bluuebunny/crossref_metadata_2025 huggingface dataset:
Homozygous Mutation of gsdf Causes Infertility in Female Nile Tilapia (Oreochromis niloticus)
Authors: Jiang Dong-Neng , Peng You-Xing , Liu Xing-Yong , Mustapha Umar Farouk , Huang Yuan-Qing , Shi Hong-Juan , Li Ming-Hui , Li Guang-Li , Wang De-Shou
Published: February 2022

Gonadal somatic cell-derived factor (Gsdf) is a member of the TGF-β superfamily, which exists mainly in fishes. Homozygous gsdf mutations in Japanese medaka and zebrafish resulted in infertile females, and the reasons for their infertility remain unknown. This study presents functional studies of Gsdf in ovary development using CRISPR/Cas9 in Nile tilapia (Oreochromis niloticus). The XX wild type (WT) female fish regularly reproduced from 12 months after hatching (mah), while the XX gsdf-/- female fish never reproduced and were infertile. Histological observation showed that at 24 mah, number of phase IV oocyte in the XX gsdf-/- female fish was significantly lower than that of the WT fish, although their gonadosomatic index (GSI) was similar. However, the GSI of the XX gsdf-/- female at 6 mah was higher than that of the WT. The mutated ovaries were hyperplastic with more phase I oocytes. Transcriptome analysis identified 344 and 51 up- and down-regulated genes in mutants compared with the WT ovaries at 6 mah. Some TGF-β signaling genes that are critical for ovary development in fish were differentially expressed. Genes such as amh and amhr2 were up-regulated, while inhbb and acvr2a were down-regulated in mutant ovaries. The cyp19a1a, the key gene for estrogen synthesis, was not differentially expressed. Moreover, the serum 17β-estradiol (E2) concentrations between XX gsdf-/- and WT were similar at 6 and 24 mah. Results from real-time PCR and immunofluorescence experiments were similar and validated the transcriptome data. Furthermore, Yeast-two-hybrid assays showed that Gsdf interacts with TGF-β type II receptors (Amhr2 and Bmpr2a). Altogether, these results suggest that Gsdf functions together with TGF-β signaling pathway to control ovary development and fertility. This study contributes to knowledge on the function of Gsdf in fish oogenesis.
Review of Analytical Approaches for Simulating Motions of Helical Vortex
Authors: Okulov V. L. , Fukumoto Y.
Published: February 2022

The study investigates helical vortices, which are fundamental structures in fluid dynamics, and a basic model of tip vortices behind wind turbines. In connection with the intensive development of wind energy, interest in modeling helical vortex wakes behind the rotors has increased. Therefore, the purpose of this mini-review is to compare the existing methods for calculating the induced velocities of screw vortices. The three methods for calculating the motion of helical vortices are compared. Two typical forms of vorticity with uniform (Rankine-type) and Gaussian distributions in the core of helical vortices are compared, and the minimum distance between the vortex filaments or their turns is identified with sufficient accuracy in both cases. The results presented in this mini-review can be used to model the helical vortices in the rotor wakes, central helical vortices in vortex devices, or natural phenomena such as tornadoes, dust tornadoes, and waterspouts.
Unit Partition Resonance Analysis Strategy for Impedance Network in Modular Power Converters
Authors: Tahir Mustafa , Hu Sideng , Liang Zipeng , Meng Yangyang
Published: February 2022

In modular power converters, the dc-link capacitor has the highest failure rate due to thermal stress, reducing system performance and reliability. Current harmonics are one of the prominent causes of thermal stress on the dc-link capacitor that may get instigated by the resonance between the dc-link capacitor and stray inductance of the busbar. The dc-link capacitor current harmonics mitigation through busbar design optimization has not been reported. The challenge lies in analyzing the profound resonance characteristics of high order dc-link busbar impedance network as no insightful information can be obtained from impedance analyzers. This paper features a new strategy for high power modular converters that splits the high order dc-link busbar impedance network into corresponding lower-order sub-units. Then, the required relationship between resonating components and corresponding resonance frequencies is attained by exploiting the structural symmetry of the standard modular power unit as well as the inheritance relationship between sub-circuit units and the combined network. Finally, leveraging the derived resonant frequencies expressions, busbar structure is optimized, and up to 23% reduction in capacitor RMS current is achieved. Simulation and experimental results are provided to validate the efficacy of the proposed analysis method. The in-depth theoretical study featured in this paper can dictate not only the busbar design optimization but also a key to improve capacitor lifetime and reliability of the system.
The Whole-Process Low-Voltage Ride-Through Control Strategy for Photovoltaic Power Generation Based on Adaptive Maximum Power Tracking
Authors: Yin Jun
Published: February 2022

The impact of the large-scale disconnection of photovoltaic generators on the grid cannot be ignored, so the low-voltage ride-through problem of photovoltaic generators needs to be solved urgently, especially in the stage after fault recovery, there is a problem that the converter is difficult to switch back to the original control strategy. Therefore, a new control strategy of the whole-process low-voltage ride-through control strategy for photovoltaic power generation based on adaptive maximum power tracking is proposed. In the initial stage of failure, an adaptive maximum power control strategy is proposed. This control strategy transforms maximum power point tracking control into adaptive maximum power control by feedback of voltage drop amplitude. It can control the output of photovoltaic power quickly and effectively and realize the zero-voltage crossing of the photovoltaic grid-connected system. In the stage after fault recovery, the switching function is established by comparing the network voltage with the rated voltage. The operating state of the photovoltaic system can be judged by different output of the switching function. It realizes the fast switching of the photovoltaic side control strategy during the fault recovery stage. Simulation results show that the proposed method can switch the control strategy reliably and realize the whole-process low-voltage crossing of photovoltaic power generation quickly.
Rapid Preparation of Manganese Monoxide by Microwave-Enhanced Selective Carbothermal Reduction
Authors: Chen Jin , He Fei , Gao Lei , Guo Shenghui , Omran Mamdouh , Chen Guo
Published: February 2022

