bluuebunny/crossref_metadata_2025 huggingface dataset:
The Vaginal Microbial Signatures of Preterm Birth Delivery in Indian Women
Authors: Kumar Shakti , Kumari Naina , Talukdar Daizee , Kothidar Akansha , Sarkar Mousumi , Mehta Ojasvi , Kshetrapal Pallavi , Wadhwa Nitya , Thiruvengadam Ramachandran , Desiraju Bapu Koundinya , Nair G. Balakrish , Bhatnagar Shinjini , Mukherjee Souvik , Das Bhabatosh ,   GARBH-Ini Study Group
Published: June 2021

Background

The incidence of preterm birth (PTB) in India is around 13%. Specific bacterial communities or individual taxon living in the vaginal milieu of pregnant women is a potential risk factor for PTB and may play an important role in its pathophysiology. Besides, bacterial taxa associated with PTB vary across populations.

Objective

Conduct a comparative analysis of vaginal microbiome composition and microbial genomic repertoires of women who enrolled in the Interdisciplinary Group for Advanced Research on Birth Outcomes – A DBT India Initiative (GARBH-Ini) pregnancy cohort to identify bacterial taxa associated with term birth (TB) and PTB in Indian women.

Methods

Vaginal swabs were collected during all three trimesters from 38 pregnant Indian women who delivered spontaneous term (n=20) and preterm (n=18) neonates. Paired-end sequencing of V3-V4 region of 16S rRNA gene was performed using the metagenomic DNA isolated from vaginal swabs (n=115). Whole genome sequencing of bacterial species associated with birth outcomes was carried out by shotgun method. Lactobacillus species were grown anaerobically in the De Man, Rogosa and Sharpe (MRS) agar culture medium for isolation of genomic DNA and whole genome sequencing.

Results

Vaginal microbiome of both term and preterm samples reveals similar alpha diversity indices. However, significantly higher abundance of Lactobacillus iners (p-value All_Trimesters<0.02), Megasphaera sp (p-value1st_Trimester <0.05), Gardnerella vaginalis (p-value2nd_Trimester= 0.01) and Sneathia sanguinegens (p-value2nd_Trimester <0.0001) were identified in preterm samples whereas higher abundance of L. gasseri (p-value3rd_Trimester =0.010) was observed in term samples by Wilcoxon rank-sum test. The relative abundance of L. iners, and Megasphaera sp. were found to be significantly different over time between term and preterm mothers. Analyses of the representative genomes of L. crispatus and L. gasseri indicate presence of secretory transcriptional regulator and several ribosomally synthesized antimicrobial peptides correlated with anti-inflammatory condition in the vagina. These findings indicate protective role of L. crispatus and L. gasseri in reducing the risk of PTB.

Conclusion

Our findings indicate that the dominance of specific Lactobacillus species and few other facultative anaerobes are associated with birth outcomes.
Security Efficiency Maximization for Multi-UAV–Aided Network With Mobile Edge Computing
Authors: Mu Guangchen
Published: June 2021

In this study, we consider a security efficiency maximization problem in a multiple unmanned aerial vehicle (UAV)-aided system with mobile edge computing (MEC). Two kinds of UAVs, including multiple computing UAVs (CUAVs) and multiple jamming UAVs (JUAVs), are considered in this system. CUAVs would receive partial computation bits and send the computation results to ground users. JUAVs do not undertake computing tasks and only send interference signals to counter potential ground eavesdroppers. We jointly optimize the ground user scheduling, UAV power, and UAV trajectory to maximize the security efficiency. The original problem is non-convex and difficult to solve. We first use the Dinkelbach method combined with continuous convex approximation technology, and then propose three corresponding subproblems, including user scheduling subproblem, UAV power subproblem, and UAV trajectory problem. Further, we apply the branch and bound method to solve the user scheduling subproblem, and optimize the two remaining subproblems by introducing auxiliary variables and Taylor expansion. The simulation results show that the proposed scheme can obtain better secure off-loading efficiency with respect to the existing schemes.
Age- and Sex-Specific Changes in CMR Feature Tracking-Based Right Atrial and Ventricular Functional Parameters in Healthy Asians
Authors: Leng Shuang , Guo Jiajun , Tan Ru-San , Chai Ping , Teo Lynette , Fortier Marielle V. , Gong Chao , Zhao Xiaodan , Ong Ching Ching , Allen John C. , Ruan Wen , Koh Angela S. , Tan Teng Hong , Yip James W. , Tan Ju Le , Chen Yucheng , Zhong Liang
Published: June 2021

Cardiovascular magnetic resonance (CMR) is the reference standard for non-invasive assessment of right-sided heart function. Recent advances in CMR post-processing facilitate quantification of tricuspid annular (TA) dynamics and longitudinal strains of the right ventricle (RV) and right atrium (RA). We aimed to determine age- and sex-specific changes in CMR-derived TA dynamics, and RV and RA functional parameters in healthy Asian adults. We studied 360 healthy subjects aged 21–79 years, with 30 men and 30 women in each of the six age groups. Functional parameters of RV and RA were measured on standard four-chamber cine CMR using fast feature tracking: (1) TA peak velocities (systolic velocity S′, early diastolic velocity E′, late diastolic velocity A′) and TA plane systolic excursion (TAPSE); (2) RV global longitudinal strain (GLS) and strain rates; and (3) RA phasic longitudinal strains and strain rates. S′ and TAPSE exhibited negative correlations with age. RV GLS was significantly higher in females than in males but not associated with age in both sexes. Females had similar E′, lower A′, and higher E′/A′ ratios compared to males. Positive associations of E′ and E′/A′, and negative association of A′ with age were observed in both sexes. Females had higher RA reservoir and conduit strains compared to males. There were significantly negative and positive associations between RA conduit and booster strains, respectively, with age. Age- and sex-specific reference ranges were established, and associations revealed, for fast CMR feature tracking parameters of right heart function in a large normal Asian population.
Case Report: Disappearance of Coronary Anastomotic Aneurysm by Steroid Therapy in Takayasu Arteritis: Pseudorepair of Pseudoaneurysm?
Authors: Naraoka Shuichi , Uchiyama Hiroki , Yano Toshiyuki , Mikami Takuma , Harada Ryo , Kuroda Yosuke , Toda Yuki , Muranaka Atsuko , Sugawara Taro , Hasegawa Tadashi , Miura Tetsuji , Kawaharada Nobuyoshi
Published: June 2021

