bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitophagy in Antiviral Immunity
Authors: Wang Hongna , Zheng Yongfeng , Huang Jieru , Li Jin
Published: September 2021

Mitochondria are important organelles whose primary function is energy production; in addition, they serve as signaling platforms for apoptosis and antiviral immunity. The central role of mitochondria in oxidative phosphorylation and apoptosis requires their quality to be tightly regulated. Mitophagy is the main cellular process responsible for mitochondrial quality control. It selectively sends damaged or excess mitochondria to the lysosomes for degradation and plays a critical role in maintaining cellular homeostasis. However, increasing evidence shows that viruses utilize mitophagy to promote their survival. Viruses use various strategies to manipulate mitophagy to eliminate critical, mitochondria-localized immune molecules in order to escape host immune attacks. In this article, we will review the scientific advances in mitophagy in viral infections and summarize how the host immune system responds to viral infection and how viruses manipulate host mitophagy to evade the host immune system.
Mechanical Stimulation via Muscle Activity Is Necessary for the Maturation of Tendon Multiscale Mechanics During Embryonic Development
Authors: Peterson Benjamin E. , Rolfe Rebecca A. , Kunselman Allen , Murphy Paula , Szczesny Spencer E.
Published: September 2021

During embryonic development, tendons transform into a hypocellular tissue with robust tensile load-bearing capabilities. Previous work suggests that this mechanical transformation is due to increases in collagen fibril length and is dependent on mechanical stimulationviamuscle activity. However, the relationship between changes in the microscale tissue structure and changes in macroscale tendon mechanics is still unclear. Additionally, the specific effect of mechanical stimulation on the multiscale structure-function relationships of developing tendons is also unknown. Therefore, the objective of this study was to measure the changes in tendon mechanics and structure at multiple length scales during embryonic development with and without skeletal muscle paralysis. Tensile testing of tendons from chick embryos was performed to determine the macroscale tensile modulus as well as the magnitude of the fibril strains and interfibrillar sliding with applied tissue strain. Embryos were also treated with either decamethonium bromide or pancuronium bromide to produce rigid or flaccid paralysis. Histology was performed to assess changes in tendon size, spacing between tendon subunits, and collagen fiber diameter. We found that the increase in the macroscale modulus observed with development is accompanied by an increase in the fibril:tissue strain ratio, which is consistent with an increase in collagen fibril length. Additionally, we found that flaccid paralysis reduced the macroscale tendon modulus and the fibril:tissue strain ratio, whereas less pronounced effects that were not statistically significant were observed with rigid paralysis. Finally, skeletal paralysis also reduced the size of collagen fibril bundles (i.e., fibers). Together, these data suggest that more of the applied tissue strain is transmitted to the collagen fibrils at later embryonic ages, which leads to an increase in the tendon macroscale tensile mechanics. Furthermore, our data suggest that mechanical stimulation during development is necessary to induce structural and mechanical changes at multiple physical length scales. This information provides valuable insight into the multiscale structure-function relationships of developing tendons and the importance of mechanical stimulation in producing a robust tensile load-bearing soft tissue.
A Functional Signature in the Developing Cerebellum: Evidence From a Preclinical Model of Autism
Authors: Soria-Ortiz María Berenice , Reyes-Ortega Pamela , Martínez-Torres Ataúlfo , Reyes-Haro Daniel
Published: September 2021

Autism spectrum disorders (ASD) are pervasive neurodevelopmental conditions detected during childhood when delayed language onset and social deficits are observed. Children diagnosed with ASD frequently display sensorimotor deficits associated with the cerebellum, suggesting a dysfunction of synaptic circuits. Astroglia are part of the tripartite synapses and postmortem studies reported an increased expression of the glial fibrillary acidic protein (GFAP) in the cerebellum of ASD patients. Astroglia respond to neuronal activity with calcium transients that propagate to neighboring cells, resulting in a functional response known as a calcium wave. This form of intercellular signaling is implicated in proliferation, migration, and differentiation of neural precursors. Prenatal exposure to valproate (VPA) is a preclinical model of ASD in which premature migration and excess of apoptosis occur in the internal granular layer (IGL) of the cerebellum during the early postnatal period. In this study we tested calcium wave propagation in the IGL of mice prenatally exposed to VPA. Sensorimotor deficits were observed and IGL depolarization evoked a calcium wave with astrocyte recruitment. The calcium wave propagation, initial cell recruitment, and mean amplitude of the calcium transients increased significantly in VPA-exposed mice compared to the control group. Astrocyte recruitment was significantly increased in the VPA model, but the mean amplitude of the calcium transients was unchanged. Western blot and histological studies revealed an increased expression of GFAP, higher astroglial density and augmented morphological complexity. We conclude that the functional signature of the IGL is remarkably augmented in the preclinical model of autism.
Irradiation Haematopoiesis Recovery Orchestrated by IL-12/IL-12Rβ1/TYK2/STAT3-Initiated Osteogenic Differentiation of Mouse Bone Marrow-Derived Mesenchymal Stem Cells
Authors: Li Fengjie , Zhang Rong , Hu Changpeng , Ran Qian , Xiang Yang , Xiang Lixin , Chen Li , Yang Yang , Li Shengwen Calvin , Zhang Gang , Li Zhongjun
Published: September 2021

Purpose

Repairing the irradiation-induced osteogenic differentiation injury of bone marrow mesenchymal stem cells (BM-MSCs) is beneficial to recovering haematopoiesis injury in radiotherapy; however, its mechanism is elusive. Our study aimed to help meet the needs of understanding the effects of radiotherapy on BM-MSC osteogenic potential.

