bluuebunny/crossref_metadata_2025 huggingface dataset:
A Perspective of the Comprehensive and Objective Assessment of Analytical Methods Including the Greenness and Functionality Criteria: Application to the Determination of Zinc in Aqueous Samples
Authors: Nowak Paweł Mateusz , Wietecha-Posłuszny Renata , Woźniakiewicz Michał , Woźniakiewicz Aneta , Król Małgorzata , Kozak Joanna , Wieczorek Marcin , Knihnicki Paweł , Paluch Justyna , Telk Anna , Mermer Karolina , Kochana Jolanta , Kościelniak Paweł , Pawliszyn Janusz
Published: October 2021

The recently proposed concept of White Analytical Chemistry (WAC), referring to the Red-Green-Blue color model, combines ecological aspects (green) with functionality (red and blue criteria), presenting the complete method as “white”. However, it is not easy to carry out an overall quantitative evaluation of the analytical method in line with the WAC idea in an objective manner. This paper outlines the perspective of the future development of such a possibility by attempting to answer selected questions about the evaluation process. Based on the study consisting in the evaluation of selected model methods by a group of 12 independent analysts, it was shown how well individual criteria are assessed, whether the variability of assessments by different people is comparable for each criterion, how large it is, and whether averaging the scores from different researchers can help to choose the best method more objectively.
Microbiota-Host-Irinotecan Axis: A New Insight Toward Irinotecan Chemotherapy
Authors: Yue Bei , Gao Ruiyang , Wang Zhengtao , Dou Wei
Published: October 2021

Irinotecan (CPT11) and its active metabolite ethyl-10-hydroxy-camptothecin (SN38) are broad-spectrum cytotoxic anticancer agents. Both cause cell death in rapidly dividing cells (e.g., cancer cells, epithelial cells, hematopoietic cells) and commensal bacteria. Therefore, CPT11 can induce a series of toxic side-effects, of which the most conspicuous is gastrointestinal toxicity (nausea, vomiting, diarrhea). Studies have shown that the gut microbiota modulates the host response to chemotherapeutic drugs. Targeting the gut microbiota influences the efficacy and toxicity of CPT11 chemotherapy through three key mechanisms: microbial ecocline, catalysis of microbial enzymes, and immunoregulation. This review summarizes and explores how the gut microbiota participates in CPT11 metabolism and mediates host immune dynamics to affect the toxicity and efficacy of CPT11 chemotherapy, thus introducing a new concept that is called “microbiota-host-irinotecan axis”. Also, we emphasize the utilization of bacterial β-glucuronidase-specific inhibitor, dietary interventions, probiotics and strain-engineered interventions as emergent microbiota-targeting strategies for the purpose of improving CPT11 chemotherapy efficiency and alleviating toxicity.
Infection of C. elegans by Haptoglossa Species Reveals Shared Features in the Host Response to Oomycete Detection
Authors: Grover Manish , Fasseas Michael K. , Essmann Clara , Liu Kenneth , Braendle Christian , Félix Marie-Anne , Glockling Sally L. , Barkoulas Michalis
Published: October 2021

Oomycetes are a group of eukaryotic organisms that includes many important pathogens of animals and plants. Within this group, the Haptoglossa genus is characterised by the presence of specialised gun cells carrying a harpoon-like infection apparatus. While several Haptoglossa pathogens have been morphologically described, there are currently no host systems developed to study the infection process or host responses in the lab. In this study, we report that Haptoglossa species are potent natural pathogens of Caenorhabditis nematodes. Using electron microscopy, we characterise the infection process in C. elegans and demonstrate that the oomycete causes excessive tissue degradation upon entry in the body cavity, whilst leaving the host cuticle intact. We also report that the host transcriptional response to Haptoglossa infection shares similarities with the response against the oomycete Myzocytiopsis humicola, a key example of which is the induction of chitinase-like (chil) genes in the hypodermis. We demonstrate that this shared feature of the host response can be mounted by pathogen detection without any infection, as previously shown for M. humicola. These results highlight similarities in the nematode immune response to natural infection by phylogenetically distinct oomycetes.
Emergence of ST63 Pandrug-Resistant Acinetobacter pittii Isolated From an AECOPD Patient in China
Authors: Yang Ling , Dong Ning , Xu Chen , Ye Lianwei , Chen Sheng
Published: October 2021

Acinetobacter sp. is among the ESKAPE organisms which represent the major nosocomial pathogens that exhibited a high resistance rate. A. pittii, frequently associated with antimicrobial resistance particularly to carbapenems, is one of the most common Acinetobacter species causing invasive infection. Pandrug resistant A. pittii has rarely been reported. Here, we report the case of a patient with acute exacerbations of chronic obstructive pulmonary disease three years after double lung transplantation and developed severe pneumonia associated with pandrug resistant A. pittii infection. Phenotypic and genomic characteristics of this pandrug resistant isolate (17-84) was identified, and the mechanisms underlying its resistance phenotypes were analyzed. Isolate 17-84 belonged to ST63, carried a non-typable and non-transferable plasmid encoding multiple acquired resistance genes including carbapenemase gene blaOXA-58. Point mutations and acquired resistance genes were identified which were associated with different drug resistance phenotypes. To our knowledge, this is the first detailed phenotypic and genomic characterization of PDR A. pittii causing severe infections in clinical settings. Findings from us and others indicate that A. pittii could serve as a reservoir for carbapenem determinants. The emergence of such a superbug could pose a serious threat to public health. Further surveillance of PDR A. pittii strains and implementation of stricter control measures are needed to prevent this emerging pathogen from further disseminating in hospital settings and the community.
U.S. Family Forest Owners' Forest Management for Climate Adaptation: Perspectives From Extension and Outreach Specialists
Authors: vonHedemann Nicolena , Schultz Courtney A.
Published: October 2021

