bluuebunny/crossref_metadata_2025 huggingface dataset:
Dexamethasone application for in vitro fertilisation in non-classic 17-hydroxylase/17,20-lyase-deficient women
Authors: Yang Xiu-Li , Zhang Ting-Ting , Shang Jing , Xue Qing , Kuai Yan-Rong , Wang Sheng , Xu Yang
Published: October 2022

Context

High progesterone levels in the follicular stage interfere with the implantation window, causing infertility in women with 17-hydroxylase/17,20-lyase deficiency (17OHD). Dexamethasone can restore cortisol deficiency and suppress inappropriate mineralocorticoid secretion to control hypertension in 17OHD patients, but poses risks to the foetus if administered during pregnancy.

Objective

We prospectively explored a rational glucocorticoid use protocol for assistive reproduction in a woman with non-classic 17OHD that reduced glucocorticoid side effects.

Method

In this study, the treatment protocol for this 17OHD patient included the following steps. First, the appropriate type and dose of glucocorticoid for endogenous progesterone suppression was determined. Then, glucocorticoid was discontinued to increase endogenous progesterone levels for ovarian stimulation. Next, dexamethasone plus GnRHa were used to reduce progesterone levels in frozen embryos for transfer. Once pregnancy was confirmed, dexamethasone was discontinued until delivery.

Results

Dexamethasone, but not hydrocortisone, reduced progesterone levels in the 17OHD woman. After endogenous progesterone-primed ovarian stimulation, 11 oocytes were retrieved. Seven oocytes were 2PN fertilised and four day-3 and two day-5 embryos were cryopreserved. After administering dexamethasone plus gonadotropin-releasing hormone agonist (GnRHa) to reduce progesterone levels to normal, hormone replacement therapy was administered until the endometrial width reached 9 mm. Exogenous progesterone (60 mg/day) was used for endometrial preparation. Two thawed embryos were transferred on day 4. Dexamethasone was continued until pregnancy confirmation on the 13th day post-transfer. Two healthy boys, weighing 2100 and 2000 g, were delivered at 36 weeks’ gestation.

Conclusion

Rational use of dexamethasone synchronised embryonic development with the endometrial implantation window, while not using in post-implantation avoided its side effects and promoted healthy live births in women non-classic 17OHD undergoing in vitro fertilisation.
The impact of digital economy development on carbon emissions -- based on the Yangtze River Delta urban agglomeration
Authors: Zha Qifen , Huang Chuan , Kumari Sonia
Published: October 2022

The dual carbon target has been the focus of domestic attention since it was proposed. At the same time, the digital economy based on new technologies such as the Internet and big data has become an important engine to boost China’s high-quality economic development. While the digital economy is promoting the development of the urban economy, can it also promote the low carbon development of cities in China? Based on panel data and multiple econometric models of 26 cities in the Yangtze River Delta urban agglomeration from 2006 to 2020, this paper empirically examines the impact of digital economy development on urban carbon emissions. The results show that the development of the digital economy can not only reduce the carbon emission intensity of this region but also effectively reduce the carbon emission intensity of surrounding areas. Therefore, it is necessary to further promote the construction of digital economy in the urban agglomeration, improve the inclusiveness and flexibility of the implementation of digital economy development strategy, and improve the construction of information infrastructure to give full play to the role of the digital economy in improving carbon emissions in urban agglomeration.
Assessment of children’s exposure to air pollutants in urban residences during the COVID-19 pandemic
Authors: Abdel-Salam Mahmoud M. M.
Published: October 2022

Indoor air pollution has been associated with adverse health effects. Sensitive people such as children spend much time at home. It is therefore important to know whether our children breath clean air inside their residences or not. Monitoring of PM10, PM2.5, TVOCs, CO, and CO2 concentrations was conducted for 24 h in 36 urban residences in Alexandria—Egypt, simultaneously outdoors and indoors (living rooms, bedrooms, and kitchens), during the summer season. During the COVID-19 pandemic, children spend 98% of their time at home (49% in living rooms, 47% in bedrooms, and 2% in kitchens). Results indicated that children are particularly exposed to high concentrations of PM10 (85.4 ± 18.7 μg/m3) and PM2.5 (57.2 ± 16.4 μg/m3) exceeding the WHO guidelines, which can be dangerous for their health. Outdoor sources were found to be a main contributor to the indoor levels of PM10, PM2.5, and CO in bedrooms and living rooms of the surveyed residences. Therefore, effective control measures to reduce outdoor air pollution can result in improved indoor air quality (IAQ). Living rooms showed the highest impact on the daily average children exposure to PM2.5, PM10, TVOCs, and CO with average contributions of 59%, 56%, 57%, and 61%, respectively. For CO2, bedrooms showed the largest contribution to the children’s average exposure with an average value of 49%, pointing to inadequate ventilation and small size of this type of room. Indoor occupants’ activities were found to considerably affect IAQ in the bedrooms and living rooms. The study also highlighted the importance of other determinants, such as occupancy and air exchange rate, on IAQ in these two microenvironments. This research provides the first data on children’s exposure to indoor air pollutants in urban residences in Egypt.
Vermiremediation: Analysis of contaminated diesel in soil using Eisenia fetida and ZnO nanoparticles with cow dung
Authors: Surendrakumar Radhakrishnan , Idhayadhulla Akbar , Ahamed Anis , Alodaini Hissah Abdulrahman , Gurusamy Raman
Published: October 2022