Most of the manganese resources in China have existed in the form of low-grade pyrolusite which is not utilized efficiently because of the high energy consumption and environmental pollution during the reduction process. Applying microwave heating to minerals reduction endows improved production efficiency and reduced production costs. In the present work, rapid preparation of manganese monoxide (MnO) was attempted through reducing low-grade pyrolusite with coal reducing agent by microwave heating, with the samples characterized by XRD, scanning electron microscopy, XPS as well as TG/DSC. The influences of the reduction reaction parameters on the reduction process of Mn in pyrolusite were comprehensively studied. The results indicated that higher temperatures and longer holding times facilitated the reduction roasting of pyrolusite, and manganese monoxide can be fabricated with a reduction ratio of 97.7% obtained at 650°C for 50 min. The mechanism of the gradual transformation of MnO2 to MnO from the macroscopic to the molecular level was also revealed in the order of MnO2 → Mn2O3 → Mn3O4 → MnO. Compared to traditional roasting, the proposed microwave-enhanced roasting process benefits from the superior kinetic conditions provided by the synergy between microwave enhancement and compact pellets, and thus reduced the roasting temperature and roasting time.
Ancestral Stem Cell Reprogramming Genes Active in Hemichordate Regeneration
Authors: Humphreys Tom , Weiser Keith , Arimoto Asuka , Sasaki Akane , Uenishi Gene , Fujimoto Brent , Kawashima Takeshi , Taparra Kekoa , Molnar Janos , Satoh Noriyuki , Marikawa Yusuke , Tagawa Kuni
Published: February 2022

Hemichordate enteropneust worms regenerate extensively in a manner that resembles the regeneration for which planaria and hydra are well known. Although hemichordates are often classified as an extant phylogenetic group that may hold ancestral deuterostome body plans at the base of the deuterostome evolutionary line leading to chordates, mammals, and humans, extensive regeneration is not known in any of these more advanced groups. Here we investigated whether hemichordates deploy functional homologs of canonical Yamanaka stem cell reprogramming factors, Oct4, Sox2, Nanog, and Klf4, as they regenerate. These reprogramming factors are not expressed during regeneration of limbs, fins, eyes or other structures that represent the best examples of regeneration in chordates. We first examined Ptychodera flava EST libraries and identified Pf-Pou3, Pf-SoxB1, Pf-Msxlx, and Pf-Klf1/2/4 as most closely related to the Yamanaka factors, respectively. In situ hybridization analyses revealed that all these homologs are expressed in a distinct manner during head regeneration. Furthermore, Pf-Pou3 partially rescued the loss of endogenous Oct4 in mouse embryonic stem cells in maintaining the pluripotency gene expression program. Based on these results, we propose that hemichordates may have co-opted these reprogramming factors for their extensive regeneration or that chordates may have lost the ability to mobilize these factors in response to damage. The robustness of these pluripotency gene circuits in the inner cell mass and in formation of induced pluripotent stem cells from mammalian somatic cells shows that these programs are intact in humans and other mammals and that these circuits may respond to as yet unknown gene regulatory signals, mobilizing full regeneration in hemichordates.
Analysis of Breast Cancer Based on the Dysregulated Network
Authors: Huo Yanhao , Li Xianbin , Xu Peng , Bao Zhenshen , Liu Wenbin
Published: February 2022

Breast cancer is a heterogeneous disease, and its development is closely associated with the underlying molecular regulatory network. In this paper, we propose a new way to measure the regulation strength between genes based on their expression values, and construct the dysregulated networks (DNs) for the four subtypes of breast cancer. Our results show that the key dysregulated networks (KDNs) are significantly enriched in critical breast cancer-related pathways and driver genes; closely related to drug targets; and have significant differences in survival analysis. Moreover, the key dysregulated genes could serve as potential driver genes, drug targets, and prognostic markers for each breast cancer subtype. Therefore, the KDN is expected to be an effective and novel way to understand the mechanisms of breast cancer.
Post-Transplantation Cyclophosphamide Uniquely Restrains Alloreactive CD4+ T-Cell Proliferation and Differentiation After Murine MHC-Haploidentical Hematopoietic Cell Transplantation
Authors: Hadjis Ashley D. , Nunes Natalia S. , Khan Shanzay M. , Fletcher Rochelle E. , Pohl Alessandra de Paula , Venzon David J. , Eckhaus Michael A. , Kanakry Christopher G.
Published: February 2022