Background: Takayasu arteritis (TA) is a large vessel vasculitis of unknown etiology characterized by chronic inflammatory changes of the aorta and its major branches. Complications such as anastomotic aneurysm and valve detachment have been reported in active TA patients who received aortic valve replacement and graft replacement of aorta.

Case Summary:A 61-year-old man with a history of emergency aortic valve replacement and patch closure of the noncoronary sinus of Valsalva due to acute heart failure induced by acute aortic regurgitation and ruptured sinus of Valsalva 4 years ago was referred for exertional dyspnea. Dilatation of the sinus of Valsalva together with protrusion of the right sinus of Valsalva and ostial stenosis of the left coronary artery were newly found by computed tomography (CT). A Bentall operation with concomitant coronary artery bypass grafting was successfully performed with a composite graft. Diagnosis of TA was made on the basis of histological analyses of the resected sinus of Valsalva, though other arterial manifestations were not detected by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography. Three months later, a follow-up study revealed left coronary ostial pseudoaneurysm at the anastomotic site together with strong 18F-FDG uptake, leading to commencement of steroid therapy. Eight months later, disappearance of left coronary ostial pseudoaneurysm was found by a follow-up CT scan.

Conclusion: This is a rare TA case in whom spontaneous resolution of coronary anastomotic aneurysm by steroid therapy was found without reconstructive surgery.
Serum Anti-Müllerian Hormone Levels Were Negatively Associated With Body Fat Percentage in PCOS Patients
Authors: Luo Er , Zhang Jinxiao , Song Jiahui , Feng Di , Meng Yaxin , Jiang Hongyu , Li Da , Fang Yuanyuan
Published: June 2021

Background

Obesity is a state of excess body fat accumulation, and appears to be closely associated with polycystic ovary syndrome (PCOS). Notably, plausible biological pathways through which obesity can regulate anti-Müllerian hormone (AMH) production have been proposed, and women with PCOS characteristically have an increased AMH level. Body fat accumulation can be described by body fat percentage (BFP). However, the relationship between BFP and AMH still remains unclear.

Materials and Methods

A total of 87 controls and 156 PCOS patients were divided into lean and overweight/obese groups, and the PCOS patients were further divided into hyper-AMH and normal-AMH subgroups. Univariate regression was used to assess the unadjusted relationship between AMH and outcome variables, multivariable regression analysis was performed to test whether and how serum AMH levels were associated with BFP after adjusting for other co-variables. Receiver-operating characteristic (ROC) curve analyses were used to test the utility of BFP for the diagnosis of PCOS.

Results

BFP was higher in PCOS patients compared with controls, regardless of obesity. Serum AMH levels were negatively associated with BFP in the PCOS group (r = -0.371; P < 0.001) but not in the control group (r = -0.095; P = 0.385). Multivariable logistic regression analysis showed that elevated BFP was associated with a high risk of PCOS (odds ratio, 1.290; 95% confidence interval, 1.084–1.534, P = 0.004). Furthermore, the combination of BFP and serum AMH into a multivariate model gave an improved area under the curve (AUC) of 88.5%, with a sensitivity of 72.4% and specificity of 87.4%; the positive and negative predictive values were 91.2% and 63.9%, respectively. One limitation of this study is all the conclusion reported was based on small sample size.

Conclusions

Herein, we described the negative correlation between BFP and serum AMH levels for the first time, and the present results highlight the importance of further investigation into the role of BFP, especially in body fat-related AMH change as it relates to the underlying pathogenesis of PCOS.
Reversal of Abnormal CD4+ T Cell Metabolism Alleviates Thyroiditis by Deactivating the mTOR/HIF1a/Glycolysis Pathway
Authors: Zhao Lei , Wu Qiong , Wang Xiaoli , Wang Shiqi , Shi Xiaoguang , Shan Zhongyan , Teng Weiping
Published: June 2021

Background

Hashimoto’s thyroiditis (HT) is an autoimmune disease that features activation of thyroid antigen-specific helper T cells. HT patients have increased Th1 and Th17 T cell subsets. Glycolysis supports chronic activation of Th1 and Th17 T cells, but how this contributes to HT remains unknown.

Methods

The metabolism of CD4+ T cells from 30 HT patients and 30 healthy controls was evaluated by determining the extracellular acidification rate (ECAR) and the oxygen consumption rate (OCR). Mice in a subacute thyroiditis (SAT) model were treated with 2DG, metformin, or combination. Metrics of mTOR/HIF-1α/HK2/glycolysis were measured by western blot and Seahorse assay methods. The severity of SAT was measured by flow cytometry and HE staining.

Results

CD4+ T cells from HT patients had enhanced ECAR and OCR. Levels of Glut1, HK2, PKM2, and LDHA in cultured HT CD4+ T cells were elevated. The expression of HK2 and PKM2 in cultured SAT CD4+ T cells was elevated compared with the control group. Activation of the mTOR and HIF-1α pathways was significant in SAT mice, and expression of HIF-1α in the 2DG treated group was reduced. Treatment with 2DG and/or metformin significantly decreased the ratio of Th17 and Th1 T cells.

