bluuebunny/crossref_metadata_2025 huggingface dataset:
Histamine activates an intracellular Ca2+ signal in normal human lung fibroblast WI-38 cells
Authors: Berra-Romani Roberto , Vargaz-Guadarrama Ajelet , Sánchez-Gómez Josué , Coyotl-Santiago Nayeli , Hernández-Arambide Efraín , Avelino-Cruz José Everardo , García-Carrasco Mario , Savio Monica , Pellavio Giorgia , Laforenza Umberto , Lagunas-Martínez Alfredo , Moccia Francesco
Published: September 2022

Histamine is an inflammatory mediator that can be released from mast cells to induce airway remodeling and cause persistent airflow limitation in asthma. In addition to stimulating airway smooth muscle cell constriction and hyperplasia, histamine promotes pulmonary remodeling by inducing fibroblast proliferation, contraction, and migration. It has long been known that histamine receptor 1 (H1R) mediates the effects of histamine on human pulmonary fibroblasts through an increase in intracellular Ca2+concentration ([Ca2+]i), but the underlying signaling mechanisms are still unknown. Herein, we exploited single-cell Ca2+imaging to assess the signal transduction pathways whereby histamine generates intracellular Ca2+signals in the human fetal lung fibroblast cell line, WI-38. WI-38 fibroblasts were loaded with the Ca2+-sensitive fluorophore, FURA-2/AM, and challenged with histamine in the absence and presence of specific pharmacological inhibitors to dissect the Ca2+release/entry pathways responsible for the onset of the Ca2+response. Histamine elicited complex intracellular Ca2+signatures in WI-38 fibroblasts throughout a concentration range spanning between 1 µM and 1 mM. In accord, the Ca2+response to histamine adopted four main temporal patterns, which were, respectively, termed peak, peak-oscillations, peak-plateau-oscillations, and peak-plateau. Histamine-evoked intracellular Ca2+signals were abolished by pyrilamine, which selectively blocks H1R, and significantly reduced by ranitidine, which selectively inhibits H2R. Conversely, the pharmacological blockade of H3R and H4R did not affect the complex increase in [Ca2+]ievoked by histamine in WI-38 fibroblasts. In agreement with these findings, histamine-induced intracellular Ca2+signals were initiated by intracellular Ca2+release from the endoplasmic reticulum through inositol-1,4,5-trisphosphate (InsP3) receptors (InsP3R) and sustained by store-operated Ca2+channels (SOCs). Conversely, L-type voltage-operated Ca2+channels did not support histamine-induced extracellular Ca2+entry. A preliminary transcriptomic analysis confirmed that WI-38 human lung fibroblasts express all the three InsP3R isoforms as well as STIM2 and Orai3, which represent the molecular components of SOCs. The pharmacological blockade of InsP3and SOC, therefore, could represent an alternative strategy to prevent the pernicious effects of histamine on lung fibroblasts in asthmatic patients.
Photocatalytic Activity Induced by Metal Nanoparticles Synthesized by Sustainable Approaches: A Comprehensive Review
Authors: Krishna Prashanth Gopala , Chandra Mishra Prabhu , Naika Mutthuraju Mahadev , Gadewar Manoj , Ananthaswamy Prashanth Paduvarahalli , Rao Srilatha , Boselin Prabhu Sivadhas Rosejanet , Yatish Kalanakoppal Venkatesh , Nagendra Holenarasipura Gundurao , Moustafa Mahmoud , Al-Shehri Mohammed , Jha Saurabh Kumar , Lal Bharat , Stephen Santhakumari Sreeja Mole
Published: September 2022

Nanotechnology is a fast-expanding area with a wide range of applications in science, engineering, health, pharmacy, and other fields. Among many techniques that are employed toward the production of nanoparticles, synthesis using green technologies is the simplest and environment friendly. Nanoparticles produced from plant extracts have become a very popular subject of study in recent decades due to their diverse advantages such as low-cost synthesis, product stability, and ecofriendly protocols. These merits have prompted the development of nanoparticles from a variety of sources, including bacteria, fungi, algae, proteins, enzymes, etc., allowing for large-scale production with minimal contamination. However, nanoparticles obtained from plant extracts and phytochemicals exhibit greater reduction and stabilization and hence have proven the diversity of properties, like catalyst/photocatalyst, magnetic, antibacterial, cytotoxicity, circulating tumor deoxy ribo nucleic acid (CT-DNA) binding, gas sensing, etc. In the current scenario, nanoparticles can also play a critical role in cleaning wastewater and making it viable for a variety of operations. Nano-sized photocatalysts have a great scope toward the removal of large pollutants like organic dyes, heavy metals, and pesticides in an eco-friendly and sustainable manner from industrial effluents. Thus, in this review article, we discuss the synthesis of several metal nanoparticles using diverse plant extracts, as well as their characterization via techniques like UV–vis (ultraviolet–visible), XRD (X-ray diffraction), SEM (scanning electron microscopy), TEM (transmission electron microscopy), FTIR (Fourier transform infrared spectroscopy), etc., and catalytic activity on various hazardous systems.
Development and validation of a machine learned algorithm to IDENTIFY functionally significant coronary artery disease
Authors: Stuckey Thomas , Meine Frederick , McMinn Thomas , Depta Jeremiah P. , Bennett Brett , McGarry Thomas , Carroll William , Suh David , Steuter John A. , Roberts Michael , Gillins Horace R. , Lange Emmanuel , Fathieh Farhad , Burton Timothy , Khosousi Ali , Shadforth Ian , Sanders William E. , Rabbat Mark G.
Published: September 2022

Introduction

Multiple trials have demonstrated broad performance ranges for tests attempting to detect coronary artery disease. The most common test, SPECT, requires capital-intensive equipment, the use of radionuclides, induction of stress, and time off work and/or travel. Presented here are the development and clinical validation of an office-based machine learned algorithm to identify functionally significant coronary artery disease without radiation, expensive equipment or induced patient stress.