Post-transplantation cyclophosphamide (PTCy) reduces the incidence and severity of graft-versus-host disease (GVHD), thereby improving the safety and accessibility of allogeneic hematopoietic cell transplantation (HCT). We have shown that PTCy works by inducing functional impairment and suppression of alloreactive T cells. We also have identified that reduced proliferation of alloreactive CD4+ T cells at day +7 and preferential recovery of CD4+CD25+Foxp3+ regulatory T cells (Tregs) at day +21 are potential biomarkers associated with optimal PTCy dosing and timing in our B6C3F1→B6D2F1 MHC-haploidentical murine HCT model. To understand whether the effects of PTCy are unique and also to understand better the biology of GVHD prevention by PTCy, here we tested the relative impact of cyclophosphamide compared with five other optimally dosed chemotherapeutics (methotrexate, bendamustine, paclitaxel, vincristine, and cytarabine) that vary in mechanisms of action and drug resistance. Only cyclophosphamide, methotrexate, and cytarabine were effective in preventing fatal GVHD, but cyclophosphamide was superior in ameliorating both clinical and histopathological GVHD. Flow cytometric analyses of blood and spleens revealed that these three chemotherapeutics were distinct in constraining conventional T-cell numerical recovery and facilitating preferential Treg recovery at day +21. However, cyclophosphamide was unique in consistently reducing proliferation and expression of the activation marker CD25 by alloreactive CD4+Foxp3- conventional T cells at day +7. Furthermore, cyclophosphamide restrained the differentiation of alloreactive CD4+Foxp3- conventional T cells at both days +7 and +21, whereas methotrexate and cytarabine only restrained differentiation at day +7. No chemotherapeutic selectively eliminated alloreactive T cells. These data suggest that constrained alloreactive CD4+Foxp3- conventional T-cell numerical recovery and associated preferential CD4+CD25+Foxp3+ Treg reconstitution at day +21 may be potential biomarkers of effective GVHD prevention. Additionally, these results reveal that PTCy uniquely restrains alloreactive CD4+Foxp3- conventional T-cell proliferation and differentiation, which may explain the superior effects of PTCy in preventing GVHD. Further study is needed to determine whether these findings also hold true in clinical HCT.
NET Release of Long-Term Surviving Neutrophils
Authors: Kolman Jan Philipp , Pagerols Raluy Laia , Müller Ingo , Nikolaev Viacheslav O. , Trochimiuk Magdalena , Appl Birgit , Wadehn Hannah , Dücker Charlotte Maria , Stoll Fabian David , Boettcher Michael , Reinshagen Konrad , Trah Julian
Published: February 2022

Background

Neutrophil extracellular traps (NETs)—as double-edged swords of innate immunity—are involved in numerous processes such as infection, inflammation and tissue repair. Research on neutrophil granulocytes is limited because of their short lifetime of only a few hours. Several attempts have been made to prolong the half-life of neutrophils using cytokines and bacterial products and have shown promising results. These long-term surviving neutrophils are reported to maintain phagocytic activity and cytokine release; however, little is known regarding their capability to release NETs.

Methods

We analysed the prolongation of neutrophil survival in vitro under various culture conditions using granulocyte colony-stimulating factor (G-CSF), lipopolysaccharide (LPS) or tumour necrosis factor alpha (TNF-α) by flow cytometry and a viability assay. Additionally, we assessed NET formation following stimulation with phorbol 12-myristate 13-acetate (PMA) by immunofluorescence staining, myeloperoxidase (MPO)-DNA sandwich-ELISA and fluorometric assays for cell-free DNA (cfDNA), neutrophil elastase (NE) and myeloperoxidase (MPO).

Results

Untreated neutrophils could form NETs after stimulation with PMA for up to 24 h. Incubation with LPS extended their ability to form NETs for up to 48 h. At 48 h, NET release of neutrophils cultured with LPS was significantly higher compared to that of untreated cells; however, no significantly different enzymatic activity of NE and MPO was observed. Similarly, incubation with G-CSF resulted in significantly higher NET release at 48 h compared to untreated cells. Furthermore, NETs showed significantly higher enzymatic activity of NE and MPO after incubation with G-CSF. Lastly, incubation with TNF-α had no influence on NET release compared to untreated cells although survival counts were altered by TNF-α.

Conclusions

G-CSF, LPS or TNF-α each at low concentrations lead to prolonged survival of cultured neutrophils, resulting in considerable differences in NET formation and composition. These results provide new information for the use of neutrophils in long-term experiments for NET formation and provide novel insights for neutrophil behaviour under inflammatory conditions.
Engineered NK Cells Against Cancer and Their Potential Applications Beyond
Authors: Karvouni Maria , Vidal-Manrique Marcos , Lundqvist Andreas , Alici Evren
Published: February 2022

Cell therapy is an innovative therapeutic concept where viable cells are implanted, infused, or grafted into a patient to treat impaired or malignant tissues. The term was first introduced circa the 19thcentury and has since resulted in multiple breakthroughs in different fields of medicine, such as neurology, cardiology, and oncology. Lately, cell and gene therapy are merging to provide cell products with additional or enhanced properties. In this context, adoptive transfer of genetically modified cytotoxic lymphocytes has emerged as a novel treatment option for cancer patients. To this day, five cell therapy products have been FDA approved, four of which for CD19-positive malignancies and one for B-cell maturation antigen (BCMA)-positive malignancies. These are personalized immunotherapies where patient T cells are engineered to express chimeric antigen receptors (CARs) with the aim to redirect the cells against tumor-specific antigens. CAR-T cell therapies show impressive objective response rates in clinical trials that, in certain instances, may reach up to 80%. However, the life-threatening side effects associated with T cell toxicity and the manufacturing difficulties of developing personalized therapies hamper their widespread use. Recent literature suggests that Natural Killer (NK) cells, may provide a safer alternative and an ‘off-the-shelf’ treatment option thanks to their potent antitumor properties and relatively short lifespan. Here, we will discuss the potential of NK cells in CAR-based therapies focusing on the applications of CAR-NK cells in cancer therapy and beyond.
Novel qEEG Biomarker to Distinguish Anti-NMDAR Encephalitis From Other Types of Autoimmune Encephalitis
Authors: Mizoguchi Tomotaka , Hara Makoto , Hirose Satoshi , Nakajima Hideto
Published: February 2022

Objective

To establish the diagnostic biomarker of electroencephalogram (EEG) to distinguish between anti-N-methyl-d-aspartate receptor encephalitis (NMDARE) and other types of autoimmune encephalitis (other AEs).

