bluuebunny/crossref_metadata_2025 huggingface dataset:
Push or Pull? Policy Barriers and Incentives to the Development and Deployment of CO2 Utilization, in Particular CO2 Mineralization
Authors: Olfe-Kräutlein Barbara , Strunge Till , Chanin Anna
Published: December 2021

Like other hard-to-abate sectors, the cement and concrete industry is facing growing pressure to reduce CO2 emissions. In this context, the carbonation of minerals or industrial wastes with CO2 (CO2 mineralization) is attracting growing interest in research and industry as well as among policy makers. Despite their technical feasibility, few of these innovative carbon capture and utilization (CCU) technologies have so far reached the commercialization stage. Due to their low maturity and potentially higher market prices, these technologies presently require policy support in order to realize their full sustainability potentials. This paper elucidates which policies are considered appropriate, in the literature, for fostering the further development and implementation of CCU technologies and thus achieving the sustainability potential of CO2 mineralization applications. First, we performed a meta-analysis of recent literature in order to identify policies and measures that potentially represent barriers or incentives to the development and deployment of CO2 mineralization technologies, and categorized them as technology-push or market-pull policies. As a second step, we conducted an online survey of policy-making priorities among experts in the field. This identified numerous relevant policies, of which the majority are market-oriented. While most existing market-pull policies do currently not support CCU technologies and would require adaptation to do so, technology-push policies already provide support for their development. However, while the need for technology-push support in the early development phases is still continued, the broad spectrum of market-pull policies that are considered relevant shows that a shifting focus of policy support is required to better address the current state of development of CO2 mineralization technologies and their upcoming market entry.
Theoretical Design of a Multilayer Based Spectrally Selective Solar Absorber Applied Under Ambient Conditions
Authors: Shi Kuang , Liu Huaiyu , Wang Lei , Bie Yu , Yang Yue
Published: December 2021

With the increasing of global energy requirements and environmental problems, the use of solar thermal energy has attracted widespread attention. The selective solar absorption coating is the most important part of a solar thermal conversion device. At present, most of the coatings work well in a vacuum at a high temperature, while not stably in the air environment. Based on the high-temperature resistant and infrared-reflective properties of ITO, a multilayer film of SiO2/Si3N4/SiO2/ITO/Cr has been designed as a selective solar absorber. The genetic algorithm is applied to optimize the material and thickness selection for each layer. The results show that the optimized multilayer film could achieve a high solar absorptance up to 90% while keeping a relatively low infrared emittance around 50% for temperature change between 600°C and 900°C. All the materials composing this film have been tested before to be chemically stable at a high temperature up to 900°C in the air environment. It is also adaptive to different incident angles from 0° to 60°. The finite-difference time-domain method was also adopted to plot the energy density distribution for different wavelengths, which provided the underlying mechanism for the selective emission spectrum. The findings in this study would provide valuable guidance to design a low-cost selective solar absorption coating without the need for vacuum generation.
Pre- and Postnatal Predator Cues Shape Offspring Anti-predatory Behavior Similarly in the Bank Vole
Authors: Sievert Thorbjörn , Bouma Kerstin , Haapakoski Marko , Matson Kevin D. , Ylönen Hannu
Published: December 2021

Prey animals can assess the risks predators present in different ways. For example, direct cues produced by predators can be used, but also signals produced by prey conspecifics that have engaged in non-lethal predator-prey interactions. These non-lethal interactions can thereby affect the physiology, behavior, and survival of prey individuals, and may affect offspring performance through maternal effects. We investigated how timing of exposure to predation-related cues during early development affects offspring behavior after weaning. Females in the laboratory were exposed during pregnancy or lactation to one of three odor treatments: (1) predator odor (PO) originating from their most common predator, the least weasel, (2) odor produced by predator-exposed conspecifics, which we call conspecific alarm cue (CAC), or (3) control odor (C). We monitored postnatal pup growth, and we quantified foraging and exploratory behaviors of 4-week-old pups following exposure of their mothers to each of the three odour treatments. Exposure to odors associated with predation risk during development affected the offspring behavior, but the timing of exposure, i.e., pre- vs. postnatally, had only a weak effect. The two non-control odors led to different behavioral changes: an attraction to CAC and an avoidance of PO. Additionally, pup growth was affected by an interaction between litter size and maternal treatment, again regardless of timing. Pups from the CAC maternal treatment grew faster in larger litters; pups from the PO maternal treatment tended to grow faster in smaller litters. Thus, in rodents, offspring growth and behavior are seemingly influenced differently by the type of predation risk perceived by their mothers.
Turtle Nest-Site Choice, Anthropogenic Challenges, and Evolutionary Potential for Adaptation
Authors: Topping Nicholas E. , Valenzuela Nicole
Published: December 2021