Cow dung is a valuable source of manure to improve soil quality. This study aims to enhance the soil quality by decreasing diesel contamination in the soil through the vermicomposting of cow dung and nanoparticles of ZnO. Using a powder made from cow dung, zinc ions may be easily converted into ZnO nanoparticles. To increase the quality of soil, Eisenia fetida and nanoparticles of ZnO mixed with cow dung was used. These nanoparticles were characterized by FT-IR, SEM, and TEM. The diesel impure soils were examined for 70 days by gas chromatography. Observations showed that the soil samples without the earthworms had a higher concentration of diesel than the earthworm present in the soil. In this method, diesel (4.5 ml) was reduced by almost 50% after 70 days. Diesel concentrations were significantly higher during sampling time than they were later in soil contaminated with E. fetida.
Analysis of spatio-temporal changes and driving forces of cultivated land in China from 1996 to 2019
Authors: Li Jianfeng , Han Jichang , Zhang Yang , Sun Yingying , Peng Biao , Xie Xiao , Guo Chao , Ye Huping
Published: October 2022

Cultivated land is an important prerequisite and guarantee for food production and security, and the change of cultivated land resources in China has always been concerned. National land survey is an effective way to accurately grasp the area and distribution of cultivated land resources. However, due to the differences in technical means and statistical standards at different stages, there are obvious breakpoints among the cultivated land area data of the three land surveys in China, which hinders the in-depth study of the spatio-temporal distribution of cultivated land resources in long-time series. The Autoregressive Integrated Moving Average model is used to reconstruct and mine the cultivated land area data from 1996 to 2019 based on the data of the third land survey in China. The spatio-temporal variation characteristics of cultivated land area are explored by using Geographic Information System spatial analysis, and the driving factors of cultivated land change are analyzed based on Geographical Detector (GeoDetector) from the perspective of social, economic, agricultural and natural. The results show that the area of cultivated land in China decreased continuously from 1996 to 2019, with a sharp decrease from 1996 to 2004 and a slow decrease from 2005 to 2019. From 1996 to 2019, there were obvious spatial differences in the change of cultivated land area in 31 provincial units. From 1996 to 2008, the cultivated land area in 29 provinces showed a downward trend, especially in the central and northern regions such as Shaanxi, Sichuan and Inner Mongolia. From 2008 to 2019, the cultivated land area in the underdeveloped areas of Heilongjiang, Jilin, Liaoning, Xinjiang, Gansu and Tibet increased significantly, while the rest showed a downward trend. Factor detection found that the q values of population, regional gross domestic product grain output, the proportion of the added value of the primary industry and average slope were all more than 0.5, which had an important impact on the change of cultivated land area. The explanatory power of the interaction between factors on the change of cultivated land area is enhanced in different degrees compared with the single factor effect, which is manifested in the enhancement of bilinear or nonlinear enhancement, and the interaction of different factors promotes the change of cultivated land area. The change of cultivated land area is the result of complex interaction between factors, and is closely related to the land policy in the same period.
Concentrations of urinary neopterin, but not suPAR, positively correlate with age in rhesus macaques
Authors: Cooper Eve B. , Watowich Marina M. , Beeby Nina , Whalen Connor ,   Cayo Biobank Research Unit, Montague Michael J. , Brent Lauren J. N. , Snyder-Mackler Noah , Higham James P.
Published: October 2022

Identifying biomarkers of age-related changes in immune system functioning that can be measured non-invasively is a significant step in progressing research on immunosenescence and inflammaging in free-ranging and wild animal populations. In the present study, we aimed to investigate the suitability of two urinary compounds, neopterin and suPAR, as biomarkers of age-related changes in immune activation and inflammation in a free-ranging rhesus macaque (Macaca mulatta) population. We also investigated age-associated variation in gene transcription from blood samples to understand the underlying proximate mechanisms that drive age-related changes in urinary neopterin or suPAR. Neopterin was significantly positively correlated with age, and had a moderate within-individual repeatability, indicating it is applicable as a biomarker of age-related changes. The age-related changes in urinary neopterin are not apparently driven by an age-related increase in the primary signaler of neopterin, IFN-y, but may be driven instead by an age-related increase in both CD14+ and CD14− monocytes. suPAR was not correlated with age, and had low repeatability within-individuals, indicating that it is likely better suited to measure acute inflammation rather than chronic age-related increases in inflammation (i.e., “inflammaging”). Neopterin and suPAR had a correlation of 25%, indicating that they likely often signal different processes, which if disentangled could provide a nuanced picture of immune-system function and inflammation when measured in tandem.
Assessment of summertime ozone formation in the Sichuan Basin, southwestern China
Authors: Yang Xianyu , Yang Tong , Lu Yaqiong , Jiang Mengjiao , Zhang Shaobo , Shao Ping , Yuan Liang , Wang Chao , Wang Lei
Published: October 2022