Conclusions

Thyroiditis results in elevation of the mTOR/HIF-1α/HK2/glycolysis pathway in CD4+ T cells. The activation of this pathway is reduced by treatment with 2DG and metformin, which also reverted imbalances in CD4+ T cell differentiation.
Historical Demographic Processes Dominate Genetic Variation in Ancient Atlantic Cod Mitogenomes
Authors: Martínez-García Lourdes , Ferrari Giada , Oosting Tom , Ballantyne Rachel , van der Jagt Inge , Ystgaard Ingrid , Harland Jennifer , Nicholson Rebecca , Hamilton-Dyer Sheila , Baalsrud Helle Tessand , Brieuc Marine Servane Ono , Atmore Lane M. , Burns Finlay , Schmölcke Ulrich , Jakobsen Kjetill S. , Jentoft Sissel , Orton David , Hufthammer Anne Karin , Barrett James H. , Star Bastiaan
Published: June 2021

Ancient DNA (aDNA) approaches have been successfully used to infer the long-term impacts of climate change, domestication, and human exploitation in a range of terrestrial species. Nonetheless, studies investigating such impacts using aDNA in marine species are rare. Atlantic cod (Gadus morhua), is an economically important species that has experienced dramatic census population declines during the last century. Here, we investigated 48 ancient mitogenomes from historical specimens obtained from a range of archeological excavations in northern Europe dated up to 6,500 BCE. We compare these mitogenomes to those of 496 modern conspecifics sampled across the North Atlantic Ocean and adjacent seas. Our results confirm earlier observations of high levels of mitogenomic variation and a lack of mutation-drift equilibrium—suggestive of population expansion. Furthermore, our temporal comparison yields no evidence of measurable mitogenomic changes through time. Instead, our results indicate that mitogenomic variation in Atlantic cod reflects past demographic processes driven by major historical events (such as oscillations in sea level) and subsequent gene flow rather than contemporary fluctuations in stock abundance. Our results indicate that historical and contemporaneous anthropogenic pressures such as commercial fisheries have had little impact on mitogenomic diversity in a wide-spread marine species with high gene flow such as Atlantic cod. These observations do not contradict evidence that overfishing has had negative consequences for the abundance of Atlantic cod and the importance of genetic variation in implementing conservation strategies. Instead, these observations imply that any measures toward the demographic recovery of Atlantic cod in the eastern Atlantic, will not be constrained by recent loss of historical mitogenomic variation.
Enhancement of Biomass Production in Colony-Forming Green Algae, Botryosphaerella sudetica, Under Mixotrophic Cultivation
Authors: Yun Hyun-Sik , Kim Young-Saeng , Yoon Ho-Sung
Published: June 2021

In this study, we characterized the potential of colony-forming green algae, Botryosphaerella sudetica KNUA107, isolated from Ulleung Island, South Korea, as a bioresource and analyzed the effects of mixotrophic cultivation on its bioresource production efficiency. Internal transcribed spacer (ITS) (ITS1, 5.8S, and ITS2), ribulose bisphosphate carboxylase large subunit (rbcL), and elongation factor Tu (tufa) regions were used for molecular identification and phylogenetic analysis. B. sudetica KNUA107 had a strong relationship with the green algae of Botryococcus and Botryosphaerella genera, which are colony-forming species, and was also associated with members of the Neochloris genus. To improve biomass productivity, we tested mixotrophic cultivation conditions using several organic carbon sources. Glucose supplementation stimulated B. sudetica KNUA107 growth and reduced the time needed to reach the stationary phase. In addition, the colony size was 1.5–2.0 times larger with glucose than in photoautotrophic cultures, and settleability improved in proportion to colony size. The total lipid content and biomass productivity were also higher in cultures supplemented with glucose. Among the lipid components, saturated fatty acids and monounsaturated fatty acids had the highest proportion. Our study suggests that B. sudetica KNUA107, which has enhanced efficiency in biomass production and lipid components under mixotrophic cultivation, has high potential as a bioresource.
SARS-CoV-2 Spike Protein Suppresses ACE2 and Type I Interferon Expression in Primary Cells From Macaque Lung Bronchoalveolar Lavage
Authors: Sui Yongjun , Li Jianping , Venzon David J. , Berzofsky Jay A.
Published: June 2021

SARS-CoV-2 virus causes upper and lower respiratory diseases including pneumonia, and in some cases, leads to lethal pulmonary failure. Angiotensin converting enzyme-2 (ACE2), the receptor for cellular entry of SARS-CoV-2 virus, has been shown to protect against severe acute lung failure. Here, we provide evidence that SARS-CoV-2 spike protein S1 reduced the mRNA expression of ACE2 and type I interferons in primary cells of lung bronchoalveolar lavage (BAL) from naïve rhesus macaques. The expression levels of ACE2 and type I interferons were also found to be correlated with each other, consistent with the recent finding that ACE2 is an interferon-inducible gene. Furthermore, induction of ACE2 and type I interferons by poly I:C, an interferon inducer, was suppressed by S1 protein in primary cells of BAL. These observations suggest that the downregulation of ACE2 and type I interferons induced by S1 protein may directly contribute to SARS-CoV-2-associated lung diseases.
Ischemia-Reperfusion Injury Reduces Kidney Folate Transporter Expression and Plasma Folate Levels
Authors: Yang Cheng , Wijerathne Charith U. B. , Tu Guo-wei , Woo Connie W. H. , Siow Yaw L. , Madduma Hewage Susara , Au-Yeung Kathy K. W. , Zhu Tongyu , O Karmin
Published: June 2021

