bluuebunny/crossref_metadata_2025 huggingface dataset:
A twenty-year journey exploring coumarin-based derivatives as bioactive molecules
Authors: Pisani Leonardo , Catto Marco , Muncipinto Giovanni , Nicolotti Orazio , Carrieri Antonio , Rullo Mariagrazia , Stefanachi Angela , Leonetti Francesco , Altomare Cosimo
Published: October 2022

The coumarin core (i.e., 1-benzopyran-2 (2H)-one) is a structural motif highly recurrent in both natural products and bioactive molecules. Indeed, depending on the substituents and branching positions around the byciclic core, coumarin-containing compounds have shown diverse pharmacological activities, ranging from anticoagulant activities to anti-inflammatory, antimicrobial, anti-HIV and antitumor effects. In this survey, we have reported the main scientific results of the 20-years investigation on the coumarin core, exploited by the research group headed by Prof. Angelo Carotti (Bari, Italy) either as a scaffold or a pharmacophore moiety in designing novel biologically active small molecules.
Enhanced thermal and photo-stability of a para-substituted dicumyl ketone intercalated in a layered double hydroxide
Authors: Costa Ana L. , Monteiro Rodrigo P. , Nunes Barradas Paulo D. , Ferreira Simone C. R. , Cunha Carla , Gomes Ana C. , Gonçalves Isabel S. , Seixas de Melo J. Sérgio , Pillinger Martyn
Published: October 2022

A ketodiacid, 4,4′-dicarboxylate-dicumyl ketone (3), has been intercalated into a Zn, Al layered double hydroxide (LDH) by a coprecipitation synthesis strategy. The structure and chemical composition of the resultant hybrid material (LDH-KDA3) were characterized by powder X-ray diffraction (PXRD), FT-IR, FT-Raman and solid-state 13C{1H} NMR spectroscopies, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), thermogravimetric analysis (TGA), and elemental analysis (CHN). PXRD showed that the dicarboxylate guest molecules assembled into a monolayer to give a basal spacing of 18.0 Å. TGA revealed that the organic guest starts to decompose at a significantly higher temperature (ca. 330°C) than that determined for the free ketodiacid (ca. 230°C). Photochemical experiments were performed to probe the photoreactivity of the ketoacid in the crystalline state, in solution, and as a guest embedded within the photochemically-inert LDH host. Irradiation of the bulk crystalline ketoacid results in photodecarbonylation and the exclusive formation of the radical-radical combination product. Solution studies employing the standard myoglobin (Mb) assay for quantification of released CO showed that the ketoacid behaved as a photoactivatable CO-releasing molecule for transfer of CO to heme proteins, although the photoreactivity was low. No photoinduced release of CO was found for the LDH system, indicating that molecular confinement enhanced the photo-stability of the hexasubstituted ketone. To better understand the behavior of 3 under irradiation, a more comprehensive study, involving excitation of this compound in DMSO-d6 followed by 1H NMR, UV-Vis and fluorescence spectroscopy, was undertaken and further rationalized with the help of time-dependent density functional theory (TDDFT) electronic quantum calculations. The photophysical study showed the formation of a less emissive compound (or compounds). New signals in the 1H NMR spectra were attributed to photoproducts obtained via Norrish type I α-cleavage decarbonylation and Norrish type II (followed by CH3 migration) pathways. TDDFT calculations predicted that the formation of a keto-enol system (via a CH3 migration step in the type II pathway) was highly favorable and consistent with the observed spectral data.
In silico immunogenicity assessment for sequences containing unnatural amino acids: A method using existing in silico algorithm infrastructure and a vision for future enhancements
Authors: Mattei Aimee E. , Gutierrez Andres H. , Martin William D. , Terry Frances E. , Roberts Brian J. , Rosenberg Amy S. , De Groot Anne S.
Published: October 2022

Thein silicoprediction of T cell epitopes within any peptide or biologic drug candidate serves as an important first step for assessing immunogenicity. T cell epitopes bind human leukocyte antigen (HLA) by a well-characterized interaction of amino acid side chains and pockets in the HLA molecule binding groove. Immunoinformatics tools, such as the EpiMatrix algorithm, have been developed to screen natural amino acid sequences for peptides that will bind HLA. In addition to commonly occurring in synthetic peptide impurities, unnatural amino acids (UAA) are also often incorporated into novel peptide therapeutics to improve properties of the drug product. To date, the HLA binding properties of peptides containing UAA are not accurately estimated by most algorithms. Both scenarios warrant the need for enhanced predictive tools. The authors developed anin silicomethod for modeling the impact of a given UAA on a peptide’s likelihood of binding to HLA and, by extension, its immunogenic potential.In silicoassessment of immunogenic potential allows for risk-based selection of best candidate peptides in further confirmatoryin vitro, ex vivo,andin vivoassays, thereby reducing the overall cost of immunogenicity evaluation. Examples demonstratingin silicoimmunogenicity prediction for product impurities that are commonly found in formulations of the generic peptides teriparatide and semaglutide are provided. Next, this article discusses how HLA binding studies can be used to estimate the binding potentials of commonly encountered UAA and “correct”in silicoestimates of binding based on their naturally occurring counterparts. As demonstrated here, thesein vitrobinding studies are usually performed with known ligands which have been modified to contain UAA in HLA anchor positions. An example using D-amino acids in relative binding position 1 (P1) of the PADRE peptide is presented. As more HLA binding data become available, new predictive models allowing for the direct estimation of HLA binding for peptides containing UAA can be established.
Environmental education and digital solutions: An analysis of the Lebanese context’s existing and possible digital actions
Authors: Khalifé Mona , Chaker Rawad , Gasparovic Slaven
Published: October 2022