The alarming increase of ambient ozone (O3) levels across China raises an urgent need in understanding underlying mechanisms of regional O3 events for highly urbanized city clusters. Sichuan Basin (SCB) situated in southwestern China has experienced severe O3 pollution at times in summer from 2013 to 2020. Here, we use the WRF-CMAQ model with the Integrated Source Apportionment Method (ISAM) to investigate the evolution mechanism and conduct source attribution of an extreme O3 episode in the SCB from June 1 to 8, 2019. This typical summer O3 episode is associated with the synoptic-driven meteorological phenomenon and transboundary flow of O3 and precursors across the SCB. Weak ventilation in combination with stagnant conditions triggered the basin-wide high O3 concentrations and enhanced BVOC emissions substantially contribute up to 57.9 μg/m3 MDA8 O3. CMAQ-ISAM indicates that precursor emissions from industrial and transportation have the largest impacts on elevating ambient O3 concentrations, while power plant emissions exhibit insignificant contributions to basin-wide O3 episodes. These results improve the understanding of the summertime O3 episode in the SCB and contribute insights into designing O3 mitigation policy.
Urban parks are a refuge for birds in park-poor areas
Authors: Vasquez Amy V. , Wood Eric M.
Published: October 2022

Urban parks provide amenities that support both human and animal communities. However, parks are often unevenly distributed within cities. One metric used to assess the distribution of parks to the public is termed the Park Score. The Park Score is an approach to measure access, acreage, investment, and amenities, and is designed to understand a city’s needs for greenspace, with a major focus on public health. In addition to issues related to public health, a disparity in the distribution of urban parks may pose a barrier for wildlife, such as birds. Yet, this remains unclear. We designed a study to quantify the role of parks in providing a refuge for birds across a park-needs gradient in Greater Los Angeles (LA), a metropolis with one of the lowest park scores in the United States. We had two objectives to address our goal. First, we quantified patterns in habitat features and avian communities within and adjacent to parks. Second, we analyzed relationships among habitat features within and adjacent to parks on avian abundance. We sampled birds and habitat features at 48 parks across a park-needs gradient in L.A. from October to March of 2017/2018 and 2018/2019. We found three lines of evidence supporting the refugia effect of parks. First, habitat features within parks were similar between low- and high-needs areas of LA, and this likely influenced avian abundance patterns, which were also alike. Second, avian communities were generally similar across the park-needs gradient, where parks in high-needs areas harbored birds affiliated with forest and shrub ecosystems. Third, bird abundance patterns were related to numerous habitat features within parks, regardless of where parks occurred in the city. The patterns we uncovered were opposite to what is found in residential areas (i.e., luxury effect), suggesting that parks provide important habitat for birds, whether in high- or low-needs sections of LA. Our results stress the role of parks as refugia in park-poor areas because they provide habitat in otherwise inhospitable urban conditions. Continued investment in park development in high-needs areas can thus potentially be a win-win when considering the benefits to people and birds.
Estimating heritability of song considering within-individual variance in a wild songbird: The collared flycatcher
Authors: Jablonszky Mónika , Canal David , Hegyi Gergely , Herényi Márton , Laczi Miklós , Lao Oscar , Markó Gábor , Nagy Gergely , Rosivall Balázs , Szász Eszter , Török János , Zsebõk Sándor , Garamszegi László Zsolt
Published: October 2022

Heritable genetic variation is a prerequisite for adaptive evolution; however, our knowledge about the heritability of plastic traits, such as behaviors, is scarce, especially in wild populations. In this study, we investigated the heritability of song traits in the collared flycatcher (Ficedula albicollis), a small oscine passerine with complex songs involved in sexual selection. We recorded the songs of 81 males in a natural population and obtained various measures describing the frequency, temporal organization, and complexity of each song. As we had multiple songs from each individual, we were able to statistically account for the first time for the effect of within-individual variance on the heritability of song. Heritability was calculated from the variance estimates of animal models relying on a genetic similarity matrix based on Single Nucleotide Polymorphism screening. Overall, we found small additive genetic variance and heritability values in all song traits, highlighting the role of environmental factors in shaping bird song.
Modification mapping by nanopore sequencing
Authors: White Laura K. , Hesselberth Jay R.
Published: October 2022