Oviparous animals, such as turtles, lay eggs whose success or demise depends on environmental conditions that influence offspring phenotype (morphology, physiology, and in many reptiles, also sex determination), growth, and survival, while in the nest and post-hatching. Consequently, because turtles display little parental care, maternal provisioning of the eggs and female nesting behavior are under strong selection. But the consequences of when and where nests are laid are affected by anthropogenic habitat disturbances that alter suitable nesting areas, expose eggs to contaminants in the wild, and modify the thermal and hydric environment experienced by developing embryos, thus impacting hatchling survival and the sexual fate of taxa with temperature-dependent sex determination (TSD) and genotypic sex determination (GSD). Indeed, global and local environmental change influences air, water, and soil temperature and moisture, which impact basking behavior, egg development, and conditions within the nest, potentially rendering current nesting strategies maladaptive as offspring mortality increases and TSD sex ratios become drastically skewed. Endocrine disruptors can sex reverse TSD and GSD embryos alike. Adapting to these challenges depends on genetic variation, and little to no heritability has been detected for nest-site behavior. However, modest heritability in threshold temperature (above and below which females or males develop in TSD taxa, respectively) exists in the wild, as well as interpopulation differences in the reaction norm of sex ratio to temperature, and potentially also in the expression of gene regulators of sexual development. If this variation reflects additive genetic components, some adaptation might be expected, provided that the pace of environmental change does not exceed the rate of evolution. Research remains urgently needed to fill current gaps in our understanding of the ecology and evolution of nest-site choice and its adaptive potential, integrating across multiple levels of organization.
Mitonuclear Genetic Interactions in the Basidiomycete Heterobasidion parviporum Involve a Non-conserved Mitochondrial Open Reading Frame
Authors: Clergeot Pierre-Henri , Olson Åke
Published: December 2021

The mitochondrial and nuclear genomes of Eukaryotes are inherited separately and consequently follow distinct evolutionary paths. Nevertheless, the encoding of many mitochondrial proteins by the nuclear genome shows the high level of integration they have reached, which makes mitonuclear genetic interactions all the more conceivable. For each species, natural selection has fostered the evolution of coadapted alleles in both genomes, but a population-wise divergence of such alleles could lead to important phenotypic variation, and, ultimately, to speciation. In this study in the Basidiomycete Heterobasidion parviporum, we have investigated the genetic basis of phenotypic variation among laboratory-designed heterokaryons carrying the same pair of haploid nuclei, but a different mitochondrial genome. Radial growth rate data of thirteen unrelated homokaryotic parents and of their heterokaryotic offspring were combined with SNP data extracted from parental genome sequences to identify nuclear and mitochondrial loci involved in mitonuclear interactions. Two nuclear loci encoding mitochondrial proteins appeared as best candidates to engage in a genetic interaction affecting radial growth rate with a non-conserved mitochondrial open reading frame of unknown function and not reported apart from the Russulales order of Basidiomycete fungi. We believe our approach could be useful to investigate several important traits of fungal biology where mitonuclear interactions play a role, including virulence of fungal pathogens.
RHD Genotypes in a Chinese Cohort of Pregnant Women
Authors: Zhang Jianjun , Zeng Yan , Wang Yuefeng , Fan Jiaming , Chen Haijiang , Yang Dan , Shi Xiaoliang , Xu Hualin , Fu Zimu , Sheng Fang , Xuan Jie , Pan Xiaoxi , Zhang Zhiming , Ai Liping , Zhang Yue , Pan Jingjing , Zhao Jing , Wang Mingming
Published: December 2021

RHD variants in D¯ Chinese pregnant women arose difficulties in management during pregnancy. Therefore, this study aims to precisely manage D¯ pregnant women by evaluating the spectrum of RHD mutations in D¯ pregnant women and getting insight into the possible rare alleles of RHD. A total of 76 D¯ pregnant women were analyzed by performing polymerase chain reactions with sequence-specific primers (PCR-SSP), the 10 RHD exons Sanger sequencing, RHD zygosity detection, and mRNA sequencing (mRNA-seq). About 40% of alleles are variations of RHD, including RHD 1227A homozygous, RHD-CE(2-9)-D, et al. Therefore, we developed a molecular diagnostic strategy for Chinese women, and most D¯ pregnant women can be diagnosed with this simple decision tree. After RHD genotyping for D¯ pregnancy women, we eliminated at least 15% unnecessary ante- and postpartum injections of Rh immunoglobulin (RhIG). As the first pedigree study and the first functional analysis under physiological conditions, mRNA-seq revealed that c.336-1G>A mutation mainly led to the inclusion of the intron 2, which indirectly explained the D¯ phenotype in this family. We also developed a robust protocol for determining fetal RhD status from maternal plasma. All 31 fetuses were predicted as RhD positive and confirmed the RhD status after birth.
Trend and Determinants of Mortality Among Women of Reproductive Age: A Twelve-Year Open Cohort Study in Eastern Ethiopia
Authors: Dheresa Merga , Tura Abera Kenay , Daraje Gamachis , Abebe Mesfin , Dingeta Tariku , Shore Hirbo , Dessie Yadeta , Yadeta Tesfaye Assebe
Published: December 2021

Background: With only less than a decade left till 2030, it is essential to research the burden and trends of women of reproductive age (WRA) mortality in order to design appropriate interventions toward achieving goal three of the sustainable development goals (SDGs), good health and well-being. For several low-income countries, such data are often lacking or sometimes extrapolated from non-representative facility-based studies. In this paper, we presented trends, causes, and determinants of mortality among reproductive-age women under follow-up for 12 years through the Health and Demographic Surveillance System (HDSS) located in eastern Ethiopia.

Methods: We used 12 years of (2008 to 2019) open cohort data of women aged 15–49 living in Kersa HDSS in Eastern Ethiopia. In the HDSS, data on socio-demographic and basic household conditions are recorded for every household member at enrollment, and data on vital events such as births, deaths, and migration were collected and updated biannually as the event happened. Mortality was determined by automated verbal autopsy (InterVA) algorism. We assessed trends in women's reproductive age mortality and the associated determinants using crude and adjusted Cox regression models.