Methods and Materials

Balb/c mice and the BM-MSCs were used to evaluate the irradiation-induced osteogenic differentiation injury in vivo. The cellular and molecular characterization were applied to determine the mechanism for recovery of irradiation-derived haematopoiesis injuries.

Results

We report a functional role of IL-12 in acute irradiation hematopoietic injury recovery and intend to dissect the possible mechanisms through BM-MSC, other than the direct effect of IL-12 on hematopoietic stem and progenitor cells (HSPCs). Specifically, we show that early use of IL-12 enhanced the osteogenic differentiation of BM-MSCs through IL-12Rβ1/TYK2/STAT3 signaling; furthermore, IL-12 induced osteogenesis facilitated bone formation and irradiation hematopoiesis recovery when transplanted BM-MSCs in the femur of Balb/c mice. For the mechanism of action, we found that IL-12 receptor beta 1 (IL-12Rβ1) expression of irradiated BM-MSCs was upregulated rapidly, coincidentally consistent with early use of IL-12 induced osteogenic differentiation enhancement. IL-12Rβ1 and tyrosine kinase 2 gene (Tyk2) silencing experiments and phosphotyrosine of signal transducer and activator of transcription 3 (p-STAT3) suppression experiments indicated the IL-12Rβ1/TYK2/STAT3 signaling was essential in IL-12-induced osteogenic differentiation enhancement of BM-MSCs.

Conclusion

These findings suggested that IL-12 may exert BM-MSCs-based hematopoietic recovery by repairing osteogenic differentiation abilities damages through IL-12Rβ1/TYK2/STAT3 signaling pathway post-irradiation.
Efficiency and Quantitative Structure-Activity Relationship of Monoaromatics Oxidation by Quinone-Activated Persulfate
Authors: Shi Jiaqi , Long Tao , Zhou Yuxuan , Wang Lei , Jiang Cuiping , Pan Dongguo , Zhu Xin
Published: September 2021

Quinones and quinone-containing organics have potential of activating persulfate to produce sulfate radical. In this work, the optimal condition for quinone activation of persulfate was investigated. It was found representative monoaromatics were degraded fastest in alkaline environment (pH 10.0), but excessive alkalinity restrained the reaction instead. The mechanisms to explain this phenomenon were speculated. The effect of initial quinone concentration on persulfate oxidation was also investigated at pH 10.0. In addition, a quantitative structure-activity relationship model was established with 15 kinds of monoaromatics, which revealed the most negative atomic net charges on carbon atom played an important role on degradation rates. Chemicals with a smaller qC- were easier oxidized in quinone-activate system. This finding helps further exploration of effective activator in alkaline environment.
Synthesis, Mesomorphic, and Solar Energy Characterizations of New Non-Symmetrical Schiff Base Systems
Authors: Alamro Fowzia S. , Ahmed Hoda A. , Gomha Sobhi M. , Shaban Mohamed
Published: September 2021

New asymmetrical Schiff base series based on lateral methoxy group in a central core, (E)-3-methoxy-4-(((4-methoxyphenyl)imino)methyl)phenyl 4-alkoxybenzoate (An), were synthesized and their optical and mesomorphic characteristics were investigated. The lateral OCH3group was inserted in the central ring in ortho position with respect to the azomethine linkage. FT-IR, and NMR spectroscopy as well as elemental analyses were used to elucidate their molecular structures. Their mesomorphic behaviors were characterized by polarized optical microscopy (POM) and differential scanning calorimetry (DSC). These examinations indicated that all the designed series were monomorphic and possessed nematic (N) mesophase enantiotropically, except A12 derivative which exhibited monotropic N phase. A comparative study was made between the present investigated series (An) and their corresponding isomers (Bn). The results revealed that the kind and stability of the mesophase as well as its temperature range are affected by the location and special orientation of the lateral methoxy group electric-resistance, conductance, energy-gap, and Urbach-energy were also reported for the present investigated An series. These results revealed that all electrodes exhibit Ohmic properties and electric-resistances in the GΩ range, whereas the electric resistance was decreased from 221.04 to 44.83 GΩ by lengthening the terminal alkoxy-chain to n = 12. The band gap of the An series was reduced from 3.43 to 2.89 eV by increasing the terminal chain length from n = 6 to n = 12 carbons. Therefore, controlling the length of the terminal chain can be used to improve the An series’ electric conductivity and optical absorption, making it suitable for solar energy applications.
Bridging the Bridging Imidazolate in the Bimetallic Center of the Cu/Zn SOD1 and ALS
Authors: Timucin Ahmet Can , Cinaroglu Suleyman Selim , Sezerman Osman Ugur , Timucin Emel
Published: September 2021