Acute or chronic kidney disease can cause micronutrient deficiency. Patients with end-stage renal disease, kidney transplantation or on dialysis have reduced circulating levels of folate, an essential B vitamin. However, the molecular mechanism is not well understood. Reabsorption of folate in renal proximal tubules through folate transporters is an important process to prevent urinary loss of folate. The present study investigated the impact of acute kidney injury (AKI) on folate transporter expression and the underlying mechanism. AKI was induced in Sprague-Dawley rats that were subjected to kidney ischemia (45 min)-reperfusion (24 h). Both male and female rats displayed kidney injury and low plasma folate levels compared with sham-operated rats. The plasma folate levels were inversely correlated to plasma creatinine levels. There was a significant increase in neutrophil gelatinase-associated lipocalin (NGAL) and IL-6 mRNA expression in the kidneys of rats with ischemia-reperfusion, indicating kidney injury and increased inflammatory cytokine expression. Ischemia-reperfusion decreased mRNA and protein expression of folate transporters including folate receptor 1 (FOLR1) and reduced folate carrier (RFC); and inhibited transcription factor Sp1/DNA binding activity in the kidneys. Simulated ischemia-reperfusion through hypoxia-reoxygenation or Sp1 siRNA transfection in human proximal tubular cells inhibited folate transporter expression and reduced intracellular folate levels. These results suggest that ischemia-reperfusion injury downregulates renal folate transporter expression and decreases folate uptake by tubular cells, which may contribute to low folate status in AKI. In conclusion, ischemia-reperfusion injury can downregulate Sp1 mediated-folate transporter expression in tubular cells, which may reduce folate reabsorption and lead to low folate status.
Immunotherapy in Acral and Mucosal Melanoma: Current Status and Future Directions
Authors: Mao Lili , Qi Zhonghui , Zhang Li , Guo Jun , Si Lu
Published: June 2021

Acral and mucosal melanomas are extremely rare in Caucasians; however, they are the predominant melanoma subtypes in Asians and other non-Caucasian populations. Acral and mucosal melanomas share many clinicopathological features, including aggressive phenotypes, similar genetic landscapes, and grim prognoses. In spite of advances in melanoma management, patients with acral and mucosal melanomas show limited benefit from current therapies. The rarity of these subtypes of melanoma is a significant factor contributing to the poor understanding of these pathological subtypes and the lack of effective interventions. Furthermore, the mechanisms contributing to disparities between different types of melanoma remain largely unclear. Herein, we comprehensively review current knowledge on the clinicopathological characteristics and mutational landscapes of acral and mucosal melanomas, as well as providing an overview of current therapies for patients with these aggressive melanoma subtypes, focusing on available immunotherapeutic interventions. We also discuss pathological differences between different melanoma subtypes and summarize current knowledge on melanoma disparities between Asians and Caucasians. Finally, we discuss emerging immunotherapeutic strategies for the treatment of acral and mucosal melanomas, focusing on combination therapies with immune checkpoint inhibitors. Unraveling the unique features of acral and mucosal melanomas is key for their early diagnosis and for the development of effective therapies.
An Immunologic Compatibility Testing Was Not Useful for Donor Selection in Fecal Microbiota Transplantation for Ulcerative Colitis
Authors: Ponce-Alonso Manuel , García-Hoz Carlota , Halperin Ana , Nuño Javier , Nicolás Pilar , Martínez-Pérez Adolfo , Ocaña Juan , García-Pérez Juan Carlos , Guerrero Antonio , López-Sanromán Antonio , Cantón Rafael , Roy Garbiñe , del Campo Rosa
Published: June 2021

Fecal microbiota transplantation (FMT) is an effective procedure against Clostridioides difficile infection (CDI), with promising but still suboptimal performance in other diseases, such as ulcerative colitis (UC). The recipient’s mucosal immune response against the donor’s microbiota could be relevant factor in the effectiveness of FMT. Our aim was to design and validate an individualized immune-based test to optimize the fecal donor selection for FMT. First, we performed an in vitro validation of the test by co-culturing lymphocytes obtained from the small intestine mucosa of organ donor cadavers (n=7) and microbe-associated molecular patterns (MAMPs) obtained from the feces of 19 healthy donors. The inflammatory response was determined by interleukin supernatant quantification using the Cytometric Bead Array kit (B&D). We then conducted a clinical pilot study with 4 patients with UC using immunocompetent cells extracted from rectal biopsies and MAMPs from 3 donor candidates. We employed the test results to guide donor selection for FMT, which was performed by colonoscopy followed by 4 booster instillations by enema in the following month. The microbiome engraftment was assessed by 16S rDNA massive sequencing in feces, and the patients were clinically followed-up for 16 weeks. The results demonstrated that IL-6, IL-8, and IL-1ß were the most variable markers, although we observed a general tolerance to the microbial insults. Clinical and colonoscopy remission of the patients with UC was not achieved after 16 weeks, although FMT provoked enrichment of the Bacteroidota phylum and Prevotella genus, with a decrease in the Actinobacteriota phylum and Agathobacter genus. The most relevant result was the lack of Akkermansia engraftment in UC. In summary, the clinical success of FMT in patients with UC appears not to be influenced by donor selection based on the explored recipient’s local immunological response to FMT, suggesting that this approach would not be valid for FMT fecal donor optimization in such patients.
Low Energy Electron Irradiation Is a Potent Alternative to Gamma Irradiation for the Inactivation of (CAR-)NK-92 Cells in ATMP Manufacturing
Authors: Walcher Lia , Kistenmacher Ann-Kathrin , Sommer Charline , Böhlen Sebastian , Ziemann Christina , Dehmel Susann , Braun Armin , Tretbar Uta Sandy , Klöß Stephan , Schambach Axel , Morgan Michael , Löffler Dennis , Kämpf Christoph , Blumert Conny , Reiche Kristin , Beckmann Jana , König Ulla , Standfest Bastian , Thoma Martin , Makert Gustavo R. , Ulbert Sebastian , Kossatz-Böhlert Uta , Köhl Ulrike , Dünkel Anna , Fricke Stephan
Published: June 2021

