bluuebunny/crossref_metadata_2025 huggingface dataset:
Geneses, Sources and Accumulation Process of Natural Gases in the Hinterland of the Junggar Basin
Authors: Zhi Dongming , Wang Xiaojun , Qin Zhijun
Published: February 2022

The Junggar Basin is rich in natural gas resources, but it has hardly been explored, with the proven rate being less than 9.0%. Although the hinterland of the Junggar Basin has a favorable condition for natural gas accumulation, the complex gas sources cause great trouble in the selection of zones and belts for exploration. Based on the molecular composition and stable carbon and hydrogen isotope data of 95 natural gas samples from 72 wells in this area, combined with the characteristics of structural evolution history, burial history, hydrocarbon generation and expulsion history, and fluid inclusions, this paper clarified the geneses and sources of natural gas, identified the secondary alteration of natural gas, and restored the process of natural gas accumulation. Natural gas in the hinterland was divided into four types: Type I was oil-type gas from the Lower Permian Fengcheng Formation; Type II was coal-type gas derived from the Carboniferous source rock; Type III was the mixture of Type I and II gases, which constituted the major fraction of natural gases in the hinterland; and Type IV that referred to secondary microbial gas formed by the biodegradation of crude oil. During the Late Cretaceous, the Carboniferous and Fengcheng source rocks entered the gas generation peak and a series of natural gas reservoirs were formed. However, affected by the later tectonic movements, some gas reservoirs were damaged or adjusted, and natural gas leakage and biodegradation occurred. This study has shifted the focus of natural gas exploration in the study area from the petroleum system associated with the Middle Permian source rocks to that with the Lower Permian and Carboniferous source rocks, which is of great significance for natural gas exploration in the Junggar Basin. Further, it provides an example to identify the geneses and sources of natural gas under complex conditions based on integrated geological and geochemical assessments.
Low Maternal DLK1 Levels at 26 Weeks Is Associated With Small for Gestational Age at Birth
Authors: Pham Aurelie , Mitanchez Delphine , Forhan Anne , Perin Laurence , Le Bouc Yves , Brioude Frederic , Sobrier Marie-Laure , Heude Barbara , Netchine Irene
Published: February 2022

Detecting SGA (small for gestational age) during pregnancy improves the fetal and neonatal prognosis. To date, there is no valid antenatal biomarker of SGA used in clinical practice. Maternal circulating DLK1 (delta-like non-canonical notch ligand 1) levels have been shown to be significantly lower in pregnant women at 36 weeks of gestation (WG) who delivered a SGA newborn than in controls. Data in the literature are contradictory on the association between maternal circulating DLK1 levels and placental vascular dysfunction. The objective was to determine if maternal DLK1 levels in the second trimester of pregnancy are predictive of SGA, and to assess whether the measurement of DLK1 levels in maternal blood could be a means to distinguish SGA with placental vascular dysfunction from that due to other causes. We conducted a nested cased-control study within the EDEN mother-child cohort. 193 SGA (birth weight < 10th percentile) and 370 mother-child control (birth weight between the 25th and 75th percentile) matched pairs were identified in the EDEN cohort. Maternal circulating DLK1 levels at 26 WG were significantly lower for children born SGA than for controls (27.7 ± 8.7 ng/mL vs 30.4 ± 10.6 ng/mL, p = 0.001). Maternal blood DLK1 levels in the first quartile (DLK1 < 22.85 ng/mL) were associated with an odds ratio for SGA of 1.98 [1.15 - 3.37]. DLK1 was less predictive of SGA than ultrasound, with an area under the curve of 0.578. Maternal circulating DLK1 levels were not significantly different in cases of SGA with signs of placental vascular dysfunction (n = 63, 27.1 ± 9.2 ng/mL) than in those without placental dysfunction (n = 129, 28.0 ± 8.5 ng/mL, p = 0.53). The level of circulating DLK1 is reduced in the second trimester of pregnancy in cases of SGA at birth, independently of signs of placental vascular dysfunction. However, DLK1 alone cannot predict the risk of SGA.
Synchronous Generator Imitation Control and Dynamic Power Sharing for Distributed Power Generation Systems
Authors: Xiao Huangqing , Liu Bicheng , Huang Xiaowei , Cai Zexiang
Published: February 2022

In this paper, a control method called synchronous generator imitation control (SGIC) as well as a dynamic power sharing for distributed power generation systems (DPGSs) are presented. In order to imitate the behavior of a synchronous generator (SG), the SGIC method for the voltage source converter (VSC) station is proposed. The SGIC includes three loops, namely active power and frequency loop (Pf loop), reactive power and voltage loop (QU loop) as well as inner current loop. The Pf loop is used to emulate the swing equation of the SG. The exciter of the SG is mimicked by the QU loop. The inner current loop is developed for fast current and voltage regulations as well as current limiting. The system stability performances are analyzed through small-signal model, and the effectiveness of the proposed control is validated by PSCAD/EMTDC simulations. The results show that the Pf loop of the VSC emulates the motion equation of the SG rotor very well, which makes the VSC station to have inertia just as a SG; the VSC station can maintain a stable output voltage and regulate the reactive power at the same time; through the dynamic power sharing, precise power control, frequency offset elimination and system stability improvement are achieved; the system has the merits of fault ride-through capability as well as good dynamic performance.
How do You Want to restore?--Assessing the Public Preferences and Social Benefits of Ecological Restoration for Natural Rubber Plantation in China
Authors: Qiao Dan , Li Weiqin , Zhang Desheng , Yan Yan , Xu Tao
Published: February 2022