Methods

We reviewed the clinical records of 90 patients with acute encephalitis who were treated in our institution between January 2014 and October 2020. We enrolled the patients who fulfilled the diagnostic criteria for possible AE (pAE) defined by Graus et al. (pAE criteria) and then classified into definite NMDARE and other AEs. We investigated the main syndrome and analyzed all admission EEGs using EEG power value (PV). Statistical significance was tested using the Mann–Whitney U test or Fisher’s exact test.

Results

Twenty-five patients fulfilled the pAE criteria and were classified into 9 with definite NMDARE (median age: 21 years; 8 women) and 12 with other AEs (median age: 37.5 years; 6 women). Four were eventually excluded. Speech dysfunction (9/9 vs. 4/12, p = 0.005) and movement disorders (6/9 vs. 1/12, p = 0.016) were more frequent in NMDARE than in other AEs. The PV analyses revealed the novel quantitative EEG (qEEG) index, namely, fast slow ratio (FSR) (PV of total beta/PV of total theta + delta). The median FSR (0.139 vs. 0.029, p = 0.004) was higher for NMDARE than other AEs, and the receiver operating characteristic curve area of FSR was 0.86 (95% CI 0.70–1.00). A cutoff value of 0.047 yielded a specificity of 0.75 and a sensitivity of 1.00. Focusing on patients who did not meet the “probable NMDARE criteria” in Graus 2016 (proNMDARE criteria) (n = 10), the pretest probability of NMDAR antibody test was 0.30 (3/10), which increased in patients with an FSR greater than the cutoff (n = 5) to 0.60 (3/5).

Conclusions

The NMDARE group highlighted speech dysfunction and movement disorders, and a novel qEEG index FSR accurately distinguished the NMDARE patients from other AEs. The FSR is a promising diagnostic marker for NMDARE that indicates the positive results of NMDAR antibodies in patients with AE when combined with the proNMDARE criteria.
Measuring the Link Between Vaccines and Antimicrobial Resistance in Low Resource Settings – Limitations and Opportunities in Direct and Indirect Assessments and Implications for Impact Studies
Authors: Holm Marianne , Zellweger Raphaël M. , Poudyal Nimesh , Smith Katherine HT , Joh Hea Sun , Marks Florian
Published: February 2022

The importance of vaccines in combatting antimicrobial resistance (AMR) is commonly accepted. Although scientific reasoning supports the putative connection between vaccines and reduction of AMR, reliably measuring the magnitude and effect of vaccines on antimicrobial resistance is inherently challenging, especially in low resource settings. We review the intrinsic challenges in estimating the effect of vaccines on AMR and discuss the limitations and opportunities in current methods from the host, pathogen, and environment perspectives. We highlight advantages and pitfalls in different epidemiological study designs with a specific focus on impact studies in low resource settings and suggest how these perspectives could be considered in future research.
Study on the Effect of Mass Selection and Hybridization on Growth Performance of Chinese Pearl Oyster Pinctada martensii
Authors: Fan Chao , Zhang Xuekai , Tang Liming , Zhang Xingzhi , Li Jinlong , Li Yangchun , Li Qiongzhen , Wang Zhaoping
Published: February 2022

The pearl oyster Pinctada martensii is an important species for sea pearl production in China. To explore the influence of the combination of mass selection and hybridization on growth performance of P. martensii, we established four selected groups and four control groups (each with two within-family crosses and two reciprocal hybrid crosses) using 1-year-old offspring of two families (Family A and Family B) from Beihai, Guangxi Province, China. Generally, the growth of the selected group was greater than that of the control group for both within-family crosses and reciprocal hybrid crosses. Shell length and width were affected by genotype, environmental factors, and the interaction between the two on Days 210 and 360. The shell widths of the four reciprocal hybrid crosses all showed heterosis on Day 360. The four within-family crosses showed a certain degree of inbreeding depression during the growth period. On Day 360, the three genetic parameters for shell width of the selected group of ♀ Family B and ♂ Family A were the largest, with values of 0.70, 1.17, and 0.06 for realized heritability, standard response to selection, and current genetic gain, respectively. Overall, the growth performance of ♀ Family B × ♂ Family A in the selected group was the best. Therefore, the combination of mass selection and hybridization could be an effective way to improve the growth performance of P. martensii.
A Protocol of a Guideline to Establish the Evidence Ecosystem of Acupuncture
Authors: Wang Qin , Li Nian , Li Juan , He Ying , Li Yuxi , Zhong Dongling , Liu Xiaobo , Fan Jin , Jin Rongjiang , Kang Deying , Zhang Yonggang
Published: February 2022

This is a protocol for developing a guideline to establish the evidence ecosystem of acupuncture. It describes all steps that will be followed in line with the World Health Organization Handbook for Guideline Development and the Reporting Items for practice Guidelines in Healthcare (RIGHT). The key steps included guideline protocol development, guideline registration, systematic review of acupuncture evidence issues, systematic review of methods for establishing evidence ecosystem, survey of acupuncture stakeholders regarding potential acupuncture evidence issues, development of potential items for guidelines, Delphi method for guideline item development, consensus meeting, drafting guideline, peer review, approval, and publishing. This future guideline will help to establish evidence ecosystem of acupuncture, which will facilitate the application of acupuncture in clinical practice.
Sepsis-Associated Coagulopathy Predicts Hospital Mortality in Critically Ill Patients With Postoperative Sepsis
Authors: Ren Chao , Li Yu-xuan , Xia De-meng , Zhao Peng-yue , Zhu Sheng-yu , Zheng Li-yu , Liang Li-ping , Yao Ren-qi , Du Xiao-hui
Published: February 2022

Background

The incidence of coagulopathy, which was responsible for poor outcomes, was commonly seen among patients with sepsis. In the current study, we aim to determine whether the presence of sepsis-associated coagulopathy (SAC) predicts the clinical outcomes among critically ill patients with postoperative sepsis.