Results: In the 12-years cohort, we followed 74,790 women of reproductive age for 339,909.26 person-years-at-risk of observation (PYO), of whom 919 died. Overall, the standardized mortality rate was 270 per 100,000 PYO. There was a notable increase in mortality in the first 3 years (2009 to 2011) which then declined significantly (p = 0.0001) until 2019. Most of the deaths were caused by HIV/AIDS (27.88%) and pulmonary tuberculosis (10.62%). In the adjusted Cox regression analysis, the hazard of death was higher among rural residents (AHR, 2.03: 95% CI: 1.60–2.58), unemployed women (AHR, 1.50: 95% CI: 1.19–1.89), and women with no formal education (AHR, 1.24: 95% CI: 1.01–1.52).

Conclusion: The study showed a high number of women of reproductive age are still dying mainly due to causes for which preventable strategies are known and have been successfully implemented. The study identified that the main causes of death were related to HIV/AIDS and tuberculosis, and there was a higher hazard of mortality among rural residents, unemployed women, and those with no formal education, who need effective implementation in achieving the SDG three.
Steroid Hormone Secretion Over the Course of the Perimenopause: Findings From the Swiss Perimenopause Study
Authors: Grub Jessica , Süss Hannah , Willi Jasmine , Ehlert Ulrike
Published: December 2021

Background: Perimenopause is characterized by a decline in the steroid hormones, estradiol, and progesterone. By contrast, the steroid hormone cortisol, a marker of the hypothalamic–pituitary–adrenal (HPA) axis, increases. Recent longitudinal studies reported fluctuations in steroid hormone levels during perimenopause, and even increases in estradiol levels. To understand these confounding results, it is necessary to conduct a longitudinal, highly standardized assessment of steroid hormone secretion patterns in perimenopausal women.

Methods: This longitudinal study investigated 127 perimenopausal women aged 40–56 years for 13 months. Estradiol, progesterone, and cortisol were assessed using saliva samples, which were collected for two (during months 2 and 12 for estradiol and progesterone) or three (during months 2, 7, and 12 for cortisol) non-consecutive months over the course of the study. A total of 14 saliva samples per participant were analyzed to investigate the courses of estradiol and progesterone. Cortisol awakening response and fluctuations of cortisol throughout the day were measured using a total of 11 saliva samples per participant (on awakening, +30 min, +60 min, at 12:00 p.m., and before going to bed) for months 2, 7, and 12.

Results: Multilevel analyses revealed variance in intercept and slope across participants for estradiol [intercept: SD = 5.16 (95% CI: 4.28, 6.21), slope: SD = 0.50 (95% CI: 0.39, 0.64)], progesterone [intercept: SD = 34.77 (95% CI: 25.55, 47.31), slope: SD = 4.17 (95% CI: 2.91, 5.99)], and cortisol (intercept: SD = 0.18 (95% CI: 0.14, 0.23), slope: SD = 0.02 (95% CI: 0.01, 0.02)]. Time predicted cortisol levels [b = −0.02, t(979) = −6.63, p < 0.0001]. Perimenopausal status (early vs. late) did not predict estradiol [b = −0.36, t(1608) = −0.84, p = 0.400], progesterone [b = −4.55, t(1723) = −0.87, p = 0.385], or cortisol [b = 0.01, t(1124) = 0.61, p = 0.542] scores over time.

Discussion: Our results are consistent with previous findings emphasizing highly individual fluctuations of estradiol and progesterone levels during perimenopause. However, our findings do not suggest a continuous decline during the observed transition phase, implying relatively stable periods of fluctuating hormone levels. Furthermore, given the lack of significant group differences, it may not be necessary to differentiate between early and late perimenopause from the standpoint of hormonal progression.
CAR-NK Cells: From Natural Basis to Design for Kill
Authors: Khawar Muhammad Babar , Sun Haibo
Published: December 2021

Chimeric antigen receptors (CARs) are fusion proteins with an extracellular antigen recognition domain and numerous intracellular signaling domains that have been genetically modified. CAR-engineered T lymphocyte-based therapies have shown great success against blood cancers; however, potential fatal toxicity, such as in cytokine release syndrome, and high costs are some shortcomings that limit the clinical application of CAR-engineered T lymphocytes and remain to overcome. Natural killer (NK) cells are the focal point of current immunological research owing to their receptors that prove to be promising immunotherapeutic candidates for treating cancer. However, to date, manipulation of NK cells to treat malignancies has been moderately successful. Recent progress in the biology of NK cell receptors has greatly transformed our understanding of how NK cells recognize and kill tumor and infected cells. CAR-NK cells may serve as an alternative candidate for retargeting cancer because of their unique recognition mechanisms, powerful cytotoxic effects especially on cancer cells in both CAR-dependent and CAR-independent manners and clinical safety. Moreover, NK cells can serve as an ‘off-the-shelf product’ because NK cells from allogeneic sources can also be used in immunotherapies owing to their reduced risk of alloreactivity. Although ongoing fundamental research is in the beginning stages, this review provides an overview of recent developments implemented to design CAR constructs to stimulate NK activation and manipulate NK receptors for improving the efficiency of immunotherapy against cancer, summarizes the preclinical and clinical advances of CAR-NK cells against both hematological malignancies and solid tumors and confronts current challenges and obstacles of their applications. In addition, this review provides insights into prospective novel approaches that further enhance the efficiency of CAR-NK therapies and highlights potential questions that require to be addressed in the future.
Disseminated Human Parvovirus B19 Infection Induced Multiple Organ Dysfunction Syndrome in an Adult Patient With Alcoholic Hepatitis Complicated by Hemolytic Anemia: A Case Report and Literature Review
Authors: Luo Jinmei , Zhang Jingcong , Lai Wenxing , Wang Shaofang , Zhou Laizhi , Shi Yunfeng , Ba Junhui , Hu Jiajia , Wang Yanhong , Li Laisheng , Wu Ben-Quan
Published: December 2021