Metallation status of human Cu/Zn superoxide dismutase 1 (SOD1) plays a pivotal role in the pathogenesis of amyotrophic lateral sclerosis (ALS). All of the amino acids found in the bimetallic center have been associated with ALS except for two positions. H63 which forms the bridging imidazolate ion in the bimetallic center and K136 which is not directly involved in coordination but located in the bimetallic center were not reported to be mutated in any of the identified ALS cases. In this study, we investigated the structure and flexibility of five SOD1 variants by using classical molecular dynamics simulations. These variants include three substitutions on the non-ALS-linked positions; H63A, H63R, K136A and ALS-linked positions; G37R, H46R/H48D. We have generated four systems for each variant differing in metallation and presence of the intramolecular disulfide bond. Overall, a total of 24 different dimers including the wild-type were generated and simulated at two temperatures, 298 and 400 K. We have monitored backbone mobility, fluctuations and compactness of the dimer structures to assess whether the hypothetical mutations would behave similar to the ALS-linked variants. Results showed that particularly two mutants, H63R and K136A, drastically affected the dimer dynamics by increasing the fluctuations of the metal binding loops compared with the control mutations. Further, these variants resulted in demetallation of the dimers, highlighting probable ALS toxicity that could be elicited by the SOD1 variants of H63R and K136A. Overall, this study bridges two putative SOD1 positions in the metallic center and ALS, underlining the potential use of atomistic simulations for studying disease variants.
Stereoisomer-Independent Stable Blue Emission in Axial Chiral Difluorenol
Authors: Yu Mengna , Jia Xiong , Lin Dongqing , Du Xue , Jin Dong , Wei Ying , Xie Linghai , Huang Wei
Published: September 2021

Bulky conjugated molecules with high stability are the prerequisite for the overall improvement of performance in wide-bandgap semiconductors. Herein, a chiral difluorenol, 2,2′-(9,9′-spirobi[fluorene]-2,2′-diyl)bis(9-(4-(octyloxy)phenyl)-9H-fluoren-9-ol) (DOHSBF), is set as a desirable model to reveal the stereoisomeric effects of wide-bandgap molecules toward controlling photophysical behavior and improving thermal and optical stability. Three diastereomers are obtained and elucidated by NMR spectra. Interestingly, the effect of modifying the stereo-centers is not observed on optical properties in solutions, pristine films, or post-treated film states. All three diastereomers as well as the mixture exhibit excellent spectral stability without undesirable green emission. Therefore, this stereoisomer-independent blue-emitting difluorenol will be a promising candidate for next-generation wide-bandgap semiconductors that would have extensive application in organic photonics.
Two New Diterpenoids from Biscogniauxia sp. and Their Activities
Authors: Zhao Huan , Liu Yue , Zhang Meng , Chen Guo-dong , Hu Dan , Guo Liang-dong , Zhao Zhong-xiang , Zhi Hui , Gao Hao
Published: September 2021

Two new diterpenoids, including a seco-isopimarane type (1) and an abietane type (2), were isolated from Biscogniauxia sp. (71-10-1-1). Their structures, including absolute configurations, were elucidated by NMR spectroscopic analyses, X-ray crystallography, 13C chemical shifts calculations, and ECD calculations. This is the first report of diterpenoids from Biscogniauxia sp. Furthermore, short-term memory enhancement against Alzheimer’s disease (AD), anti-inflammatory, and cytotoxic activities of 1–2 were also evaluated. The results showed that compound 1 exhibited short-term memory enhancement activity against AD.
Identification of Immune Activation Markers in the Early Onset of COVID-19 Infection
Authors: Kovarik Johannes J. , Kämpf Anna K. , Gasser Fabian , Herdina Anna N. , Breuer Monika , Kaltenecker Christopher C. , Wahrmann Markus , Haindl Susanne , Mayer Florian , Traby Ludwig , Touzeau-Roemer Veronique , Grabmeier-Pfistershammer Katharina , Kussmann Manuel , Robak Oliver , Willschke Harald , Ay Care , Säemann Marcus D. , Schmetterer Klaus G. , Strassl Robert
Published: September 2021

This study aimed to determine the specific cytokine profile in peripheral blood during the early onset of COVID-19 infection. This was a cross-sectional exploratory, single center study. A total of 55 plasma samples were studied. Serum samples of adults showing symptoms of COVID-19 infection who were tested positive for SARS-CoV-2 infection (CoV+, n=18) at the COVID-19 outpatient clinic of the Medical University of Vienna were screened for immune activation markers by Luminex technology. Additionally, age and gender-matched serum samples of patients displaying COVID-19 associated symptoms, but tested negative for SARS-CoV-2 (CoV-, n=16) as well as healthy controls (HC, n=21) were analyzed. COVID-19 positive (CoV+) patients showed a specific upregulation of BLC (141; 74-189 pg/mL), SCD30 (273; 207-576 pg/mL), MCP-2 (18; 12-30 pg/mL) and IP-10 (37; 23-96 pg/mL), compared to patients with COVID19-like symptoms but negative PCR test (CoV-), BLC (61; 22-100 pg/mL), sCD30L (161; 120-210 pg/mL), MCP-2 (8; 5-12 pg/mL) and IP-10 (9; 6-12 pg/mL) and healthy controls (HC) (BLC 22; 11-36 pg/mL, sCD30 74; 39-108 pg/mL, MCP-2 6; 3-9. pg/mL, IP-10 = 8; 5-13). The markers APRIL, sIL-2R, IL7, MIF, MIP-1b, SCF, SDF-1a, sTNF-RII were elevated in both CoV+ and CoV- patient groups compared to healthy controls. HGF, MDC and VEGF-A were elevated in CoV- but not CoV+ compared to healthy controls. BLC, sCD30, MCP-2 and IP-10 are specifically induced during early stages of COVID-19 infection and might constitute attractive targets for early diagnosis and treatment of this disease.
Basic Research of Plasmodium vivax Biology Enabling Its Management as a Clinical and Public Health Problem
Authors: Baird J. Kevin
Published: September 2021