Revealing the public’s preference for ecological restoration projects will help increase public support and improve social benefits evaluation accuracy, which is a prerequisite for implementing ecological restoration projects. This study aimed to reveal the public’s preference for natural rubber plantation restoration projects and then quantify the social benefits of these projects to provide valuable references for related policy design. Based on choice experiments, we built a hypothetical market of ecological products and conducted a field survey to obtain the public’s preferences and willingness to pay (WTP) for natural rubber plantation restoration projects. Then, a random parameters logit model was applied to obtain public preference information, and then the social benefits brought by different restoration scenarios were calculated and compared. The results showed that: 1) residents of Hainan Province had a positive attitude toward ecological restoration for natural rubber plantations and were willing to bear a personal cost. 2) respondents had significant differences in preference for attributes of restoration projects. 3) a restoration project covering 2.1 million mu of rubber plantations, prioritizing the water source protection area, focusing the implementation on state farms, and developing the under-forest breeding economy would gain more social benefits, precisely, 337.543 million yuan/year. Ecological restoration policies should pay more attention to public needs and incorporate them into future guidelines. Policymakers should focus on restoration quality instead of the restoration area. Priority should be given to rubber plantations close to the water source protection area and small householders, and an appropriate under-forest economy should be considered. This study can provide a valuable reference for policy-making related to rubber plantation restoration.
The Behavioral Responses of the Chiguanco Thrush to Urbanization in a Neotropical City Comes From Preadapted Behavioral Traits
Authors: Garitano-Zavala Álvaro , Calbimonte Rodrigo , Esteve-Herraiz Guillermo
Published: February 2022

Several animal species can survive within cities by changing their behavior; such changes could be the result of evolutionary adaptation, epigenetic effects, or come from preadapted traits through phenotypic plasticity or non-random dispersal. Exploring whether behavioral preadapted traits are present in non-urbanized populations could improve our understanding of the processes that allow animals to cope with urbanization. We compared the boldness, neophobia, and solving-test skills of adult individuals of the Chiguanco Thrush (Turdus chiguanco) between urban and extra-urban habitats in La Paz (Bolivia), a high-altitude Neotropical city. The urban Chiguanco Thrushes were bolder, less neophobic, and performed better in problem-solving tests. Extra-urban individuals varied significantly more among them in boldness and neophobia, and although a smaller proportion of individuals were able to solve the simplest problem-solving test, they did so in the same way as the urban ones. This evidence suggests that the behavioral responses of the Chiguanco Thrush to urbanization in La Paz come from preadapted traits.
Identification of the Crucial Role of CCL22 in F. nucleatum-Related Colorectal Tumorigenesis that Correlates With Tumor Microenvironment and Immune Checkpoint Therapy
Authors: Wang Hufei , Luo Kangjia , Guan Zilong , Li Zhi , Xiang Jun , Ou Suwen , Tao Yangbao , Ran Songlin , Ye Jinhua , Ma Tianyi , Qiao Tianyu , Zhang Zhiming , Jin Yinghu , Song Yanni , Huang Rui
Published: February 2022

Colorectal cancer (CRC) is the third most common malignant cancer worldwide with the second highest mortality. Gut microbiota can educate the tumor microenvironment (TME), consequently influencing the efficacy of immune checkpoint inhibitors (ICIs). Fusobacterium nucleatum is one of the most crucial bacteria contributing to colorectal tumorigenesis, but the molecular mechanisms between F. nucleatum and TME or ICIs are poorly investigated. In the present study, we firstly analyzed differentially expressed genes and the biological functions between F. nucleatum-infected and uninfected CRC cell lines, with the findings that CCL22 mRNA expression was markedly upregulated after F. nucleatum infection. Moreover, the survival analysis showed that CCL22 was significantly associated with the overall survival of CRC patients. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis suggested that CCL22 was related to immune-related terms. Furthermore, the ESTIMATE analysis indicated that the high-CCL22-expression subgroup had a higher immune/stromal/estimate score and lower tumor purity. The CIBERSORT analysis indicated that the high-CCL22-expression group had more immune-suppressive cells and less antitumor immune cells. In addition, immune checkpoint genes and cytotoxic genes were positively correlated with CCL22 expression. The immunophenoscore analysis suggested that CCL22 was associated with the IPS-CTLA4 and PD1/PD-L1/PD-L2 score. Interestingly, CCL22 expression in the KRAS and APC mutation groups was markedly reduced compared to that of the wild groups. In summary, our study provided evidence that CCL22 might play a crucial role in F. nucleatum-related colorectal tumorigenesis and correlate with TME and ICIs, which deserves further study.
SAWRPI: A Stacking Ensemble Framework With Adaptive Weight for Predicting ncRNA-Protein Interactions Using Sequence Information
Authors: Ren Zhong-Hao , Yu Chang-Qing , Li Li-Ping , You Zhu-Hong , Guan Yong-Jian , Li Yue-Chao , Pan Jie
Published: February 2022