One of the main purposes of environmental education is to tackle the youth belief system and raise specific concerns linked to ecology and sustainability. Nonetheless, the educational approach to ecological concerns is partly about the methods used to reach effective results. The advancement of technologies and the rapid spread of social media have accelerated the use of online means of communication. While technology and digital tools have proven effective for educational purposes, it becomes necessary to examine the relationship between technology and environmental education, particularly in the Lebanese context. This position paper provides a review of studies on education, the environment, and digital tools, more specifically, studies conducted in Lebanon. It particularly focuses on the engagement of educational institutions and social incentives to raise environmental awareness and develop ecological behaviors in Lebanon. The results of this study will help stakeholders and researchers for future implementation of digital solutions in the Lebanese context toward a greener agenda.
Proteomics analysis of cancer tissues identifies IGF2R as a potential therapeutic target in laryngeal carcinoma
Authors: Liu Bing , Hu Yuqiang , Wan Lixia , Wang Luan , Cheng Liangjun , Sun Hai , Liu Yaran , Wu Di , Zhu Jiefei , Hong Xiu , Li Yang , Zhou Chong
Published: October 2022

Background

Laryngeal cancer (LC) is a prevalent head and neck malignancy; however, the essential pathophysiological mechanism underlying its tumorigenesis and progression remains elusive. Due to the perduring scarcity of effective targeted drugs for laryngeal cancer, insights into the disease’s pathophysiological mechanisms would substantially impact the treatment landscape of laryngeal cancer.

Methods

To ensure quality consistency, 10 tumor and 9 non-tumor samples underwent proteomic analysis on a single mass spectrometer using a label-free technique. Subsequently, gene expression variations between laryngeal squamous cell carcinoma and normal tissues were analyzed using The Cancer Genome Atlas (TCGA) database. Immunohistochemical expressions of insulin-like growth factor 2 receptor (IGF2R), fibronectin (FN), vimentin, and α-smooth muscle actin (SMA) in LC tissues and normal tissues were determined.

Results

In the tumor group, significant variations were detected for 433 upregulated and 61 downregulated proteins. Moreover, the heatmap revealed that the expressions of RNA translation-related proteins and proteins involved in RNA metabolism, such as IGF2R, tenascin C (TNC), periostin (POSTN), proteasome 26S subunit ATPase 4 (PSMC4), serpin family A member 3 (SERPINA3), heat shock protein family B (small) member 6 (HSPB6), osteoglycin (OGN), chaperonin containing TCP1 subunit 6A (CCT6A), and chaperonin containing TCP1 subunit 6B (CCT6B), were prominently elevated in the tumor group. Nonsense-mediated RNA decay (NMD), RNA translation, and protein stability were significantly altered in LC tumors. IGF2R was remarkably upregulated in LC tumors. In the TCGA database, the IGF2R mRNA level was significantly upregulated in LSCC tissues. Additionally, IGF2R mRNA expression was lowest in clinical grade 1 samples, with no significant difference between grades 2 and 3. In LSCC patients, a significant positive correlation between IGF2R expression and the stromal score was detected using the ESTIMATE algorithm to estimate the immune score, stromal score, and tumor purity in the tumor microenvironment. Lastly, immunohistochemical analysis revealed that IGF2R is overexpressed in LC.

Conclusion

These results demonstrate the vital role of IGF2R in LC carcinogenesis and progression and may facilitate the identification of new therapeutic targets for the prevention and treatment of LC.
Obesity paradox and aging: Visceral Adiposity Index and all-cause mortality in older individuals: A prospective cohort study
Authors: Wang Lei , Yi Zhong
Published: October 2022

Background

The relationship between body mass index (BMI) and mortality in older adults diminished. It is necessary to examine other factors that may accurately predict mortality in older adults. The visceral adiposity index (VAI) is an uncomplicated marker specific to the gender that incorporates anthropometric data and lipid profiles. VAI has been proposed as a marker of visceral adipose tissue dysfunction and of the related cardiometabolic risk. The aim of this study was to evaluate the link of VAI with all-cause mortality among the elderly.

Methods

The present prospective cohort study included data from 1999 to 2014 provided by the National Health and Nutrition Examination Survey (NHANES) in the United States. NHANES participants at or above the age of 65 were included. Data collection was carried out by taking face-to-face interviews, mobile-physical examinations, and lab tests. From the start of the survey to the end of December 2015, mortality-related follow-up statistics are available. The shape of the link between VAI and all-cause mortality was investigated using a restricted cubic spline model. Univariate- and multivariate-adjusted Cox proportional hazard models were estimated for VAI, and the results were presented as regression coefficients and 95% confidence intervals (CI).