Methods

We conducted a single-center retrospective cohort study by including patients with sepsis admitted to surgical ICU of Chinese PLA General Hospital from January 1, 2014 to December 31, 2018. Baseline characteristics and clinical outcomes were compared with respect to the presence of SAC. Kaplan-Meier analysis was applied to calculate survival rate, and Log-rank test was carried out to compare the differences between two groups. Furthermore, multivariable Cox and logistic and linear regression analysis were performed to assess the relationship between SAC and clinical outcomes, including hospital mortality, development of septic shock, and length of hospital stay (LOS), respectively. Additionally, both sensitivity and subgroup analyses were performed to further testify the robustness of our findings.

Results

A total of 175 patients were included in the current study. Among all included patients, 41.1% (72/175) ICU patients were identified as having SAC. In-hospital mortality rates were significantly higher in the SAC group when compared to that of the No SAC group (37.5% vs. 11.7%; p < 0.001). By performing univariable and multivariable regression analyses, presence of SAC was demonstrated to significantly correlate with an increased in-hospital mortality for patients with sepsis in surgical ICU [Hazard ratio (HR), 3.75; 95% Confidence interval (CI), 1.90–7.40; p < 0.001]. Meanwhile, a complication of SAC was found to be the independent predictor of the development of septic shock [Odds ratio (OR), 4.11; 95% CI, 1.81–9.32; p = 0.001], whereas it was not significantly associated with prolonged hospital LOS (OR, 0.97; 95% CI, 0.83–1.14; p = 0.743).

Conclusion

The presence of SAC was significantly associated with increased risk of in-hospital death and septic shock among postoperative patients with sepsis admitted to ICU. Moreover, there was no statistical difference of hospital LOS between the SAC and no SAC groups.
Health Behavior, Level of Hemoglobin A1c, and Quality of Life Among Agricultural Workers of Various Ethnicities in Thai Border Communities
Authors: Boonyathee Sorawit , Ong-Artborirak Parichat , Seangpraw Katekaew , Tonchoy Prakasit , Kantow Supakan , Bootsikeaw Sasivimol , Auttama Nisarat , Choowanthanapakorn Monchanok , Dokpuang Dech , Panta Pitakpong
Published: February 2022

Background

Little is known about the glycated hemoglobin (HbA1c) levels and quality of life (QoL) in ethnic minority agricultural workers. We investigated the links among health behaviors, HbA1c levels, and QoL ethnic agricultural workers living in rural areas.

Methods

A cross-sectional study was conducted in three northern Provinces of Thailand. Agricultural workers of Indigenous, Hmong, Karen, and Lua communities were recruited. The number of 468 samples were selected using multistage sampling. Data collection was done from interviews using questionnaires, and blood samples were taken.

Results

We revealed 56.8% of participants to be female, with an average age of 49.6 years. Also, 56.0 and 34.8% of participants had low and moderate levels of knowledge on non-communicable diseases, respectively. In addition, 56.8 and 30.6% of participants had moderate and low health behaviors, respectively. Also, 51.5% had a HbA1c level (≥6.5%). We found that 64.7, 22.9, and 12.4% had moderate, low, and high QoL, respectively. Multiple linear regression analysis revealed that having an underlying disease and knowledge score were both significantly related to the health behaviors score (p < 0.05), accounting for 68.6% of the variance. Five variables (ethnicity, BMI, having an underlying disease, smoking, and health behaviors) were significantly related to the HbA1c level (p < 0.05), accounting for 24.6% of the variance. Education, health behaviors, and HbA1c level were significantly associated with QoL (p < 0.05). These three factors could explain 79.4% of the variance in QoL among ethnic agricultural workers.

Conclusion

Health behaviors of ethnic minority agricultural workers influenced their HbA1c level and QoL. Effective health behaviors modification programs should be developed in accordance with the problems and needs among ethnic minority agricultural workers to enhance their QoL.
Frailty as an Independent Risk Factor for Depression in Patients With End-Stage Renal Disease: A Cross-Sectional Study
Authors: Chi Chun-Yi , Lee Szu-Ying , Chao Chia-Ter , Huang Jenq-Wen
Published: February 2022

Background

Depression confers substantial disease burden globally, especially among those with chronic kidney disease (CKD). The presence of depression significantly impairs one's quality of life. Risk factors for depression in patients with CKD remain under-appreciated, and whether frailty, a geriatric phenotype, constitutes a risk factor for depression in this population is unknown.

Methods

We prospectively enrolled patients with end-stage renal disease (ESRD) undergoing hemodialysis for >3 months from National Taiwan University Hospital Yunlin Branch between 2019 and 2021. Clinical, physical, functional, and performance parameters were recorded, followed by frailty/sarcopenia assessment. Depression was screened for using the Geriatric Depression Scale. We analyzed the independent relationship between frailty and depression in these patients, using multiple regression analyses.