In the United States (US), family forest owners, a group that includes individuals, families, trusts, and estates, are the largest single landowner category, owning approximately one-third of the nation's forests. These landowners' individualized decision-making on forest management has a profound impact on US forest cover and function at both local and regional scales. We sought to understand perceptions among family forest specialists of: climate impacts and adaptation options across different forested US regions; how family forest owners are taking climate adaptation into consideration in their forest management, if at all; and major barriers to more active management for adaptation among family forest owners. We conducted semi-structured interviews with 48 forest experts across the US who work with family forest owners, including extension specialists, state forestry agency employees, and consulting foresters who focus on family forest engagement. Our interviewees shared details on how both climate change impacts and forest management for climate adaptation vary across the US, and they perceived a lack of active forest management by family forest owners. They explained that western forest landowners confronting the imminent threat of catastrophic wildfires are more likely to see a need for active forest management. By contrast, in the east, where most forestland is privately owned, interviewees said that landowners see relatively fewer climate impacts on their forests and less need for forest management to respond to climate change. Perceived barriers to more active family forest management for climate adaptation include the lack of more robust markets for a wide range of forest products, a higher capacity forestry workforce, education and assistance in planning forest management, and addressing the issue of increased parcelization of family forest lands. We situate these perceptions in conversations on the role of boundary organizations in climate adaptation, how individual adaptation occurs, and how governing methods frame adaptation possibilities.
The Good Is Never Perfect: Why the Current Flaws of Voluntary Carbon Markets Are Services, Not Barriers to Successful Climate Change Action
Authors: Miltenberger Oliver , Jospe Christophe , Pittman James
Published: October 2021

The world's current level of climate change action does not match its ambitions to tackle the issue, and its ambitions do not currently meet the levels of action science recommends. Voluntary carbon markets (VCMs) are one option proposed to lessen those disparities, and have been both criticized and championed by various groups. Critiques note them as being opaque, flawed, and ineffective. Yet they demonstrate tremendous potential for impact and unprecedented levels of finance. We contend that the critiques of these markets are not only resolvable, but are unavoidable challenges that must be addressed on the path to mobilizing climate change ambition and achieving targets. Furthermore, we believe that by 2050, the current discrete market-based solutions in climate action will become internalized aspects of our economies rather than separate remediations. This goal of internalizing the externalities that cause climate change will result in massive, sustained decarbonization, rapid reorganization of global economies, and an extraordinary push to invent, solve, and scale strategies that facilitate the transition. Pricing carbon is a key contemporary step for transitioning to that future. Voluntary carbon markets are one means to catalyze this action and while needing improvements, should be given appropriate leeway to improve and fulfill that role.
Inverse Associations Between Circulating Secreted Frizzled Related Protein 2 (sFRP2) and Cardiometabolic Risk Factors
Authors: Cao Mengying , Wang Hao , Li Wenshu , Jiang Xueli , Wang Xiaolin , Guo Wei , Gao Pan , Zou Yunzeng
Published: October 2021

Background: Secreted frizzled-related protein 2 (sFRP2) plays an important role in metabolic syndrome and cardiovascular diseases (CVDs); However, its relevance with cardiometabolic diseases remains to be elucidated. We aimed to determine the serum levels of sFRP2 in patients at different stages of heart failure (HF) with or without type 2 diabetes mellitus (T2DM), and assess the correlation between circulating sFRP2 levels and cardiometabolic risk factors.

Methods: In this study, serum samples from 277 patients visiting Zhongshan Hospital affiliated to Fudan University were collected. These patients were clinically diagnosed and categorized as five groups, including the control group, pre-clinical HF group, pre-clinical HF+T2DM group, HF group and HF+T2DM group. Serum sFRP2 levels were measured with enzyme-linked immunosorbent assay (ELISA) tests and the clinical characteristics of each patient were recorded. Spearman rank correlation analysis and multiple stepwise linear regression analysis were conducted. Univariate and multivariate logistic regression analysis were performed to screen risk factors for HF in patients with CVDs.

Results: Serum sFRP2 levels were significantly lower in the HF+T2DM group compared with the other four groups. Spearman rank correlation analysis showed that sFRP2 was negatively correlated with parameters including patients' age, fasting plasma glucose (FPG), glycated hemoglobin A1c (HbA1c), cardiac troponin T (cTNT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), left atrial dimension (LAD) and left ventricular posterior wall (LVPW), and positively correlated with hemoglobin, estimated glomerular filtration rate (eGFR), albumin, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and left ventricular ejection fraction (LVEF). However, in multiple regression analysis, significant associations with ln(sFRP2) were observed only in FPG, hs-CRP and LAD. Higher serum sFRP2 was significantly linked to lower odds of HF in patients with CVDs.

