Study
Authors: Fortune Jennifer , Norris Meriel , Stennett Andrea , Kilbride Cherry , Lavelle Grace , Hendrie Wendy , DeSouza Lorraine , Victor Christina , Ryan Jennifer Mary
Published: December 2021

Background: Identifying correlates of physical activity (PA) for people with multiple sclerosis (MS) is essential to design effective PA interventions.

Methods: Participants completed a battery of questionnaires and wore an ActiGraph accelerometer. Light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) (min/day) were calculated. Associations were examined using multiple linear regression adjusted for demographic and clinical confounders.

Results: Fifty-eight adults with MS participated (mean ± SD age: 56.8 ± 9.2 yr; 67% women). MS type was associated with time in LPA. Participants with secondary progressive MS (B = −54.0, 95% CI −84.7 to −23.3) and primary progressive MS (B = −42.9, 95% CI −77.5 to −8.3) spent less time in LPA than those with relapsing remitting MS. Walking capacity, assessed using the 12-item MS walking scale (MSWS-12), was associated with time in MVPA (B = −0.36, 95% CI −0.72 to −0.01).

Conclusion: This work identifies walking capacity and type of MS as correlates of PA, which may indicate development of interventions to promote PA.