Results

The 82,091 NHANES participants represented 442.2 million non-institutionalized residents of the United States. A total of 11,173 older individuals (representing 23.3 million; aged 73.4 ± 5.8 years; 56.3% women, 82.7% non-Hispanic Whites, 6.8% non-Hispanic Blacks, and 3.3% Mexican Americans) were included in the study. During the 80-month follow-up period, 4466 fatalities were reported, including 825 deaths from cancer, 867 from heart disease, and 211 from cerebrovascular disease. The restricted cubic spline model demonstrated a robust J-shaped link between VAI and all-cause mortality, revealing a significant decrease in risk within the lower range of VAI, which attained the lowest risk close to 1.7. With VAI greater than 1.7, the risk of mortality increased with the increase of VAI (P for non-linearity = 0.025). In the multivariate-adjusted model, the risk of all-cause mortality was 0.73 (0.56-0.97) and 1.05 (1.01-1.09) in participants with VAI less than 1.7 and VAI greater than or equal to 1.7, respectively.

Conclusion

This investigation is a population-based cohort study with high sample sizes and a long-term in older individuals follow-up that showed a J-shaped link between VAI levels and all-cause mortality. Understanding the independent roles of VAI in the relationship between BMI and mortality is crucial to understanding the obesity paradox phenomenon.
Sediment oxygen demand rate in a flow regulated lagoon (Venice, Italy)
Authors: Leoni Simone , Dominik Janusz , Cassin Daniele , Manfè Giorgia , Tagliapietra Davide , Acri Francesco , Zonta Roberto
Published: October 2022

From October 2020, the MOSE system went into operation in the three inlets to protect Venice and its lagoon from flooding caused by high tide events in the Adriatic Sea. While the MOSE increases the prospect of physical defense, how will the new status of a regulated lagoon affect the functioning of the waterbody? In particular, the dissolved oxygen balance in the water column can be affected by the expected increase in water residence times. Sediments play an important role in oxygen consumption in the water column and for this reason sediment oxygen demand (SOD) was studied in situ for the first time, in 16 sites at four lagoon areas. SOD rate, measured throughout 2021 with specially made benthic chambers, varied in the different areas and with seasons (from 0.63 to 24.00 g m−2 d−1), with higher values at the more confined sites and significantly lower values in those belonging to the open lagoon. Based on SOD rate, consumption times of dissolved oxygen in the water column were estimated at the MOSE closures, from saturation values to hypoxia and in the temperature range of 11.7–33.3°C. Especially in the confined sites, sediments can exert an important depleting action on dissolved oxygen already at water temperatures above 20°C, which are not particularly high for the lagoon.
Inappropriateness of space-for-time and variability-for-time approaches to infer future dryland productivity changes
Authors: Zhan Weiwei , Lian Xu , Liu Jiangong , Gentine Pierre
Published: October 2022

Drylands are among the most susceptible ecosystems to global climate change. It has been suggested that a future surface drying trend would largely reduce gross primary productivity (GPP) in drylands, given that water is the dominant factor controlling the spatial distributions (i.e., space-for-time analogy) and inter-annual fluctuations (i.e., variability-for-time analogy) of dryland GPP. However, whether these approaches using spatial and inter-annual diagnostics are valid to infer long-term dryland GPP remains unknown. In this study, we evaluate whether space-for-time and variability-for-time approaches, which are based on the empirical scaling between GPP and dryness, are able to capture future changes in dryland GPP as simulated by 18 Earth system models (ESMs). Using observational data during 1958–2014, we identify a strong coupling between dryland GPP and the annual aridity index (AI, the ratio of precipitation to potential evapotranspiration) over both spatial and inter-annual scales. This GPP-AI scaling is used to predict future GPP changes throughout the 21st Century based on the future AI changes projected by ESMs. The space-for-time, and variability-for-time approaches predict an overall decrease of dryland GPP by -23.66 ± 10.93 (mean ±1 standard deviation) and -3.86 ± 2.22 gC m−2 yr−1, respectively, in response to future surface drying, however, the ESM projections exhibit a strong dryland GPP increase (+81.42 ± 36.82 gC m−2 yr−1). This inconsistency is because the space- and variability-based approaches, which rely on the spatial or short-term GPP-AI relationships, cannot capture the slowly-evolving but key determinant of dryland GPP changes over multi-decadal or longer timescales, which, in ESMs, is the ecosystem physiological response to rising CO2. Our study questions the validity of “the drier the less productive” hypothesis rooted in the space-for-time and variability-for-time theories, and the implementation of such theories to constrain future ecosystem changes.
Environmental collaboration and blockchain technology adoption in green medical supply chain management during the COVID-19 pandemic
Authors: Bai Yang , Song Wenqi
Published: October 2022

In recent years, the resource shortage and environmental degradation have made enterprises and governments increasingly aware of the importance of sustainable development. Meanwhile, the COVID-19 pandemic has also increased the shortage of medical materials. Based on this, we investigate the tradeoff of the critical medical devices refurbishing strategies when blockchain is used in three different structures: manufacturer refurbishing, retailer refurbishing, and third-party refurbishing in the two-period refurbishing strategies. We find that the manufacturer always benefits from the adoption of blockchain technology strategy in the manufacturer refurbishing scenario. However, for the retailer in the second period, the retailer references the adoption of blockchain only if the willingness to pay is extremely high. Additionally, when the medical supply chain channel member chooses retailer refurbishing or third-party strategy, the manufacturer always likes to use blockchain technology. That’s because it will help the information value spillover from the retailer to the manufacturer, which leads the manufacturer to get more profits and a lower profit for the retailer. However, in the retailer refurbishing or third-part strategy, the whole channel profits are higher than not adopting blockchain technology. Therefore, business managers can be based on our research to achieve profits Pareto-improving.
Interactive effects of benthivorous fish disturbance and ammonium loading on two submersed macrophytes of contrasting growth forms based on a mesocosm study
Authors: Yu Qing , Wang Haijun , Liu Miao , Xu Chao , Ma Yu , Guo Weihua , Jeppesen Erik
Published: October 2022