Results

Totally 151 patients with ESRD were enrolled (mean 61.1 years, 66.9% male), among whom 16.6% had screening-identified depression. ESRD participants with depression did not differ from those without regarding most parameters except serum creatinine, functional indices, and sarcopenia/frailty status. We found that having greater frail severities was independently associated with a higher probability of depression; having FRAIL- (odds ratio [OR] 5.418) and SOF-based (OR 2.858) frailty independently correlated with a higher depression probability. A linear relation exists between a greater frail severity and the probability of depression. Using a more relaxed criterion for detecting depression, higher SOF scores remained significantly associated with an increased depression risk.

Conclusions

In patients with CKD, frailty independently correlated with a higher probability of having depression. Strategies aiming to attenuate frailty may be able to benefit those with depression simultaneously in this population.
Diagnostic Significance of Metagenomic Next-Generation Sequencing for Community-Acquired Pneumonia in Southern China
Authors: Liu Hanying , Zhang Ying , Chen Guiyang , Sun Shenghua , Wang Jiangang , Chen Fengyi , Liu Chun , Zhuang Quan
Published: February 2022

Background

The morbidity and mortality of community-acquired pneumonia are relatively high, but many pneumonia pathogens cannot be identified accurately. As a new pathogen detection technology, metagenomic next-generation sequencing (mNGS) has been applied more and more clinically. We aimed to evaluate the diagnostic significance of mNGS for community-acquired pneumonia (CAP) in the south of China.

Methods

Our study selected CAP patients who visited the 3rd Xiangya Hospital from May 2019 to April 2021. Pathogens in bronchoalveolar lavage fluid (BALF) specimens were detected using mNGS and traditional microbiological culture. mNGS group: detected by both mNGS and BALF culture; control group: detected only by BALF or sputum culture. The diagnostic performance of pathogens and the antibiotic adjustments were compared within mNGS group.

Results

The incidence of acute respiratory distress syndrome (ARDS) was 28.3% in the mNGS group and 17.3% in the control group. Within the mNGS group, the positive rate of pathogens detected by mNGS was 64%, thus by BALF culture was only 28%. Pathogens detected by mNGS were consisted of bacteria (55%), fungi (18%), special pathogens (18%), and viruses (9%). The most detected pathogen by mNGS was Chlamydia psittaci. Among the pathogen-positive cases, 26% was not pathogen-covered by empirical antibiotics, so most of which were made an antibiotic adjustment.

Conclusions

mNGS can detect pathogens in a more timely and accurate manner and assist clinicians to adjust antibiotics in time. Therefore, we recommend mNGS as the complementary diagnosis of severe pneumonia or complicated infections.
The Role of Intestinal Microbiota in Regulating the Metabolism of Bile Acids Is Conserved Across Vertebrates
Authors: Xiong Fan , Chen Sijia , Jakovlić Ivan , Li Wenxiang , Li Ming , Zou Hong , Wang Guitang , Wu Shangong
Published: February 2022

In mammals, bile acid (BA) concentrations are regulated largely by the gut microbiota, and a study has shown that some metabolic responses to the gut microbiota are conserved between zebrafish and mice. However, it remains unknown whether the influence of specific intestinal microbes on BA metabolism is conserved between higher and lower vertebrates (i.e., mammals and fish). In the present study, Citrobacter freundii GC01 isolated from the grass carp (Ctenopharyngodon idella) intestine was supplemented to the fish and mice feed. We found the changes in the bile acid profile, especially significant changes in secondary BAs in both grass carp and mice fed on C. freundii. Also, lipid metabolism was significantly affected by C. freundii. Analysis of liver transcriptome sequencing data and validation by RT-qPCR revealed that the CYP7A1 gene was significantly up-regulated in both grass carp and mice. In addition, the overexpression of HNF4B from grass carp resulted in a significant increase in the expression level of CYP7A1. Generally, our results suggest that the metabolism of BAs by intestinal microbiota is conserved across vertebrates. Furthermore, specific intestinal bacteria may regulate the bile salt synthesis through CYP7A1 and that HNF4B might be an important regulator of BA metabolism in fish.
Serum Metabonomics Reveals Risk Factors in Different Periods of Cerebral Infarction in Humans
Authors: Chen Guoyou , Guo Li , Zhao Xinjie , Ren Yachao , Chen Hongyang , Liu Jincheng , Jiang Jiaqi , Liu Peijia , Liu Xiaoying , Hu Bo , Wang Na , Peng Haisheng , Xu Guowang , Tao Haiquan
Published: February 2022