Conclusion: sFRP2 progressively decreased when glucose homeostasis and cardiac function deteriorated. sFRP2 acted as a risk factor for HF in patients with CVDs, especially in those with concomitant T2DM.
Sex Differences in Coronary Function Test Results in Patient With Angina and Nonobstructive Disease
Authors: Jansen Tijn P. J. , Elias-Smale Suzette E. , van den Oord Stijn , Gehlmann Helmut , Dimitiriu-Leen Aukelien , Maas Angela H. E. M. , Konst Regina E. , van Royen Niels , Damman Peter
Published: October 2021

Introduction: Invasive coronary function testing (CFT) has become the recommended diagnostic tool to assess the various endotypes of coronary vasomotor dysfunction in patients with angina and no obstructive coronary artery disease (ANOCA), which has implications for therapy and prognosis. Although the expanding performance of CFT is leading to increased knowledge of coronary vasomotor dysfunction, little is known about sex-related differences in the results of comprehensive CFT.

Methods: We conducted a prospective study of all consecutive patients with ANOCA that underwent clinically indicated CFT in a tertiary interventional from February 2019 to February 2021. CFT consisted of acetylcholine testing to diagnose epicardial or microvascular spasm, and adenosine testing to diagnose CMD. CMD was defined as an index of microvascular resistance (IMR) ≥ 25 and/or coronary flow reserve (CFR) < 2.0.

Results: In total, 228 women and 38 men underwent CFT. No differences in traditional risk factors were seen, but women had a higher prevalence of migraine (45 vs. 14%, p = 0.001). Men more often had a history of percutaneous coronary intervention (12 vs. 49%, p = 0.001). We found no difference in clinical presentation. Coronary vasomotor dysfunction was present in 95% of men and 88% of women (p = 0.25), but males show more often epicardial spasm and less microvascular spasm than women (63 vs. 42% and 29 vs. 40% respectively, p = 0.039). Impaired CFR was more prevalent among females (6 vs 20%, p = 0.033). IMR [median of 23 (15–32) vs. 19 (13–25), p = 0.08] did not differ between the sexes.

Conclusion: Men undergoing CFT show a comparable prevalence of coronary vascular dysfunction as women. However, men have a higher prevalence of epicardial spasm and a lower prevalence of microvascular spasm compared with women. An impaired CFR was more often present in women, with an equally impairment of IMR.
MicroRNAs Regulation in Osteogenic Differentiation of Mesenchymal Stem Cells
Authors: Han Xiao , Fan Zhipeng
Published: October 2021

Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cell with the potential of self-renewal and multidirectional differentiation. They can be obtained from a variety of tissues and can differentiate into a variety of cell types under different induction conditions, including osteoblasts. Because of this osteogenic property, MSCs have attracted much attention in the treatment of bone metabolism-related diseases. MicroRNAs (miRNAs), as an epigenetic factor, are thought to play an important regulatory role in the process of osteogenic differentiation of MSCs. In recent years, increasingly evidence shows that miRNAs imbalance is involved in the regulation of osteoporosis and fracture. In this review, miRNAs involved in osteogenic differentiation and their mechanisms for regulating the expression of target genes are reviewed. In addition, we also discuss the potential clinical applications and possible directions of this field in the future.
The Concept of Steady State, Cyclicity and Debris Unloading of Debris-Covered Glaciers
Authors: Mayer Christoph , Licciulli Carlo
Published: October 2021

It can easily be expected that debris-covered glaciers show a different response on external forcing compared to clean-surface glaciers. The supra-glacial debris cover acts as an additional transfer layer for the energy exchange between atmosphere and ice. The related glacier reaction is the integral of local effects, which changes strongly between enhanced melt for thin debris layers and considerably reduced melt for thicker debris. Therefore, a realistic feedback study can only be performed, if both the ice flow and the debris-influenced melt is treated with a high degree of detail. We couple a full Stokes representation of ice dynamics and the most complete description of energy transfer through the debris layer, in order to describe the long-term glacier reaction in the coupled system. With this setup, we can show that steady-state conditions are highly unlikely for glaciers, in case debris is not unloaded from the surface. For continuous and complete debris removal from the lowermost glacier tongue, however, a balance of the debris budget and the glacier conditions are possible. Depending on displacement and removal processes, our results demonstrate that debris-covered glaciers have an inherent tendency to switch to an oscillating state. Then, glacier mass balance and debris balance are out of phase, such that glacier advance periods end with the separation of the heavily debris-loaded lowermost glacier tongue, at time scales of decades to centuries. As these oscillations are inherent and happen without any variations in climatic forcing, it is difficult to interpret modern observations on the fluctuation of debris-covered glaciers on the basis of a changing climate only.
CDK5 Regulatory Subunit-Associated Protein 1-Like 1 Gene Polymorphisms and Gestational Diabetes Mellitus Risk: A Trial Sequential Meta-Analysis of 13,306 Subjects
Authors: Yu Xiang-yuan , Song Li-ping , Wei Shu-dan , Wen Xiao-lan , Liu Da-bin
Published: October 2021

Objectives

The CDK5 regulatory subunit-associated protein 1-like 1 (CDKAL1) contributes to islet β-cell function and insulin secretion by inhibiting the activation of CDK5. The current studies on the relationship between CDKAL1 polymorphisms rs7756992 A>G and rs7754840 C>G and the risk of gestational diabetes mellitus (GDM) have drawn contradictory conclusions.

Materials and Methods

A meta-analysis with a fixed- or random-effects model was conducted to estimate the correlation between studied CDKAL1 polymorphisms and GDM risk with the summary odds ratio (OR) and 95% confidence interval (CI). In addition, trial sequential analysis (TSA) and false-positive report probability (FPRP) analysis were performed to confirm the study findings.