Background

With increasing clinical use of NK-92 cells and their CAR-modified derivatives in cancer immunotherapy, there is a growing demand for efficient production processes of these “off-the-shelf” therapeutics. In order to ensure safety and prevent the occurrence of secondary tumors, (CAR-)NK-92 cell proliferation has to be inactivated before transfusion. This is commonly achieved by gamma irradiation. Recently, we showed proof of concept that low energy electron irradiation (LEEI) is a new method for NK-92 inactivation. LEEI has several advantages over gamma irradiation, including a faster reaction time, a more reproducible dose rate and much less requirements on radiation shielding. Here, LEEI was further evaluated as a promising alternative to gamma irradiation yielding cells with highly maintained cytotoxic effector function.

Methods

Effectiveness and efficiency of LEEI and gamma irradiation were analyzed using NK-92 and CD123-directed CAR-NK-92 cells. LEE-irradiated cells were extensively characterized and compared to gamma-irradiated cells via flow cytometry, cytotoxicity assays, and comet assays, amongst others.

Results

Our results show that both irradiation methods caused a progressive decrease in cell viability and are, therefore, suitable for inhibition of cell proliferation. Notably, the NK-mediated specific lysis of tumor cells was maintained at stable levels for three days post-irradiation, with a trend towards higher activities after LEEI treatment as compared to gamma irradiation. Both gamma irradiation as well as LEEI led to substantial DNA damage and an accumulation of irradiated cells in the G2/M cell cycle phases. In addition, transcriptomic analysis of irradiated cells revealed approximately 12-fold more differentially expressed genes two hours after gamma irradiation, compared to LEEI. Analysis of surface molecules revealed an irradiation-induced decrease in surface expression of CD56, but no changes in the levels of the activating receptors NKp46, NKG2D, or NKp30.

Conclusions

The presented data show that LEEI inactivates (CAR-)NK-92 cells as efficiently as gamma irradiation, but with less impact on the overall gene expression. Due to logistic advantages, LEEI might provide a superior alternative for the manufacture of (CAR-)NK-92 cells for clinical application.
Integrated Analysis of mRNA and miRNA Changes in Two Haliotis diversicolor Genotypes and Their Hybrid
Authors: Liang Shuang , You Weiwei , Luo Xuan , Ke Jinwei , Huang Miaoqin , Guo Yongjun , Ke Caihuan
Published: June 2021

Heterosis is a widely distributed phenomenon in mollusks. It is vital in aquaculture by bringing beneficial traits into hybrids. People have utilized the heterosis theory in aquaculture for years. However, the molecular basis of heterosis remains elusive. Evident growth and survival heterosis were shown in the hybrid (“Dongyou-1”) of two Haliotis diversicolor geographic genotypes (Japan and Taiwan). To explore the molecular basis underlying the hybrid abalone’s heterosis, we conducted comparative mRNA and miRNA transcriptional analysis in the hybrid and parental genotypes. Differentially expression analysis identified 5,562 differentially expressed genes (DEGs) and 102 differentially expressed miRNAs (DEMs) between the three genotypes. 1,789 DEGs and 71 DEMs were found to be non-additively expressed in the hybrid. Meanwhile, both the expression level dominance pattern (ELD) and expression level overdominance pattern (ELOD) were found in the DEGs and DEMs, showing the existence of dominance and overdominance models in the hybrid’s transcriptome and post-transcriptional regulation. Functional analysis showed the non-additively expressed genes, ELD genes, and ELOD genes were significantly enriched in growth, immunity, and stress response related pathways, while some of the pathways were regulated by the mRNA-miRNA interactions. The expression levels of FGF, C1Q, HC, CAT, SEGPX, and MGST were significantly up-regulated in the hybrid compared to the middle parent value. In conclusion, we identified the existence of non-additivity, dominance, and overdominance models in the transcriptome and miRNAome of the H. diversicolor hybrid; these models facilitate the advantageous parental alleles’ integration into the hybrid, contributing to the hybrid’s growth and survival heterosis.
Influence and Mechanism Research of Hydration Heat Inhibitor on Low-Heat Portland Cement
Authors: Jia Fujie , Yao Yan , Wang Jingyu
Published: June 2021

A kind of microcapsule sustained-release–type hydration heat inhibitor (MSR) was prepared. The effect of MSR on semi-adiabatic temperature rise, setting time, and strength of low-heat Portland cement was investigated. Microcalorimetry, XRD, SEM, and TG-DSC were used to investigate the mechanism of MSR on hydration of low-heat Portland cement. The results showed that the MSR had good regulating effect on hydration of low-heat Portland cement. When the dosage of MSR was 0.3%, the heat release rate decreased by 10% and the peak temperature decreased by 52%. The 3D compressive strength decreased by 50%, and the 28-day strength was the same as control. The MSR can delay the hydration of low-heat Portland cement by inhibiting the heat release rate of C2S and C3S minerals.
Subacute Cutaneous Lupus Erythematosus-Like Eruption Induced by EGFR -Tyrosine Kinase Inhibitor in EGFR-Mutated Non-small Cell Lung Cancer: A Case Report
Authors: Ferro Alessandra , Filoni Angela , Pavan Alberto , Pasello Giulia , Guarneri Valentina , Conte PierFranco , Alaibac Mauro , Bonanno Laura
Published: June 2021