Background

Human parvovirus B19 (B19) can cause acute hepatitis and is attributed to the high mortality of alcoholic hepatitis (AH). B19 infection is generally self-healing in previously healthy people, but it can cause fatal effects in some high-risk groups and increase its virulence and infectivity. Disseminated B19 infection-induced multiple organ dysfunction syndrome (MODS) in patients with AH has not been reported yet. Here, we described B19 viremia in an adult patient with AH accompanied by hemolytic anemia (HA), leading to disseminated infection and secondary MODS, as well as self-limiting B19 infections in seven nurses caring for him. Meanwhile, we reviewed the literature on AH and B19 infection.

Case Presentation

A 43-year-old male patient with AH accompanied by HA was transferred to the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China, on March 31, 2021. After supportive treatment, his transaminase and bilirubin levels were reduced, but his anemia worsened. He received a red blood cell (RBC) infusion on April 9 for hemoglobin (Hb) lower than 6 g/dl. On April 13, he suddenly had a high fever. Under empirical anti-infection, his high fever dropped and maintained at a low fever level; however, his anemia worsened. On April 25, he was transferred to the medical intensive care unit (MICU) due to severe pneumonia, acute respiratory distress syndrome (ARDS), acute aplastic crisis (AAC), and hemophagocytic syndrome (HPS), which were subsequently confirmed to be related to B19 infection. After methylprednisolone, intravenous immunoglobulin (IVIG), empirical anti-infection, and supportive treatment, the lung infection improved, but hematopoietic and liver abnormalities aggravated, and systemic B19 infection occurred. Finally, the patient developed a refractory arrhythmia, heart failure, and shock and was referred to a local hospital by his family on May 8, 2021. Unfortunately, he died the next day. Fourteen days after he was transferred to MICU, seven nurses caring for him in his first two days in the MICU developed self-limiting erythema infectiosum (EI).

Conclusions

B19 infection is self-limiting in healthy people, with low virulence and infectivity; however, in AH patients with HA, it can lead to fatal consequences and high contagion.
CD8+ T Cell-Based Molecular Classification With Heterogeneous Immunogenomic Landscapes and Clinical Significance of Clear Cell Renal Cell Carcinoma
Authors: Wu Xiangkun , Jiang Dongmei , Liu Hongling , Lu Xiaofan , Lv Daojun , Liang Li
Published: December 2021

The tumor microenvironment (TME) exerts a high impact on tumor biology and immunotherapy. The heterogeneous phenotypes and the clinical significance of CD8+ T cells in TME have not been fully elucidated. Here, a comprehensive immunogenomic analysis based on multi-omics data was performed to investigate the clinical significance and tumor heterogeneity between CD8+ T cell-related molecular clusters. We identified two distinct molecular clusters of ccRCC (C1 and C2) in TCGA and validated in E-MTAB-1980 cohorts. The C1 cluster was characterized by unfavorable prognosis, increased expression levels of CD8+ T cell exhaustion markers, high immune infiltration levels as well as more immune escape mechanisms. The C2 cluster was featured by favorable prognosis, elevated expression levels of CD8+ T cell effector markers, low load of copy number loss and low frequency of 9p21.3 deletion. Moreover, the effect of molecular classifications on Nivolumab therapeutic efficacy in the CheckMate 025 cohort was examined, and the C2 cluster exhibited a better prognosis. Taken together, we determine two CD8+ T cell-related molecular clusters in ccRCC, and provide new insights for evaluating the functions of CD8+ T cells. Our molecular classification is a potential strategy for prognostic prediction and immunotherapeutic guidance for ccRCC patients.
Immune Complex Formation Is Associated With Loss of Tolerance and an Antibody Response to Both Drug and Target
Authors: Kroenke Mark A. , Barger Troy E. , Hu Jenny , Miller Mieke Jill , Kalenian Kevin , He Lidong , Hsu Hailing , Bartley Yessenia , Chow Vincent Fung-Sing , Teixeira dos Santos Marcia Cristina , Sullivan Barbara A. , Cheng Laurence E. , Parnes Jane R. , Padaki Rupa , Kuhns Scott , Mytych Daniel T.
Published: December 2021