Benthivorous fish disturbance and nitrogen loading are two important factors that influence the community structure of submersed macrophytes, but their interactive effect is not well elucidated. We conducted an outdoor mesocosm experiment to examine the individual and combined effects of these two factors on the growth of two submersed macrophytes of different growth forms, i.e., the rosette-forming Vallisneria natans and the canopy-forming Myriophyllum spicatum. The treatments involved two levels of fish (Carassius auratus) disturbance crossed with two levels (0 and 12 g NH4Cl per month) of ammonium (NH4+-N) loading. For M. spicatum, we found that maximum height (MH) was reduced by 30.7%, 26.4%, and 51.0% in fish addition alone (F) and nitrogen addition treatments (N, F + N), respectively, compared with the control (C) treatment. The density of M. spicatum declined by 20%, 62% and 68.8% in the F, N and F + N treatment. The above-ground biomass (AGB) of M. spicatum respectively reduced by 56.7%, 94%, and 96.5% in the F, N and F + N treatments, and the roots/shoots ratio (R/S) increased by 114%, and 176% in N and N + F treatments, respectively. Regarding V. natans, only the MH in the N treatment was reduced (71.9%), and the density exhibited a reduction of 59.1% and 64.5% in the N and F + N treatments, respectively. The AGB of V. natans was significantly lower in the N (90.3%) and N + F (78.4%) treatments compared with the C treatment, while increased by 60.3% in F treatment. The R/S of V. natans increased by 227%, and 74.4% in the N and F + N treatments compared with the C treatment. The interactive effect of fish disturbance and high N on MH and AGB of V. natans and density of M. spicatum were antagonistic. However, the interactive effect on density and BGB of V. natans and AGB of M. spicatum were negatively synergistic. Moreover, fish activity significantly increased the concentration of total suspended solids (TSS) in the water, while total nitrogen (TN), ammonium, total phosphorus (TP), light, pH and salinity were unaffected. When fish and nitrogen were combined, TN, TP, TSS and salinity increased significantly, while pH decreased. Our study reveals that the interactive effects of fish disturbance and high N are synergistic and/or antagonistic, suggesting that the same stressor interaction may vary from synergistic to antagonistic depending on the response variables and growth forms of the macrophytes examined. Our study contributes to the understanding of how different factors can interact with each other and affect submersed macrophytes in aquatic ecosystems. This is timely and relevant knowledge, considering the range of multiple stressors involved in the decline of aquatic ecosystems worldwide at present.
Role of oil price volatility, energy efficiency, and financial stability on sustainable energy production
Authors: Du Xinke , Ouyang Tianzhi , Shi Guanqing , Deng Lingxiao , Gul Rubab
Published: October 2022

In the COVID-19 crisis, many economies suffered from sustainable energy production. The emergence of the COVID-19 crises, extreme volatility in oil prices, limited energy efficiency in energy systems, and weak form of financial stability were the key reasons for it. However, considering these issues, a recent study aims to analyze them. ASEAN countries’ energy efficiency and crude oil price volatility are examined as a solution to how financial conditions might be utilized to handle energy efficiency issues and crude oil price volatility. Extending it, the study aims to identify the influence of financial stability on crude oil price volatility and energy efficiency issues. To do this, GMM is used. According to the study’s findings, environmental mitigation was determined to be important at 18%, and financial stability and carbon risk significant at 21%. Global warming concerns have been raised due to the ASEAN nations’ 19.5% link between financial stability and emissions drift. A country’s financial stability is necessary for implementing green economic recovery strategies, among the most widely accepted measures to reduce energy efficiency and guarantee long-term financial potential on the national scale. The study on green economic growth also provides the associated stakeholders with sensible policy consequences on this importance.
Study on the change monitoring of typical estuarine wetland and its effect on ecological factors in Bohai Rim region, China
Authors: Li Xiaodong , Liu Ge
Published: October 2022