Non-coding RNAs (ncRNAs) take essential effects on biological processes, like gene regulation. One critical way of ncRNA executing biological functions is interactions between ncRNA and RNA binding proteins (RBPs). Identifying proteins, involving ncRNA-protein interactions, can well understand the function ncRNA. Many high-throughput experiment have been applied to recognize the interactions. As a consequence of these approaches are time- and labor-consuming, currently, a great number of computational methods have been developed to improve and advance the ncRNA-protein interactions research. However, these methods may be not available to all RNAs and proteins, particularly processing new RNAs and proteins. Additionally, most of them cannot process well with long sequence. In this work, a computational method SAWRPI is proposed to make prediction of ncRNA-protein through sequence information. More specifically, the raw features of protein and ncRNA are firstly extracted through the k-mer sparse matrix with SVD reduction and learning nucleic acid symbols by natural language processing with local fusion strategy, respectively. Then, to classify easily, Hilbert Transformation is exploited to transform raw feature data to the new feature space. Finally, stacking ensemble strategy is adopted to learn high-level abstraction features automatically and generate final prediction results. To confirm the robustness and stability, three different datasets containing two kinds of interactions are utilized. In comparison with state-of-the-art methods and other results classifying or feature extracting strategies, SAWRPI achieved high performance on three datasets, containing two kinds of lncRNA-protein interactions. Upon our finding, SAWRPI is a trustworthy, robust, yet simple and can be used as a beneficial supplement to the task of predicting ncRNA-protein interactions.
Trinucleotide CGG Repeat Diseases: An Expanding Field of Polyglycine Proteins?
Authors: Boivin Manon , Charlet-Berguerand Nicolas
Published: February 2022

Microsatellites are repeated DNA sequences of 3–6 nucleotides highly variable in length and sequence and that have important roles in genomes regulation and evolution. However, expansion of a subset of these microsatellites over a threshold size is responsible of more than 50 human genetic diseases. Interestingly, some of these disorders are caused by expansions of similar sequences, sizes and localizations and present striking similarities in clinical manifestations and histopathological features, which suggest a common mechanism of disease. Notably, five identical CGG repeat expansions, but located in different genes, are the causes of fragile X-associated tremor/ataxia syndrome (FXTAS), neuronal intranuclear inclusion disease (NIID), oculopharyngodistal myopathy type 1 to 3 (OPDM1-3) and oculopharyngeal myopathy with leukoencephalopathy (OPML), which are neuromuscular and neurodegenerative syndromes with overlapping symptoms and similar histopathological features, notably the presence of characteristic eosinophilic ubiquitin-positive intranuclear inclusions. In this review we summarize recent finding in neuronal intranuclear inclusion disease and FXTAS, where the causing CGG expansions were found to be embedded within small upstream ORFs (uORFs), resulting in their translation into novel proteins containing a stretch of polyglycine (polyG). Importantly, expression of these polyG proteins is toxic in animal models and is sufficient to reproduce the formation of ubiquitin-positive intranuclear inclusions. These data suggest the existence of a novel class of human genetic pathology, the polyG diseases, and question whether a similar mechanism may exist in other diseases, notably in OPDM and OPML.
Familial Hypercholesterolemia: Real-World Data of 1236 Patients Attending a Czech Lipid Clinic. A Retrospective Analysis of Experience in More than 50 years. Part I: Genetics and Biochemical Parameters
Authors: Todorovova Veronika , Altschmiedova Tereza , Vrablik Michal , Ceska Richard
Published: February 2022

Introduction:The cause of familial hypercholesterolemia (FH) is defect in LDL receptor or familial defect of apolipoprotein B-100 (FDB) or, rarely, defect in proprotein convertase subtilisin/kexin type 9. Identification and treatment of patients with FH improves their prognosis. Our data represent retrospective analysis of 50 years of specialised care in our center.

Patients and Methods:A group of 1236 FH patients (841 women, 395 men; 993 study subjects and 243 relatives; mean age 44.8 ± 16.7 years) included 154 FDB patients followed at the Lipid Clinic of the General University Hospital in Prague since the mid-1960s to the present. Clinical diagnosis was based on the Dutch Lipid Clinic Network Criteria. Genetic analysis was performed using PCR-RFLP to detect FDB and apolipoprotein E (APOE) polymorphism. Biochemical data were collected and statistically analysed.

Results:At baseline, mean LDL-C and total cholesterol (TC) levels of all FH patients combined were 6.49 ± 1.92 mmol/L and 8.95 ± 1.95 mmol/L, respectively. Their LDL-C levels decreased to 3.26 ± 1.57 mmol/L and TC levels to 5.43 ± 1.69 mmol/L during follow-up. In the subgroup of LDL receptor-mediated FH (non-FDB) patients, baseline LDL-C and TC levels of 6.61 ± 1.95 mmol/L and 9.09 ± 1.97 mmol/L declined to 3.21 ± 1.60 mmol/L and 5.39 ± 1.72 mmol/L, respectively, during follow-up. In the FDB subgroup of patients, baseline levels of LDL-C and TC were 5.57 ± 1.46 mmol/L and 7.88 ± 1.58 mmol/L decreasing to 3.45 ± 0.24 mmol/L and 5.58 ± 1.37 mmol/L, respectively, during follow-up. Differences were also found in the effects of various APOE isoforms on lipid lowering. A significant decrease in lipid parameters was observed with the E2E2 isoform whereas a minimal decrease was seen with the E4E4 and E3E3 isoforms.