EGFR tyrosine kinase inhibitors (TKIs) are the front-line treatment in EGFR mutation positive advanced non-small cell lung cancer (aNSCLC) patients. Generally, they are well-tolerated but skin toxicity is common (45–100% of patients) and may adversely affect quality of life. Pathogenesis of cutaneous side effects is usually linked to EGFR expression in normal cells of the epidermis and not immune-related. Subacute cutaneous lupus erythematosus (SCLE) is an autoimmune disease and about 40% of SCLE cases are drug related, but no reports are available involving osimertinib. Our report depicts a drug induced-SCLE (DI-SCLE) caused by erlotinib and worsened by osimertinib. The adverse event is characterized by the absence of systemic symptoms. Diagnosis has been performed by skin biopsy and the conditions improved with systemic steroids administration and EGFR-TKIs discontinuation. The report underlines the importance of a complete dermatologic diagnosis of skin lesions induced by EGFR inhibitors, according to symptom severity and timing of improving with standard clinical management. The diagnosis of immune-related skin toxicity in this context affects the treatment and the outcome of skin toxicity and must be taken into account when planning subsequent treatments, potentially including immune checkpoint inhibitors (ICIs).
Acute Kidney Injury Due to COVID-19 in Intensive Care Unit: An Analysis From a Latin-American Center
Authors: Neves Precil Diego Miranda de Menezes , Sato Victor Augusto Hamamoto , Mohrbacher Sara , Ferreira Bernadete Maria Coelho , Oliveira Érico Souza , Pereira Leonardo Victor Barbosa , Bales Alessandra Martins , Nardotto Luciana Loureiro , Ferreira Jéssica Nogueira , Machado David José , Bassi Estêvão , Silva-Júnior Amilton , Chocair Pedro Renato , Cuvello-Neto Américo Lourenço
Published: June 2021

Introduction: The kidney may be affected by coronavirus (COVID-19) in the setting of acute kidney injury (AKI). Data about AKI in intensive care unit (ICU) patients in Latin America are scarce. We aimed to evaluate the risk of AKI, dialysis (HD), and death in ICU COVID-19 patients in a Brazilian center.

Methods: Analysis from medical records of COVID-19 patients in a Brazilian center.

Results: A total of 95 patients were analyzed. There was male predominance (64.2%), median age: 64.9 years, and previous history of hypertension and diabetes in 51.6 and 27.4%, respectively. AKI was diagnosed in 54 (56.8%) patients, and 32 (59.2%) of them required HD. Mortality rate was 17.9%. AKI patients when compared with no-AKI were more frequently hypertensive/diabetic and more often needed organ support therapies. Workups depicted more anemia, lymphopenia, and higher levels of inflammatory markers and higher mortality. Comparing patients who had undergone death to survivors, they were older, more frequently diabetic, and had worse SAPS3 and SOFA scores and need for organ support therapies, AKI, and HD. Multinomial logistic regression revealed that hypertension (p = 0.018) and mechanical ventilation (p = 0.002) were associated with AKI; hypertension (p = 0.002), mechanical ventilation (p = 0.008), and use of vasopressor (p = 0.027) to HD patients; and age >65 years (p = 0.03) and AKI (p = 0.04) were risk factors for death.

Conclusions: AKI was a common complication of ICU COVID-19 patients, and it was more frequent in patients with hypertension and need of organ support therapies. As well as age >65 years, AKI was an independent risk factor for death.
Management of Chronic Hyperkalemia in Patients With Chronic Kidney Disease: An Old Problem With News Options
Authors: Morales Enrique , Cravedi Paolo , Manrique Joaquin
Published: June 2021

Hyperkalemia is one of the main electrolyte disorders in patients with chronic kidney disease (CKD). The prevalence of hyperkalemia increases as the Glomerular Filtration Rate (GFR) declines. Although chronic hyperkalemia is not a medical emergency, it can have negative consequences for the adequate cardio-renal management in the medium and long term. Hyperkalemia is common in patients on renin-angiotensin-aldosterone system inhibitors (RAASi) or Mineralocorticoid Receptor Antagonists (MRAs) and can affect treatment optimization for hypertension, diabetes mellitus, heart failure (HF), and CKD. Mortality rates are higher with suboptimal dosing among patients with CKD, diabetes or HF compared with full RAASi dosing, and are the highest among patients who discontinue RAASis. The treatment of chronic hyperkalemia is still challenging. Therefore, in the real world, discontinuation or reduction of RAASi therapy may lead to adverse cardiorenal outcomes, and current guidelines differ with regard to recommendations on RAASi therapy to enhance cardio and reno-protective effects. Treatment options for hyperkalemia have not changed much since the introduction of the cation exchange resin over 50 years ago. Nowadays, two new potassium binders, Patiromer Sorbitex Calcium, and Sodium Zirconium Cyclosilicate (SZC) already approved by FDA and by the European Medicines Agency, have demonstrated their clinical efficacy in reducing serum potassium with a good safety profile. The use of the newer potassium binders may allow continuing and optimizing RAASi therapy in patients with hyperkalemia keeping the cardio-renal protective effect in patients with CKD and cardiovascular disease. However, further research is needed to address some questions related to potassium disorders (definition of chronic hyperkalemia, monitoring strategies, prediction score for hyperkalemia or length for treatment).
The Addition of Other Fecal Biomarkers Does Not Improve the Diagnostic Accuracy of Immunochemical Fecal Occult Blood Test Alone in a Colorrectal Cancer Screening Cohort
Authors: Hijos-Mallada Gonzalo , Lué Alberto , Velamazan Raul , Saura Nuria , Abril Carlos , Lorenzo Marta , Navarro Mercedes , Chueca Eduardo , Arechavaleta Samantha , Gomollón Fernando , Lanas Ángel , Sostres Carlos
Published: June 2021

Background: Screening with fecal occult blood test reduces colorectal cancer (CRC) incidence and mortality, and is currently implemented in most countries. However, around 40% of screening colonoscopies are normal. Thus, strategies to avoid these colonoscopies are highly necessary. Adding other fecal biomarkers, such as fecal calprotectin (FC), lactoferrin, and transferrin may be useful, but evidence is scarce.