AMG 966 is a bi-specific, heteroimmunoglobulin molecule that binds both tumor necrosis factor alpha (TNFα) and TNF-like ligand 1A (TL1A). In a first-in-human clinical study in healthy volunteers, AMG 966 elicited anti-drug antibodies (ADA) in 53 of 54 subjects (98.1%), despite a paucity of T cell epitopes observed in T cell assays. ADA were neutralizing and bound to all domains of AMG 966. Development of ADA correlated with loss of exposure.In vitrostudies demonstrated that at certain drug-to-target ratios, AMG 966 forms large immune complexes with TNFα and TL1A, partially restoring the ability of the aglycosylated Fc domain to bind FcγRIa and FcγRIIa, leading to the formation of ADA. In addition to ADA against AMG 966, antibodies to endogenous TNFα were also detected in the sera of subjects dosed with AMG 966. This suggests that the formation of immune complexes between a therapeutic and target can cause loss of tolerance and elicit an antibody response against the target.
Acute Atherosis Lesions at the Fetal-Maternal Border: Current Knowledge and Implications for Maternal Cardiovascular Health
Authors: Pitz Jacobsen Daniel , Fjeldstad Heidi Elisabeth , Johnsen Guro Mørk , Fosheim Ingrid Knutsdotter , Moe Kjartan , Alnæs-Katjavivi Patji , Dechend Ralf , Sugulle Meryam , Staff Anne Cathrine
Published: December 2021

Decidua basalis, the endometrium of pregnancy, is an important interface between maternal and fetal tissues, made up of both maternal and fetal cells. Acute atherosis is a uteroplacental spiral artery lesion. These patchy arterial wall lesions containing foam cells are predominantly found in the decidua basalis, at the tips of the maternal arteries, where they feed into the placental intervillous space. Acute atherosis is prevalent in preeclampsia and other obstetric syndromes such as fetal growth restriction. Causal factors and effects of acute atherosis remain uncertain. This is in part because decidua basalis is challenging to sample systematically and in large amounts following delivery. We summarize our decidua basalis vacuum suction method, which facilitates tissue-based studies of acute atherosis. We also describe our evidence-based research definition of acute atherosis. Here, we comprehensively review the existing literature on acute atherosis, its underlying mechanisms and possible short- and long-term effects. We propose that multiple pathways leading to decidual vascular inflammation may promote acute atherosis formation, with or without poor spiral artery remodeling and/or preeclampsia. These include maternal alloreactivity, ischemia-reperfusion injury, preexisting systemic inflammation, and microbial infection. The concept of acute atherosis as an inflammatory lesion is not novel. The lesions themselves have an inflammatory phenotype and resemble other arterial lesions of more extensively studied etiology. We discuss findings of concurrently dysregulated proteins involved in immune regulation and cardiovascular function in women with acute atherosis. We also propose a novel hypothesis linking cellular fetal microchimerism, which is prevalent in women with preeclampsia, with acute atherosis in pregnancy and future cardiovascular and neurovascular disease. Finally, women with a history of preeclampsia have an increased risk of premature cardiovascular disease. We review whether presence of acute atherosis may identify women at especially high risk for premature cardiovascular disease.
Establishment of a Hyperacute Rejection Model of ABO-Incompatible Renal Transplantation in Nonhuman Primates
Authors: Wang Junxiang , Feng Hao , Zhang Chi , Zhong Shan , Wang Lu , Zhu Lan , Chen Song , Chen Gang
Published: December 2021

The establishment of a hyperacute rejection (HAR) model of ABO-incompatible kidney transplantation (ABOi-KTx) in nonhuman primates is of great significance for the study of the relevant clinical pathophysiological processes and related interventions in ABOi-KTx. In this study, blood group B cynomolgus monkeys were presensitized with synthetic blood group A-antigen conjugated to keyhole limpet hemocyanin (A-KLH) to boost circulating anti-A antibody levels. The serum anti-A antibody levels were measured by flow cytometry using type A human reagent red blood cells (RBCs) or monkey primary renal tubular epithelial cells (RTECs) as target cells. ABOi-KTx was performed in type B monkeys using type A monkeys as donors. After 14 days of A-KLH sensitization, 12 of 16 (75%) type B monkeys had significantly elevated anti-A antibody levels. We found that in order to avoid irregular results in the detection of blood group antibodies by flow cytometry, it was more effective to use RTECs rather than RBCs as target cells. In the absence of presensitization, ABOi-KTx in three monkeys with relatively high levels of natural anti-A antibodies did not produce HAR. However, when four Type B monkeys with significantly increased anti-A antibodies after presensitization were randomly selected as recipients for ABOi-KTx, the allografts in all four monkeys developed HAR with typical pathologic characteristics. Thus, we have successfully established a monkey model of HAR in ABOi-KTx via blood group antigen presensitization, which will be helpful for the further study of rejection, accommodation, and clinical intervention in ABOi-KTx.
Intensive Commercialization of Endangered Sharks and Rays (Elasmobranchii) Along the Coastal Amazon as Revealed by DNA Barcode
Authors: Martins Thais , Santana Paula , Lutz Ítalo , da Silva Raimundo , Guimarães-Costa Aurycéia , Vallinoto Marcelo , Sampaio Iracilda , Evangelista-Gomes Grazielle
Published: December 2021