Estuarine wetlands provide an especially ecological home for various flora and fauna, with fragile ecological structures and functions easily affected by the external disturbances of both anthropogenic and natural activities. Recently, wetlands (such as water and marsh) of the Bohai Rim region have been, and continue to be, lost or altered under the influence of both local urbanization and economic development. There is an increasing need for crucial essential wetland change detection as one of the most critical works for relevant research. The paper’s objective focuses on detecting the annual and interannual changes at a large spatial scale for understanding the mainly changed cover type of estuarine wetlands and measuring its impact on coastline ecological factors. Two typical study areas, including the Shuangtai Estuary wetland and Yellow River Delta, are selected for the assessment of changes to wetlands in Bohai Rim region, China. Additionally, Landsat TM/OLI images between 2005 and 2015, as the standard years for change detection, are used as the experimental data resources. To realize the rapid and automatic detection of change to wetland at a larger scale, a method is constructed to extract the change information from satellite images integrating the dynamic ratio and the max-difference algorithm. Based on the remote sensing base ecological index (RSEI), three ecological indexes include water body index, vegetation index, and soil index, calculated the annual maximum difference and the inter-annual dynamic rate of change to wetland. Furthermore, wetland changes are graded and evaluated five significant levels from the annual yearly and interannual scales. Results show several significant findings: (1) from 2005 to 2015, the ecological change with an overall improvement trend was in two monitoring areas of Bohai Rim region. The annual change of ecological factors in the positively changed area (improve) was more and more significant, with the mainly converted type of the expansion of paddy field. In the negatively changing area (degrade), annual ecological change was more and more insignificant, with the main expansion of bare land. (2) The significantly increased accumulation of normalized difference vegetation index (NDVI) was the main ecological change feature of the Shuangtai Estuary wetland. The significant regional changes in the Yellow River Delta were the interaction of ecological factors, included modified normalized difference water index (MNDWI), NDVI, and normalized difference soil index (NDSI). The study on the change detection of wetland and its influence on ecological factors in Bohai Rim region between two different periods enriches remote sensing monitoring technology of change to wetlands, betters quantitative evaluation of ecological factors, and provides updated data support for the wetland natural resource inventory at the various scales.
Genome-wide identification and analysis of the cytokinin oxidase/dehydrogenase (ckx) gene family in finger millet (Eleusine coracana)
Authors: Blume Rostyslav , Yemets Alla , Korkhovyi Vitaliy , Radchuk Volodymyr , Rakhmetov Dzhamal , Blume Yaroslav
Published: October 2022

Cytokinin dehydrogenase/oxidase (CKX) enzymes play a key role in regulating cytokinin (CK) levels in plants by degrading the excess of this phytohormone. CKX genes have proven an attractive target for genetic engineering, as their silencing boosts cytokinin accumulation in various tissues, thereby contributing to a rapid increase in biomass and overall plant productivity. We previously reported a similar effect in finger millet (Eleusine coracana) somaclonal lines, caused by downregulation of EcCKX1 and EcCKX2. However, the CKX gene family has numerous representatives, especially in allopolyploid crop species, such as E. coracana. To date, the entire CKX gene family of E. coracana and its related species has not been characterized. We offer here, for the first time, a comprehensive genome-wide identification and analysis of a panel of CKX genes in finger millet. The functional genes identified in the E. coracana genome are compared with the previously-identified genes, EcCKX1 and EcCKX2. Exon-intron structural analysis and motif analysis of FAD- and CK-binding domains are performed. The phylogeny of the EcCKX genes suggests that CKX genes are divided into several distinct groups, corresponding to certain isotypes. Finally, the phenotypic effect of EcCKX1 and EcCKX2 in partially silencing the SE7 somaclonal line is investigated, showing that lines deficient in CKX-expression demonstrate increased grain yield and greater bushiness, enhanced biomass accumulation, and a shorter vegetation cycle.
Characterization of fatty acid metabolism-related lncRNAs in lung adenocarcinoma identifying potential novel prognostic targets
Authors: Liu Yang , Zhang Xingshu , Cheng Xuechao , Luo Qian , Yu Mingyang , Long Kaijun , Qu Wendong , Tang Yang , Gong Ming , Liang Lubiao , Ke Xixian , Song Yongxiang
Published: October 2022

Lung adenocarcinoma (LUAD), a malignant respiratory tumor with an extremely poor prognosis, has troubled the medical community all over the world. According to recent studies, fatty acid metabolism (FAM) and long non-coding RNAs (lncRNAs) regulation have shown exciting results in tumor therapy. In this study, the original LUAD patient data was obtained from the TCGA database, and 12 FAM-related lncRNAs (AL390755.1, AC105020.6, TMPO-AS1, AC016737.2, AC127070.2, LINC01281, AL589986.2, GAS6-DT, AC078993.1, LINC02198, AC007032.1, and AL021026.1) that were highly related to the progression of LUAD were finally identified through bioinformatics analysis, and a risk score model for clinical reference was constructed. The window explores the immunology and molecular mechanism of LUAD, aiming to shed the hoping light on LUAD treatment.
Case Report: De novo DDX3X mutation caused intellectual disability in a female with skewed X-chromosome inactivation on the mutant allele
Authors: Sun Yixi , Qian Yangwen , Sun Hai-Xi , Chen Min , Luo Yuqin , Xu Xiaojing , Yan Kai , Wang Liya , Hu Junjie , Dong Minyue
Published: October 2022

Skewed XCI plays an important role in the phenotypic heterogeneities of many X-linked disorders, even involving in diseases caused by XCI-escaping genes. DDX3X-related intellectual disability is more common in females and less common in males, who usually inherit from unaffected heterozygous mothers. As an X inactivation (XCI) escaping gene, the role of skewed XCI in the phenotype of DDX3X mutant female is unknown. Here we reported a DDX3X: c.694_711dup18 de novo heterozygous mutation in a female with intellectual disability on the maternal X chromosome on the basis of SNPs detected by PCR-sanger sequencing. AR assay revealed that the maternal mutant X chromosome was extremely inactivated in the proband. Using RNA sequencing and whole-exome sequencing, we quantified allelic read counts and allele-specific expression, and confirmed that the mutant X chromosome was inactive. Further, we verified that the mutant DDX3X allele had a lower expression level by RNA sequencing and RT-PCR, and the normal and mutated DDX3X expression accounted for respectively 70% and 30% of total. In conclusion, we found a symptomatic female with extreme skewing XCI in the DDX3X mutant allele. It was discovered that XCI in the mutant allele was insufficient to reverse the phenotype of DDX3X-related neurodevelopmental disorder. It contributed to a better understanding of the role of skewed XCI in phenotypic differences, which can aid in the genetic counseling and prenatal diagnosis of disorders in females with DDX3X defects.
Advancing maternal and perinatal health in low- and middle-income countries: A multi-country review of policies and programmes
Authors: Syed Uzma , Kinney Mary V. , Pestvenidze Ekaterine , Vandy Alren O. , Slowing Karin , Kayita Janet , Lewis Alyona F. , Kenneh Sartie , Moses Francis L. , Aabroo Atiya , Thom Ellen , Uzma Qudsia , Zaka Nabila , Rattana Kim , Cheang Kannitha , Kanke Robert M. , Kini Brigitte , Epondo Jean-Bertin E. , Moran Allisyn C.
Published: October 2022