Next generation sequencing (NGS) has provided biologists with an unprecedented view into biological processes and their regulation over the past 2 decades, fueling a wave of development of high throughput methods based on short read DNA and RNA sequencing. For nucleic acid modifications, NGS has been coupled with immunoprecipitation, chemical treatment, enzymatic treatment, and/or the use of reverse transcriptase enzymes with fortuitous activities to enrich for and to identify covalent modifications of RNA and DNA. However, the majority of nucleic acid modifications lack commercial monoclonal antibodies, and mapping techniques that rely on chemical or enzymatic treatments to manipulate modification signatures add additional technical complexities to library preparation. Moreover, such approaches tend to be specific to a single class of RNA or DNA modification, and generate only indirect readouts of modification status. Third generation sequencing technologies such as the commercially available “long read” platforms from Pacific Biosciences and Oxford Nanopore Technologies are an attractive alternative for high throughput detection of nucleic acid modifications. While the former can indirectly sense modified nucleotides through changes in the kinetics of reverse transcription reactions, nanopore sequencing can in principle directly detect any nucleic acid modification that produces a signal distortion as the nucleic acid passes through a nanopore sensor embedded within a charged membrane. To date, more than a dozen endogenous DNA and RNA modifications have been interrogated by nanopore sequencing, as well as a number of synthetic nucleic acid modifications used in metabolic labeling, structure probing, and other emerging applications. This review is intended to introduce the reader to nanopore sequencing and key principles underlying its use in direct detection of nucleic acid modifications in unamplified DNA or RNA samples, and outline current approaches for detecting and quantifying nucleic acid modifications by nanopore sequencing. As this technology matures, we anticipate advances in both sequencing chemistry and analysis methods will lead to rapid improvements in the identification and quantification of these epigenetic marks.
From a documented past of the Jersey breed in Africa to a profit index linked future
Authors: Opoola Oluyinka , Shumbusho Felicien , Hambrook David , Thomson Sam , Dai Harvey , Chagunda Mizeck G. G. , Capper Jude L. , Moran Dominic , Mrode Raphael , Djikeng Appolinaire
Published: October 2022

The paper reports on the prevalence and performance of the Jersey cattle breed in Africa, highlighting its geographic distribution and describing the reported performance and other related characteristics from the early 1900s to the present day. The review examines the contribution of Jersey cattle in increasing the volume and efficiency of milk production across the continent. Data relating to the Jersey cattle breed has been reported in more than 30 African countries based on available material published between 1964 and 2020. A key encompassing parameter of any reference was a well-described consideration of the Jersey cattle breed (as pure or crossbred with other exotic and/or indigenous breeds) with reported performance within a variety of production systems and agro-ecologies in Africa. The main focus was on breed and performance parameters, breed types, percentage of different breed types in specific environments, reproduction method and fertility; survival and longevity; disease incidence; and production efficiency metrics such as: feed efficiency (milk unit per dry matter intake, DMI) and milk yield (MY) per unit of body weight (BW). The main performance descriptors identified were based on observations on resilience under both abiotic (heat, nutrition) and biotic (incidences of pests and diseases) stressors, milk production, BW, nutrition and utilisation of feed resources. From the literature consulted, we grouped key dairy cattle performance characteristics reported in each country under the following areas to aid comparisons; a. Milk production (Milk nutrient value, daily MY, lifetime MY and annual MY); b. Fertility traits and AFC; c. Survival and longevity, d. Production efficiency (Feed efficiency, milk per unit BW and milk per unit DMI and e. Disease incidences. Results of the review showed that the smaller stature and lower maintenance nutrient requirements of the Jersey breed means that it is better suited to tolerate the tropical production conditions in the African small-scale dairy farming sector. Detailed analyses on MY and survival showed that Jersey crosses with exotic and African indigenous breeds performed better than purebred cattle with strong evidence to support the suitability of the Jersey breed in crossbreeding with indigenous breeds for use in smallholder production systems.
Dysregulation and chronicity of pathogenic T cell responses in the pre-diseased stage of lupus
Authors: Ohmes Justus , Comdühr Sara , Akbarzadeh Reza , Riemekasten Gabriela , Humrich Jens Y.
Published: October 2022

In the normal immune system, T cell activation is tightly regulated and controlled at several levels to ensure that activation occurs in the right context to prevent the development of pathologic conditions such as autoimmunity or other harmful immune responses. CD4+FoxP3+regulatory T cells (Treg) are crucial for the regulation of T cell responses in the peripheral lymphatic organs and thus for the prevention and control of autoimmunity. In systemic lupus erythematosus (SLE), a prototypic systemic autoimmune disease with complex etiology, a disbalance between Treg and pathogenic effector/memory CD4+T cells develops during disease progression indicating that gradual loss of control over T cell activation is an important event in the immune pathogenesis. This progressive failure to adequately regulate the activation of autoreactive T cells facilitates chronic activation and effector/memory differentiation of pathogenic T cells, which are considered to contribute significantly to the induction and perpetuation of autoimmune processes and tissue inflammation in SLE. However, in particular in humans, little is known about the factors which drive the escape from immune regulation and the chronicity of pathogenic T cell responses in an early stage of autoimmune disease when clinical symptoms are still unapparent. Here we briefly summarize important findings and discuss current views and models on the mechanisms related to the dysregulation of T cell responses which promotes chronicity and pathogenic memory differentiation with a focus on the early stage of disease in lupus-prone individuals.
Blood transcriptome analysis revealed the crosstalk between COVID-19 and HIV
Authors: Yan Cheng , Niu Yandie , Wang Xuannian
Published: October 2022

Background

The severe coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has resulted in the most devastating pandemic in modern history. Human immunodeficiency virus (HIV) destroys immune system cells and weakens the body’s ability to resist daily infections and diseases. Furthermore, HIV-infected individuals had double COVID-19 mortality risk and experienced worse COVID-related outcomes. However, the existing research still lacks the understanding of the molecular mechanism underlying crosstalk between COVID-19 and HIV. The aim of our work was to illustrate blood transcriptome crosstalk between COVID-19 and HIV and to provide potential drugs that might be useful for the treatment of HIV-infected COVID-19 patients.