Materials and methods

The IDENTIFY trial (NCT03864081) is a prospective, multicenter, non-randomized, selectively blinded, repository study to collect acquired signals paired with subject meta-data, including outcomes, from subjects with symptoms of coronary artery disease. Time synchronized orthogonal voltage gradient and photoplethysmographic signals were collected for 230 seconds from recumbent subjects at rest within seven days of either left heart catheterization or coronary computed tomography angiography. Following machine learning on a proportion of these data (N = 2,522), a final algorithm was selected, along with a pre-specified cut point on the receiver operating characteristic curve for clinical validation. An unseen set of subject signals (N = 965) was used to validate the algorithm.

Results

At the pre-specified cut point, the sensitivity for detecting functionally significant coronary artery disease was 0.73 (95% CI: 0.68–0.78), and the specificity was 0.68 (0.62–0.74). There exists a point on the receiver operating characteristic curve at which the negative predictive value is the same as coronary computed tomographic angiography, 0.99, assuming a disease incidence of 0.04, yielding sensitivity of 0.89 and specificity of 0.42. Selecting a point at which the positive predictive value is maximized, 0.12, yields sensitivity of 0.39 and specificity of 0.88.

Conclusion

The performance of the machine learned algorithm presented here is comparable to common tertiary center testing for coronary artery disease. Employing multiple cut points on the receiver operating characteristic curve can yield the negative predictive value of coronary computed tomographic angiography and a positive predictive value approaching that of myocardial perfusion imaging. As such, a system employing this algorithm may address the need for a non-invasive, no radiation, no stress, front line test, and hence offer significant advantages to the patient, their physician, and healthcare system.
Application of a new ultrasound criterion for the diagnosis of polycystic ovary syndrome
Authors: Giménez-Peralta Iván , Lilue Mariela , Mendoza Nicolás , Tesarik Jan , Mazheika Marina
Published: September 2022

Objective

To define which ultrasound criteria could replace the classic Rotterdam criteria as the best indicator of the risk of developing endocrine–metabolic changes in women with polycystic ovary syndrome (PCOS).

Materials and methods

This multicenter cross-sectional study included 200 women with PCOS and one control group of 111 women without PCOS. The primary outcomes to be considered were follicular count, hirsutism, total testosterone levels, free androgen index (FAI), and insulin sensitivity (HOMA-IR), and the secondary outcome was the anti-Müllerian hormone (AMH) level.

Results

The main finding in this study points toward a different ultrasound criterion—23 or more follicles of any size in at least one ovary, which is postulated as an alternative to the classic criterion described in the Rotterdam consensus. This criterion correlates better with the other two PCOS criteria and also identifies women at increased risk of hirsutism (Ferriman–Gallwey score: 6.08 ± 3.54 vs. 4.44 ± 3.75, p < 0.0001), total testosterone levels (2.24 ± 0.298 vs. 1.42 ± 1.530, p = 0.0001), FAI (4.85 ± 0.83 vs. 2.12 ± 1.93, p < 0.001), and insulin resistance (HOMA-IR: 1.74 ± 0.182 vs. 1.504 ± 0.230, p = 0.001) more accurately. Regarding AMH, large differences in their mean values were observed between the groups (7.07 vs. 4.846 ng/ml, p = 0.000). However, these differences depended on age.

Conclusion

The ovarian ultrasound examination with 23 or more follicles of any size in any of the ovaries constitutes a powerful tool to accurately diagnose PCOS and to associate it with metabolic–endocrine processes such as hyperandrogenism and insulin resistance.
Risk of preterm birth for placenta previa or low-lying placenta and possible preventive interventions: A systematic review and meta-analysis
Authors: Jansen Charlotte H. J. R. , van Dijk Charlotte E. , Kleinrouweler C. Emily , Holzscherer Jacob J. , Smits Anouk C. , Limpens Jacqueline C. E. J. M. , Kazemier Brenda M. , van Leeuwen Elisabeth , Pajkrt Eva
Published: September 2022

Objective

To investigate the risk of preterm birth in women with a placenta previa or a low-lying placenta for different cut-offs of gestational age and to evaluate preventive interventions.

Search and methods

MEDLINE, EMBASE, CENTRAL, Web of Science, WHO-ICTRP and clinicaltrials.gov were searched until December 2021. Randomized controlled trials, cohort studies and case-control studies assessing preterm birth in women with placenta previa or low-lying placenta with a placental edge within 2 cm of the internal os in the second or third trimester were eligible for inclusion. Pooled proportions and odds ratios for the risk of preterm birth before 37, 34, 32 and 28 weeks of gestation were calculated. Additionally, the results of the evaluation of preventive interventions for preterm birth in these women are described.