The emerging understanding of Plasmodium vivax as an infection seated in extravascular spaces of its human host carries fundamentally important implications for its management as a complex clinical and public health problem. This progress begins to reverse decades of neglected research borne of the false dogma of P. vivax as an intrinsically benign and inconsequential parasite. This Review provides real world context for the on-going laboratory explorations of the molecular and cellular events in the life of this parasite. Chemotherapies against the latent reservoir impose extraordinarily complex and difficult problems of science and medicine, but great strides in studies of the biology of hepatic P. vivax promise solutions. Fundamental assumptions regarding the interpretation of parasitaemia in epidemiology, clinical medicine, and public health are being revisited and reassessed in light of new studies of P. vivax cellular/molecular biology and pathogenesis. By examining these long overlooked complexities of P. vivax malaria, we open multiple new avenues to vaccination, chemoprevention, countermeasures against transmission, epidemiology, diagnosis, chemotherapy, and clinical management. This Review expresses how clarity of vision of biology and pathogenesis may rationally and radically transform the multiple means by which we may combat this insidiously harmful infection.
Bacterial and Host Determinants of Group B Streptococcal Vaginal Colonization and Ascending Infection in Pregnancy
Authors: Brokaw Alyssa , Furuta Anna , Dacanay Matthew , Rajagopal Lakshmi , Adams Waldorf Kristina M.
Published: September 2021

Group B streptococcus (GBS) is a gram-positive bacteria that asymptomatically colonizes the vaginal tract. However, during pregnancy maternal GBS colonization greatly predisposes the mother and baby to a wide range of adverse outcomes, including preterm birth (PTB), stillbirth, and neonatal infection. Although many mechanisms involved in GBS pathogenesis are partially elucidated, there is currently no approved GBS vaccine. The development of a safe and effective vaccine that can be administered during or prior to pregnancy remains a principal objective in the field, because current antibiotic-based therapeutic strategies do not eliminate all cases of invasive GBS infections. Herein, we review our understanding of GBS disease pathogenesis at the maternal-fetal interface with a focus on the bacterial virulence factors and host defenses that modulate the outcome of infection. We follow GBS along its path from an asymptomatic colonizer of the vagina to an invasive pathogen at the maternal-fetal interface, noting factors critical for vaginal colonization, ascending infection, and vertical transmission to the fetus. Finally, at each stage of infection we emphasize important host-pathogen interactions, which, if targeted therapeutically, may help to reduce the global burden of GBS.
Cysticercus cellulosae Regulates T-Cell Responses and Interacts With the Host Immune System by Excreting and Secreting Antigens
Authors: Fan Xianmin , Zhang Yue , Ouyang Renhui , Luo Bo , Li Lizhu , He Wei , Liu Meichen , Jiang Nan , Yang Fengjiao , Wang Lingjun , Zhou Biying
Published: September 2021

Cysticercus cellulosae (C. cellulosae) excretes and secretes antigens during the parasitic process to regulate the host immune response; however, resulting immune response and cytokine production in the host during infection still remains unclear. We used C. cellulosae crude antigens (CAs) as controls to explore the effect of excretory secretory antigens (ESAs) on T-cell immune responses in piglets. C. cellulosae ESAs induced imbalanced CD4+/CD8+ T-cell proportions, increased the CD4+Foxp3+ and CD8+Foxp3+ T-cell frequencies, and induced lymphocytes to produce interleukin-10, which was mainly attributed to CD4+ and CD4−CD8− T cells. The ESAs also induced Th2-type immune responses. The results showed that the ability of C. cellulosae to escape the host immune attacks and establish a persistent infection may be related to host immune response regulation by the ESAs.
Ten-Year Molecular Surveillance of Drug-Resistant Plasmodium spp. Isolated From the China–Myanmar Border
Authors: Tang Tongke , Xu Yanchun , Cao Long , Tian Penghai , Shao Jiang , Deng Yan , Zhou Hongning , Xiao Bo
Published: September 2021

Antimalarial drug resistance has emerged as a major threat to global malaria control efforts, particularly in the Greater Mekong Subregion (GMS). In this study, we analyzed the polymorphism and prevalence of molecular markers associated with resistance to first-line antimalarial drugs, such as artemisinin, chloroquine, and pyrimethamine, using blood samples collected from malaria patients in the China–Myanmar border region of the GMS from 2008 to 2017, including 225 cases of Plasmodium falciparum and 194 cases of Plasmodium vivax. In artemisinin resistance, only the C580Y mutation with low frequency was detected in pfk13, and no highly frequent stable mutation was found in pvk12. In chloroquine resistance, the frequency of K76T mutation in pfcrt was always high, and the frequency of double mutations in pvmdr1 of P. vivax has been steadily increasing every year. In pyrimidine resistance, pfdhfr and pvdhfr had relatively more complex mutant types associated with drug resistance sites, and the overall mutation rate was still high. Therefore, artemisinin-based combination therapies are still suitable for use as the first choice of antimalarial strategy in the China–Myanmar border region in the future.
Antibiotic Resistance and Virulence Profiles of Klebsiella pneumoniae Strains Isolated From Different Clinical Sources
Authors: Ballén Victoria , Gabasa Yaiza , Ratia Carlos , Ortega Raquel , Tejero Marc , Soto Sara
Published: September 2021

Klebsiella pneumoniae is a Gram-negative bacterium capable of colonizing, invading, and causing infections in different anatomical sites of the human body. Its ability to evade the immune system, its increasing antimicrobial resistance and the emergence of hypervirulent pathotypes have become a major challenge in the medical field. In this study, 127 strains from different clinical sources (urine, respiratory tract or blood) were characterized for antimicrobial resistance, the presence of virulence factor genes, serum resistance, hypermucoviscosity and the ability to form biofilms. Specific characteristics of the uropathogenic strains were examined and compared with the other clinical groups.