The Sustainable Development Goals prioritize maternal mortality reduction, with a global average target of < 70 per 100,000 live births by 2030. Current pace of reduction is far short of what is needed to achieve the global target. It is estimated that globally there are 300,000 maternal deaths, 2.4 million newborn deaths and 2 million stillbirths annually. Majority of these deaths occur in low-and-middle-income countries. Global initiatives like, Ending Preventable Maternal Mortality (EPMM) and Every Newborn Action Plan (ENAP), have outlined the broad strategies for maternal and newborn health programmes. A set of coverage targets and ten milestones were launched to support low-and-middle-income countries in accelerating progress in improving maternal, perinatal and newborn health and wellbeing. WHO, UNICEF and UNFPA, undertook a scoping review to understand how country strategies evolved in different contexts over the past two decades to improve maternal survival and wellbeing, and how countries in similar settings could accelerate progress considering the changing epidemiology and demography. Case studies were conducted to inform countries in similar settings and various global initiatives. Six countries were selected based on standard criteria—Cambodia, Democratic Republic of the Congo, Georgia, Guatemala, Pakistan and Sierra Leone representing different stages of the obstetric transition. A conceptual framework, encapsulating the interrelated factors impacting maternal health outcomes, was used to organize data collection and analysis. While all six countries made remarkable progress in improving maternal and perinatal health, the pace of progress and the factors influencing the successes and challenges varied across the countries. The context, opportunities and challenges varied from country to country. Two strategic directions were identified for next steps including the need to implement and evaluate innovative service delivery models using an updated obstetric transition as an organizing framework and expanding our vision to address equity and well-being.
SOT101 induces NK cell cytotoxicity and potentiates antibody-dependent cell cytotoxicity and anti-tumor activity
Authors: Antosova Zuzana , Podzimkova Nada , Tomala Jakub , Augustynkova Katerina , Sajnerova Katerina , Nedvedova Eva , Sirova Milada , de Martynoff Guy , Bechard David , Moebius Ulrich , Kovar Marek , Spisek Radek , Adkins Irena
Published: October 2022

SOT101 is a superagonist fusion protein of interleukin (IL)-15 and the IL-15 receptor α (IL-15Rα) sushi+ domain, representing a promising clinical candidate for the treatment of cancer. SOT101 among other immune cells specifically stimulates natural killer (NK) cells and memory CD8+T cells with no significant expansion or activation of the regulatory T cell compartment. In this study, we showed that SOT101 induced expression of cytotoxic receptors NKp30, DNAM-1 and NKG2D on human NK cells. SOT101 stimulated dose-dependent proliferation and the relative expansion of both major subsets of human NK cells, CD56brightCD16-and CD56dimCD16+, and these displayed an enhanced cytotoxicityin vitro. Using human PBMCs and isolated NK cells, we showed that SOT101 added concomitantly or used for immune cell pre-stimulation potentiated clinically approved monoclonal antibodies Cetuximab, Daratumumab and Obinutuzumab in killing of tumor cellsin vitro. The anti-tumor efficacy of SOT101 in combination with Daratumumab was assessed in a solid multiple myeloma xenograft in CB17 SCID mouse model testing several combination schedules of administration in the early and late therapeutic setting of established tumorsin vivo. SOT101 and Daratumumab monotherapies decreased with various efficacy tumor growthin vivoin dependence on the advancement of the tumor development. The combination of both drugs showed the strongest anti-tumor efficacy. Specifically, the sequencing of both drugs did not matter in the early therapeutic setting where a complete tumor regression was observed in all animals. In the late therapeutic treatment of established tumors Daratumumab followed by SOT101 administration or a concomitant administration of both drugs showed a significant anti-tumor efficacy over the respective monotherapies. These results suggest that SOT101 might significantly augment the anti-tumor activity of therapeutic antibodies by increasing NK cell-mediated activity in patients. These results support the evaluation of SOT101 in combination with Daratumumab in clinical studies and present a rationale for an optimal clinical dosing schedule selection.
Nitrogen deposition may increase litter accumulative CO2 release in a subtropical estuarine marsh
Authors: Hu Weifang , Zeng Congsheng , Tong Chuan , Li Guoliang , Lan Xue , Zhou Jiacong , Zhang Meiying , Chen Yuehmin , Zhang Linhai
Published: October 2022