Conclusion:Whereas, overall, non-FDB patients had higher baseline lipid levels, these levels declined more appreciably compared with FDB patients during follow-up. Our retrospective analysis also found different effects of APOE isoforms on the decrease in lipid levels.
Impact of Dietary Fiber on West Nile Virus Infection
Authors: Ni Duan , Tan Jian , Niewold Paula , Spiteri Alanna Gabrielle , Pinget Gabriela Veronica , Stanley Dragana , King Nicholas Jonathan Cole , Macia Laurence
Published: February 2022

Dietary fiber supports healthy gut bacteria and their production of short-chain fatty acids (SCFA), which promote anti-inflammatory cell development, in particular, regulatory T cells. It is thus beneficial in many diseases, including influenza infection. While disruption of the gut microbiota by antibiotic treatment aggravates West Nile Virus (WNV) disease, whether dietary fiber is beneficial is unknown. WNV is a widely-distributed neurotropic flavivirus that recruits inflammatory monocytes into the brain, causing life-threatening encephalitis. To investigate the impact of dietary fiber on WNV encephalitis, mice were fed on diets deficient or enriched with dietary fiber for two weeks prior to inoculation with WNV. To induce encephalitis, mice were inoculated intranasally with WNV and maintained on these diets. Despite increased fecal SCFA acetate and changes in gut microbiota composition, dietary fiber did not affect clinical scores, leukocyte infiltration into the brain, or survival. After the brain, highest virus loads were measured in the colon in neurons of the submucosal and myenteric plexuses. Associated with this, there was disrupted gut homeostasis, with shorter colon length and higher local inflammatory cytokine levels, which were not affected by dietary fiber. Thus, fiber supplementation is not effective in WNV encephalitis.
Immunological Classification of Tumor Types and Advances in Precision Combination Immunotherapy
Authors: Ren Xiufang , Guo Songyi , Guan Xiaojiao , Kang Ye , Liu Jiamei , Yang Xianghong
Published: February 2022

Immunity is an important physiological function acquired throughout evolution as a defense system against the invasion of pathogenic microorganisms. The immune system also eliminates senescent cells and maintains homeostasis, monitoring cell mutations and preventing tumor developmentviathe action of the immune cells and molecules. Immunotherapy often relies on the interaction of immune cells with the tumor microenvironment (TME). Based on the distribution of the number of lymphocytes (CD3 and CD8) in the center and edge of the tumor and the expression level of B7-H1/PD-L1, tumors are divided into hot tumors, cold tumors, and intermediate tumors (including immune-suppressed and isolated). This review focuses on the advances in precision combination immunotherapy, which has been widely explored in recent years, and its application in different tumor types.
APE1/Ref-1 Role in Inflammation and Immune Response
Authors: Oliveira Thais Teixeira , Coutinho Leonam Gomes , de Oliveira Laysa Ohana Alves , Timoteo Ana Rafaela de Souza , Farias Guilherme Cavalcanti , Agnez-Lima Lucymara Fassarella
Published: February 2022

Apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1) is a multifunctional enzyme that is essential for maintaining cellular homeostasis. APE1 is the major apurinic/apyrimidinic endonuclease in the base excision repair pathway and acts as a redox-dependent regulator of several transcription factors, including NF-κB, AP-1, HIF-1α, and STAT3. These functions render APE1 vital to regulating cell signaling, senescence, and inflammatory pathways. In addition to regulating cytokine and chemokine expression through activation of redox sensitive transcription factors, APE1 participates in other critical processes in the immune response, including production of reactive oxygen species and class switch recombination. Furthermore, through participation in active chromatin demethylation, the repair function of APE1 also regulates transcription of some genes, including cytokines such as TNFα. The multiple functions of APE1 make it an essential regulator of the pathogenesis of several diseases, including cancer and neurological disorders. Therefore, APE1 inhibitors have therapeutic potential. APE1 is highly expressed in the central nervous system (CNS) and participates in tissue homeostasis, and its roles in neurodegenerative and neuroinflammatory diseases have been elucidated. This review discusses known roles of APE1 in innate and adaptive immunity, especially in the CNS, recent evidence of a role in the extracellular environment, and the therapeutic potential of APE1 inhibitors in infectious/immune diseases.
Vaccine Type-, Age- and Past Infection-Dependence of the Humoral Response to SARS-CoV-2 Spike S Protein
Authors: Romero-Pinedo Salvador , Quesada Marina , Horndler Lydia , Álvarez-Fernández Stela , Olmo Asunción , Abia David , Alarcón Balbino , Delgado Pilar
Published: February 2022

The emergence of COVID-19 has led to a worldwide challenge for the rapid development of vaccines. Several types of safe and effective vaccines have been available in a time frame never seen before. Now that several hundred million people have been vaccinated there is an opportunity to compare vaccines in terms of protection and immune response. Here, we have applied a highly sensitive multiplexed flow cytometry method to measure simultaneously IgM, IgG1 and IgA anti-spike protein antibodies generated in response to three vaccines: ChAdOx1 (Oxford-AstraZeneca), mRNA-1273 (Moderna), and BNT162b2 (Pfizer-BioNTech). We have found that mRNA vaccines (mRNA-1273 and BNT162b2) induce a stronger humoral response, both after the first and the second dose, than the adenovirus-based ChAdOx1 vaccine. We also found that, in the elderly, antibody titers negatively correlate with the age of the donor but, also, that antibody titers remain stable for at least 6 months after complete vaccination. Finally, we found that one dose of BNT162b2 is sufficient to induce the highest antibody titers in seropositive pre-vaccination donors. We hope these data will help to guide future decisions on vaccination strategies.
Assessing Fish Immunotoxicity by Means of In Vitro Assays: Are We There Yet?
Authors: Segner Helmut , Rehberger Kristina , Bailey Christyn , Bo Jun
Published: February 2022