Results

In total, 34 studies were included, 24 reporting on preterm birth and 9 on preventive interventions. The pooled proportions were 46% (95% CI [39 – 53%]), 17% (95% CI [11 – 25%]), 10% (95% CI [7 – 13%]) and 2% (95% CI [1 – 3%]), regarding preterm birth <37, <34, <32 and <28 weeks in women with placenta previa. For low-lying placentas the risk of preterm birth was 30% (95% CI [19 – 43%]) and 1% (95% CI [0 – 6%]) before 37 and 34 weeks, respectively. Women with a placenta previa were more likely to have a preterm birth compared to women with a low-lying placenta or women without a placenta previa for all gestational ages. The studies about preventive interventions all showed potential prolongation of pregnancy with the use of intramuscular progesterone, intramuscular progesterone + cerclage or pessary.

Conclusions

Both women with a placenta previa and a low-lying placenta have an increased risk of preterm birth. This increased risk is consistent across all severities of preterm birth between 28-37 weeks of gestation. Women with placenta previa have a higher risk of preterm birth than women with a low-lying placenta have. Cervical cerclage, pessary and intramuscular progesterone all might have benefit for both women with placenta previa and low-lying placenta, but data in this population are lacking and inconsistent, so that solid conclusions about their effectiveness cannot be drawn.

Systematic review registration

PROSPERO https://www.crd.york.ac.uk/prospero/, identifier CRD42019123675.
PRDX6: A protein bridging S-palmitoylation and diabetic neuropathy
Authors: Cao Yan , Wang Wantao , Zhan Xiaorong , Zhang Yitong
Published: September 2022

Diabetic neuropathy is regarded as one of the most debilitating outcomes of diabetes. It can affect both the peripheral and central nervous systems, leading to pain, decreased motility, cognitive decline, and dementia. S-palmitoylation is a reversible posttranslational lipid modification, and its dysregulation has been implicated in metabolic syndrome, cancers, neurological disorders, and infections. However, the role of S-palmitoylation in diabetic neuropathy remains unclear. Here we demonstrate a potential association between activating protein palmitoylation and diabetic neuropathy. We compared the proteomic data of lumbar dorsal root ganglia (DRG) of diabetes mice and palmitoylome profiling data of the HUVEC cell line. The mapping results identified peroxiredoxin-6 (PRDX6) as a novel target in diabetic neuropathy, whose biological mechanism was associated with S-palmitoylation. Bioinformatic prediction revealed that PRDX6 had two palmitoylation sites, Cys47 and Cys91. Immunofluorescence results indicated PRDX6 translocating between the cytoplasm and cell membrane. Protein function analysis proposed that increased palmitoylation could competitively inhibit the formation of disulfide-bond between Cys47 and Cys91 and change the spatial topology of PRDX6 protein. Cl–HCO3- anion exchanger 3 (AE3) was one of the AE family members, which was proved to express in DRG. AE3 activity evoked Cl- influx in neurons which was generally associated with increased excitability and susceptibility to pain. We demonstrated that the S-palmitoylation status of Cys47 could affect the interaction between PRDX6 and the C-terminal domain of AE3, thereby regulating the activity of AE3 anion exchanger enzyme in the nervous system. The results highlight a central role for PRDX6 palmitoylation in protection against diabetic neuropathy.
Blockchain-based bilateral bidding market mechanism with carbon allocation on both supply and demand sides
Authors: Luo Renjie , Wang Hanyi , Deng Hui , Jiang Haiyang , Xu Chengwei , Li Zhiyi
Published: September 2022

Recently, the interaction between power generation and load has been continuously strengthened, providing a new method for realizing the decarbonization of the power system. An auction method that enables a low-carbon economic dispatch is designed in this study, where blockchain technology is employed to record the whole process data credibly. According to the regional division of market entities, carbon emissions are allocated to regions and entities by using the Owen value method. In order to reduce the expected carbon emission of entities, an additional carbon price is added to the original quotation through the allocation results. Case studies are conducted based on the typical output characteristics of wind and photovoltaic power generation in the bilateral bidding market hourly. The results have validated that the proposed method can reduce expected carbon emissions in the power system by prioritizing zero-carbon and low-carbon generation units.
Logistics performance and environmental sustainability: Do green innovation, renewable energy, and economic globalization matter?
Authors: Wan Bin , Wan Weiqing , Hanif Nadia , Ahmed Zahoor
Published: September 2022

The logistics sector plays an imperative role in the economic development of a country. However, it can also affect environmental quality as it the viewed as a major energy-consuming sector. The current literature on the relationship between logistics performance and environmental quality is scant and most studies neglect its environmental impact in the context of emerging countries. In this context, this study investigates the impact of logistics performance index (LPI), green innovation, renewable energy, and economic globalization on the environmental quality in the 22 emerging countries. Using the panel data from 2007 to 2018, we employed the Method of Moments Quantile Regression (MM-QR) for empirical analysis. The empirical results show that LPI deteriorates the environmental quality by increasing CO2 emissions across all quantiles (10th–90th). Moreover, green innovation is significantly and negatively related to CO2 emission in all the quantiles except at the 10th quantiles, while renewable energy use significantly improves the environmental quality across all quantiles (10th–90th). Economic globalization shows a significant and negative impact on CO2 emission across quantiles (10th–90th) in emerging countries. Based on these findings, this study proposes that emerging countries need to align their logistics sector policies with sustainable development goals. At the same time, more resources should be allocated for green innovation and the renewable energy sector and promote economic globalization to foster sustainable development.
Linc00996 is a favorable prognostic factor in LUAD: Results from bioinformatics analysis and experimental validation
Authors: Shen Zhenghai , Li Xin , Hu Zaoxiu , Yang Yanlong , Yang Zhenghong , Li Shanshan , Zhou Yongchun , Ma Jie , Li Hongsheng , Liu Xi , Cai Jingjing , Pu Lisa , Wang Xiaoxiong , Huang Yunchao
Published: September 2022

Background: Linc00996 has been reported in a variety of malignant tumors, but its potential role and significance in lung adenocarcinoma (LUAD) are not fully understood. The authors investigated the expression and biological behavior of Linc00996 in LUAD and elucidated the function of its potential target genes.