Aims: To evaluate the diagnostic accuracy of fecal occult blood immunochemical test (FIT), FC, and a one-step combo card test for the simultaneous semi-qualitative detection of human hemoglobin (hHb), transferrin (hTf), calprotectin (hCp) and lactoferrin (hLf) in a CRC screening program population.

Methods: Single-center, prospective observational study, enrolling patients included in a CRC screening program, referred for a colonoscopy due to a positive FIT test. Participants collected a stool sample prior to bowel preparation, and FIT, FC and the combo semi-qualitative tests were performed on the sample. Sensitivity, specificity, positive and negative predictive values and area under receiver operator curve (AUC) for diagnosis of advanced neoplasia, advanced adenoma and CRC were estimated for each biomarker and their combinations. The primary endpoint of the study was to assess whether these biomarkers could improve the diagnostic accuracy of FIT alone.

Results: 336 consecutive patients (64% males) were recruited. Advanced neoplasia was found in 129/336 (38.4%) patients, and of these, 22/336 (6.5%) were diagnosed of CRC. 153/336 (45.5%) colonoscopies were completely normal. The AUC for the diagnosis of advanced neoplasia were 0.725 (95%CI 0.665–0.784) for FIT, 0.477 (95%CI 0.413–0.541) for FC and 0.732 (95%CI 0.674–0.791) for the combination of both (FIT + FC) quantitative tests. The AUCs for the combo test were 0.70 (95%CI 0.641–0.760) for hHb, 0.625 (95%CI 0.562–0.698) for hTf, 0.532 (95%CI 0.469–0.595) for hCp, 0.531 (95%CI 0.466–0.595 ) for hLf and 0.681 (95%CI 0.620–0.741) for the combination of the four biomarkers.

Conclusion: In average-risk population, FIT appears to be the best fecal marker for the diagnosis of CRC and advanced adenoma. None of the other biomarkers explored or their combinations provided a better diagnostic accuracy. Only hTF showed an acceptable diagnostic accuracy. FC and hLF were not useful in this setting.
Detection of Vibrio vulnificus in Seafood With a DNAzyme-Based Biosensor
Authors: Fan Shihui , Ma Chao , Tian Xiaopeng , Ma Xiaoyi , Qin Mingcan , Wu Hangjie , Tian Xueqing , Lu Jing , Lyu Mingsheng , Wang Shujun
Published: June 2021

Vibrio vulnificus is an important pathogenic bacterium that is often associated with seafood-borne illnesses. Therefore, to detect this pathogen in aquatic products, a DNAzyme-based fluorescent sensor was developed for the in vitro detection of V. vulnificus. After screening and mutation, a DNAzyme that we denominated “RFD-VV-M2” exhibited the highest activity, specificity, and sensitivity. The limit of detection was 2.2 × 103 CFU/ml, and results could be obtained within 5–10 min. Our findings suggested that the target of DNAzyme RFD-VV-M2 was a protein with a molecular weight between 50 and 100 kDa. The proposed biosensor exhibited an excellent capacity to detect marine products contaminated with V. vulnificus. Therefore, our study established a rapid, simple, sensitive, and highly specific detection method for V. vulnificus in aquatic products.
Dissolved Nitrogen Acquisition in the Symbioses of Soft and Hard Corals With Symbiodiniaceae: A Key to Understanding Their Different Nutritional Strategies?
Authors: Pupier Chloé A. , Grover Renaud , Fine Maoz , Rottier Cécile , van de Water Jeroen A. J. M. , Ferrier-Pagès Christine
Published: June 2021

Nitrogen is one of the limiting nutrients for coral growth and primary productivity. Therefore, the capacity of different associations between corals and their algal symbionts (Symbiodiniaceae) to efficiently exploit the available nitrogen sources will influence their distribution and abundance. Recent studies have advanced our understanding of nitrogen assimilation in reef-building scleractinian (hard) coral-Symbiodiniaceae symbioses. However, the nutrient metabolism of other coral taxa, such as Alcyoniina (soft corals), remains underexplored. Using stable isotope labeling, we investigated the assimilation of dissolved nitrogen (i.e., ammonium, nitrate, and free amino acids) by multiple species of soft and hard corals sampled in the Gulf of Aqaba in shallow (8–10 m) and mesophotic (40–50 m) reefs. Our results show that dissolved nitrogen assimilation rates per tissue biomass were up to 10-fold higher in hard than in soft coral symbioses for all sources of nitrogen. Although such differences in assimilation rates could be linked to the Symbiodiniaceae density, Symbiodiniaceae species, or the C:N ratio of the host and algal symbiont fractions, none of these parameters were different between the two coral taxa. Instead, the lower assimilation rates in soft coral symbioses might be explained by their different nutritional strategy: whereas soft corals may obtain most of their nitrogen via the capture of planktonic prey by the coral host (heterotrophic feeding), hard corals may rely more on dissolved nitrogen assimilation by their algal symbionts to fulfill their needs. This study highlights different nutritional strategies in soft and hard coral symbioses. A higher reliance on heterotrophy may help soft corals to grow in reefs with higher turbidity, which have a high concentration of particles in suspension in seawater. Further, soft corals may benefit from lower dissolved nitrogen assimilation rates in areas with low water quality.
Exploration of Microbial Factories for Synthesis of Nanoparticles – A Sustainable Approach for Bioremediation of Environmental Contaminants
Authors: Kapoor Riti T. , Salvadori Marcia R. , Rafatullah Mohd , Siddiqui Masoom R. , Khan Moonis A. , Alshareef Shareefa A.
Published: June 2021