Results

A total of 13,306 subjects were included in the present study. Meta-analysis results showed that the variant heterozygous and homozygous genotypes of the two polymorphisms were associated with increased GDM risk in comparison with the wild-type AA genotype (AG vs. AA: OR = 1.23, 95% CI = 1.08, 1.41, p = 0.002; GG vs. AA: OR = 1.47, 95% CI = 1.05, 2.05, p = 0.024 for rs7756992; and CG vs. GG: OR = 1.36, 95% CI = 1.13, 1.65, p = 0.002; CC vs. GG: OR = 1.76, 95% CI = 1.37, 2.26, p < 0.001 for rs7754840). The TSA confirmed a significant association between rs7754840 and the susceptibility to GDM because the cumulative Z-curve crossed both the conventional cutoff value and the TSA boundaries under the heterozygote and homozygote models.

Conclusions

This study supported the finding that rs7756992 and rs7754840 are associated with susceptibility to GDM. However, further functional studies are warranted to clarify the mechanism.
Associations Between Sleep Duration, Wake-Up Time, Bedtime, and Abdominal Obesity: Results From 9559 Chinese Children Aged 7–18 Years
Authors: Liu Meijuan , Cao Bingyan , Luo Qipeng , Wang Qiao , Liu Min , Liang Xuejun , Wu Di , Li Wenjing , Su Chang , Chen Jiajia , Gong Chunxiu
Published: October 2021

Objective

To investigate the associations of sleep duration, wake-up time, bedtime, and childhood abdominal obesity, and to test whether there is a weekday/weekend difference and the potential modifying role of sex.

Methods

This cross-sectional study was based on the Students’ Constitution and Health Survey and included 9559 students (4840 boys and 4719 girls) aged 7–18 years (7227 aged 7–12 years, 2332 aged 13–18 years). They were divided into two groups (control group and group with abdominal obesity). The physical measurements included children and youth body height, body weight, and waist circumference (WC). A parent-report questionnaire was used to collect the information about parent characteristics as well as lifestyle and sleep patterns (sleep duration, bedtime, and wake-up time of weekdays and weekends) of children and youth.

Results

The prevalence of abdominal obesity was 30.57% and the percentages of sleep duration <9 hours/day, wake-up time before 07:00 am on weekdays and weekends, bedtime after 10:00 pm on weekends were significantly higher in the group with abdominal obesity. After adjusting for confounders, sleep duration <9 hours/day on weekends was inversely related to abdominal obesity in the overall subjects, regardless of their sex and age, while bedtime after 10:00 pm on weekends was inversely related to abdominal obesity only in the overall subjects, boys, and children aged 7–12 years. Logistic regression models in all subjects showed that shorter hours of weekends sleep duration were associated with greater risks of abdominal obesity, even after adjusting for all confounders, including wake-up time and bedtime. The adjusted odds ratios and 95% confidence intervals of abdominal obesity (with ≥10 hours/day as the reference group) for children with 9–10 hours/day, 8–9 hours/day, and <8 hours/day of weekend sleep duration were 1.23 (1.04–1.46), 1.59 (1.32–1.91) and 1.83 (1.42–2.36), respectively. Specifically, after stratification by sex and age, this phenomenon was only observed in boys and children aged 7–12 years.

Conclusions

Sleep duration and bedtime on weekends were independently associated with the risk of childhood abdominal obesity, particularly in boys and children aged 7–12 years.
Fibroblast Growth Factor in Diabetic Foot Ulcer: Progress and Therapeutic Prospects
Authors: Liu Ye , Liu Yiqiu , Deng Junyu , Li Wei , Nie Xuqiang
Published: October 2021

Diabetic foot ulcer (DFU) is a combination of neuropathy and various degrees of peripheral vasculopathy in diabetic patients resulting in lower extremity infection, ulcer formation, and deep-tissue necrosis. The difficulty of wound healing in diabetic patients is caused by a high glucose environment and various biological factors in the patient. The patients’ skin local microenvironment changes and immune chemotactic response dysfunction. Wounds are easy to be damaged and ulcerated repeatedly, but difficult to heal, and eventually develop into chronic ulcers. DFU is a complex biological process in which many cells interact with each other. A variety of growth factors released from wounds are necessary for coordination and promotion of healing. Fibroblast growth factor (FGF) is a family of cell signaling proteins, which can mediate various processes such as angiogenesis, wound healing, metabolic regulation and embryonic development through its specific receptors. FGF can stimulate angiogenesis and proliferation of fibroblasts, and it is a powerful angiogenesis factor. Twenty-three subtypes have been identified and divided into seven subfamilies. Traditional treatments for DFU can only remove necrotic tissue, delay disease progression, and have a limited ability to repair wounds. In recent years, with the increasing understanding of the function of FGF, more and more researchers have been applying FGF-1, FGF-2, FGF-4, FGF-7, FGF-21 and FGF-23 topically to DFU with good therapeutic effects. This review elaborates on the recently developed FGF family members, outlining their mechanisms of action, and describing their potential therapeutics in DFU.
Adverse Impact of Environmental Chemicals on Developmental Origins of Kidney Disease and Hypertension
Authors: Hsu Chien-Ning , Tain You-Lin
Published: October 2021