There is growing awareness that a range of environmental chemicals target the immune system of fish and may compromise the resistance towards infectious pathogens. Existing concepts to assess chemical hazards to fish, however, do not consider immunotoxicity. Over recent years, the application ofin vitroassays for ecotoxicological hazard assessment has gained momentum, what leads to the question whetherin vitroassays using piscine immune cells might be suitable to evaluate immunotoxic potentials of environmental chemicals to fish.In vitrosystems using primary immune cells or immune cells lines have been established from a wide array of fish species and basically from all immune tissues, and in principal these assays should be able to detect chemical impacts on diverse immune functions. In fact,in vitroassays were found to be a valuable tool in investigating the mechanisms and modes of action through which environmental agents interfere with immune cell functions. However, at the current state of knowledge the usefulness of these assays for immunotoxicity screening in the context of chemical hazard assessment appears questionable. This is mainly due to a lack of assay standardization, and an insufficient knowledge of assay performance with respect to false positive or false negative signals for the different toxicant groups and different immune functions. Also the predictivity of thein vitroimmunotoxicity assays for thein vivoimmunotoxic response of fishes is uncertain. In conclusion, the currently available database is too limited to support the routine application of piscinein vitroassays as screening tool for assessing immunotoxic potentials of environmental chemicals to fish.
Risk Factors for Severe COVID-19 and Hospital Admission in Patients With Inborn Errors of Immunity - Results From a Multicenter Nationwide Study
Authors: Milota Tomas , Sobotkova Marta , Smetanova Jitka , Bloomfield Marketa , Vydlakova Jana , Chovancova Zita , Litzman Jiri , Hakl Roman , Novak Jiri , Malkusova Ivana , Hanzlikova Jana , Jilek Dalibor , Hutyrova Beata , Novak Vitezslav , Krcmova Irena , Sediva Anna , Kralickova Pavlina
Published: February 2022

Despite the progress in the understanding how COVID-19 infection may impact immunocompromised patients, the data on inborn errors of immunity (IEI) remain limited and ambiguous. Therefore, we examined the risk of severe infection course and hospital admission in a large cohort of patients with IEI. In this multicenter nationwide retrospective survey-based trial, the demographic, clinical, and laboratory data were collected by investigating physicians from 8 national referral centers for the diagnosis and treatment of IEI using a COVID-19-IEI clinical questionnaire. In total, 81 patients with IEI (including 16 with hereditary angioedema, HAE) and confirmed SARS-CoV-2 infection were enrolled, and were found to have a 2.3-times increased (95%CI: 1.44–3.53) risk ratio for hospital admission and a higher mortality ratio (2.4% vs. 1.7% in the general population). COVID-19 severity was associated with the presence of clinically relevant comorbidities, lymphopenia, and hypogammaglobulinemia, but not with age or BMI. No individuals with HAE developed severe disease, despite a hypothesized increased risk due to perturbed bradykinin metabolism. We also demonstrated a high seroconversion rate in antibody-deficient patients and the safety of anti-spike SARS CoV-2 monoclonal antibodies and convalescent plasma. Thus, IEI except for HAE, represent significant risk factors for a severe COVID-19. Therefore, apart from general risk factors, immune system dysregulation may also be involved in the poor outcomes of COVID-19. Despite the study limitations, our results support the findings from previously published trials.
D-Mannose Suppresses γδ T Cells and Alleviates Murine Psoriasis
Authors: Li Mingyang , Cheng Haiyan , Tian Dan , Yang Lu , Du Xiaonan , Pan Yuhualei , Zhang Dong , Mei Xueling
Published: February 2022

Psoriasis is a chronic skin disorder associated with multiple sequelae, such as psoriatic arthritis and cardiovascular diseases. Increasing evidence has shown that γδ T cells, as sources of IL-17A, play critical roles in psoriatic inflammations. However, there still lack effective ways to manipulate these pathogenic γδ T cells, which are less well studied than αβ T cells. The present study aims to characterize the phenotype of γδ T cells and evaluate the impact of D-mannose (a C-2 epimer of glucose) on γδ T cell-mediated psoriasis. We found that skin-draining LN γδ T cells underwent robust proliferation and acquired an IL-17-producing phenotype during psoriasis. The transcriptomic profiles of these psoriatic γδ T cells had elevated glycolytic signatures. Importantly, D-mannose treatment suppressed the γδ T cell reaction and successfully alleviated the local and systematic inflammation induced by imiquimod. The decreased AKT/mTOR/HIF-1α signaling and glycolytic ability may contribute to the suppression of γδ T cells achieved by D-mannose. Our study increased understanding of γδ T cells in psoriasis and promoted D-mannose utilization as a potential clinical application for autoimmune diseases driven by γδ T cells.
Peramivir, an Anti-Influenza Virus Drug, Exhibits Potential Anti-Cytokine Storm Effects
Authors: Zhang Chen-xi , Tu Ye , Sun Xiao-chen , Chen Da-gui , Zhang Wan-nian , Zhuang Chun-lin , Wang Zhi-bin , Su Li
Published: February 2022

Coronavirus Disease 2019 (COVID-19) infected by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has been declared a public health emergency of international concerns. Cytokine storm syndrome (CSS) is a critical clinical symptom of severe COVID-19 patients, and the macrophage is recognized as the direct host cell of SARS-CoV-2 and potential drivers of CSS. In the present study, peramivir was identified to reduce TNF-α by partly intervention of NF-κB activity in LPS-induced macrophage model. In vivo, peramivir reduced the multi-cytokines in serum and bronchoalveolar lavage fluid (BALF), alleviated the acute lung injury and prolonged the survival time in mice. In human peripheral blood mononuclear cells (hPBMCs), peramivir could also inhibit the release of TNF-α. Collectively, we proposed that peramivir might be a candidate for the treatment of COVID-19 and other infections related CSS.
Method for Nest Detection of the Yellow-Legged Hornet in High Density Areas
Authors: Rojas-Nossa Sandra V. , Álvarez Patricia , Garrido Josefina , Calviño-Cancela María
Published: February 2022