Microbial evolution-mediated CO2 from litter has aroused widespread concern, and knowing the factors controlling litter-derived CO2 is important when considering the effects of accumulative CO2 release from litter on the global greenhouse. We conducted a short-term N addition (6, 16, and 24 g N m‒2 yr‒1) experiment in Cyperus malaccensis var. brevifolius (shichito matgrass) litter decomosition. Phospholipid fatty acid (PLFA) method and enzyme method were used to analysis litter microbial community composition and enzymatic activity. During a 220-day decomposition period, there was little effect of the N amendments on litter CO2 evolution rates (9.97‒307.54 μg C g−1 h−1) with a notable exception regarding the increase of the high-N treatment at day 20. The accumulative CO2 release significantly increased after N addition in the medium and late phases. The facilitation effect on accumulative CO2 release by N amendments was more and more obvious over the decomposition time, especially for the low- and intermediate-N treatments. At the end of our experiment, compared with the control treatment, accumulative CO2 release increased 69.75%, 76.62%, and 39.93% for low-, intermediate-, and high-N treatments, respectively. These observations highlight that N deposition could cause high losses of litter C as CO2.
The potential effects of COVID-19 lockdown and the following restrictions on the status of eight target stocks in the Adriatic Sea
Authors: Scarcella Giuseppe , Angelini Silvia , Armelloni Enrico Nicola , Costantini Ilaria , De Felice Andrea , Guicciardi Stefano , Leonori Iole , Masnadi Francesco , Scanu Martina , Coro Gianpaolo
Published: October 2022

The COVID-19 pandemic had major impacts on the seafood supply chain, also reducing fishing activity. It is worth asking if the fish stocks in the Mediterranean Sea, which in most cases have been in overfishing conditions for many years, may have benefitted from the reduction in the fishing pressure. The present work is the first attempt to make a quantitative evaluation of the fishing effort reduction due to the COVID-19 pandemic and, consequently, its impact on Mediterranean fish stocks, focusing on Adriatic Sea subareas. Eight commercially exploited target stocks (common sole, common cuttlefish, spottail mantis shrimp, European hake, red mullet, anchovy, sardine, and deepwater pink shrimp) were evaluated with a surplus production model, separately fitting the data for each stock until 2019 and until 2020. Results for the 2019 and 2020 models in terms of biomass and fishing mortality were statistically compared with a bootstrap resampling technique to assess their statistical difference. Most of the stocks showed a small but significant improvement in terms of both biomass at sea and reduction in fishing mortality, except cuttlefish and pink shrimp, which showed a reduction in biomass at sea and an increase in fishing mortality (only for common cuttlefish). After reviewing the potential co-occurrence of environmental and management-related factors, we concluded that only in the case of the common sole can an effective biomass improvement related to the pandemic restrictions be detected, because it is the target of the only fishing fleet whose activity remained far lower than expectations for the entire 2020.
Promising CoSe2-CNT composite catalyst for efficient photoelectrochemical hydrogen evolution reaction
Authors: Pi Zhi-Gang , Ye Hongfeng , Han Zuqi , Yu Peng , Yin Zhuoxun , Ma Xinzhi
Published: October 2022

CoSe2 is a typical transition metal chalcogenide and an hydrogen evolution reaction hydrogen evolution catalyst due to its efficient and inexpensive characteristics. In this work, CoSe2/CNT composite was synthesized through a one-step solvothermal method. Specifically, a current density of 10 mA cm−2 can be achieved under an overpotential of 163 mV, and the Tafel slope is 69.4 mV dec−1. The reasons for these excellent performances are: 1) the abundant catalytic active sites of CoSe2; 2) the high conductivity of CNTs; and 3) the synergistic effect between CoSe2 and CNTs; iv the solar irradiation excites electrons to join the reaction. This work proposes a new way to reasonably design the high-efficiency and low-cost transition metal chalcogenide hydrogen evolution catalysts.
A modified lower-order theory for FG beam with circular cross-section
Authors: Duan T. C. , Li X. Y. , Xiao Y. , Zhang L. , Chen C. , Li Z. J.
Published: October 2022

The modified uncoupled lower-order beam theory (LBT) based on the third-order shear deformation model was established for functionally graded (FG) beams with circular cross-section in this paper. Based on the shear stress free condition on the boundary of the circular cross-section, the bidirectional warping function of the axial displacement is mathematically derived for the first time. The power-law form in the radial direction is adopted to describe continuous variation of material properties. Generalized stresses are defined through the orthogonal form of the axial displacement and then expressed in the decoupling form, in which the shear correction factor and three relatively small coefficients are involved. The frame independent uncoupled equilibrium equations and the corresponding boundary conditions are obtained via the asymptotic principle of virtual work. The present LBT is validated through the pure bending of a Clamped-Clamped FG beam by comparing the obtained deflections with the published results. Accordingly, the effects of shear, warping and stress mitigation acting on the cross-section influenced by the power-law exponent have been described graphically and discussed.
Hepatic perfusion as a new predictor of prognosis and mortality in critical care patients with acute-on-chronic liver failure
Authors: Vogg Johannes , Maier-Stocker Constantin , Munker Stefan , Mehrl Alexander , Schlosser Sophie , Tews Hauke Christian , Gülow Karsten , Müller Martina , Schmid Stephan
Published: October 2022

Background and aims

Liver diseases are frequent causes of morbidity and mortality worldwide. Liver diseases can lead to cirrhosis, with the risk of acute-on-chronic liver failure (ACLF). For the detection of changes in hepatic hemodynamics, Doppler ultrasonography is a well-established method. We investigated hepatic hemodynamics via serial Doppler ultrasonography to determine the predictive value of changes in hepatic perfusion for the outcome in patients with severe liver diseases compared to established prognostic models such as the MELD (Model for End-Stage Liver Disease) or CLIF-C (Chronic Liver Failure-Consortium) ACLF score.