Chronic kidney disease (CKD) and hypertension are becoming a global health challenge, despite developments in pharmacotherapy. Both diseases can begin in early life by so-called “developmental origins of health and disease” (DOHaD). Environmental chemical exposure during pregnancy can affect kidney development, resulting in renal programming. Here, we focus on environmental chemicals that pregnant mothers are likely to be exposed, including dioxins, bisphenol A (BPA), phthalates, per- and polyfluoroalkyl substances (PFAS), polycyclic aromatic hydrocarbons (PAH), heavy metals, and air pollution. We summarize current human evidence and animal models that supports the link between prenatal exposure to environmental chemicals and developmental origins of kidney disease and hypertension, with an emphasis on common mechanisms. These include oxidative stress, renin-angiotensin system, reduced nephron numbers, and aryl hydrocarbon receptor signaling pathway. Urgent action is required to identify toxic chemicals in the environment, avoid harmful chemicals exposure during pregnancy and lactation, and continue to discover other potentially harmful chemicals. Innovation is also needed to identify kidney disease and hypertension in the earliest stage, as well as translating effective reprogramming interventions from animal studies into clinical practice. Toward DOHaD approach, prohibiting toxic chemical exposure and better understanding of underlying mechanisms, we have the potential to reduce global burden of kidney disease and hypertension.
GnRH Antagonist Protocol With Cessation of Cetrorelix on Trigger Day Improves Embryological Outcomes for Patients With Sufficient Ovarian Reserve
Authors: Xu Huihui , Zhao Shen , Gao Xinxing , Wu Xian , Xia Lan , Zhang Dan , Li Jian , Zhang Aijun , Xu Bufang
Published: October 2021

Objective

To evaluate the efficiency and validity of cessation of cetrorelix on trigger day during gonadotropin releasing hormone antagonist (GnRH-ant)-controlled ovarian stimulation of in vitro fertilization (IVF) cycles.

Methods

In this retrospective study, a total of 1271 patients undergoing initial IVF cycles following the GnRH-ant protocol were enrolled; 832 patients received cetrorelix on trigger day (Group A) and 439 patients ceased cetrorelix on trigger day (Group B). We compared demographic characteristics, embryological and clinical outcomes between the two groups. A Poisson regression model was used to identify factors that significantly affected embryological outcomes. Patients were further divided into subgroups according to anti-Mullerian hormone (AMH) and age, to assess associations between ceasing cetrorelix on trigger day and embryological outcomes.

Results

There was a significant improvement on embryological outcomes in patients who ceased cetrorelix on trigger day, and there were no significant differences in clinical outcomes or preovulation rates between the two groups. Furthermore, for patients with 1.1 ≤ AMH ≤ 4.7 ng/ml, all embryological outcomes were significantly higher in Group B compared with Group A. For patients with AMH > 4.7 ng/ml, the number of oocytes retrieved, fertilization rate (2PN) of IVF cycles and proportion of day 3 good quality embryos were all significantly higher in Group B. For patients with age < 35 years, all the embryological outcomes, besides the number of available embryos, were significantly higher in Group B than in Group A. There were no differences in embryological outcomes between the two groups when patients were stratified based on age > 35 years or AMH < 1.1 ng/ml.

Conclusion

GnRH-ant protocol with cessation of cetrorelix on trigger day improved embryological outcomes for young patients or patients with sufficient ovarian reserve, and was effective at preventing preovulation.
Transcriptome Analysis and Characterization of Chemosensory Genes in the Forest Pest, Dioryctria abietella (Lepidoptera: Pyralidae)
Authors: Wang Zheng-Quan , Wu Chun , Li Gen-Ceng , Nuo Shu-Mei , Yin Ning-Na , Liu Nai-Yong
Published: October 2021

In Lepidoptera, RNA sequencing has become a useful tool in identifying chemosensory genes from antennal transcriptomes, but little attention is paid to non-antennal tissues. Though the antennae are primarily responsible for olfaction, studies have found that a certain number of chemosensory genes are exclusively or highly expressed in the non-antennal tissues, such as proboscises, legs and abdomens. In this study, we report a global transcriptome of 16 tissues from Dioryctria abietella, including chemosensory and non-chemosensory tissues. Through Illumina sequencing, totally 952,658,466 clean reads were generated, summing to 142.90 gigabases of data. Based on the transcriptome, 235 chemosensory-related genes were identified, comprising 42 odorant binding proteins (OBPs), 23 chemosensory proteins (CSPs), 75 odorant receptors (ORs), 62 gustatory receptors (GRs), 30 ionotropic receptors (IRs), and 3 sensory neuron membrane proteins (SNMPs). Compared to a previous study in this species, 140 novel genes were found. A transcriptome-wide analysis combined with PCR results revealed that except for GRs, the majority of other five chemosensory gene families in Lepidoptera were expressed in the antennae, including 160 chemosensory genes in D. abietella. Using phylogenetic and expression profiling analyses, members of the six chemosensory gene repertoires were characterized, in which 11 DabiORs were candidates for detecting female sex pheromones in D. abietella, and DabiOR23 may be involved in the sensing of plant-derived phenylacetaldehyde. Intriguingly, more than half of the genes were detected in the proboscises, and one fourth of the genes were found to have the expression in the legs. Our study not only greatly extends and improves the description of chemosensory genes in D. abietella, but also identifies potential molecular targets involved in olfaction, gustation and non-chemosensory functions for control of this pest.
Apolipoprotein E Genetic Variation and Its Association With Cognitive Function in Rural-Dwelling Older South Africans
Authors: Soo Cassandra C. , Farrell Meagan T. , Tollman Stephen , Berkman Lisa , Nebel Almut , Ramsay Michèle
Published: October 2021