The Asian hornet Vespa velutina is a social predator that has invaded several countries of Europe and Asia, impacting pollinators, apiculture and human health. One of the few effective control methods developed so far is the early destruction of nests. However, they are often built within dense vegetation, being difficult to detect. The aim of the method described here is to detect nests with a simple procedure, utilizing readily available materials, for widespread use in infested areas. The method has two phases, the first phase involves capturing and marking hornets, lured to a protein bait, and recording the flight directions of individuals to the nest and the time needed to complete a bait-nest-bait round trip, to estimate the distance. Collecting this information from two (or more) bait stations allows to delineate the approximate location of the nest. The second phase aims to determine the precise location of the nest, using sugary baits in the vicinity of the nest and conspicuous marks attached to the released hornets, to visually follow them up to their nest. This method is an alternative to other methods that are either ineffective in areas with high nest density or require expensive equipment and specialized training.
Ecdysis Triggering Hormone, Eclosion Hormone, and Crustacean Cardioactive Peptide Play Essential but Different Roles in the Molting Process of Mud Crab, Scylla paramamosain
Authors: Zhao Yan-Fei , Wen Qi-Qiao , Ao Chun-Mei , Wang Wei , Shi Li-Li , Wang Cheng-Gui , Chan Siuming-Francis
Published: February 2022

Molting behavior in insects is controlled by the ecdysis triggering hormone (ETH), eclosion hormone (EH) and the crustacean cardioactive peptide (CCAP). At present, the regulation of molting behavior in crustaceans remains unclear. Here, we studied the roles of ETH, EH, and CCAP in the molt regulation of the crab, Scylla paramamosain from their expression pattern and in vivo assays. The results showed that transcripts of ETH, EH, and CCAP were mainly localized in thoracic ganglia and fluctuated periodically with the molting cycle. When ETH or CCAP was knockdown at early premolt stage (D0), molting of crabs was interrupted and all animals died at late premolt stage (D2). While the EH gene was knock-down, most crabs were dead before D2. Injection of synthetic peptide for ETH or CCAP rescued ETH- or CCAP-gene knock-down crabs separately. However, none of peptides could rescue dsEH-injected crabs. At D0 stage, knockdown of ETH down-regulated the transcriptions of EH and CCAP; while ETH was up-regulated when EH was knockdown. At D2 stage, ETH transcripts levels were reduced with the injection of dsEH but increased with the same dose of dsETH as crabs at D0 stage. Co-injection of dsETH and dsEH down-regulated ETH at D2 stage. Results showed that ETH, EH, and CCAP play essential but different roles in molt regulation in mud crab. In summary, the result of this study contributes to the discovery of different molecular mechanisms between Insecta and Crustacea and may provide insight to develop fishery drugs that helps aquacultured crustaceans to molt successfully.
Novel Stimuli-Responsive Pectin-PVP-Functionalized Clay Based Smart Hydrogels for Drug Delivery and Controlled Release Application
Authors: Rehmat Shabnam , Rizvi Nayab Batool , Khan Saba Urooge , Ghaffar Abdul , Islam Atif , Khan Rafi Ullah , Mehmood Azra , Butt Hira , Rizwan Muhammad
Published: February 2022

Stimuli-responsive drug delivery systems are urgently required for injectable site-specific delivery and release of drugs in a controlled manner. For this purpose, we developed novel pH-sensitive, biodegradable, and antimicrobial hydrogels from bio-macromolecule pectin, polyvinylpyrrolidone (PVP), 3-aminopropyl (diethoxy)methyl silane (3-APDEMS), and sepiolite clay via blending and solution casting technique. The purified sepiolite (40 um) was functionalized with 3-APDEMS crosslinker (ex-situ modification) followed by hydrogels fabrication. FTIR and SEM confirmed crosslinked structural integrity and rod-like morphology of hydrogels respectively. The swelling properties of hydrogels could be controlled by varying the concentration of modified clay in pectin/PVP blends. Moreover, the decrease in pH increased the swelling of hydrogels indicating the pH-responsiveness of hydrogels. All hydrogels were degraded after 21 days in phosphate buffer saline pH 7.4 (human blood pH). In-vitro cytotoxicity against 3T3 mouse fibroblast cell line analysis confirmed cytocompatibility of all hydrogels. Ceftriaxone sodium (CTX-S) was selected as a model drug. The release profile of the hydrogel showed 91.82% release in PBS for 2 h in a consistent and controlled manner. The chemical structure of the drug remained intact during and after release confirmed through UV-Visible spectroscopy. Overall, these hydrogels could be used as potential scaffolds for future biomedical applications.
Dynamics of Serum Pregenome RNA in Chronic Hepatitis B Patients Receiving 96-Month Nucleos(t)ide Analog Therapy
Authors: Tao Yachao , Wang Menglan , Liao Juan , Cheng Xing , He Min , Zhang Dongmei , Zhou Taoyou , Chen Jie , Chen Enqiang , Tang Hong
Published: February 2022

Background

Tissue covalently closed circular DNA (cccDNA) can reflect the activity of HBV replication. However, it is impractical to assess intrahepatic cccDNA in every outpatient. Serum pregenome RNA (pgRNA) is transcribed from intrahepatic cccDNA and may reflect the activity of intrahepatic cccDNA. We explored the dynamics and the potential role of serum pgRNA in patients receiving long-term NAs treatment.

Methods

Serum pgRNA, HBV DNA, HBsAg, HBeAg, and ALT levels were quantified, and the relationships between serum pgRNA and these common clinical indicators before and after the treatment were investigated.