Methods

In this prospective cohort study, hepatic perfusion was quantified at baseline before the initiation of treatment and every third day by means of serial measurements of the hepatic artery resistance index (HARI) and the maximum portal vein velocity (PVv) using Doppler ultrasonography in 50 consecutive patients with severe liver diseases admitted to a medical intensive care unit (MICU). The recorded hemodynamic parameters were compared to the MELD score, and the CLIF-C ACLF score to analyze their utility for the prediction of the outcome of patients with severe liver diseases, liver cirrhosis, and ACLF.

Results

The changes (delta) obtained by serial measurements of the MELD score, HARI, and PVv were analyzed through scatter plots. Bivariate correlation analysis yielded a new positive linear correlation between the delta-HARI and the delta-MELD score (r = 0.469; p < 0.001). In addition, our data revealed a new negative linear correlation between delta-PVv and the delta-MELD score (r = −0.279, p = 0.001). The leading cause of MICU mortality was acute-on-chronic liver failure (ACLF). A subgroup analysis of patients with liver cirrhosis revealed a positive linear correlation between the delta-HARI and the delta-CLIF-C-ACLF score (r = 0.252, p = 0.005). Of clinical relevance, non-survivors of ACLF exhibited a significantly higher mean value for the delta-HARI (0.010 vs. −0.005; p = 0.015) and a lower mean value for the delta-PVv (−0.7 vs. 1.9 cm/s; p = 0.037) in comparison to survivors of ACLF.

Conclusion

This study shows the prognostic value of the assessment of hepatic perfusion in critical care patients with severe liver diseases by bedside Doppler ultrasound examination and its utility as an accurate predictor of the outcome in patients with ACLF. Increasing HARI and a decreasing PVv are predictors of an adverse outcome. Delta-HARI and delta-PVv are new biomarkers of prognosis and ACLF-related mortality in patients with liver diseases. Delta-HARI and delta-PVv may be helpful in guiding clinical decision-making, especially in catecholamine and fluid management.
Recent topics related to etiology and clinical manifestations of cutaneous arteritis
Authors: Ikeda Takaharu
Published: October 2022

Cutaneous polyarteritis nodosa (cPAN) was first reported by Lindberg in 1931. It has been recognized as a skin-limited vasculitis whose cutaneous histopathological features are indistinguishable from those of PAN. Cutaneous arteritis (CA) was defined as a form of single-organ vasculitis in the revised Chapel Hill Classification and was recognized as the same disease as cPAN. It became known that deficiency of adenosine deaminase 2 (DADA2) cases were included in cases that had been diagnosed with CA. Because of their similarity and differences in the treatment methods, DADA2 should be considered in CA cases, especially if they are diagnosed or developed in early childhood. Cutaneous arteritis may be classified as an immune complex-mediated vasculitis. It was reported that the pathogenesis of anti-lysosomal-associated membrane protein-2 (LAMP-2) antibodies and anti-phosphatidylserine-prothrombin complex (PS/PT) antibodies as good parameters in CA. The main skin manifestations include livedo racemosa, subcutaneous nodules, and ulcers. Although CA is recognized to have a benign clinical course, it has become known that it is easy to relapse. The existence of skin ulcers upon diagnosis or sensory neuropathies was suggested to be a predictor of poor prognosis. Cutaneous arteritis with them may need to be treated with more intensive therapies.
Clinical characteristics and risk factors for 90-day overall survival among 204 adult patients with secondary hemophagocytic lymphohistiocytosis: Experience from a single-center retrospective study
Authors: Wang Dongguang , Tong Xiang , Liu Sitong , Zhang Wentao , Wang Lian , Zhang Shijie , Zhang Tianli , Wang Qian , Fan Hong
Published: October 2022

Objectives

To describe the clinical characteristics of secondary hemophagocytic lymphohistiocytosis (HLH) among adult patients, investigate its risk factors for 90-day overall survival (OS) from diagnosis, and establish a new prognostic model applicable to adult patients with secondary HLH.

Methods

We conducted a retrospective cohort study of 204 adult patients with secondary HLH, between January 2010 and December 2020. All patients met at least five HLH-2004 criteria. Clinical features, laboratory results, treatments, and clinical outcomes of the patients were reviewed. Prognostic factors associated with 90-day overall survival from diagnosis were screened using Cox proportional hazard models.

Results

The most common trigger was malignancy (61.3%). Multivariate analysis showed that age, coagulopathy, levels of hemoglobin, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatinine, ferritin, and prothrombin time (PT) were independent prognostic factors for 90-day OS from the diagnosis of HLH. Based on the above risk factors, the patients were further divided into two groups: low-risk (≤4 risk factors) and high-risk (>4 risk factors), with overall 90-day survival rates of 82.7 and 28.1%, respectively (P < 0.001).

Conclusion

Patients with older age, coagulopathy, lower hemoglobin, and AST levels, elevated LDH, creatinine and ferritin levels, and prolonged PT tended to have a worse prognosis. Moreover, our prognostic model provides the possibility of forecasting the clinical outcome of adult secondary HLH patients, although a larger sample, multicenter, randomized controlled clinical study is needed to verify the accuracy of the prognostic model.