Materials and methods: The data of Linc00996 expression in cancers were derived from GEPIA. GEO and TCGA datasets were used to identify the differential expression of Linc00996 in LUAD and analyze the respective correlation between different expression levels and LUAD stage and survival prognosis. We further elucidated the potential biological processes and pathways involved with Linc00996 in LAUD by GSEA. ssGSEA was applied to explore the relationship between Linc00996 and immune activity. Finally, the clinical impact of Linc00996 was assessed in 61 patients with LUAD, and the biological functions of Linc00996 were determined by a series of experiments in vitro, such as CCK8, colony formation, migration, and invasion assays.

Results: Compared with adjacent normal lung tissues, Linc00996 was significantly downregulated in LUAD, and its expression was negatively correlated with T stage, N stage, and pathological stage. An in vitro study suggested that enhanced Linc00996 expression could inhibit cell proliferation, clonal formation, migration, and invasion in LUAD cell lines. Via GSEA and ssGSEA, we observed that Linc00996 might be connected with immune infiltration in LUAD, and Linc00996 might inhibit tumorigenesis and metastasis by regulating antigen processing and presentation, JAK-STAT3, and cell adhesion molecular signaling pathways.

Conclusion: Linc00996 is a novel tumor suppressor in LUAD and may suppress the tumorigenesis and metastasis of LUAD via the tumor-related signaling pathway, such as antigen processing and presentation, JAK-STAT3, and cell adhesion molecular signaling pathways.
Application of artificial liver in immune-related liver injury induced by immune checkpoint inhibitor: Case reports and review of the literature
Authors: Li Xuewei , Ji Lina , Li Xiaofang , Sun Dong , Yang Wenhui
Published: September 2022

The use of immune checkpoint inhibitors (ICIs) can improve survival of patients with malignant tumors, however, the ICI treatment is associated with unpredictable toxicity as immune-related adverse effects (irAEs). Here we report two cases of metastatic malignant gastrointestinal tumors where severe immune-mediated hepatotoxicity (IMH) developed, characterized by liver failure, after the ICI therapy. Through a strong immunosuppressive treatment and a non-biological artificial liver and supportive treatment, the liver function was restored in both cases, and the anti-tumor treatment effect was guaranteed. These results showed that the non-biological artificial liver could be capable of improve prognosis during the ICI therapy.
Gain-of-function defects in toll-like receptor 8 shed light on the interface between immune system and bone marrow failure disorders
Authors: Bleesing Jack
Published: September 2022

In this article, we will share lessons that patients with gain-of-function defects in Toll-like receptor 8 (TLR8-GOF) can teach us about the interface between bone marrow failure (BMF) disorders and inborn errors of immunity (IEI), subsequently referred to as “Interface Disorders”. TLR8-GOF is a relatively young entity (from a discovery standpoint) that—through both similar and dissimilar disease characteristics—can increase our understanding of interface disorders, for example, as it pertains to pathophysiology, the genetic mechanism of disease, and related diagnostics and therapeutics. From a genetics point of view, TLR8-GOF joins a growing list of (interface) disorders that can cause disease both with germline and somatic (mosaic) genetic variants. This not only has repercussions for the diagnostic workup of these disorders, inasmuch that routine genetic testing may miss somatic variants, but has therapeutic implications as well, for example, with the approach to curative treatment, such as hematopoietic stem cell transplantation. Following an introduction and schematic rendering of the interface, we will review the salient features of TLR8-GOF, with the understanding that the phenotype of this new disorder is likely not written in stone yet. In keeping with the principle of “Form Follows Function”, we will discuss specific immunological biomarkers that can be measured in clinical laboratories and highlight key disease features that pertain to TLR8-GOF, and can be found in several interface disorders. As can be seen from a schematic representation, the interface provides not only opportunities for learning and collaboration with respect to shared diagnostics but also the potential for drug repurposing and precision therapeutics. Ideally, collaboration also focuses on education and teaching, such that cross-fertilization and collaboration across these disciplines can create a framework for complementary research.
Increased serum level of alpha-2 macroglobulin and its production by B-lymphocytes in chronic lymphocytic leukemia
Authors: Michelis Regina , Milhem Lama , Galouk Evleen , Stemer Galia , Aviv Ariel , Tadmor Tamar , Shehadeh Mona , Shvidel Lev , Barhoum Masad , Braester Andrei
Published: September 2022