Results

Serum pgRNA showed dynamic change during the 96-month NAs therapy, and serum pgRNA levels were positive and detectable in 19 patients with undetectable serum HBV DNA. Serum pgRNA showed strong and positive correlation with serum HBV DNA (r = 0.693, p < 0.001) and serum HBsAg levels (r = 0.621, p < 0.001) at baseline. Patients with HBeAg seroconversion had lower baseline serum pgRNA levels (p = 0.002). The area under the curve (AUC) of baseline serum pgRNA for predicting HBeAg seroconversion was 0.742 (95% CI: 0.606–0.850) with 63.16% sensitivity and 80.56% specificity. The cumulative HBeAg seroconversion rate was higher in patients with low serum pgRNA (p = 0.001).

Conclusion

Serum pgRNA of low level at baseline or great decline at month 6 may independently predict the high incidence of undetectable serum pgRNA at year 4 following NAs therapy, and the baseline serum pgRNA may serve as a novel predictor for HBeAg seroconversion during NAs therapy.
Methylprednisolone Pulses in Hospitalized COVID-19 Patients Without Respiratory Failure: A Randomized Controlled Trial
Authors: Les Iñigo , Loureiro-Amigo Jose , Capdevila Ferran , Oriol Isabel , Elejalde Iñaki , Aranda-Lobo Judit , Modesto Joao , Güell-Farré Elena , García Ruth , Murgadella-Sancho Anna , Anniccherico Javier , Martín-Fernández Miguel , Lorza José Javier , Monteys-Montblanch Joan-Pol , Librero Julián , Pintado-Lalueza Sara , Delgado Marina , Gracia-García Berta , Sánchez-Álvarez Julio , Pestaña-Fernández Melani , Fanlo Patricia , Funalleras-Puig Gisela , Sarobe Maite , Mediavilla Eduardo , Ibero Carlos
Published: February 2022

Background

Corticosteroids are the cornerstone of the treatment of patients with COVID-19 admitted to hospital. However, whether corticosteroids can prevent respiratory worsening in hospitalized COVID-19 patients without oxygen requirements is currently unknown.

Aims

To assess the efficacy of methylprednisolone pulses (MPP) in hospitalized COVID-19 patients with increased levels of inflammatory markers not requiring oxygen at baseline.

Methods

Multicenter, parallel, randomized, double-blind, placebo-controlled trial conducted in Spain. Patients admitted for confirmed SARS-CoV-2 pneumonia with raised inflammatory markers (C-reactive protein >60 mg/L, interleukin-6 >40 pg/ml, or ferritin >1,000 μg/L) but without respiratory failure after the first week of symptom onset were randomized to receive a 3-day course of intravenous MPP (120 mg/day) or placebo. The primary outcome was treatment failure at 14 days, a composite variable including mortality, the need for ICU admission or mechanical ventilation, and clinical worsening, this last parameter defined as a PaO2/FiO2 ratio below 300; or a 15% decrease in the PaO2 from baseline, together with an increase in inflammatory markers or radiological progression. If clinical worsening occurred, patients received tocilizumab and unmasked corticosteroids. The secondary outcomes were 28-day mortality, adverse events, need for ICU admission or high-flow oxygen, length of hospital stay, SARS-CoV-2 clearance, and changes in laboratory parameters.

Results

A total of 72 patients were randomized and 71 patients were analyzed (34 in the MPP group and 37 in the placebo group). Twenty patients presented with treatment failure (29.4 in the MPP group vs. 27.0% in the placebo group, p = 0.82), with no differences regarding the time to treatment failure between groups. There were no cases of death or mechanical ventilation requirements at 14 days post-randomization. The secondary outcomes were similar in MPP and placebo groups.

Conclusions

A 3-day course of MPP after the first week of disease onset did not prevent respiratory deterioration in hospitalized COVID-19 patients with an inflammatory phenotype who did not require oxygen.
Comparison of 24-h Urine Protein, Urine Albumin-to-Creatinine Ratio, and Protein-to-Creatinine Ratio in IgA Nephropathy
Authors: Yu Guizhen , Cheng Jun , Li Heng , Li Xiayu , Chen Jianghua
Published: February 2022

Background

Proteinuria is a strong risk factor for renal outcomes in IgA nephropathy. Random urine protein-to-creatinine ratio (PCR), random albumin-to-creatinine ratio (ACR), and 24-h urine protein excretion (24-h UP) have been widely used in clinical practice. However, the measurement which is the best predictor of long-term renal outcomes remains controversial. This study aimed to compare the three measurements in IgA nephropathy.

Methods

We conducted a retrospective study of 766 patients with IgA nephropathy. The associations among baseline ACR, PCR, and 24-h UP with chronic kidney disease (CKD) progression event, defined as 50% estimated glomerular filtration rate (eGFR) decline or end stage kidney disease (ESKD), were tested and compared.

Results

In this study, ACR, PCR, and 24-h UP showed high correlation (r = 0.671–0.847, P < 0.001). After a median follow-up of 29.88 (14.65–51.65) months, 51 (6.66%) patients reached the CKD progression event. In univariate analysis, ACR performed better in predicting the prognosis of IgA nephropathy, with a higher area under the receiver operating curve (ROC) curve than PCR and 24-h UP. After adjustment for traditional risk factors, ACR was most associated with composite CKD progression event [per log-transformed ACR, hazard ratio (HR): 2.82; 95% (95% CI): 1.31–6.08; P = 0.008].