Apolipoprotein E (APOE) 𝜀4 allele carrier status is well known for its association with an increased likelihood of developing Alzheimer’s disease, but its independent role in cognitive function is unclear. APOE genetic variation is understudied in African populations; hence, this cross-sectional study in a rural South African community examined allele and genotype frequencies, and their associations with cognitive function. Cognitive function was assessed using two different screening methods to produce a total cognition score and four domain-specific cognition scores for verbal episodic memory, executive function, language, and visuospatial ability. Cognitive phenotype and APOE genotype data were used to determine whether APOE variation was significantly associated with cognitive function in this population. Observed allele frequencies for 1776 participants from the HAALSI study [age 40–80years (mean=56.19); 58.2% female] were 58.1% (𝜀3), 25.4% (𝜀4) and 16.5% (𝜀2). Allele distributions were similar to the African super population, but different from all non-African super populations from the 1,000 Genomes Project. The 𝜀3 homozygous genotype was most common (34.9%) and used as the base genotype for comparison in regression models. Four models were tested for each of the five cognitive phenotypes to explore association of APOE variation with cognitive function. In the first model assessing association with all genotypes for all individuals, marginally significant associations were observed for 𝜀2 homozygotes where executive function scored higher by ~0.5 standard deviations (p=0.037, SE=0.23), and for 𝜀3/𝜀4 heterozygotes where visuospatial ability scores were lower (p=0.046, SE=0.14). These did not survive correction for multiple testing. Regional African population differences were observed at the APOE locus. Marginally, significant associations between APOE genotype, and executive function and visuospatial ability indicate the need for larger studies to better examine these associations in African populations. Furthermore, longitudinal data could shed light on APOE genetic association with rate of change, or decline, in cognitive function.
SMRT Sequencing of the Full-Length Transcriptome of the Coelomactra antiquata
Authors: Deng Aiping , Li Jinpeng , Yao Zebin , Afriyie Gyamfua , Chen Ziyang , Guo Yusong , Luo Jie , Wang Zhongduo
Published: October 2021

Coelomactra antiquata is an important aquatic economic shellfish with high medicinal value. However, because C. antiquata has no reference genome, a lot of molecular biology research cannot be carried out, so the analysis of its transcripts is an important step to study the regulatory genes of various substances in C. antiquata. In the present study, we conducted the first full-length transcriptome analysis of C. antiquata by using PacBio single-molecule real-time (SMRT) sequencing technology. The results identified a total of 39,209 unigenes with an average length of 2,732 bp, 23,338 CDSs, 251 AS events, 9,881 lncRNAs, 20,106 SSRs, and 2,316 TFs. Subsequently, 59.22% (23,220) of the unigenes were successfully annotated, of which 23,164, 18,711, 15,840, 13,534, and 13,474 unigenes could be annotated using NR, Swiss-prot, KOG, GO, and KEGG databases, respectively. This study lays the foundation for the follow-up research of molecular biology and provides a reference for studying the more medicinal value of C. antiquata.
Pumpkin (Cucurbita moschata) HSP20 Gene Family Identification and Expression Under Heat Stress
Authors: Hu Yanping , Zhang Tingting , Liu Ying , Li Yuxin , Wang Min , Zhu Baibi , Liao Daolong , Yun Tianhai , Huang Wenfeng , Zhang Wen , Zhou Yang
Published: October 2021

Pumpkin (Cucurbita moschata) is an important cucurbit vegetable crop that has strong resistance to abiotic stress. While heat shock protein 20 (HSP20) has been implicated in vegetable response to heat stress, little is known regarding activity of HSP20 family proteins in C. moschata. Here, we performed a comprehensive genome-wide analysis to identify and characterize the functional dynamics of the Cucurbita moschata HSP20 (CmoHSP20) gene family. A total of 33 HSP20 genes distributed across 13 chromosomes were identified from the pumpkin genome. Our phylogenetic analysis determined that the CmoHSP20 proteins fell into nine distinct subfamilies, a division supported by the conserved motif composition and gene structure analyses. Segmental duplication events were shown to play a key role in expansion of the CmoHSP20 gene family. Synteny analysis revealed that 19 and 18 CmoHSP20 genes were collinear with those in the cucumber and melon genomes, respectively. Furthermore, the expression levels of pumpkin HSP20 genes were differentially induced by heat stress. The transcript level of CmoHSP20-16, 24 and 25 were down-regulated by heat stress, while CmoHSP20-7, 13, 18, 22, 26 and 32 were up-regulated by heat stress, which could be used as heat tolerance candidate genes. Overall, these findings contribute to our understanding of vegetable HSP20 family genes and provide valuable information that can be used to breed heat stress resistance in cucurbit vegetable crops.
Agent Repurposing for the Treatment of Advanced Stage Diffuse Large B-Cell Lymphoma Based on Gene Expression and Network Perturbation Analysis
Authors: Xiang Chenxi , Ni Huimin , Wang Zhina , Ji Binbin , Wang Bo , Shi Xiaoli , Wu Wanna , Liu Nian , Gu Ying , Ma Dongshen , Liu Hui
Published: October 2021