The nanomaterials synthesis is an intensifying research field due to their wide applications. The high surface-to-volume ratio of nanoparticles and quick interaction capacity with different particles make them as an attractive tool in different areas. Conventional physical and chemical procedures for development of metal nanoparticles become outmoded due to extensive production method, energy expenditure and generation of toxic by-products which causes significant risks to the human health and environment. Hence, there is a growing requirement to search substitute, non-expensive, reliable, biocompatible and environmental friendly methods for development of nanoparticles. The nanoparticles synthesis by microorganisms has gained significant interest due to their potential to synthesize nanoparticles in various sizes, shape and composition with different physico-chemical properties. Microbes can be widely applied for nanoparticles production due to easy handling and processing, requirement of low-cost medium such as agro-wastes, simple scaling up, economic viability with the ability of adsorbing and reducing metal ions into nanoparticles through metabolic processes. Biogenic synthesis of nanoparticles offers clean, non-toxic, environmentally benign and sustainable approach in which renewable materials can be used for metal reduction and nanoparticle stabilization. Nanomaterials synthesized through microbes can be used as a pollution abatement tool as they also contain multiple functional groups that can easily target pollutants for efficient bioremediation and promotes environmental cleanup. The objective of the present review is to highlight the significance of micro-organisms like bacteria, actinomycetes, filamentous fungi, yeast, algae and viruses for nanoparticles synthesis and advantages of microbial approaches for elimination of heavy metals, dyes and wastewater treatment.
Sequencing and Comparative Genomic Analysis of a Highly Metal-Tolerant Penicillium janthinellum P1 Provide Insights Into Its Metal Tolerance
Authors: Chi Bin-Bin , Lu Ya-Nan , Yin Ping-Chuan , Liu Hong-Yan , Chen Hui-Ying , Shan Yang
Published: June 2021

Heavy metal pollution is a global knotty problem and fungi hold promising potential for the remediation of wastewater containing heavy metals. Here, a new highly chromium-tolerance species, Penicillium janthinellum P1, is investigated. The genome of P1 was sequenced and assembled into 30 Mb genome size containing 10,955 predicted protein-coding genes with a GC content of 46.16% through an integrated method of Illumina short-read sequencing and single-molecule real-time Pacific Biosciences sequencing platforms. Through a phylogenetic analysis with model species of fungi, the evolutionary divergence time of Penicillium janthinellum P1 and Penicillium oxalicum 114-2 was estimated to be 74 MYA. 33 secondary metabolism gene clusters were identified via antiSMASH software, mainly including non-ribosomal peptide synthase genes and T1 polyketide synthase genes. 525 genes were annotated to encode enzymes that act on carbohydrates, involving 101 glucose-degrading enzymes and 24 polysaccharide synthase. By whole-genome sequence analysis, large numbers of metal resistance genes were found in strain P1. Especially ABC transporter and Superoxide dismutase ensure that the P1 fungus can survive in a chromium-polluted environment. ChrA and ChrR were also identified as key genes for chromium resistance. Analysis of their genetic loci revealed that the specific coding-gene arrangement may account for the fungus’s chromium resistance. Genetic information and comparative analysis of Penicillium janthinellum are valuable for further understanding the mechanism of high resistance to heavy metal chromium, and gene loci analysis provides a new perspective for identifying chromium-resistant strains.
RIPK3-Dependent Necroptosis Limits PRV Replication in PK-15 Cells
Authors: Gou Hongchao , Bian Zhibiao , Cai Rujian , Chu Pinpin , Song Shuai , Li Yan , Jiang Zhiyong , Zhang Kunli , Yang Dongxia , Li Chunling
Published: June 2021

Pigs infected by pseudorabies virus (PRV) display necrotic pathology in multiple organs. The mechanism by which PRV induces cell death is still unclear. Recently, necroptosis was identified as a programmed process dependent on the receptor interacting protein kinase 3 (RIPK3) and mixed lineage kinase-like protein (MLKL). In this study, we demonstrated that PRV induced RIPK3-dependent necroptosis in PK-15 cells. The data showed that PRV infection caused cell death with Propidium Iodide (PI)-positive staining. Transmission electron microscopy analysis indicated plasma membrane disruption in PRV-infected cells. A pan-caspase inhibitor did not prevent PRV-induced necrotic cell death. Western blot analysis indicated that caspase-3 and caspase-8 were not cleaved during PRV infection. Although the transcription of tumor necrosis factor-alpha (TNF-α) was increased by PRV infection, RIPK1 was shown to be not involved in PRV-induced necrotic cell death by use of its specific inhibitor. Further experiments indicated that the phosphorylation of RIPK3 and MLKL was upregulated in PRV-infected cells. Stable shRNA knockdown of RIPK3 or MLKL had a recovery effect on PRV-induced necrotic cell death. Meanwhile, viral titers were enhanced in RIPK3 and MLKL knockdown cells. Hence, we concluded that initiation of necroptosis in host cells plays a limiting role in PRV infection. Considering that necroptosis is an inflammatory form of programmed cell death, our data may be beneficial for understanding the necrotic pathology of pigs infected by PRV.