Methods

COVID-19 datasets (GSE171110 and GSE152418) were downloaded from Gene Expression Omnibus (GEO) database, including 54 whole-blood samples and 33 peripheral blood mononuclear cells samples, respectively. HIV dataset (GSE37250) was also obtained from GEO database, containing 537 whole-blood samples. Next, the “Deseq2” package was used to identify differentially expressed genes (DEGs) between COVID-19 datasets (GSE171110 and GSE152418) and the “limma” package was utilized to identify DEGs between HIV dataset (GSE37250). By intersecting these two DEG sets, we generated common DEGs for further analysis, containing Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) functional enrichment analysis, protein-protein interaction (PPI) analysis, transcription factor (TF) candidate identification, microRNAs (miRNAs) candidate identification and drug candidate identification.

Results

In this study, a total of 3213 DEGs were identified from the merged COVID-19 dataset (GSE171110 and GSE152418), and 1718 DEGs were obtained from GSE37250 dataset. Then, we identified 394 common DEGs from the intersection of the DEGs in COVID-19 and HIV datasets. GO and KEGG enrichment analysis indicated that common DEGs were mainly gathered in chromosome-related and cell cycle-related signal pathways. Top ten hub genes (CCNA2, CCNB1, CDC20, TOP2A, AURKB, PLK1, BUB1B, KIF11, DLGAP5, RRM2) were ranked according to their scores, which were screened out using degree algorithm on the basis of common DEGs. Moreover, top ten drug candidates (LUCANTHONE, Dasatinib, etoposide, Enterolactone, troglitazone, testosterone, estradiol, calcitriol, resveratrol, tetradioxin) ranked by their P values were screened out, which maybe be beneficial for the treatment of HIV-infected COVID-19 patients.

Conclusion

In this study, we provide potential molecular targets, signaling pathways, small molecular compounds, and promising biomarkers that contribute to worse COVID-19 prognosis in patients with HIV, which might contribute to precise diagnosis and treatment for HIV-infected COVID-19 patients.
Comparative transcriptomics reveals small RNA composition and differential microRNA responses underlying interferon-mediated antiviral regulation in porcine alveolar macrophages
Authors: Li Jiuyi , Sang Eric R. , Adeyemi Oluwaseun , Miller Laura C. , Sang Yongming
Published: October 2022

Previous studies have shown that interferon-mediated antiviral activity is subtype-dependent. Using a whole transcriptome procedure, we aimed to characterize the small RNA transcriptome (sRNA-Seq) and specifically the differential microRNA (miRNA) responses in porcine alveolar macrophages (PAMs) upon antiviral activation during viral infection and interferon (IFN) stimulation. Data showed that near 90% of the qualified reads of sRNA were miRNAs, and about 10% of the other sRNAs included rRNA, snoRNA, snRNA, and tRNA in order of enrichment. As the majority of sRNA (>98%) were commonly detected in all PAM samples under different treatments, about 2% sRNA were differentially expressed between the different antiviral treatments. Focusing on miRNA, 386 miRNA were profiled, including 331 known and 55 novel miRNA sequences, of which most were ascribed to miRNA families conserved among vertebrates, particularly mammalian species. Of the miRNA profiles comparably generated across the different treatments, in general, significantly differentially expressed miRNA (SEM) demonstrated that: (1) the wild-type and vaccine strains of a porcine arterivirus (a.k.a., PRRSV) induced nearly reversed patterns of up- or down-regulated SEMs; (2) similar SEM patterns were found among the treatments by the vaccine strain and antiviral IFN-α1/-ω5 subtypes; and (3) the weak antiviral IFN-ω1, however, remarked a suppressive SEM pattern as to SEMs upregulated in the antiviral treatments by the vaccine and IFN-α1/-ω5 subtypes. Further articulation identified SEMs commonly or uniquely expressed in different treatments, and experimentally validated that some SEMs including miR-10b and particularly miR-9-1 acted significantly in regulation of differential antiviral reactions stimulated by different IFN subtypes. Therefore, this study provides a general picture of porcine sRNA composition and pinpoints key SEMs underlying antiviral regulation in PAMs correlated to a typical respiratory RNA virus in pigs.
The effect of prolactin on immune cell subsets involved in SLE pathogenesis
Authors: Legorreta-Haquet Maria Victoria , Santana-Sánchez Paola , Chávez-Sánchez Luis , Chávez-Rueda Adriana Karina
Published: October 2022