Over 50% of diffuse large B-cell lymphoma (DLBCL) patients are diagnosed at an advanced stage. Although there are a few therapeutic strategies for DLBCL, most of them are more effective in limited-stage cancer patients. The prognosis of patients with advanced-stage DLBCL is usually poor with frequent recurrence and metastasis. In this study, we aimed to identify gene expression and network differences between limited- and advanced-stage DLBCL patients, with the goal of identifying potential agents that could be used to relieve the severity of DLBCL. Specifically, RNA sequencing data of DLBCL patients at different clinical stages were collected from the cancer genome atlas (TCGA). Differentially expressed genes were identified using DESeq2, and then, weighted gene correlation network analysis (WGCNA) and differential module analysis were performed to find variations between different stages. In addition, important genes were extracted by key driver analysis, and potential agents for DLBCL were identified according to gene-expression perturbations and the Crowd Extracted Expression of Differential Signatures (CREEDS) drug signature database. As a result, 20 up-regulated and 73 down-regulated genes were identified and 79 gene co-expression modules were found using WGCNA, among which, the thistle1 module was highly related to the clinical stage of DLBCL. KEGG pathway and GO enrichment analyses of genes in the thistle1 module indicated that DLBCL progression was mainly related to the NOD-like receptor signaling pathway, neutrophil activation, secretory granule membrane, and carboxylic acid binding. A total of 47 key drivers were identified through key driver analysis with 11 up-regulated key driver genes and 36 down-regulated key diver genes in advanced-stage DLBCL patients. Five genes (MMP1, RAB6C, ACCSL, RGS21 and MOCOS) appeared as hub genes, being closely related to the occurrence and development of DLBCL. Finally, both differentially expressed genes and key driver genes were subjected to CREEDS analysis, and 10 potential agents were predicted to have the potential for application in advanced-stage DLBCL patients. In conclusion, we propose a novel pipeline to utilize perturbed gene-expression signatures during DLBCL progression for identifying agents, and we successfully utilized this approach to generate a list of promising compounds.
Regulatory T-Cell Therapy in Liver Transplantation and Chronic Liver Disease
Authors: Hann Angus , Oo Ye H. , Perera M. Thamara P. R.
Published: October 2021

The constant exposure of the liver to gut derived foreign antigens has resulted in this organ attaining unique immunological characteristics, however it remains susceptible to immune mediated injury. Our understanding of this type of injury, in both the native and transplanted liver, has improved significantly in recent decades. This includes a greater awareness of the tolerance inducing CD4+CD25+CD127lowT-cell lineage with the transcription factor FoxP3, known as regulatory T-Cells (Tregs). These cells comprise 5-10% of CD4+T cells and are known to function as an immunological “braking” mechanism, thereby preventing immune mediated tissue damage. Therapies that aim to increase Treg frequency and function have proved beneficial in the setting of both autoimmune diseases and solid organ transplantations. The safety and efficacy of Treg therapy in liver disease is an area of intense research at present and has huge potential. Due to these cells possessing significant plasticity, and the potential for conversion towards a T-helper 1 (Th1) and 17 (Th17) subsets in the hepatic microenvironment, it is pre-requisite to modify the microenvironment to a Treg favourable atmosphere to maintain these cells’ function. In addition, implementation of therapies that effectively increase Treg functional activity in the liver may result in the suppression of immune responses and will hinder those that destroy tumour cells. Thus, fine adjustment is crucial to achieve this immunological balance. This review will describe the hepatic microenvironment with relevance to Treg function, and the role these cells have in both native diseased and transplanted livers.
Two Distinct Lysosomal Targeting Strategies Afford Trojan Horse Antibodies With Pan-Filovirus Activity
Authors: Wirchnianski Ariel S. , Wec Anna Z. , Nyakatura Elisabeth K. , Herbert Andrew S. , Slough Megan M. , Kuehne Ana I. , Mittler Eva , Jangra Rohit K. , Teruya Jonathan , Dye John M. , Lai Jonathan R. , Chandran Kartik
Published: October 2021

Multiple agents in the family Filoviridae (filoviruses) are associated with sporadic human outbreaks of highly lethal disease, while others, including several recently identified agents, possess strong zoonotic potential. Although viral glycoprotein (GP)-specific monoclonal antibodies have demonstrated therapeutic utility against filovirus disease, currently FDA-approved molecules lack antiviral breadth. The development of broadly neutralizing antibodies has been challenged by the high sequence divergence among filovirus GPs and the complex GP proteolytic cleavage cascade that accompanies filovirus entry. Despite this variability in the antigenic surface of GP, all filoviruses share a site of vulnerability—the binding site for the universal filovirus entry receptor, Niemann-Pick C1 (NPC1). Unfortunately, this site is shielded in extracellular GP and only uncovered by proteolytic cleavage by host proteases in late endosomes and lysosomes, which are generally inaccessible to antibodies. To overcome this obstacle, we previously developed a ‘Trojan horse’ therapeutic approach in which engineered bispecific antibodies (bsAbs) coopt viral particles to deliver GP:NPC1 interaction-blocking antibodies to their endo/lysosomal sites of action. This approach afforded broad protection against members of the genus Ebolavirus but could not neutralize more divergent filoviruses. Here, we describe next-generation Trojan horse bsAbs that target the endo/lysosomal GP:NPC1 interface with pan-filovirus breadth by exploiting the conserved and widely expressed host cation-independent mannose-6-phosphate receptor for intracellular delivery. Our work highlights a new avenue for the development of single therapeutics protecting against all known and newly emerging filoviruses.
Efficacy and Safety of Dupilumab in Moderate-to-Severe Bullous Pemphigoid
Authors: Zhang Yihua , Xu Qiuyun , Chen Lihong , Chen Jiawen , Zhang Jing , Zou Ying , Gong Ting , Ji Chao
Published: October 2021

Background

Bullous pemphigoid (BP) is an autoimmune blistering disorder that predominantly affects the elderly. As the main treatment for BP, systemic corticosteroids are often limited by their side effects. Safer treatment modalities are therefore needed. Dupilumab is a biologic agent used to treat BP in recent years.