Elasmobranchs represent a well-defined group, composed of about 1,150 species inhabiting diverse aquatic environments. Currently, several of these species have been classified as threaten due to overexploitation. Therefore, we used DNA barcode to identify traded species of sharks and stingrays in the municipality of Bragança (Amazon coastal region), a major fishery landing site in northern Brazil. We collected a total of 127 samples labeled into 24 commercial nomenclatures over 1-year period. Twenty species were discriminated and 13 of them are recognized under some threatening status. In relation to sharks, Carcharhinidae showed the highest number of species, half of them classified as endangered, followed by hammerhead sharks (Sphyrnidae), with four species also regarded as threatened with extinction. The Rhinopteridae and Dasyatidae rays were the most abundant groups, with trade records of the following threatened species: Rhinoptera brasiliensis, Rhinoptera bonasus, Hypanus berthalutzae, and Fontitrygon geijskesi. It is noteworthy that threatened species of elasmobranchs have been frequently and regularly exploited because of inefficient fishery management policies. Therefore, effective inspection practices need to be incorporated in fisheries, including the use of DNA barcode to enable a reliable method of species authentication and to assure the proper commercialization.
Serum Uric Acid and Risk of Chronic Heart Failure: A Systematic Review and Meta-Analysis
Authors: Miao Lina , Guo Ming , Pan Deng , Chen Pengfei , Chen Zhuhong , Gao Jie , Yu Yanqiao , Shi Dazhuo , Du Jianpeng
Published: December 2021

Objectives: A systematic review and meta-analysis was performed to evaluate the potential prognostic role of serum uric acid (SUA) in patients with chronic heart failure (CHF).

Methods: The Embase, PubMed, Web of Science and Cochrane Library databases were searched up to 5 April 2021 for relevant publications. Random effects model was used to pool data. STATA15.0 software was used to perform meta-analysis. Heterogeneity was assessed using the Cochran Q statistic (significance level of P < 0.10) and I2 statistics (significance level of 50%).

Results: Ultimately, 18 publications reporting adverse events in CHF patients were included. The results indicate reveal associations between a high level of SUA and the risk of all-cause mortality (HR 2.24, 95% CI 1.49–3.37), cardiovascular mortality (HR 1.14, 95% CI 1.06–1.23), and the composite of death or cardiac events (HR 1.26, 95% CI 1.01–1.56) in CHF patients. A 1 mg/dL increase in serum uric acid led to 4% (HR 1.04, 95% CI 1.02–1.05) and 9% (HR 1.09, 95% CI 1.03–1.17) increases in the risk of all-cause mortality and the composite endpoint of death or cardiac events in CHF patients, respectively.

Conclusion: Serum uric acid is positively associated with the risk of adverse events in CHF patients. This study protocol has been registered at PROSPERO as CRD42021247084 (https://www.crd.york.ac.uk/PROSPERO).

Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO.
YTHDF2 Gene rs3738067 A>G Polymorphism Decreases Neuroblastoma Risk in Chinese Children: Evidence From an Eight-Center Case-Control Study
Authors: Zeng Huijuan , Li Meng , Liu Jiabin , Zhu Jinhong , Cheng Jiwen , Li Yong , Zhang Jiao , Yang Zhonghua , Li Li , Zhou Haixia , Li Suhong , Xia Huimin , Zou Yan , He Jing , Yang Tianyou
Published: December 2021

Neuroblastoma is a primary malignancy mainly occurring in children. We have reported that polymorphisms of several N6-methyladenosine (m6A) RNA modification-related genes contributed to neuroblastoma risk in previous studies. YTHDF2, a “reader” of RNA m6A modification, is involved in cancer progression. Here, we estimated the association between a YTHDF2 gene rs3738067 A>G polymorphism and neuroblastoma susceptibility in 898 neuroblastoma patients and 1,734 healthy individuals from China. We found that the rs3738067 A>G could decrease neuroblastoma risk [AG vs. AA: adjusted odds ratio (OR) = 0.76, 95% confidence interval (CI) = 0.64–0.90, P = 0.002; AG/GG vs. AA: adjusted OR = 0.81, 95% CI = 0.69–0.95, P = 0.011). Besides, the rs3738067 AG/GG genotype was related to reduced neuroblastoma risk in the following subgroups: children aged 18 months and under, boys, patients with tumors originating from retroperitoneal, patients at clinical stage IV, and cases at clinical stages III plus IV. Importantly, false-positive report probability analysis proved our significant results worthy of close attention of. The expression quantitative trait locus analysis results revealed that the rs3738067 was associated with the expression of YTHDF2.
WAY-100635 Alleviates Corneal Lesions Through 5-HT1A Receptor-ROS-Autophagy Axis in Dry Eye
Authors: Zhou Xujiao , Dai Yiqin , Zhai Zimeng , Hong Jiaxu
Published: December 2021

Purpose: To explore whether 5-HT1A receptors are involved in the dry eye disease (DED) mouse model and reveal its underlying mechanism.

Methods: A C57BL/6J mouse DED model was established via the administration of 0.2% benzalkonium chloride twice a day for 14 days. Corneal fluorescein sodium staining score and Schirmer I test were checked before, and on days 7, 14, and 21 after treatment. The experiment was randomly divided into control, DED, 5-HT1A receptor agonist with or without N-acetylcysteine (NAC) and 5-HT1A receptor antagonist with or without NAC groups. The mRNA expression of inflammatory cytokines was measured by reverse transcription-quantitative polymerase chain reaction. Cellular reactive oxygen species (ROS) were detected by 2', 7'-dichlorodihydrofluorescein diacetate assays. Western blot analysis was used to measure the expression levels of autophagic proteins microtubule-associated protein 1 light chain 3 (LC3B-I/II) and autophagy-related gene 5 (ATG5).