Differences were found between urine and the other groups of strains. Urine strains showed the highest antibiotic resistance (64.91%) compared to blood (63.64%) or respiratory strains (51.35%) as well as the highest extended-spectrum beta-lactamases (ESBL) production. These strains also showed statistically significant high resistance to fosfomycin (24.56%) compared to the other groups (p = 0.008). Regarding virulence, 84.21% of the urine strains presented the uge gene, showing a statistically significant difference (p = 0.03) compared to the other clinical sources, indicating a possible role of this gene in the development of urinary tract infection. In addition, 46% of biofilm-forming strains belonged to the urine sample group (p = 0.043). In conclusion, K. pneumoniae strains isolated from urine samples showed higher antimicrobial resistance, ESBL production, and biofilm-forming ability compared to those isolated from respiratory or blood samples. The rapid spread of clinical strains with these characteristics is of concern, and new therapeutic alternatives are essential to mitigate their harmful effects.
Roses Strewn Upon the Path: Rehearsing Familial Devotion in Late Eighteenth-Century German Songs for Parents and Children
Authors: Mueller Adeline
Published: September 2021

Intra- and inter-generational family singing is found throughout the world’s cultures. Children’s songs across many traditions are often performed with adult family members, whether simultaneously (in unison or harmony) or sequentially (as in call-and-response). In one corpus of printed children’s songs, however, such musical partnering between young and old was scripted, arguably for the first time. Children’s periodicals and readers in late eighteenth-century Germany offered a variety of poems, theatricals, riddles, songs, stories, and non-fiction content, all promoting norms around filial obedience, virtue, and productivity. Readers were encouraged to share and read aloud with members of their extended families. But the “disciplining” going on in this literature was as much emotional as it was moral. Melodramatic plots to dialogues, plays, and Singspiele allowed for tenderness and affection to be role-played in the family drawing room. And the poems and songs included in and spun off from these periodicals constituted, for the first time, a shared repertoire meant to be sung and played by young and old together. Duets for brothers and sisters, parents and children—with such prescriptive titles as “Brotherly Harmony” and “Song from a Young Girl to Her Father, On the Presentation of a Little Rosebud”—not only trained children how to be ideal sons, daughters, and siblings. They also habituated mothers and fathers to the new culture of sentimental, devoted parenthood. In exploring songs for family members to sing together in German juvenile print culture from 1700 to 1800, I uncover the reciprocal learning implied in text, music, and the act of performance itself, as adults and children alike rehearsed the devoted bourgeois nuclear family.
Husbandry and Herding: A Community-Based Approach to Addressing Illegal Wildlife Trade in Northern Botswana
Authors: Heermans Ben , van Rooyen Jacques , Fynn Richard , Biggs Duan , Lewis Matthew , McNutt John
Published: September 2021

Illegal bushmeat hunting is a major driver of wildlife population declines in Northern Botswana. Such declines raise concerns about the principles and integrity of the Kavango-Zambezi Transfrontier Conservation Area (KAZA) and regional economic stability which is heavily reliant on wildlife-based tourism. The KAZA landscape between Northern Botswana's protected areas consists of non-state land utilized communally by small agropastoralist communities. These communities are economically challenged by international beef trade policies, restricted access to grazing in nearby wildlife management areas and high conflict costs from living in close proximity to wildlife; some of the key factors identified as drivers of bushmeat hunting in the region. Here we describe how a model called Herding for Health (H4H) could address these drivers. We discuss strategies using a socio-economic centered Theory of Change (ToC) model to identify the role agropastoral communities can have in addressing illegal wildlife trade (IWT). The ToC conceptual framework was developed with input from a resource team consisting of scientific and implementation experts in H4H, wildlife conservation, illegal wildlife trade and livelihood development between September and December 2018, and with a validation workshop in March 2019 with government representatives from relevant ministries, NGO's, community-based organizations and private sector participants. We identify three pathways deriving from the ToC driven by community level actions to address IWT in the region. These include: increasing institutions for local enforcement, developing incentives for ecosystem stewardship and decreasing the costs of living alongside wildlife. The success of these pathways depends on underlying enabling actions: support for the development of institutional frameworks; building community capacity to facilitate informed best farming practices; and strengthening commitments to sustainable resource management to increase resilience to climatic and economic shocks.
LncRNA TUG1 Regulates Proliferation of Cardiac Fibroblast via the miR-29b-3p/TGF-β1 Axis
Authors: Guo Yini , Sun Zongli , Chen Minghe , Lun Junjie
Published: September 2021

Background:Atrial fibrillation (AF) is a very common clinical arrhythmia, accompanied by the overproliferation of cardiac fibroblasts (CFs). This study aimed to investigate the role of the long non-coding RNA(lncRNA) taurine upregulated gene 1 (TUG1) in the proliferation of CFs and further investigated its underlying mechanism.