Methods

Medical records of patients with moderate-to-severe BP were retrospectively reviewed. Twenty-four patients were included (follow-up period: 32 weeks), eight of whom received dupilumab in combination with methylprednisolone and azathioprine (dupilumab group) while the other 16 patients received methylprednisolone and azathioprine (conventional group). Response to dupilumab was evaluated by comparison of several parameters (time to stop new blister formation, time to reduce the systemic glucocorticoids to minimal dose, and total amount of methylprednisolone).

Results

The median age of patients in the dupilumab and conventional groups were 64.50 years (range: 22–90 years) and 64.50 years (range: 17–86 years), respectively. The median duration of disease before admission in the dupilumab group was 2 months (range: 1–240 months) and 2.5 months (range: 1–60 months) in the conventional group. The median time to stop new blister formation was 8 days (range: 1–13 days) and 12 days (range: 5–21 days) in patients of the dupilumab and conventional groups, respectively (p = 0.028 by Kaplan-Meier analysis). In addition, the median time to reduce the systemic glucocorticoids to minimal dose (methylprednisolone 0.08 mg/kg/day) was 121.5 and 148.5 days for the dupilumab and conventional therapy groups, respectively (p = 0.0053 by Kaplan-Meier analysis). The median total amount of methylprednisolone (at the time of reaching the minimal dose) used in the dupilumab group was 1,898 mg (range: 1,624–2,932 mg) while the cumulative dose of conventional group was 2,344 mg (range: 1,708–4,744 mg) (p = 0.036 by Mann-Whitney U test). The median total amount of azathioprine (at the time of reaching the minimal dose) used in dupilumab group was 8,300 mg (range: 7,100–10,400 mg) while the total dose of conventional group was 10,300 mg (range: 8,900–14,400 mg) (p = 0.0048 by Mann-Whitney U test). No adverse event related to dupilumab was recorded.

Conclusions

Dupilumab in addition to methylprednisolone and azathioprine seems superior to methylprednisolone/azathioprine alone in controlling disease progression and accelerating the tapering of glucocorticoids.
Vaccination of Gilthead Seabream After Continuous Xenoestrogen Oral Exposure Enhances the Gut Endobolome and Immune Status via GPER1
Authors: Castejón Pablo , Cabas Isabel , Gómez Victoria , Chaves-Pozo Elena , Cerezo-Ortega Isabel , Moriñigo Miguel Ángel , Martínez-Manzanares Eduardo , Galindo-Villegas Jorge , García-Ayala Alfonsa
Published: October 2021

In fish culture settings, the exogenous input of steroids is a matter of concern. Recently, we unveiled that in the gilthead seabream (Sparus aurata), the G protein-coupled estrogen receptor agonist G-1 (G1) and the endocrine disruptor 17α-ethinylestradiol (EE2) are potent modulators in polyreactive antibody production. However, the integral role of the microbiota upon immunity and antibody processing in response to the effect of EE2 remains largely unexplored. Here, juvenile seabreams continuously exposed for 84 days to oral G1 or EE2 mixed in the fish food were intraperitoneally (i.p.) immune primed on day 42 with the model antigen keyhole limpet hemocyanin (KLH). A critical panel of systemic and mucosal immune markers, serum VTG, and humoral, enzymatic, and bacteriolytic activities were recorded and correlated with gut bacterial metagenomic analysis 1 day post-priming (dpp). Besides, at 15 dpp, animals received a boost to investigate the possible generation of specific anti-KLH antibodies at the systemic and mucosal interphases by the end of the trial. On day 43, EE2 but not G1 induced a significant shift in the serum VTG level of naive fish. Simultaneously, significant changes in some immune enzymatic activities in the serum and gut mucus of the EE2-treated group were recorded. In comparison, the vaccine priming immunization resulted in an attenuated profile of most enzymatic activities in the same group. The gut genes qPCR analysis exhibited a related pattern, only emphasized by a significant shift in the EE2 group’s il1b expression. The gut bacterial microbiome status underwent 16S rRNA dynamic changes in alpha diversity indices, only with the exposure to oral G1, supporting functional alterations on cellular processes, signaling, and lipid metabolism in the microbiota. By the same token, the immunization elevated the relative abundance of Fusobacteria only in the control group, while this phylum was depleted in both the treated groups. Remarkably, the immunization also promoted changes in the bacterial class Betaproteobacteria and the estrogen-associated genus Novosphingobium. Furthermore, systemic and mucosal KLH-specific immunoglobulin (Ig)M and IgT levels in the fully vaccinated fish showed only slight changes 84 days post-estrogenic oral administration. In summary, our results highlight the intrinsic relationship among estrogens, their associated receptors, and immunization in the ubiquitous fish immune regulation and the subtle but significant crosstalk with the gut endobolome.