The higher frequency of autoimmune diseases in the female population compared to males suggests that certain hormones, such as prolactin (PRL), play a role in determining the prevalence of autoimmunity in women, particularly during childbearing age. PRL can act not only as a hormone but also as a cytokine, being able to modulate immune responses. Hyperprolactinemia has been implicated in the pathogenesis of various autoimmune diseases where it may affect disease activity. One of the conditions where PRL has such a role is systemic lupus erythematosus (SLE). PRL regulates the proliferation and survival of both lymphoid and myeloid cells. It also affects the selection of T-cell repertoires by influencing the thymic microenvironment. In autoimmune conditions, PRL interferes with the activity of regulatory T cells. It also influences B cell tolerance by lowering the activation threshold of anergic B cells. The production of CD40L and cytokines, such as interleukin IL-6, are also promoted by PRL. This, in turn, leads to the production of autoantibodies, one of the hallmarks of SLE. PRL increases the cytotoxic activity of T lymphocytes and the secretion of proinflammatory cytokines. The production of proinflammatory cytokines, particularly those belonging to the type 1 interferon (IFN) family, is part of the SLE characteristic genetic signature. PRL also participates in the maturation and differentiation of dendritic cells, promoting the presentation of autoantigens and high IFNα secretion. It also affects neutrophil function and the production of neutrophil traps. Macrophages and dendritic cells can also be affected by PRL, linking this molecule to the abnormal behavior of both innate and adaptive immune responses.This review aimed to highlight the importance of PRL and its actions on the cells of innate and adaptive immune responses. Additionally, by elucidating the role of PRL in SLE etiopathogenesis, this work will contribute to a better understanding of the factors involved in SLE development and regulation.
Tumor-infiltrating lymphocytes for treatment of solid tumors: It takes two to tango?
Authors: Kazemi Mohammad Hossein , Sadri Maryam , Najafi Alireza , Rahimi Ali , Baghernejadan Zeinab , Khorramdelazad Hossein , Falak Reza
Published: October 2022

Tumor-infiltrating lymphocytes (TILs), frontline soldiers of the adaptive immune system, are recruited into the tumor site to fight against tumors. However, their small number and reduced activity limit their ability to overcome the tumor. Enhancement of TILs number and activity against tumors has been of interest for a long time. A lack of knowledge about the tumor microenvironment (TME) has limited success in primary TIL therapies. Although the advent of engineered T cells has revolutionized the immunotherapy methods of hematologic cancers, the heterogeneity of solid tumors warrants the application of TILs with a wide range of specificity. Recent advances in understanding TME, immune exhaustion, and immune checkpoints have paved the way for TIL therapy regimens. Nowadays, TIL therapy has regained attention as a safe personalized immunotherapy, and currently, several clinical trials are evaluating the efficacy of TIL therapy in patients who have failed conventional immunotherapies. Gaining favorable outcomes following TIL therapy of patients with metastatic melanoma, cervical cancer, ovarian cancer, and breast cancer has raised hope in patients with refractory solid tumors, too. Nevertheless, TIL therapy procedures face several challenges, such as high cost, timely expansion, and technical challenges in selecting and activating the cells. Herein, we reviewed the recent advances in the TIL therapy of solid tumors and discussed the challenges and perspectives.
IL-7: A promising adjuvant ensuring effective T cell responses and memory in combination with cancer vaccines?
Authors: Zhao Yue , Wei Kongyuan , Chi Hao , Xia Zhijia , Li Xiaosong
Published: October 2022

Cancer vaccines exhibit specificity, effectiveness, and safety as an alternative immunotherapeutic strategy to struggle against malignant diseases, especially with the rapid development of mRNA cancer vaccines in recent years. However, how to maintain long-term immune memory after vaccination, especially T cells memory, to fulfill lasting surveillance against cancers, is still a challenging issue for researchers all over the world. IL-7 is critical for the development, maintenance, and proliferation of T lymphocytes, highlighting its potential role as an adjuvant in the development of cancer vaccines. Here, we summarized the IL-7/IL-7 receptor signaling in the development of T lymphocytes, the biological function of IL-7 in the maintenance and survival of T lymphocytes, the performance of IL-7 in pre-clinical and clinical trials of cancer vaccines, and the rationale to apply IL-7 as an adjuvant in cancer vaccine-based therapeutic strategy.
Research progress of bile biomarkers and their immunoregulatory role in biliary tract cancers
Authors: Li Yun-cheng , Li Kang-shuai , Liu Zeng-li , Tang Yong-chang , Hu Xiao-Qiang , Li Xing-yong , Shi An-da , Zhao Li-ming , Shu Li-Zhuang , Lian Shuo , Yan Zhang-di , Huang Shao-hui , Sheng Guo-li , Song Yan , Liu Yun-jia , Huan Fan , Zhang Ming-hui , Zhang Zong-li
Published: October 2022

Biliary tract cancers (BTCs), including cholangiocarcinoma and gallbladder carcinoma, originate from the biliary epithelium and have a poor prognosis. Surgery is the only choice for cure in the early stage of disease. However, most patients are diagnosed in the advanced stage and lose the chance for surgery. Early diagnosis could significantly improve the prognosis of patients. Bile has complex components and is in direct contact with biliary tract tumors. Bile components are closely related to the occurrence and development of biliary tract tumors and may be applied as biomarkers for BTCs. Meanwhile, arising evidence has confirmed the immunoregulatory role of bile components. In this review, we aim to summarize and discuss the relationship between bile components and biliary tract cancers and their ability as biomarkers for BTCs, highlighting the role of bile components in regulating immune response, and their promising application prospects.
Phage therapy for Clostridioides difficile infection
Authors: Fujimoto Kosuke , Uematsu Satoshi
Published: October 2022