Methods:One hundred four paroxysmal AF patients and 94 healthy controls were recruited. Human cardiac fibroblasts (HCFs) were applied to establish an AF cell model through treatment with angiotensin II (AngII). qRT-PCR was used for the measurement of gene levels. The cell proliferation was detected by cell counting kit-8 (CCK-8). Luciferase reporter assay was performed for target gene analysis.

Results:Elevated levels of TUG1 and low expression of miR-29b-3p were detected in the serum of AF patients compared with the healthy controls. Pearson's correlation analysis exhibited an inverse relationship between TUG1 and miR-29b-3p expression in AF patients (r= −7.106,p< 0.001). Knockdown of TUG1 inhibited AngII-induced CF proliferation. Taurine upregulated gene 1 (TUG1) functions as a competing endogenous RNA (ceRNA) for miR-29b-3p, and downregulation of miR-29b-3p reversed the role of TUG1 in CF proliferation. TGF-β1 is a direct target gene of miR-29b-3p.

Conclusions:Long non-coding RNA taurine upregulated gene 1 is a key regulator in the occurrence of AF. Slicing TUG1 inhibits CF proliferation by regulating the miR-29b-3p/TGF-β1 axis.
Platelet Endothelial Aggregation Receptor 1 Polymorphism Is Associated With Functional Outcome in Small-Artery Occlusion Stroke Patients Treated With Aspirin
Authors: Li Zhizhang , Jiang Huayu , Ding Ying , Zhang Dong , Zhang Xiaoguang , Xue Jie , Ma Ruinan , Hu Liang , Yue Yunhua
Published: September 2021

Background: The role of genetic polymorphisms is important in defining the patient's prognosis and outcomes in coronary artery disease. The present study aimed to explore the association between platelet endothelial aggregation receptor 1 (PEAR1) rs12041331 polymorphism and the outcomes in patients with acute ischemic stroke treated with aspirin or dual antiplatelet therapy (DAPT) with clopidogrel.

Methods: A total of 868 ischemic stroke patients admitted to our hospital from January 1, 2016 to December 30, 2018 were retrospectively studied. The Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification defined stroke subtypes. These patients were treated with aspirin alone or DAPT. The genotype distribution of PEAR1 rs12041331 single-nucleotide polymorphism (AA, AC, and CC) between different TOAST subtypes and treatment groups was assessed, and the clinical impact of genetic variants on functional outcomes defined by the National Institutes of Health Stroke Scale, modified Rankin Scale, and Barthel Index was analyzed using univariate and multivariate logistic regression models.

Results: Among the 868 stroke patients, the PEAR1 AA genotype was 16%, GA was 47%, and GG was 36%. Forty-four percent had aspirin alone, and 56% had DAPT. Overall, the distribution of PEAR single-nucleotide polymorphism was not significant among the two treatment groups or subtypes of TOAST. In contrast, in patients treated with aspirin alone, PEAR1 AA tended to be higher in the small-artery occlusion (SAO) subtype when compared with the no-lacunar subtype, including cardioembolism and large-artery atherosclerosis. PEAR1 AA genotype was significantly associated with favorable functional outcomes at day 7 and discharge only in SAO patients treated with aspirin alone compared with the GG genotype. Multivariate regression models further suggested that AA genotype was independently associated with favorable outcomes in this group after being adjusted for three common stroke risk factors such as age, hypertension history, and C-reactive protein level [odds ratio (OR) 0.23, 95% confidence interval (CI), 0.07–0.64, P = 0.02 for 7-day National Institutes of Health Stroke Scale; OR 0.2, 95% CI, 0.06–0.66, P = 0.03 for 7-day modified Rankin Scale, and OR 0.25, 95% CI, 0.08–0.72, P = 0.03 for 7-day Barthel Index, respectively].

Conclusion: The impact of PEAR1 rs12041331 polymorphism on aspirin depends on the TOAST subtype. PEAR1 AA carrier with SAO stroke is most sensitive to aspirin therapy. PEAR1 AA is an independent factor for the short-term functional outcomes in SAO patients treated with aspirin alone.

Clinical Registration Number: 1800019911.
TANK Promotes Pressure Overload Induced Cardiac Hypertrophy via Activating AKT Signaling Pathway
Authors: Pang Yanan , Ma Minglu , Wang Dong , Li Xun , Jiang Li
Published: September 2021

Background: TANK (TRAF family member associated NF-κB activator) acts as a member of scaffold proteins participated in the development of multiple diseases. However, its function in process of cardiac hypertrophy is still unknown.

Methods and Results: In this study, we observed an increased expression of TANK in murine hypertrophic hearts after aortic banding, suggesting that TANK may be involved in the pathogenesis of cardiac hypertrophy. We generated cardiac-specific TANK knockout mice, and subsequently subjected to aortic banding for 4–8 weeks. TANK knockout mice showed attenuated cardiac hypertrophy and dysfunction compared to the control group. In contrast, cardiac-specific TANK transgenic mice showed opposite signs. Consistently, in vitro experiments revealed that TANK knockdown decreased the cell size and expression of hypertrophic markers. Mechanistically, AKT signaling was inhibited in TANK knockout mice, but activated in TANK transgenic mice after aortic banding. Blocking AKT signaling with a pharmacological AKT inhibitor alleviated the cardiac hypertrophy and dysfunction in TANK transgenic mice.