Results: 5-HT1A receptor agonist (8-OH-DPAT) increased corneal fluorescein sodium staining spots and 5-HT1A receptor antagonist (WAY-100635) decreased them. Treatment with 8-OH-DPAT was associated with the gene expression of more inflammatory cytokines, such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-C motif chemokine ligand 2 (CCL2) and C-X-C motif chemokine ligand 10 (CXCL10) compared with treatment with WAY-100635. An increased expression of LC3B-I/II and ATG5 was observed in corneal epithelial cells in the mouse model of DED. 8-OH-DPAT significantly enhanced the expression of LC3B-I/II and ATG5 by disrupting ROS levels. WAY-100635 alleviates autophagy by inhibiting ROS production.

Conclusion: Excessive ROS release through 8-OH-DPAT induction can lead to impaired autophagy and increased inflammatory response in DED. WAY-100635 reduces corneal epithelial defects and inflammation in DED, as well as alleviates autophagy by inhibiting ROS production. The activation of the 5-HT1A receptor-ROS-autophagy axis is critically involved in DED development.
Recapitulating Trafficking of Nucleosides Into the Active Site of Polymerases of RNA Viruses: The Challenge and the Prize
Authors: Boulard Yves , Bressanelli Stéphane
Published: December 2021

Nucleoside analogs are very effective antiviral agents with currently over 25 compounds approved for the therapy of viral infections. Still, their successful use against RNA viruses is very recent, despite RNA viruses comprising some of the most damaging human pathogens (e.g., Coronaviruses, Influenza viruses, or Flaviviridae such as dengue, Zika and hepatitis C viruses). The breakthrough came in 2013–2014, when the nucleoside analog Sofosbuvir became one of the cornerstones of current curative treatments for hepatitis C virus (HCV). An analog designed on the same principles, Remdesivir, has been the first approved compound against SARS-CoV-2, the coronavirus that causes the current COVID-19 pandemic. Both of these nucleoside analogs target the RNA-dependent RNA polymerase (RdRp) (NS5B for HCV, nsp12 for SARS-CoV-2). RdRps of RNA viruses display a peculiar elaboration of the classical polymerase architecture that leads to their active site being caged. Thus, triphosphate nucleosides and their analogs must access this active site in several steps along a narrow and dynamic tunnel. This makes straightforward computational approaches such as docking unsuitable for getting atomic-level details of this process. Here we give an account of ribose-modified nucleoside analogs as inhibitors of viral RdRps and of why taking into account the dynamics of these polymerases is necessary to understand nucleotide selection by RdRps. As a case study we use a computational protocol we recently described to examine the approach of the NTP tunnel of HCV NS5B by cellular metabolites of Sofosbuvir. We find major differences with natural nucleotides even at this early stage of nucleotide entry.
Characterization of Oral Enterobacteriaceae Prevalence and Resistance Profile in Chronic Kidney Disease Patients Undergoing Peritoneal Dialysis
Authors: Costa Carolina F. F. A. , Merino-Ribas Ana , Ferreira Catarina , Campos Carla , Silva Nádia , Pereira Luciano , Garcia Andreia , Azevedo Álvaro , Mesquita Raquel B. R. , Rangel António O. S. S. , Manaia Célia M. , Sampaio-Maia Benedita
Published: December 2021

Chronic Kidney Disease (CKD) is a growing public-health concern worldwide. Patients exhibit compromised immunity and are more prone to infection than other populations. Therefore, oral colonization by clinically relevant members of the Enterobacteriaceae family, major agents of both nosocomial and dialysis-associated infections with frequent prevalence of antibiotic resistances, may constitute a serious risk. Thus, this study aimed to assess the occurrence of clinically relevant enterobacteria and their antibiotic resistance profiles in the oral cavity of CKD patients undergoing peritoneal dialysis (CKD-PD) and compare it to healthy controls. Saliva samples from all the participants were cultured on MacConkey Agar and evaluated regarding the levels of urea, ammonia, and pH. Bacterial isolates were identified and characterized for antibiotic resistance phenotype and genotype. The results showed that CKD-PD patients exhibited significantly higher salivary pH, urea, and ammonia levels than controls, that was accompanied by higher prevalence and diversity of oral enterobacteria. Out of all the species isolated, only the prevalence of Raoultella ornithinolytica varied significantly between groups, colonizing the oral cavity of approximately 30% of CKD-PD patients while absent from controls. Antibiotic resistance phenotyping revealed mostly putative intrinsic resistance phenotypes (to amoxicillin, ticarcillin, and cephalothin), and resistance to sulfamethoxazole (~43% of isolates) and streptomycin (~17%). However, all isolates were resistant to at least one of the antibiotics tested and multidrug resistance isolates were only found in CKD-PD group (31,6%). Mobile genetic elements and resistance genes were detected in isolates of the species Raoultella ornithinolytica, Klebsiella pneumoniae, Klebsiella oxytoca, Escherichia coli, and Enterobacter asburiae, mostly originated from CKD-PD patients. PD-related infection history revealed that Enterobacteriaceae were responsible for ~8% of peritonitis and ~ 16% of exit-site infections episodes in CKD-PD patients, although no association was found to oral enterobacteria colonization at the time of sampling. The results suggest that the CKD-induced alterations of the oral milieu might promote a dysbiosis of the commensal oral microbiome, namely the proliferation of clinically relevant Enterobacteriaceae potentially harboring acquired antibiotic resistance genes. This study highlights the importance of the oral cavity as a reservoir for pathobionts and antibiotic resistances in CKD patients undergoing peritoneal dialysis.
Extended Bacteria Culture-Based Clustering Identifies a Phenotype Associating Increased Cough and Enterobacterales in Stable Chronic Obstructive Pulmonary Disease
Authors: Muggeo Anaëlle , Perotin Jeanne-Marie , Brisebarre Audrey , Dury Sandra , Dormoy Valérian , Launois Claire , Ancel Julien , Mulette Pauline , de Champs Christophe , Deslée Gaëtan , Guillard Thomas
Published: December 2021