Chronic lymphocytic leukemia (CLL), the most common adult’s leukemia in the western world, is caused in 95% of the cases by uncontrolled proliferation of monoclonal B-lymphocytes. The complement system in CLL is chronically activated at a low level via the classical pathway (CP). This chronic activation is induced by IgG-hexamers, which are formed after binding to alpha-2-macroglobulin (A2M). The study investigated for the first time the serum levels of A2M in CLL patients, their association with the disease severity, and A2M production by the malignant B-lymphocytes. Blood samples were collected from 65 CLL patients and 30 normal controls (NC) subjects, and used for quantifications of the A2M levels, the complement activation marker (sC5b-9), the complement components C2, C3 and C4, and clinical biochemistry and hematology parameters. The production of A2M was studied in B-lymphocytes isolated from blood samples as well as in CLL and non-CLL cell lines.The serum A2M levels were significantly higher in CLL patients vs NCs, showing values of 3.62 ± 0.22 and 1.97 ± 0.10 mg/ml, respectively. Within the CLL group, A2M levels correlated significantly with the disease stage, with sC5b-9, and with clinical indicators of the disease severity. Increased A2M production was showed in three out of four CLL B-lymphocytic lines that were studied, as compared to non-CLL lines, to a non-lymphocytic line, and to blood-derived primary B-lymphocytes. A2M production was further increased both in primary cells and in the CLL cell-line after incubation with CLL sera, compared to NC sera. This study shows for the first time that serum A2M levels in CLL are significantly increased, likely due to A2M production by the malignant B-lymphocytes, and are correlated with the disease severity and with chronic complement activation. The moderate change in A2M production after incubation with NC sera in-vitro supports the hypothesis that inhibition of excess A2M production can be achieved, and that this may potentially down-regulate the IgG-hexamerization and the resulting chronic CP activation. This may also help restore complement system activity, and eventually improve complement activity and immunotherapy outcomes in CLL.
Outbreak of Ichthyophthirius multifiliis associated with Aeromonas hydrophila in Pangasianodon hypophthalmus: The role of turmeric oil in enhancing immunity and inducing resistance against co-infection
Authors: Kumar V. , Das B. K. , Swain H. S. , Chowdhury H. , Roy S. , Bera A. K. , Das R. , Parida S. N. , Dhar S. , Jana A. K. , Behera B. K.
Published: September 2022

Ichthyophthirius multifiliis, a ciliated parasite causing ichthyophthiriasis (white spot disease) in freshwater fishes, results in significant economic loss to the aquaculture sector. One of the important predisposing factors for ichthyophthiriasis is low water temperature (i.e., below 20°C), which affects the health and makes freshwater fishes more susceptible to parasitic infections. During ichthyophthiriasis, fishes are stressed and acute immune reactions are compromised, which enables the aquatic bacterial pathogens to simultaneously infect the host and increase the severity of disease. In the present work, we aimed to understand the parasite–bacteria co-infection mechanism in fish. Later, Curcuma longa (turmeric) essential oil was used as a promising management strategy to improve immunity and control co-infections in fish. A natural outbreak of I. multifiliis was reported (validated by 16S rRNA PCR and sequencing method) in Pangasianodon hypophthalmus from a culture facility of ICAR-CIFRI, India. The fish showed clinical signs including hemorrhage, ulcer, discoloration, and redness in the body surface. Further microbiological analysis revealed that Aeromonas hydrophila was associated (validated by 16S rRNA PCR and sequencing method) with the infection and mortality of P. hypophthalmus, confirmed by hemolysin and survival assay. This created a scenario of co-infections, where both infectious agents are active together, causing ichthyophthiriasis and motile Aeromonas septicemia (MAS) in P. hypophthalmus. Interestingly, turmeric oil supplementation induced protective immunity in P. hypophthalmus against the co-infection condition. The study showed that P. hypophthalmus fingerlings supplemented with turmeric oil, at an optimum concentration (10 ppm), exhibited significantly increased survival against co-infection. The optimum concentration induced anti-stress and antioxidative response in fingerlings, marked by a significant decrease in cortisol and elevated levels of superoxide dismutase (SOD) and catalase (CAT) in treated animals as compared with the controls. Furthermore, the study indicated that supplementation of turmeric oil increases both non-specific and specific immune response, and significantly higher values of immune genes (interleukin-1β, transferrin, and C3), HSP70, HSP90, and IgM were observed in P. hypophthalmus treatment groups. Our findings suggest that C. longa (turmeric) oil modulates stress, antioxidant, and immunological responses, probably contributing to enhanced protection in P. hypophthalmus. Hence, the application of turmeric oil treatment in aquaculture might become a management strategy to control co-infections in fishes. However, this hypothesis needs further validation.
Single-cell analysis of the adaptive immune response to SARS-CoV-2 infection and vaccination
Authors: Qi Furong , Cao Yingyin , Zhang Shuye , Zhang Zheng
Published: September 2022

Amid the ongoing Coronavirus Disease 2019 (COVID-19) pandemic, vaccination and early therapeutic interventions are the most effective means to combat and control the severity of the disease. Host immune responses to SARS-CoV-2 and its variants, particularly adaptive immune responses, should be fully understood to develop improved strategies to implement these measures. Single-cell multi-omic technologies, including flow cytometry, single-cell transcriptomics, and single-cell T-cell receptor (TCR) and B-cell receptor (BCR) profiling, offer a better solution to examine the protective or pathological immune responses and molecular mechanisms associated with SARS-CoV-2 infection, thus providing crucial support for the development of vaccines and therapeutics for COVID-19. Recent reviews have revealed the overall immune landscape of natural SARS-CoV-2 infection, and this review will focus on adaptive immune responses (including T cells and B cells) to SARS-CoV-2 revealed by single-cell multi-omics technologies. In addition, we explore how the single-cell analyses disclose the critical components of immune protection and pathogenesis during SARS-CoV-2 infection through the comparison between the adaptive immune responses induced by natural infection and by vaccination.
Multiple functions of heterogeneous nuclear ribonucleoproteins in the positive single-stranded RNA virus life cycle
Authors: Wang Jingming , Sun Di , Wang Mingshu , Cheng Anchun , Zhu Yukun , Mao Sai , Ou Xuming , Zhao Xinxin , Huang Juan , Gao Qun , Zhang Shaqiu , Yang Qiao , Wu Ying , Zhu Dekang , Jia Renyong , Chen Shun , Liu Mafeng
Published: September 2022