Conclusions: Collectively, we identified TANK accelerates the progression of pathological cardiac hypertrophy and is a potential therapeutic target.
Novel Wide-Band Dielectric Imaging System Guided Lead Deployment for His Bundle Pacing: A Feasibility Study
Authors: Hua Wei , Liu Xi , Gu Min , Niu Hong-xia , Chen Xuhua , Tang Min , Zhang Shu
Published: September 2021

Introduction: His bundle pacing (HBP) is the most widely used physiological pacing modality, but difficulties in locating the His bundle lead to high fluoroscopic exposure. An electroanatomical mapping (EAM) system can be an efficient tool to achieve HBP implantation with near-zero fluoroscopic visualization.

Methods: In the study, 20 patients who had indications for pacemaker implantation were prospectively enrolled and underwent HBP implantation either with the conventional fluoroscopy approach (the standard group) or guided by a novel KODEX-EPD mapping system (the EAM-guided group). The success rate, procedural details, pacing parameters, and procedure-related complications were compared between the two groups.

Results: In the study, 20 consecutive patients were randomized with 10 patients in each group. HBP was successfully achieved in nine patients in the standard group and nine patients in the EAM-guided group. The procedural time was similar between the EAM-guided group vs. the standard group (85.40 ± 22.34 vs. 86.50 ± 15.05 min, p = 0.90). In comparison with the standard group, the EAM-guided group had a significant shorter total fluoroscopic time (FT) (1.45 ± 0.58 vs. 12.36 ± 5.46 min, p < 0.01) and His lead fluoroscopic time (HL-FT) (0.84 ± 0.56 vs. 9.27 ± 5.44 min, p < 0.01), while lower total fluoroscopic dose (3.13 ± 1.24 vs. 25.38 ± 11.15 mGy, p < 0.01) and His lead fluoroscopic dose (1.85 ± 1.17 vs. 19.06 ± 11.03 mGy, p < 0.01). No significant differences were observed in paced QRS duration and pacing parameters between the two groups. During a 3-month follow-up, one patient had a capture threshold increased >1 V/1.0 ms in the standard group, while no other complications were recorded in either group.

Conclusion: The KODEX-EPD system could facilitate HBP implantation with significantly reduced FT and dose without compromising the procedural time.
Pan-Cancer Analysis of Atrial-Fibrillation-Related Innate Immunity Gene ANXA4
Authors: Yan Tao , Zhu Shijie , Shi Yu , Xie Changming , Zhu Miao , Zhang Yangyang , Wang Chunsheng , Guo Changfa
Published: September 2021

Background: Atrial fibrillation (AF) is the most common tachyarrhythmia around the world. Cancer is one of the main causes of death worldwide. A recent study demonstrated that cancer was associated with an increased incidence of AF. In the present study, we aimed to explore possible mechanisms and potential common therapeutic targets between AF and cancer.

Methods: Differentially expressed proteins between AF and sinus rhythm were identified utilizing proteomics analysis. Weighted gene correlation network analysis was applied to cluster proteins into different modules and investigate associations between modules and AF. Hub immune-related genes were selected via InnateDB database and verified using qRT-PCR. RNA sequencing and clinical data of 33 different cancer types were achieved from The Cancer Genome Atlas (TCGA). The correlations between ANXA4 expression and the prognosis were calculated utilizing Cox regression analysis and Kaplan-Meier survival analysis. Spearman's rank correlation test was used to assess associations between ANXA4 and immune infiltration and DNA methylation. Enrichment analysis was performed through gene ontology and gene set enrichment analysis (GSEA).

Results:ANXA4 was identified as hub immune-related gene between AF and sinus rhythm. Expression levels of ANXA4 increased in diverse cancer types. Survival analysis suggested prognostic significance of ANXA4 expression levels in various cancer types. Immune correlation analysis indicated that ANXA4 expression levels were associated with tumor immune infiltration in most cancer types. ANXA4 might influence the efficacy of immunotherapy via tumor burden and microsatellite instability. GSEA results indicated that high ANXA4 expression groups were mainly enriched in peroxisome, bile acid biosynthesis, and p53 pathway.

Conclusion:ANXA4 was identified as a hub immune-related gene in AF, which has never been reported. Pan-cancer analysis indicated its potential as a novel clinical prognostic marker and therapeutic target in diverse cancer types. ANXA4 might play crucial roles in AF and cancer, and targeted therapy for ANXA4 might reduce the incidence of AF in cancer patients.
Invasive Blood Pressure Measurement and In-hospital Mortality in Critically Ill Patients With Hypertension
Authors: Zhou Bin , Lin Liang-Ying , Liu Xiao-Ai , Ling Ye-Sheng , Zhang Yuan-Yuan , Luo An-Qi , Wu Meng-Chun , Guo Ruo-Mi , Chen Hua-Li , Guo Qi
Published: September 2021

Background: Invasive blood pressure (IBP) measurement is common in the intensive care unit, although its association with in-hospital mortality in critically ill patients with hypertension is poorly understood.