Clostridioides difficile is endemic in the intestinal tract of healthy people. However, it is responsible for many healthcare-associated infections, such as nosocomial diarrhea following antibiotic treatment. Importantly, there have been cases of unsuccessful treatment and relapse related to the emergence of highly virulent strains of C. difficile and resistance to antimicrobial agents. Fecal microbiota transplantation (FMT) is considered an effective therapy for recurrent C. difficile infection. However, its safety is of concern because deaths caused by antibiotic-resistant bacterial infections after FMT were reported. Therefore, the development of effective C. difficile-specific treatments is urgently needed. In this review, we summarize the importance of phage therapy against C. difficile, and describe a novel next-generation phage therapy developed using metagenomic data.
Identification of a novel sepsis prognosis model and analysis of possible drug application prospects: Based on scRNA-seq and RNA-seq data
Authors: He Haihong , Huang Tingting , Guo Shixing , Yu Fan , Shen Hongwei , Shao Haibin , Chen Keyan , Zhang Lijun , Wu Yunfeng , Tang Xi , Yuan Xinhua , Liu Jiao , Zhou Yiwen
Published: October 2022

Sepsis is a disease with a high morbidity and mortality rate. At present, there is a lack of ideal biomarker prognostic models for sepsis and promising studies using prognostic models to predict and guide the clinical use of medications. In this study, 71 differentially expressed genes (DEGs) were obtained by analyzing single-cell RNA sequencing (scRNA-seq) and transcriptome RNA-seq data, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analyses were performed on these genes. Then, a prognosis model with CCL5, HBD, IFR2BP2, LTB, and WFDC1 as prognostic signatures was successfully constructed after univariate LASSO regression analysis and multivariate Cox regression analysis. Kaplan–Meier (K-M) survival analysis, receiver operating characteristic (ROC) time curve analysis, internal validation, and principal component analysis (PCA) further validated the model for its high stability and predictive power. Furthermore, based on a risk prediction model, gene set enrichment analysis (GSEA) showed that multiple cellular functions and immune function signaling pathways were significantly different between the high- and low-risk groups. In-depth analysis of the distribution of immune cells in healthy individuals and sepsis patients using scRNA-seq data revealed immunosuppression in sepsis patients and differences in the abundance of immune cells between the high- and low-risk groups. Finally, the genetic targets of immunosuppression-related drugs were used to accurately predict the potential use of clinical agents in high-risk patients with sepsis.
Anti-inflammatory, antioxidant and anti-virulence roles of atractylodin in attenuating Listeria monocytogenes infection
Authors: Xu Lei , Zhou Yonglin , Xu Jingwen , Xu Xiangzhu , Lu Gejin , Lv Qianghua , Wei Lijuan , Deng Xuming , Shen Xue , Feng Haihua , Wang Jianfeng
Published: October 2022

Background

Listeria monocytogenes (L. monocytogenes), as a pandemic foodborne pathogen, severely threatens food security and public health care worldwide, which evolves multiple bacterial virulence factors (such as listeriolysin O, LLO) for manipulating the immune response of L. monocytogenes-host interactions.

Methods

Hemolysis assay was employed to screen a potential LLO inhibitor and the underlying mechanisms were investigated using molecular dynamics (MD) simulation and oligomerization assay. The effects of candidates on immune response were examined by qRT-PCR and immunoblotting analysis. Histological analysis, ELISA assay and biochemistry detection were conducted to assess in vivo efficacy of candidates.

Results

In the present study, natural terpenoid atractylodin was characterized as an alternative drug candidate for the treatment of L. monocytogenes by the regulation of LLO function and host Nrf2/NLRP3 signaling pathway. Notably, in vivo infection model by L. monocytogenes also highlighted that atractylodin treatment provided effective therapeutic benefits, as evidenced by decreased bacterial burden and diminished inflammation. Congruently, the survival rate of L. monocytogenes-infection mice increased significantly from 10.0% to 40.0% by atractylodin treatment.

Conclusion

Collectively, our study showed for the first time that atractylodin has tremendous potential to attenuate L. monocytogenes pathogenicity by blocking LLO pore formation and mediating the suppression of inflammation and oxidative stress, providing a promising therapeutic strategy and broadening the applications of atractylodin against L. monocytogenes infection.
Overexpression of transcriptional regulator and tailoring enzyme leads to the discovery of anti-inflammatory meroterpenoids from marine-derived fungus Alternaria alternata JJY-32
Authors: Liu Guowei , Liu Dan , Li Zongyuan , Jiao Jieying , Hou Xuewen , Zhang Xiaomin , Che Qian , Zhu Tianjiao , Li Dehai , Zhang Guojian
Published: October 2022

Four new ACTG-toxins like meroterpenoids tricycloalternarenes O-R were discovered from a marine-derived fungus Alternaria alternata JJY-32 by the overexpression of a LaeA-like global transcriptional regulator and a MpaB-like biosynthetic tailoring enzyme. Among those structures, tricycloalternarene O possesses a non-canonical cyclohexanone-pyran fused furan ring structure and tricycloalternarene R contains a truncated isoprenoid terminal. The structures were elucidated based on comprehensive 1D and 2D NMR data and assisted by ECD calculations. Tricycloalternarenes O-R showed potent anti-inflammatory activity in TLR4-transfected microphage cells (RAW264.7).
Experimental investigations on the hydrodynamics of a multi-body floating aquaculture platform exposed to sloping seabed environment
Authors: Zhao Yunpeng , Xie Sida , Ma Chao
Published: October 2022