The heterogeneous nuclear ribonucleoproteins (hnRNPs) are a diverse family of RNA binding proteins that are implicated in RNA metabolism, such as alternative splicing, mRNA stabilization and translational regulation. According to their different cellular localization, hnRNPs display multiple functions. Most hnRNPs were predominantly located in the nucleus, but some of them could redistribute to the cytoplasm during virus infection. HnRNPs consist of different domains and motifs that enable these proteins to recognize predetermined nucleotide sequences. In the virus-host interactions, hnRNPs specifically bind to viral RNA or proteins. And some of the viral protein-hnRNP interactions require the viral RNA or other host factors as the intermediate. Through various mechanisms, hnRNPs could regulate viral translation, viral genome replication, the switch of translation to replication and virion release. This review highlights the common features and the distinguish roles of hnRNPs in the life cycle of positive single-stranded RNA viruses.
Ciltacabtagene autoleucel: The second anti-BCMA CAR T-cell therapeutic armamentarium of relapsed or refractory multiple myeloma
Authors: Chekol Abebe Endeshaw , Yibeltal Shiferaw Mestet , Tadele Admasu Fitalew , Asmamaw Dejenie Tadesse
Published: September 2022

Ciltacabtagene autoleucel (also known as cilta-cel) is a chimeric antigen receptor (CAR) T-cell therapy that targets B-cell maturation antigen (BCMA) on the surface of cancer cells in B cell malignancies, such as multiple myeloma (MM). It is a second-generation CAR that is outfitted with an ectodomain comprising two BCMA-binding single chain variable fragment (ScFv) domains, a transmembrane domain, and an endodomain possessing CD3ζ and 4-1BB. Cilta-cel is an autologous, gene-edited CAR T-cell that is prepared by collecting and modifying the recipient’s T-cells to create a patient personalized treatment in the laboratory to be infused back. This CAR T-cell product exceptionally entails CARs with two BCMA-targeting single-domain antibodies that detect two epitopes of BCMA expressed on the malignant cells of MM. Cilta-cel is the current addition to the treatment armamentarium of relapsed or refractory (r/r) MM after its approval by the FDA on February 28, 2022, based on the results of the Phase 1b/2 CARTITUDE-1 study. It was the second approved anti-BCMA CAR T-cell product after idecabtagene vicleucel (ide-cel) to treat myeloma patients. It induces early, deep, and long-lasting responses with a tolerable safety profile in r/r MM. Cilta-cel-treated myeloma patients may potentially experience adverse effects ranging from mild to life-threatening, but they are mostly manageable toxicities. Besides, it has a consistent safety profile upon a longer follow-up of patients. Cilta-cel generally outperforms ide cel in terms of efficacy in MM, but shows comparable adverse events. This review highlights the current updates on cilta-cel efficacy, adverse events, comparison with ide-cel, and its future direction in the treatment of MM.
Multiscale distribution patterns of pelagic rafts of sargasso (Sargassum spp.) in the Mexican Caribbean (2014–2020)
Authors: Uribe-Martínez Abigail , Berriel-Bueno Diana , Chávez Valeria , Cuevas Eduardo , Almeida Karla L. , Fontes Jassiel V. H. , van Tussenbroek Brigitta I. , Mariño-Tapia Ismael , Liceaga-Correa Maria de los Ángeles , Ojeda Elena , Castañeda-Ramírez D. Gerardo , Silva Rodolfo
Published: September 2022

As the biomass of pelagic Sargassum spp. increased across the North Atlantic equatorial recirculation region from 2011 onwards, massive rafts of sargasso appeared in the Western Caribbean in 2015, 2018, 2019, and 2020. These events raised concerns regarding their negative consequences on the environment, local income, and human wellbeing. As adequate monitoring and analysis tools are needed for designing in-water and on-beach control strategies to reduce potential negative impacts, more robust and spatially explicit information is needed in order to improve sargasso management and focus restoration efforts. In this paper, we offer a spatiotemporal multiscale description of sargasso distribution and dynamics for 2014–2020 in the Mexican Caribbean: (1) for the entire region (millions of km2); (2) at the local scale (thousands of km2) evaluating the dynamics inside the reef lagoon at Puerto Morelos, Mexico; and finally, (3) specific beach observations (hundreds of km2) derived from data on beach cleaning volumes. Fifteen areas in the Mexican Caribbean, with different sargasso dispersions and on-shore accumulations, were evaluated. The areas around Tulum, Solidaridad, and Puerto Morelos have the most extreme and most frequent episodes but also exhibited the greatest seasonal variability. Extreme sargasso presence can occur in the Western Caribbean in any season, albeit with increasing coverage and recurrence in the summer. Images from a coastal video monitoring station at Puerto Morelos showed that massive sargasso beaching was associated with low energy conditions (Hs< 0.25 m, wind speed<4 m/s, neap tide), while non-accumulation of sargasso on the beach occurred under high energy conditions (Hs >0.4 m, wind speed = 8 m/s, spring tide). Time-series analyses of sargasso beaching showed different periods of historic maximum sargasso coverage over July–October 2018 and others in January–February 2019. Wind and wave regimes influenced sargasso in distinct ways, depending on the coastal section, probably related to coastline morphology, oceanic regime, or the extent of the continental platform. This work presents the longest systematic time series (2014-2020) of high resolution satellite detected sargasso in Mexico. Spatial and temporal patterns are proposed as fundamental steps for managing sargasso accumulations.
Enzyme assisted extraction for seaweed multiproduct biorefinery: A techno-economic analysis
Authors: Herrera Barragán José Alberto , Olivieri Giuseppe , Boboescu Iulian , Eppink Michel , Wijffels Rene , Kazbar Antoinette
Published: September 2022