Methods and Results: A total of 11,732 critically ill patients with hypertension from the eICU-Collaborative Research Database (eICU-CRD) were enrolled. Patients were divided into 2 groups according to whether they received IBP. The primary outcome in this study was in-hospital mortality. Propensity score matching (PSM) and inverse probability of treatment weighing (IPTW) models were used to balance the confounding covariates. Multivariable logistic regression was used to evaluate the association between IBP measurement and hospital mortality. The IBP group had a higher in-hospital mortality rate than the no IBP group in the primary cohort [238 (8.7%) vs. 581 (6.5%), p < 0.001]. In the PSM cohort, the IBP group had a lower in-hospital mortality rate than the no IBP group [187 (8.0%) vs. 241 (10.3%), p = 0.006]. IBP measurement was associated with lower in-hospital mortality in the PSM cohort (odds ratio, 0.73, 95% confidence interval, 0.59–0.92) and in the IPTW cohort (odds ratio, 0.81, 95% confidence interval, 0.67–0.99). Sensitivity analyses showed similar results in the subgroups with high body mass index and no sepsis.

Conclusions: In conclusion, IBP measurement was associated with lower in-hospital mortality in critically ill patients with hypertension, highlighting the importance of IBP measurement in the intensive care unit.
DeepStrain: A Deep Learning Workflow for the Automated Characterization of Cardiac Mechanics
Authors: Morales Manuel A. , van den Boomen Maaike , Nguyen Christopher , Kalpathy-Cramer Jayashree , Rosen Bruce R. , Stultz Collin M. , Izquierdo-Garcia David , Catana Ciprian
Published: September 2021

Myocardial strain analysis from cinematic magnetic resonance imaging (cine-MRI) data provides a more thorough characterization of cardiac mechanics than volumetric parameters such as left-ventricular ejection fraction, but sources of variation including segmentation and motion estimation have limited its wider clinical use. We designed and validated a fast, fully-automatic deep learning (DL) workflow to generate both volumetric parameters and strain measures from cine-MRI data consisting of segmentation and motion estimation convolutional neural networks. The final motion network design, loss function, and associated hyperparameters are the result of a thorough ad hoc implementation that we carefully planned specific for strain quantification, tested, and compared to other potential alternatives. The optimal configuration was trained using healthy and cardiovascular disease (CVD) subjects (n = 150). DL-based volumetric parameters were correlated (>0.98) and without significant bias relative to parameters derived from manual segmentations in 50 healthy and CVD test subjects. Compared to landmarks manually-tracked on tagging-MRI images from 15 healthy subjects, landmark deformation using DL-based motion estimates from paired cine-MRI data resulted in an end-point-error of 2.9 ± 1.5 mm. Measures of end-systolic global strain from these cine-MRI data showed no significant biases relative to a tagging-MRI reference method. On 10 healthy subjects, intraclass correlation coefficient for intra-scanner repeatability was good to excellent (>0.75) for all global measures and most polar map segments. In conclusion, we developed and evaluated the first end-to-end learning-based workflow for automated strain analysis from cine-MRI data to quantitatively characterize cardiac mechanics of healthy and CVD subjects.
Probiotics in the Management of Gingivitis and Periodontitis. A Review
Authors: Schlagenhauf Ulrich , Jockel-Schneider Yvonne
Published: September 2021

In the management of intestinal health problems, the targeted use of probiotic microorganisms is a common therapeutic measure with a long-standing tradition. In clinical dentistry however, probiotics-based therapy is still a rather new and developing field, whose usefulness for the control of gingivitis and periodontitis has been questioned by recent meta-analyses and systematic reviews. The purpose of the subsequent descriptive review is to provide an introduction to the concept of probiotic microorganisms and their multifaceted health-promoting interactions with the human host and microbial competitors, followed by a detailed comparison of the results of available controlled clinical trials assessing the use of probiotics in the control of gingival and periodontal inflammations. It aims at contributing to a deeper understanding of the unique capabilities of probiotics to resolve chronic plaque-induced inflammation even in the absence of mechanical plaque control and will discuss how possible misconceptions about the rationale for using probiotics may have led to the present controversies about their usefulness as a therapeutic option.
Rockburst Prediction From the Perspective of Energy Release: A Case Study of a Diversion Tunnel at Jinping II Hydropower Station
Authors: Fan Yong , Cui Xianze , Leng Zhendong , Zheng Junwei , Wang Feng , Xu Xiaole
Published: September 2021

As a man-made engineering hazard, it is widely accepted that the rockbursts are the result of energy release. Previous studies have examined the unloading of in-situ stress resulting from deep tunnel excavation as a quasi-static process but the transient stress variation during excavation has received less attention. This research discusses rockbursts that happened during the construction of a diversion tunnel at Jinping II hydropower station. The brittle-ductile-plastic (BDP) transition property of Jinping marble was numerically described by the Hoek-Brown strength criterion, and the dynamic energy release process derived from the transient unloading of in-situ stress was studied using an index, local energy release rate. Studies have shown that, due to transient unloading, the strain energy of the surrounding rock mass goes through a dynamic process of decreasing at first, increasing second, then reducing before finally stabilizing. The first decrease of strain energy results from elastic unloading waves and does not cause brittle failure in rock masses, which is consistent with the elastic condition but the secondary reduction of strain energy is because the accumulated strain energy in rock masses exceeds the storage limit, which will inevitably trigger the brittle failure in the rock mass. Thus, the shorter the distance to the tunnel wall the bigger and more intense the energy release. Finally, a relationship between the average value of the local energy release rate and the rockburst intensity was established to assess the risk of rockburst induced by the blasting excavation of a deep tunnel.