The coastal area near islands has become a key area for aquaculture because of the long offshore distance and suitable wave conditions. There is a topographic change near the islands, and the reflected waves generated by the topography modify the wave field in the aquaculture area, which may cause structural damage to the offshore net cage. Most studies on the hydrodynamic characteristics of aquaculture structures do not consider the effects of topography. Therefore, we investigated the hydrodynamic characteristics and wave field of a multi-body floating aquaculture platform under the influence of sloping seabed by leveraging a physical model approach. The results show that the low-frequency component of the surge motion of the cage on the weather side increases significantly under the influence of sloping seabed. However, the heave and pitch motions change slightly. Considering the presence of the sloping seabed, the wave elevations inside cages have been changed too., The wave breaking inside the cage on the weather side becomes more evident when the incident wavelength is equal to the width of the cage. And its wave response gradually shifts from wave frequency to high frequency. Regarding the cage on the lee side, the wave response inside it is positively correlated with the incident wavelength. The results of this study provide a reference for the design and optimization of aquaculture structures anchored near islands.
A Lagrangian model-based physical connectivity atlas of the Red Sea coral reefs
Authors: Wang Yixin , Raitsos Dionysios E. , Krokos George , Zhan Peng , Hoteit Ibrahim
Published: October 2022

Connectivity, the exchange of individuals and genes among geographically separated marine populations, plays a key role in coral reef biodiversity and resilience. The Red Sea is a semi-enclosed basin with dynamic circulation and abundant coral reefs, making it a natural laboratory for coral reef connectivity research. Previous studies broadly investigated Red Sea connectivity, but were spatially restricted to regional or sparsely-distributed reef sites. Here, using hydrodynamic and particle tracking models, a high-resolution circulation-driven physical connectivity atlas covering every Red Sea coral reef, including seasonality, was simulated and further validated against availablein-situgenetic datasets. The simulation was conducted without incorporating larval traits to isolate and quantify the connectivity contributed by circulation. Our validation experiment suggests the importance of circulation in shaping the genetic structure of Red Sea reef species, supporting the Isolation By Circulation (IBC) theory in the Red Sea seascape genetics. The simulated atlas reveals that reefs in the northern Red Sea are better sources and destinations than those in the southern basin, regardless of season. The east-west connections between the southern reefs are identified to be weak. Complex circulation dynamics drive a regional-specific seasonality, e.g., the Farasan Islands reefs are better sources during summer while the nearby Bab-Al-Mandeb strait reefs are better sources during winter. The west-coast reefs are generally winter-intensified sources whereas the east-coast reefs are generally summer-intensified sources. The revealed seasonality of physical connectivity is important for larval dispersal processes as reef species may spawn in different seasons. This physical connectivity atlas provides a reference for designing marine conservation strategies from a circulation perspective and easy-to-access physical connectivity datasets for the future Red Sea seascape genetic studies.
Methylene blue dosing strategies in critically ill adults with shock—A retrospective cohort study
Authors: Sari-Yavuz Sibel , Heck-Swain Ka-Lin , Keller Marius , Magunia Harry , Feng You-Shan , Haeberle Helene A. , Wied Petra , Schlensak Christian , Rosenberger Peter , Koeppen Michael
Published: October 2022

Background

Shock increases mortality in the critically ill and the mainstay of therapy is the administration of vasopressor agents to achieve hemodynamic targets. In the past, studies have found that the NO-pathway antagonist methylene blue improves hemodynamics. However, the optimal dosing strategy remains elusive. Therefore, we investigated the hemodynamic and ICU outcome parameters of three different dosing strategies for methylene blue.

Methods

We performed a retrospective cohort study of patients in shock treated with methylene blue. Shock was defined as norepinephrine dose >0.1 μg/kg/min and serum lactate level >2 mmol/l at the start of methylene blue administration. Different demographic variables, ICU treatment, and outcome parameters were evaluated. To compare the differences in the administration of vasopressors or inotropes, the vasoactive inotropic score (VIS) was calculated at different time points after starting the administration of methylene blue. Response to methylene blue or mortality at 28 days were assessed.

Results

262 patients from July 2014 to October 2019 received methylene blue. 209 patients met the inclusion criteria. Three different dosing strategies were identified: bolus injection followed by continuous infusion (n = 111), bolus injection only (no continuous infusion; n = 59) or continuous infusion only (no bolus prior; n = 39). The groups did not differ in demographics, ICU scoring system, or comorbidities. In all groups, VIS decreased over time, indicating improved hemodynamics. Cardiogenic shock and higher doses of norepinephrine increased the chance of responding to methylene blue, while bolus only decreased the chance of responding to methylene blue treatment. 28-day mortality increased with higher SAPSII scores and higher serum lactate levels, while bolus injection followed by continuous infusion decreased 28-day mortality. No severe side effects were noted.

Conclusion

In this cohort, methylene blue as a bolus injection followed by continuous infusion was associated with a reduced 28-day mortality in patients with shock. Prospective studies are needed to systematically evaluate the role of methylene blue in the treatment of shock.