The biorefinery concept facilitates the extraction of different constituents from seaweed, ensuring full usage of resources and generating few residues through a succession of steps. Innovative and environmentally-friendly extraction techniques, dubbed “green processing technologies,” have been developed in recent years. Using the bioprocess simulation software SuperPro Designer®, a model was developed and used to demonstrate the feasibility of two different multi-product biorefinery scenarios applying green technologies to one of the most promising species in Europe, the brown alga Saccharina latissima (sugar kelp). Analyzing the current state of the art and commercial applications, enzyme-assisted extraction was chosen as an emerging sustainable technology to simulate the production of alginate and the functional saccharides laminarin and fucoidan. These simulations were compared to an additional simulation of alginate production using the low-yield alkaline extraction technique currently used in the industry, which has been proven not feasible for the expected prices of cultivated seaweed in Europe. Complete biomass valorization is achieved by the sub-processing of the by-streams into complementary products such as biostimulants and animal feed. The valorization of up to 1.07 € per kilogram of fresh weight biomass was achieved using enzyme-assisted extraction and prioritizing laminarin and fucoidan as main products. Extraction yields and raw biomass alginate composition have the largest sensitivity effects on the profitability of biorefineries. This provides further insight into the crucial research opportunities on downstream processing and seaweed cultivation targets.
Atomic positions and displacements in piezoelectric materials Ca3TaGa3Si2O14 and Ca3TaGa1.5Al1.5Si2O14 investigated by Ta-Lα X-ray fluorescence holography
Authors: Kitaura Mamoru , Ang Artoni Kevin R. , Yamamoto Yuta , Happo Naohisa , Kimura Koji , Hayashi Kouichi , Watanabe Shinta , Yokota Yuui , Ohashi Yuji , Kamada Kei , Yoshikawa Akira , Yamane Hisanori , Ohnishi Akimasa
Published: September 2022

The atomic positions and displacements of atoms around the Ta atom in piezoelectric materials Ca3TaGa3Si2O7 (CTGS) and Ca3TaGa1.5Al1.5Si2O7 (CTGAS) were investigated at 100 K by Ta-Lα X-ray fluorescence holography (XFH). The experimental atomic images were compared with the simulated ones using the crystal structures of CTGS and CTGAS, which were determined by single crystal X-ray diffractometry (SC-XRD). The atomic positions agreed between XFH and SC-XRD experiments. With the help of XFH simulation, the displacements of Ta, Ca, Si, and Ga atoms relative to the Ta atom were qualitatively analyzed using experimental atomic image intensities. The relative displacement of the Ca atom was increased by Al substitution, while those of the Ta and Ga atoms were decreased. The first principles calculation based on density-functional theory (DFT) was performed to understand bonding character between constituents. The evaluation of the crystal orbital Hamilton population (COHP) clarified that the Ca-O bond has strong ionic character different with the other bonds, suggesting that the positional shift of the Ca atom is responsible for the piezoelectricity in CTGS. The effect of Al substitution on piezoelectricity was also considered based on the change in the Ca-O bond.
Performance of urinary liver-type fatty acid-binding protein in diabetic nephropathy: A meta-analysis
Authors: Zhang Li , Xue Shuai , Wu Meiyan , Dong Dan
Published: September 2022

Aims

Diabetic nephropathy (DN) is one of the main causes of chronic kidney disease (CKD), which increases the risk of cardiovascular diseases and progresses to end-stage renal failure. Thus, early diagnostic markers for diabetic patients are urgently needed to improve the prognosis of DN and predict DN progression.

Materials and methods

PubMed, MEDLINE, EMBASE, and Scopus were searched for publications until February 24, 2021. Review Manager 5.4 software was used for meta-analysis. We performed the heterogeneity test using the I2 statistic: P < 0.1 and I2> 50% meant statistical significance.

Results

We included 13 studies. The urinary liver-type fatty acid-binding protein (uL-FABP) concentrations in the normal albuminuria group were significantly higher than those in the normal control group without diabetes mellitus (DM) [P = 0.009, SMD 1.72, 95% CI (0.44, 2.99)]. Urinary F-LABP levels were elevated in the macroalbuminuria group compared with those in the microalbuminuria group with DM [P = 0.002, SMD 2.82, 95% CI (1.03, 4.61)]. Urinary L-FABP levels were also significantly increased in the progression and CKD groups compared with non-progression and CKD subjects with DM [P = 0.02, P < 0.00001, respectively]. Furthermore, uL-FABP concentrations were positively correlated with the albumin-to-creatinine ratio and systolic blood pressure in patients with DM [Summary Fisher’s Z = 0.58 P < 0.00001; Summary Fisher’s Z = 0.24 P < 0.0001, respectively] and negatively correlated with estimated glomerular filtration rate in patients with DM [Summary Fisher’s Z = −0.36, P < 0.0001].