Studies of key metabolite variations and their biological mechanisms in cerebral infarction (CI) have increased our understanding of the pathophysiology of the disease. However, how metabolite variations in different periods of CI influence these biological processes and whether key metabolites from different periods may better predict disease progression are still unknown. We performed a systematic investigation using the metabonomics method. Various metabolites in different pathways were investigated by serum metabolic profiling of 143 patients diagnosed with CI and 59 healthy controls. Phe-Phe, carnitine C18:1, palmitic acid, cis-8,11,14-eicosatrienoic acid, palmitoleic acid, 1-linoleoyl-rac-glycerol, MAG 18:1, MAG 20:3, phosphoric acid, 5α-dihydrotestosterone, Ca, K, and GGT were the major components in the early period of CI. GCDCA, glycocholate, PC 36:5, LPC 18:2, and PA showed obvious changes in the intermediate time. In contrast, trans-vaccenic acid, linolenic acid, linoleic acid, all-cis-4,7,10,13,16-docosapentaenoic acid, arachidonic acid, DHA, FFA 18:1, FFA 18:2, FFA 18:3, FFA 20:4, FFA 22:6, PC 34:1, PC 36:3, PC 38:4, ALP, and Crea displayed changes in the later time. More importantly, we found that phenylalanine metabolism, medium-chain acylcarnitines, long-chain acylcarnitines, choline, DHEA, LPC 18:0, LPC 18:1, FFA 18:0, FFA 22:4, TG, ALB, IDBIL, and DBIL played vital roles in the development of different periods of CI. Increased phenylacetyl-L-glutamine was detected and may be a biomarker for CI. It was of great significance that we identified key metabolic pathways and risk metabolites in different periods of CI different from those previously reported. Specific data are detailed in the Conclusion section. In addition, we also explored metabolite differences of CI patients complicated with high blood glucose compared with healthy controls. Further work in this area may inform personalized treatment approaches in clinical practice for CI by experimentally elucidating the pathophysiological mechanisms.
A Global Phosphorylation Atlas of Proteins Within Pathological Site of Rotator Cuff Tendinopathy
Authors: Wang Yezhou , Zhang Jiawei , Lin Yuan , Cheng Shi , Wang Duanyang , Rao Man , Jiang Yuheng , Huang Xiang , Chen Ruijing , Xie Yong , Yin Pengbin , Cheng Biao
Published: February 2022

Rotator cuff tendinopathy (RCT) is the most common cause of shoulder pain, therefore posing an important clinical problem. Understanding the mechanism and biochemical changes of RCT would be of crucial importance and pave the path to targeting novel and effective therapeutic strategies in translational perspectives and clinical practices. Phosphorylation, as one of the most important and well-studied post-translational modifications, is tightly associated with protein activity and protein functional regulation. Here in this study, we generated a global protein phosphorylation atlas within the pathological site of human RCT patients. By using Tandem Mass Tag (TMT) labeling combined with mass spectrometry, an average of 7,741 phosphorylation sites (p-sites) and 3,026 proteins were identified. Compared with their normal counterparts, 1,668 p-sites in 706 proteins were identified as upregulated, while 73 p-sites in 57 proteins were downregulated. GO enrichment analyses have shown that majority of proteins with upregulated p-sites functioned in neutrophil-mediated immunity whereas downregulated p-sites are mainly involved in muscle development. Furthermore, pathway analysis identified NF-κB–related TNF signaling pathway and protein kinase C alpha type (PKCα)–related Wnt signaling pathway were associated with RCT pathology. At last, a weighted kinase-site phosphorylation network was built to identify potentially core kinase, from which serine/threonine-protein kinase 39 (STLK3) and mammalian STE20-like protein kinase 1 (MST1) were proposed to be positively correlated with the activation of Wnt pathway.
Antrodia camphorata-Derived Antrodin C Inhibits Liver Fibrosis by Blocking TGF-Beta and PDGF Signaling Pathways
Authors: Xu Xin-Yi , Geng Yan , Xu Hao-Xiang , Ren Yilin , Liu Deng-Yang , Mao Yong
Published: February 2022

Hepatic stellate cells (HSCs) play an essential role in the development of liver fibrosis. Antrodia camphorata (A. camphorata) is a medicinal fungus with hepatoprotective effect. This study investigated whether Antrodin C, an A. camphorata-fermented metabolite, could exert a protective role on liver fibrosis both in vitro and in vivo. The anti-fibrotic effect of Antrodin C was investigated in CFSC-8B cell (hepatic stellate cell) stimulated by transforming growth factor-β1 (TGF-β1) or platelet-derived growth factor-BB (PDGF-BB) in vitro and in CCl4 induced liver fibrosis in mice. Antrodin C (50 μM) inhibited TGF-β1 or PDGF-BB stimulated CFSC-8B cell activation, migration and extracellular matrix (ECM) accumulation (all p < 0.05). Antrodin C (3, 6 mg/kg/d) oral administration reduced the degree of liver fibrosis induced by CCl4 in mice. Antrodin C down-regulated the expression of α-smooth muscle actin (α-SMA) and collagen I in fibrotic livers. Furthermore, Antrodin C ameliorated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevation in serum (all p < 0.05). Mechanistically, Antrodin C executes its anti-fibrotic activity through negatively modulate TGF-β1 downstream SMAD Family Member 2 (Smad2), AKT Serine/Threonine Kinase 1 (AKT), extracellular signal-regulated kinase (ERK), and P38 MAP Kinase (P38), as well as PDGF-BB downstream AKT and ERK signaling pathways. Antrodin C ameliorates the activation, migration, ECM production in HSCs and CCl4-induced liver fibrosis in mice, suggesting that Antrodin C could serve as a protective molecule against liver fibrosis.
Pre-stroke Physical Activity and Cerebral Collateral Circulation in Ischemic Stroke: A Potential Therapeutic Relationship?
Authors: Hung Stanley Hughwa , Kramer Sharon , Werden Emilio , Campbell Bruce C. V. , Brodtmann Amy
Published: February 2022