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease characterized by airflow limitation. This chronic respiratory disease represents the third leading cause of death worldwide. Alteration of the airway microbiota has been reported to be associated with exacerbation frequency in COPD, but its role on the symptoms in patients at stable state is still incompletely described. This study aimed to determine whether bacteria isolated in sputum can be associated with the clinical features of COPD patients within stable state. Our study highlights, for the first time, that altered microbiota with Enterobacterales is associated with pejorative clinical symptoms in stable COPD patients. The airway microbiota of 38 patients was analyzed using an extended culture approach and mass spectrometry identification. Cluster analysis by principal coordinate analysis of the bacterial communities showed that the patients could be classified into three distinct clusters in our cohort. The clusters showed no differences in proportions of the phylum, but one of them was associated with a high prevalence of Enterobacterales (71.4% in cluster 1 vs. 0% in cluster 3), loss of microbiota diversity, and higher bacterial load (107 vs. 105 CFU/ml, respectively) and characterized by predominant cough and impact on mental health. These novel findings, supported by further studies, could lead to modifying the processing of COPD sputum in the everyday practice of clinical microbiology laboratories.
Involvement of the Autophagy Protein Atg6 in Development and Virulence in the Gray Mold Fungus Botrytis cinerea
Authors: Liu Na , Zhou Shanyue , Li Baohua , Ren Weichao
Published: December 2021

Gray mold caused by Botrytis cinerea is a devastating disease that leads to huge economic losses worldwide. Autophagy is an evolutionarily conserved process that maintains intracellular homeostasis through self-eating. In this study, we identified and characterized the biological function of the autophagy-related protein Atg6 in B. cinerea. Targeted deletion of the BcATG6 gene showed block of autophagy and several phenotypic defects in aspects of mycelial growth, conidiation, sclerotial formation and virulence. All of the phenotypic defects were restored by targeted gene complementation. Taken together, these results suggest that BcAtg6 plays important roles in the regulation of various cellular processes in B. cinerea.
RIGI, TLR7, and TLR3 Genes Were Predicted to Have Immune Response Against Avian Influenza in Indigenous Ducks
Authors: Pal Aruna , Pal Abantika , Baviskar Pradyumna
Published: December 2021

Avian influenza is a disease with every possibility to evolve as a human-to-human pandemic arising out of frequent mutations and genetic reassortment or recombination of avian influenza (AI) virus. The greatest concern is that till date, no satisfactory medicine or vaccines are available, leading to massive culling of poultry birds, causing huge economic loss and ban on export of chicken products, which emphasizes the need to develop an alternative strategy for control of AI. In the current study, we attempt to explore the molecular mechanism of innate immune potential of ducks against avian influenza. In the present study, we have characterized immune response molecules such as duck TLR3, TLR7, and RIGI that are predicted to have potent antiviral activities against the identified strain of avian influenza through in silico studies (molecular docking) followed by experimental validation with differential mRNA expression analysis. Future exploitation may include immunomodulation with the recombinant protein, and transgenic or gene-edited chicken resistant to bird flu.
An Integrated Fibrosis Signature for Predicting Survival and Immunotherapy Efficacy of Patients With Hepatocellular Carcinoma
Authors: Liu Long , Liu Zaoqu , Meng Lingfang , Li Lifeng , Gao Jie , Yu Shizhe , Hu Bowen , Yang Han , Guo Wenzhi , Zhang Shuijun
Published: December 2021

Introduction: Fibrosis, a primary cause of hepatocellular carcinoma (HCC), is intimately associated with inflammation, the tumor microenvironment (TME), and multiple carcinogenic pathways. Currently, due to widespread inter- and intra-tumoral heterogeneity of HCC, the efficacy of immunotherapy is limited. Seeking a stable and novel tool to predict prognosis and immunotherapy response is imperative.

Methods: Using stepwise Cox regression, least absolute shrinkage and selection operator (LASSO), and random survival forest algorithms, the fibrosis-associated signature (FAIS) was developed and further validated. Subsequently, comprehensive exploration was conducted to identify distinct genomic alterations, clinical features, biological functions, and immune landscapes of HCC patients.

Results: The FAIS was an independent prognostic predictor of overall survival and recurrence-free survival in HCC. In parallel, the FAIS exhibited stable and accurate performance at predicting prognosis based on the evaluation of Kaplan–Meier survival curves, receiver operator characteristic curves, decision curve analysis, and Harrell’s C-index. Further investigation elucidated that the high-risk group presented an inferior prognosis with advanced clinical traits and a high mutation frequency of TP53, whereas the low-risk group was characterized by superior CD8+ T cell infiltration, a higher TIS score, and a lower TIDE score. Additionally, patients in the low-risk group might yield more benefits from immunotherapy.

Conclusion: The FAIS was an excellent scoring system that could stratify HCC patients and might serve as a promising tool to guide surveillance, improve prognosis, and facilitate clinical management.