Conclusions

In IgA nephropathy, ACR, PCR, and 24-h UP had a high correlation. ACR performed better in predicting the prognosis of IgA nephropathy.
PET Molecular Imaging in Drug Development: The Imaging and Chemistry Perspective
Authors: Nerella Sridhar Goud , Singh Priti , Sanam Tulja , Digwal Chander Singh
Published: February 2022

Positron emission tomography with selective radioligands advances the drug discovery and development process by revealing information about target engagement, proof of mechanism, pharmacokinetic and pharmacodynamic profiles. Positron emission tomography (PET) is an essential and highly significant tool to study therapeutic drug development, dose regimen, and the drug plasma concentrations of new drug candidates. Selective radioligands bring up target-specific information in several disease states including cancer, cardiovascular, and neurological conditions by quantifying various rates of biological processes with PET, which are associated with its physiological changes in living subjects, thus it reveals disease progression and also advances the clinical investigation. This study explores the major roles, applications, and advances of PET molecular imaging in drug discovery and development process with a wide range of radiochemistry as well as clinical outcomes of positron-emitting carbon-11 and fluorine-18 radiotracers.
Exploring the Utility of Radiomic Feature Extraction to Improve the Diagnostic Accuracy of Cardiac Sarcoidosis Using FDG PET
Authors: Mushari Nouf A. , Soultanidis Georgios , Duff Lisa , Trivieri Maria G. , Fayad Zahi A. , Robson Philip , Tsoumpas Charalampos
Published: February 2022

Background

This study aimed to explore the radiomic features from PET images to detect active cardiac sarcoidosis (CS).

Methods

Forty sarcoid patients and twenty-nine controls were scanned using FDG PET-CMR. Five feature classes were compared between the groups. From the PET images alone, two different segmentations were drawn. For segmentation A, a region of interest (ROI) was manually delineated for the patients' myocardium hot regions with standardized uptake value (SUV) higher than 2.5 and the controls' normal myocardium region. A second ROI was drawn in the entire left ventricular myocardium for both study groups, segmentation B. The conventional metrics and radiomic features were then extracted for each ROI. Mann-Whitney U-test and a logistic regression classifier were used to compare the individual features of the study groups.

Results

For segmentation A, the SUVmin had the highest area under the curve (AUC) and greatest accuracy among the conventional metrics. However, for both segmentations, the AUC and accuracy of the TBRmax were relatively high, >0.85. Twenty-two (from segmentation A) and thirty-five (from segmentation B) of 75 radiomic features fulfilled the criteria: P-value < 0.00061 (after Bonferroni correction), AUC >0.5, and accuracy >0.7. Principal Component Analysis (PCA) was conducted, with five components leading to cumulative variance higher than 90%. Ten machine learning classifiers were then tested and trained. Most of them had AUCs and accuracies ≥0.8. For segmentation A, the AUCs and accuracies of all classifiers are >0.9, but k-neighbors and neural network classifiers were the highest (=1). For segmentation B, there are four classifiers with AUCs and accuracies ≥0.8. However, the gaussian process classifier indicated the highest AUC and accuracy (0.9 and 0.8, respectively).

Conclusions

Radiomic analysis of the specific PET data was not proven to be necessary for the detection of CS. However, building an automated procedure will help to accelerate the analysis and potentially lead to more reproducible findings across different scanners and imaging centers and consequently improve standardization procedures that are important for clinical trials and development of more robust diagnostic protocols.
Bullous Pemphigoid Associated With COVID-19 Vaccines: An Italian Multicentre Study
Authors: Maronese Carlo Alberto , Caproni Marzia , Moltrasio Chiara , Genovese Giovanni , Vezzoli Pamela , Sena Paolo , Previtali Giulia , Cozzani Emanuele , Gasparini Giulia , Parodi Aurora , Atzori Laura , Antiga Emiliano , Maglie Roberto , Moro Francesco , Mariotti Elena Biancamaria , Corrà Alberto , Pallotta Sabatino , Didona Biagio , Marzano Angelo Valerio , Di Zenzo Giovanni
Published: February 2022

Bullous pemphigoid (BP) is an autoimmune bullous disease caused by circulating autoantibodies toward the hemidesmosomal antigens BP180 and BP230. Cases of BP have been described following vaccinations against tetanus, poliomyelitis, diphtheria, influenza, pneumococcus, meningococcus, hepatitis B and rabies. The putative mechanism by which COVID-19-vaccines may induce BP has not been clarified. An Italian multicentre study was conducted to collect clinical, histopathological and immunopathological data of patients with BP associated with COVID-19-vaccines. Twenty-one cases were collected, including 9 females and 12 males (M/F = 1.3) with a median age at diagnosis of 82 years. Seventeen patients received the COMIRNATY Pfizer-BioNTech vaccine, two the Moderna mRNA-1273 vaccine, one the ChAdOx1/nCoV-19-AstraZeneca/ Vaxzevria vaccine and one received the first dose with the ChAdOx1/nCoV-19-AstraZeneca/Vaxzevria vaccine and the second dose with the COMIRNATY Pfizer-BioNTech vaccine. Median latency time between the first dose of anti-SARS-CoV-2 vaccine and the onset of cutaneous manifestations was 27 days. Median BPDAI at onset was 42. Eleven out of seventeen patients (65%) had positive titres for anti-BP180 antibodies with a median value of 106.3 U/mL on ELISA; in contrast, only five out of seventeen (29%) were positive for anti-BP230 antibodies, with a median of 35.3 U/mL. In conclusion, in terms of mean age, disease severity at diagnosis and clinical phenotype vaccine-associated BP patients seem to be similar to idiopathic BP with an overall benign course with appropriate treatment. On the other hand, the slight male predominance and the reduced humoral response to BP230 represent peculiar features of this subset of patients.