Favorable cerebral collateral circulation contributes to hindering penumbral tissue from progressing to infarction and is associated with positive clinical outcomes after stroke. Given its clinical importance, improving cerebral collateral circulation is considered a therapeutic target to reduce burden after stroke. We provide a hypothesis-generating discussion on the potential association between pre-stroke physical activity and cerebral collateral circulation in ischemic stroke. The recruitment of cerebral collaterals in acute ischemic stroke may depend on anatomical variations, capacity of collateral vessels to vasodilate, and individual risk factors. Physical activity is associated with improved cerebral endothelial and vascular function related to vasodilation and angiogenic adaptations, and risk reduction in individual risk factors. More research is needed to understand association between cerebral collateral circulation and physical activity. A presentation of different methodological considerations for measuring cerebral collateral circulation and pre-stroke physical activity in the context of acute ischemic stroke is included. Opportunities for future research into cerebral collateral circulation, physical activity, and stroke recovery is presented.
Lipidomics Profiles Revealed Alterations in Patients With Meibomian Gland Dysfunction After Exposure to Intense Pulsed Light
Authors: Zhao Hui , Wu Shi-Nan , Shao Yi , Xiao Dong , Tang Li-Ying , Cheng Zhe , Peng Jie
Published: February 2022

So far, intense pulsed light (IPL) has been widely used in the treatment of meibomian gland dysfunction (MGD), but there was still a lack of research on its specific mechanism. Determining whether there was a correlation between liposome changes and remission of clinical signs in patients with MGD treated with IPL was of great significance in the clinical evaluation of efficacy in patients with MGD. Our study enrolled the 10 healthy subjects and 26 adult patients, who were diagnosed with MGD and had not received any alternative treatments for at least 3 months. Each patient received a series of three treatments at 3-week intervals. The meibum was collected before the first treatment (T0) and the third treatment (T2). The significant changes in ocular surface parameters before and after IPL treatment were analyzed. The results showed that IPL significantly improved the symptoms of MGD, including ocular surface disease index (OSDI), tear breakup time (TBUT), redness of conjunctival (CR), corneal fluorescein staining (CF), the meibomian gland expressibility (MGE), and meibum quality (all p < 0.05). Lipidomics analysis of the meibum characterized the changes in lipid profiles induced by IPL. A total of 323 lipid species compounds were identified in the spectrum. A total of 41 lipid species were significantly different in patients with MGD (T0) vs. healthy controls. Following IPL treatment (T2), 24 lipid species were significantly different compared with T0: TG (10 lipid species), LPC (6 lipid species), OAHFA (4 lipid species), Cer (2 lipid species), SM (1 lipid species), and PE (1 lipid specie). Among these lipids, 4 of the lipids was a high correlation with TBUT, 5 was TH, 6 was CR, and 11 was meibum quality. In a ward, IPL treatment can achieve the therapeutic effect by changing the alternations of tear film lipids in patients with MGD. The changes in lipid expression profiles are potential indexes to evaluate the therapeutic effectiveness of IPL treatment or other treatments on MGD.
Altered Expression of Specific MicroRNAs in Plasma of Aneurysmal Subarachnoid Hemorrhage Patients
Authors: Zheng Lina , Zhang Xin , Liu Liping , Pu Yuehua
Published: February 2022

Background

Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening condition with high disability and mortality. MicroRNAs (miRNAs) are reported to play a modulating role in aSAH. We investigated specific plasma microRNAs (miRNAs) associated with aSAH and gained comprehensive insight into its pathological mechanisms.

Methods

This is a prospective case–control study. We used a two-stage approach, with primary screening and ensuing two-step validation stages. Significantly differentially expressed plasma miRNAs between aSAH patients and neurologically healthy controls were initially screened by microarray analysis. These miRNAs were then validated in two groups of independent cohorts using reverse transcription quantitative real-time polymerase chain reaction assays. Functional annotation of these miRNA targets was performed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses.

Results

In the primary screening stage, 14 miRNAs were identified as differentially expressed at a significance level of P < 0.05 and fold change >2 between 5 aSAH patients and 5 neurologically healthy controls. In the two validation steps (20 patients vs. 20 control; 40 patients vs. 30 controls), miR-23b-3p, miR-590-5p, miR-20b-5p, miR-142-3p, and miR-29b-3p were found to be significantly down-regulated in patients with aSAH compared with controls. Through these 5 miRNAs, we obtained 32 overlapping target genes, including TGM2, EREG, EDN1, and COL4A1, in three databases that may affect the progression of aSAH. The results of functional annotation revealed mechanisms mainly related to inflammation, smooth muscle cell proliferation and cell adhesion, potentially contributing to the occurrence of aSAH.

Conclusion

We demonstrate that specific miRNAs in plasma, including miR-23b-3p, miR-590-5p, miR-20b-5p, miR-142-3p, and miR-29b-3p, are significantly down-regulated in aSAH patients and may play a modulating role in its progression.
New Insights Into the Pivotal Role of CREB-Regulated Transcription Coactivator 1 in Depression and Comorbid Obesity
Authors: Rossetti Clara , Cherix Antoine , Guiraud Laetitia F. , Cardinaux Jean-René
Published: February 2022

Depression and obesity are major public health concerns, and there is mounting evidence that they share etiopathophysiological mechanisms. The neurobiological pathways involved in both mood and energy balance regulation are complex, multifactorial and still incompletely understood. As a coactivator of the pleiotropic transcription factor cAMP response element-binding protein (CREB), CREB-regulated transcription coactivator 1 (CRTC1) has recently emerged as a novel regulator of neuronal plasticity and brain functions, while CRTC1 dysfunction has been associated with neurodegenerative and psychiatric diseases. This review focuses on recent evidence emphasizing the critical role of CRTC1 in the neurobiology of depression and comorbid obesity. We discuss the role of CRTC1 downregulation in mediating chronic stress-induced depressive-like behaviors, and antidepressant response in the light of the previously characterized Crtc1 knockout mouse model of depression. The putative role of CRTC1 in the alteration of brain energy homeostasis observed in depression is also discussed. Finally, we highlight rodent and human studies supporting the critical involvement of CRTC1 in depression-associated obesity.