Conclusion

Urinary L-FABP may be a potential marker for the detection of all stages of DN and for the prediction of the progression and severity of DN in patients with type 1 and 2 DM.
The Remote Emerging Disease Intelligence—NETwork
Authors: Achee Nicole L. ,   The Remote Emerging Disease Intelligence—NETwork (REDI-NET) Consortium
Published: September 2022

Accurate prediction of zoonotic spillover events requires a detailed understanding of baseline pathogens circulating in differing global environments. By characterizing the diversity and determining the natural baseline of pathogens in a given biological system, any perturbations to this balance can be detected, leading to estimates of risk for emerging diseases. As epidemics and probability for pandemics increase, there is a fundamental need for building global collaborations to fill gaps in the surveillance effort, especially to build remote in-county capacity and standardize timely sample processing and data analysis. To this point, a new consortium, the Remote Emerging Disease Intelligence-NETwork (REDI-NET) has been established to enhance surveillance approaches and characterize natural pathogens in temperate, tropical forest, and tropical grassland biomes. The REDI-NET is envisioned to be a long-term, phased initiative. All phases will integrate accompanying training resources such as videos reflecting SOPs and Quick Reference Guides. Routine bio- and xenosurveillance will facilitate the characterization of ecological parameters, enhance the accuracy of vector species identification using artificial intelligence technology, and guide the establishment of epidemiological risk thresholds critical for mitigating disease outbreaks in a timely manner. A key deliverable of the REDI-NET is a custom-designed electronically merged (e-MERGE) data pipeline and alert dashboard that integrates remotely captured data with state-of-the-art metagenomic next-generation sequencing technology. This pipeline incorporates data generated from field and laboratory best practices, to furnish health decision-makers with a centralized, timely, and rigorous database to efficiently search interdisciplinary and heterogeneous data sources necessary to alert, prepare and mitigate health threats. The e-MERGE pipeline, once fully established, will be a flexible, scalable, and expandable tool for varied health applications. Program success will result in an operational framework that addresses resource gaps in pathogen surveillance and enhances health protection with broad global applicability. The objective of this manuscript is to introduce the REDI-NET framework to anticipated stakeholders engaged in metagenomics, epidemiological surveillance, and One Health with a focus on Phase 1.
Characterization of a novel β-agarase from Antarctic macroalgae-associated bacteria metagenomic library and anti-inflammatory activity of the enzymatic hydrolysates
Authors: Gu Xiaoqian , Zhao Luying , Tan Jiaojiao , Zhang Qian , Fu Liping , Li Jiang
Published: September 2022

An agarase gene (aga1904) that codes a protein with 640 amino acids was obtained from the metagenomic library of macroalgae-associated bacteria collected from King George Island, Antarctica. Gene aga1904 was expressed in Escherichia coli BL21 (DE3) and recombinant Aga1904 was purified by His Bind Purification kit. The optimal temperature and pH for the activity of Aga1904 were 50°C and 6.0, respectively. Fe3+ and Cu2+ significantly inhibited the activity of Aga1904. The Vmax and Km values of recombinant Aga1904 were 108.70 mg/ml min and 6.51 mg/ml, respectively. The degradation products of Aga1904 against agarose substrate were mainly neoagarobiose, neoagarotetraose, and neoagarohexaose analyzed by thin layer chromatography. The cellular immunoassay of enzymatic hydrolysates was subsequently carried out, and the results showed that agaro-oligosaccharides dominated by neoagarobiose significantly inhibited key pro-inflammatory markers including, nitric oxide (NO), interleukins 6 (IL-6), and tumor necrosis factor α (TNF-α). This work provides a promising candidate for development recombinant industrial enzyme to prepare agaro-oligosaccharides, and paved up a new path for the exploitation of natural anti-inflammatory agent in the future.
Construction of a tumor immune infiltration macrophage signature for predicting prognosis and immunotherapy response in liver cancer
Authors: Huang Anmin , Lv Bei , Zhang Yunjie , Yang Junhui , Li Jie , Li Chengjun , Yu Zhijie , Xia Jinglin
Published: September 2022

Liver cancer is an extraordinarily heterogeneous malignant disease. The tumor microenvironment (TME) and tumor-associated macrophages (TAMs) are the major drivers of liver cancer initiation and progression. It is critical to have a better understanding of the complicated interactions between liver cancer and the immune system for the development of cancer immunotherapy. Based on the gene expression profiles of tumor immune infiltration cells (TIICs), upregulated genes in TAMs and downregulated genes in other types of immune cells were identified as macrophage-specific genes (MSG). In this study, we combined MSG, immune subtypes, and clinical information on liver cancer to develop a tumor immune infiltration macrophage signature (TIMSig). A four-gene signature (S100A9, SLC22A15, TRIM54, and PPARGC1A) was identified as the TAM-related prognostic genes for liver cancer, independent of multiple clinicopathological parameters. Survival analyses showed that patients with low TIMSig had a superior survival rate than those with high TIMSig. Additionally, clinical immunotherapy response and TIMSig was observed as highly relevant. In addition, TIMSig could predict the response to chemotherapy. Collectively, the TIMSig could be a potential tool for risk-stratification, clinical decision making, treatment planning, and oncology immunotherapeutic drug development.